Background: The brain contains the highest level of cholesterol in the body, and the total amount of serum cholesterol in the blood has a huge impact on brain aging and cognitive performance. However, the association of total serum cholesterol with cognitive function remains uncertain. This study determines whether there is an association between the total amount of cholesterol in the blood and cognitive performance in elderly females without a history of stroke. Methods: This population-based cross-sectional study was conducted on elderly (over 60 years old) females and males without a history of stroke from 2011 to 2014 in the US National Health and Nutrition Examination Survey (NHANES). The primary exposure was total blood cholesterol, and the main outcome was cognitive performance; this association was assessed with logistic regression analysis and restricted cubic splines. Results: 1309 female and 1272 male participants were included. In females, higher total cholesterol was significantly associated with higher cognitive scores, particularly in the digit symbol substitution test ) and the animal fluency test ). This association remained significant in models adjusted for age, race, smoking status, education level, and chronic conditions ). This association was not significant in males, however. Conclusions: A higher concentration of total cholesterol measured in later life may be a protective factor for cognitive performance among females over 60 years old without a history of stroke. Further, this association was more pronounced among women with higher levels of education than women with lower or no education. Dementia, or Alzheimer’s disease, is the fifth leading cause of death for individuals 65 years of age and older in the United States . WorldwiIt has been hypothesized that lipid metabolism is associated with cardiovascular health problems . HoweverHowever, in clinical practice, the relationship between total cholesterol and cognitive performance , and theThus, we analyzed a sample of older females over 60 years old in the National Health and Nutrition Examination Survey (NHANES) to elucidate the association between total cholesterol and cognition in late life.The National Health and Nutrition Examination Survey (NHANES) is a survey research program conducted to assess the health and nutritional status of adults and children in the United States, tracking changes over time. It began in 1971 and became an annual event in 1999. In each cycle, approximately 5000 representative people are selected via a complex process of multistage probability sampling. All participants complete an informed consent document. The survey combines interviews, physical examinations, and laboratory tests. The participants first take part in an interview at home; physical examination and laboratory tests are conducted in the mobile examination center (MEC) before a call-back consultation is carried out within the next few days.N = 157) and participants with a history of stroke (N = 197). Next, the study enrolled 1309 female and 1272 male participants aged 60 or older (Two cycles (2011–2012 and 2013–2014) of data with the most recent information on cognitive function measures were collected and combined for our research. A total of 19,931 individuals participated in the NHANES from 2011 to 2014. A total of 2934 of the participants aged 60 or older were used in our research because only this sample of participants received a cognitive assessment. Among these participants, we further excluded those without total cholesterol measurements  were used to measure total cholesterol. A heparin–manganese precipitation method or a direct immunoassay technique was used to measure high-density lipoprotein cholesterol ,32,33,34The cognitive function of older participants (aged 60 or over) was estimated using four tests ,36: (1) The CERAD  includesThe AFT is widely used to estimate the cognitive abilities of patients with various neurological diseases. The test requires participants to name as many animals as possible in a short period of time. A low AFT score reflects an impairment of language function ,44. It hThe DSST consisted of digit–symbol pairs followed by a list of digits. The participants aim to write the corresponding symbol from the 133 boxes that hold adjacent numbers as quickly as possible. The number of correct symbols within the allowed time (2 min) is the score .Due to the ceiling and floor effect caused by a wide range of cognitive function in the elderly population, namely, the scale attenuation effect ,49, we c2; overweight: 25 to 30 kg/m2; obese: ≥30 kg/m2), marital status, drinking , diabetes , and cht-test or Mann–Whitney U-test was used to compare different levels of continuous variables between groups. A two-sided p < 0.05 was considered statistically significant.Statistical analysis was performed on the original datasets extracted from the NHANES and a complex sample analysis was performed using the stratification, cluster, and sample weight variables provides in the NHANES . A new sIn this study, the total cholesterol values among female and male participants were categorized into four groups according to first quartile, medium, and third quartile. For the main outcome , single-variable logistic regression was performed to analyze the association between cognitive performance and total cholesterol in an unadjusted model. Multivariable logistic regression was performed and controlled for the effects of the following covariates of cognitive function: age, education level, race, smoking and drinking status, poverty–income ratio, BMI, chronic conditions (including diabetes and hypertension), and marriage status. The variables including age, race, education level, marriage status, poverty–income ratio, and BMI were used for adjustment in Model 2; the variables, including Model 2 plus drinking status, smoking status, and chronic conditions (hypertension and diabetes), were used for adjustment in Model 3.N = 2581) and of the female (N = 1309) and the male (N = 1272) participants in the final study sample were summarized and shown in p < 0.01). Participants who were considered to have a cognitive impairment were more likely to be Mexican American, other Hispanic, non-Hispanic Black, and other races; have lower educational level and poverty–income ratio; have chronic conditions (including diabetes and hypertension); drink more; be widowed, divorced, separated, or never married; or have lower total cholesterol levels. For DSST, the prevalence of smoking (including currently smoking or previously smoked) in participants with low cognitive performance was significantly higher than that of people with normal cognitive performance. However, a higher concentration of total cholesterol was significantly associated with cognitive function only among older female participants; in older male participants, this association was not significant. The demographic characteristics of all the participants  with a 95% confidence interval (CI) of 0.72  for AST score, 0.53  for DSST score, and 0.49  for global cognitive performance; those reporting more than 229 mg/dL had an odds ratio (OR) with a 95% confidence interval (CI) of 0.51  for AST score, 0.64  for DSST score, 0.69  for CERAD test, and 0.41  for global cognitive performance.After adjustments for age, race, education level, the ratio of family income to poverty line, marriage status, and BMI, 201–229 mg/dL of total cholesterol was associated with the DSST ) and global cognitive performance ), whereas more than 229 mg/dL of total cholesterol was associated with different dimensions of cognitive performance  for AST score, 0.70  for CERAD score, and 0.34  for global cognitive performance).ptrend < 0.05) in an adjusted model, and that a higher dose of total cholesterol had a greater advantage for the protection of cognition.Additionally, in Model 3, compared with low total cholesterol levels, those who had 201–229 mg/dL of total cholesterol had a multivariate-adjusted OR (95% CI) of 0.62  for DSST, and 0.58  for global cognitive performance, and those who had more than 229 mg/dL of total cholesterol had a multivariate-adjusted OR (95% CI) of 0.57  for AST score, and 0.40  for global cognitive performance. The trend test shown in However, Restricted cubic spline analyses between total cholesterol and the Animal Fluency Test score (A), the DDST (B), the CERAD test (C), and the global cognitive performance (D). The solid line and dashed lines represent the estimated ORs and their 95% confidence intervals .The baseline characteristics of the approximately 25 million persons represented by the 1309 female participants are shown in With the increase in life expectancy, cognitive impairment is an important public health problem; furthermore, the incidence of cognitive impairment is increasing. A systematic review has reported that the global prevalence of cognitive impairment ranged from 5.1% to 41% . The facIn this study, we combined data including NHANES 2011–2012 and 2013–2014. This research explored data provided by 1309 female Americans aged 60 years or older who had no history of stroke. The 1309 female participants are representative of approximately twenty-five million people in America. In the unadjusted model, a high concentration of total cholesterol was statistically associated with higher global cognitive and animal fluency test scores. In the model adjusted for age, race, education levels, income–poverty ratio, history of diabetes, and smoking status, total cholesterol remained associated with global cognitive and animal fluency scores.To date, evidence for the relationship between total cholesterol and cognitive function in elderly populations has been equivocal and inconclusive, likely due to the effects of aging. Our findings on the relation between total cholesterol and cognition were consistent with some previous studies. Research based on 382 people studied the relationship between concentrations of total cholesterol and cognitive performance in participants ranging from 70 to 90 years old, revealing that a lower total cholesterol value is associated with poorer cognition in both non-dementia and dementia cases . AnotherThere have also been studies revealing total cholesterol’s harmful effects on cognition. A study found that higher blood concentrations of total cholesterol were related to faster global cognitive decline in a population of 1159 Chinese adults aged over 60 ; the assSome studies have suggested that this relationship could be age-dependent, i.e., the higher concentration of total cholesterol measured at midlife was a risk factor for late-life cognition , while tAlthough genetic susceptibility and metabolic function determine an individual’s lipid profile to a great extent, factors related to lifestyle may affect the clearance of cholesterol. Different kinds of diet may affect cognitive function ,69. In aThere are several limitations and strengths in our study. First, we chose the NHANES as our data source, which provided a sufficiently large sample size. Second, we used four standard scores of four cognitive tests to create a global compound cognitive score to minimize the ceiling and floor effects. Third, considering that age was the major risk factor for cognitive impairment, age was used to divide the population and to calculate the cut-off values (the lowest quartile) of each group. However, as a cross-sectional study, this research could not reveal the relationship between total cholesterol and cognitive performance for the population at different ages. Further longitudinal studies need to be conducted to investigate the nonlinear longitudinal relationship between total cholesterol and neuropsychological function and cognitive performance.Investigating the relationship between total cholesterol and cognitive function can provide information that is significant for the prevention of cognition decline. Because this effect could be age-related, we might consider adopting different strategies in different ages in future work.In America, a higher concentration of total cholesterol measured in late life may be a protective factor for cognitive performance among females over 60 years without a history of stroke. This association was more significant among females with higher education levels and was not as apparent in females with lower education levels or without an education. We postulate that a better total cholesterol concentration could be 200 mg/dL in elderly females without a medical history of strokes.


Planktothrix dominating in the Thames River and Microcystis and Synechococcus in Lake St. Clair and Lake Erie. Mantel correlations highlighted the importance of geographic distance in shaping the microbial community structure. The fact that a high proportion of microbial sequences found in the Western Basin of Lake Erie were also identified in the Thames River, indicated a high degree of connectivity and dispersal within the system, where mass effect induced by passive transport play an important role in microbial community assembly. Nevertheless, some cyanobacterial amplicon sequence variants (ASVs) related to Microcystis, representing less than 0.1% of relative abundance in the upstream Thames River, became dominant in Lake St. Clair and Erie, suggesting selection of those ASVs based on the lake conditions. Their extremely low relative abundances in the Thames suggest additional sources are likely to contribute to the rapid development of summer and fall blooms in the Western Basin of Lake Erie. Collectively, these results, which can be applied to other watersheds, improve our understanding of the factors influencing aquatic microbial community assembly and provide new perspectives on how to better understand the occurrence of cHABs in Lake Erie and elsewhere.Lake Erie is subject to recurring events of cyanobacterial harmful algal blooms (cHABs), but measures of nutrients and total phytoplankton biomass seem to be poor predictors of cHABs when taken individually. A more integrated approach at the watershed scale may improve our understanding of the conditions that lead to bloom formation, such as assessing the physico-chemical and biological factors that influence the lake microbial community, as well as identifying the linkages between Lake Erie and the surrounding watershed. Within the scope of the Government of Canada’s Genomics Research and Development Initiative (GRDI) Ecobiomics project, we used high-throughput sequencing of the 16S rRNA gene to characterize the spatio-temporal variability of the aquatic microbiome in the Thames River–Lake St. Clair-Detroit River–Lake Erie aquatic corridor. We found that the aquatic microbiome was structured along the flow path and influenced mainly by higher nutrient concentrations in the Thames River, and higher temperature and pH downstream in Lake St. Clair and Lake Erie. The same dominant bacterial phyla were detected along the water continuum, changing only in relative abundance. At finer taxonomical level, however, there was a clear shift in the cyanobacterial community, with  Howevermunities .Aphanizomenon and Dolichospermum) and non N-fixing cyanobacteria , specific conductivity (Cond), pH, and dissolved oxygen (DO) were measured at each site with a SBE 25plus Sealogger (Seabird) on board the CCGS Limnos, and with a Quatro Pro (YSI Inc.) in Lake St. Clair, Detroit and Thames Rivers. Water samples for total phosphorus (TP), total dissolved phosphorus (TDP), total nitrogen (TN), total dissolved nitrogen (TDN), and particulate organic carbon (POC), were submitted to Environment and Climate Change Canada’s National Laboratory for Analytical Testing  and prepared following their Standard Operating Procedures for filtration and preservation. Chlorophyll a (chla) concentrations were determined spectrophotometrically after extraction in acetone following the NLET method  were collected between January 2016 and October 2019  and stored at −80°C until further processing. All genomic procedures were carried out following a standard approach for genomic research conducted by the government of Canada . DNA was2.3.a) based on the following: a matrix of Spearman correlations among all environmental variables was calculated and those with high correlation (ρ > 0.8 and p < 0.01) with more than one other variable were removed. Hence, TDP and TN were removed for downstream analyses. The remaining environmental variables were projected onto the NMDS ordination using envfit function available in package vegan  were used to assess the relationship between the proportion (from 0 to 1) of cyanobacterial genera relative abundance (arcsine and squared-root transformed) and the following environmental variables: temperature, pH, log-transformed TP, TDP, TN, TDN, and the ratio between TN and TP. GAMs have the advantage of mixing linear model terms with a smoothed and flexible model term and are therefore best suited for non-linear relationships because they can fit non-linear models to data . GAMs wh3.3.1.−1. TP decreased downstream in Lake St. Clair and averaged below 25 μgL−1 in Lake Erie, even in the Western Basin, which experiences annual cyanobacterial blooms and normally corresponds to a mesotrophic state. However, a brief peak of 79.3 μgL−1 TP was measured during spring 2017 in the Western Erie Basin. In fact, the average TP concentration in the Western Basin was only marginally higher than observed in the two other basins during the sampling period. A similar trend was observed for TDP, where concentrations were on average higher in the Thames River than in the rest of the aquatic continuum. No TN data were collected in the Thames River from 2016 to 2018, so reported values are only based on 2019 sampling. This showed a clear gradient of decreasing TN and TDN concentrations from the Thames River to Lake St. Clair and Lake Erie, where concentrations were on average one order of magnitude lower than in the Thames River . Since there was a strong overlap among the centroids for the 4 years in dispersion plots , all furR2 = 0.21, p < 0.01) and presented a longitudinal dissimilarity gradient along the hydrological continuum, as pointed out by two different multivariate ordinations . Our analyses indicated that the Thames River microbial community was influenced by higher nutrient concentrations, while those of Lake St. Clair and Lake Erie appeared to be mediated by higher pH, Cond, and temperature. Across the whole aquatic continuum, the microbial community showed distinct patterns across seasons , although there seemed to be more overlapping across season than system, for example, between summer and fall  for the variation partitioning analysis. This analysis explained 35% of the microbial community composition, and attributed 24% (p < 0.01) of the variance in microbial community to the environmental and 23% (p < 0.01) to the spatial variables, with a 12% intersection between the two. This indicates that 12% (p < 0.01) of the variation was solely due to the measured environmental variable and 11% (p < 0.01) solely to the geographic location. Sixty-five percent of the variation was left unexplained.The microbial and cyanobacterial communities showed the same type of spatial patterns, as inferred by the Mantel correlations, which suggested that both were significantly correlated with spatial extent. Both communities showed the highest positive and significant spatial autocorrelation across samples that were less than 7 km apart . SpatialAnabaena, Aphanizomenon, and Dolichospermum, which were then classified as the Anabaena-Aphanizomenon-Dolichospermum complex (AAD complex). During winter, the relative abundance of cyanobacteria was very low and only reached 0.3% of the microbial community in Lake Erie (only one winter sample available) and was mostly composed of Synechococcus and the AAD complex . In spring, the relative abundance of cyanobacteria reached a maximum of 1.4% (2%) in the Lower Thames River  of the Lake Erie’s Western Basin, with Microcystis as the dominant cyanobacterial genus , while Pseudanabaena dominated in the Central and Eastern Basins. Planktothrix was dominant in Lake St. Clair composing 32% of the cyanobacterial community.The following proportions of phyla, genera, and ASVs represent average relative abundances of the 4 years of sampling with the standard deviation in parentheses. The phylum Proteobacteria dominated the Upper Thames River, representing 53% (9%) of the winter microbial community, and then decreasing in relative abundance through the water continuum as observed in each season . A similes River , and wasontinuum . In summontinuum , and wasrn Basin . Microcy3.3.The genetic connectivity was assessed amongst part of the system that were closely connected from upstream and downstream, and because of their poor connection with the rest of the water continuum, notably highlighted by the NMDS analysis , Lake ErThe highest number of ASVs was found in the Thames River, followed by Lake St. Clair (including the Detroit River) and Lake Erie  seemed to become more abundant in Lake Erie during the fall, reaching 5% (8.3%) and 1.8% (1.4%) of the microbial community, respectively, but stayed in lower relative abundance in Lake St. Clair. ASV 12 clustered with the culture representativeGloeocapsa, which peaked in relative abundance in the Western Basin during summer but represented only 0.5% (0.7%) of the microbial community. The next cluster in the phylogenetic tree contained two ASVs of the genus Planktothrix (ASV 1 and 3) that both dominated in the Thames River during summer and fall, especially ASV 1 which accounted for 9.9% (10.3%) of the microbial community in the Lower Thames River during fall. ASV 4 clustered closely with the sequence of the culture representative Aphanizomenon flos-aquae that was more abundant in the Thames River, reaching 4.4% (7.6%) of relative abundance in the Lower Thames during the fall. This ASV was also present in Lake St. Clair and Erie, although in lower relative abundance. Finally, the last cluster of the phylogenetic tree gathered sequences of 6 different ASVs clustering with the genus Synechococcus and two with the genus Anathece, both genera belonging to the Order Synechococcales. Those ASVs started to become more abundant in Lake St. Clair, followed by the Detroit River, and Lake Erie during summer and fall, and some were not detectable at all in the Upper Thames River .Genetic connectivity within the watershed was further explored for the 15 most abundant cyanobacterial ASVs using a phylogenetic analysis. Those ASVs clustered with the genera hococcus . Three Ant times , and cou3.4.p < 0.01), the explanatory power of the R2 remained relatively low (from 0.02 to 0.47), and no clear pattern was observed between the set of selected environmental variables and the relative abundance of dominant Cyanobacteria . Compared to Planktothrix, both Microcystis and Synechoccocus genera seemed to peak at lower nutrient (N and P) concentrations which corresponded to concentrations found in Lake Erie in comparison to the Thames River  compared to Synechococcus (R2 = 0.3). No clear relationship was observed between cyanobacterial relative abundance and pH. Finally, the relative abundance of Microcystis seemed to peak at a TN/TP mass ratio ≥ 30, which generally corresponds to the multi-annual average TN/TP mass ratio (35) of Lake Erie’s Western Basin, while the other systems had higher average TN/TP mass ratio values . However, no clear trend was observed between Synechoccocus or Planktothrix relative abundances and nutrient mass ratios.Because of the non-linear nature of the relationships, Generalized Additive Models (GAMs) were used to test those correlations, and, although all the relationships presented here were significant  as a major influence for Lake Erie’s communities.rd behind the Maumee and Sandusky Rivers in contributing TP and SRP to Lake Erie (3/s), which flows directly from Lake Huron, the Thames River has a disproportionate effect on the TP load, to the extent that P reduction in the Thames River basin will be more effective in reducing the P export from Lake St. Clair than from the equivalent in-flow Sydenham or Clinton Rivers , which is the second in importance after the Maumee River which contributes up to 48%  have been identified as variables which significantly influenced microbial community structure. Water chemistry parameters often shape aquatic system due to their direct impact on microbial metabolism. Nutrients, and by extension, trophic status, have a prime effect on microbial community structure  and diverobiomes , and higrobiomes , and takrobiomes .Microcystis and Cylindrospermopsis; ρ = −0.05, p < 0.01), and Proteobacteria were found in higher relative abundance in the Thames River compared to the downstream systems. ρ = 0.4, p < 0.01) and were found in higher relative abundances in the downstream Lakes St. Clair and Erie. Some taxa belonging to the Verrucomicrobia have been shown to display a higher diversity in the presence of cyanobacteria , which suggests that other factors not investigated in this study are important. In contrast, the relative abundance of Planctomycetes and Cyanobacteria were positively correlated , consistent with other reported associations between Planctomycetes and phytoplankton blooms  and in the Western and Central Basins of Lake Erie  addition while, under the same conditions, Microcystis decreased in relative abundance  dominated samples collected from the high P environment near the mouth of the Maumee River. On the other hand, Planktothrix dominance has also been observed in the Sandusky river plume, where it’s capacity to accumulate N through cyanophycin compounds provided a competitive advantage under N limiting conditions ; hence it is difficult to draw conclusions regarding the link between cyanobacteria relative abundance and temperature. However, climate projections predict that Lake Erie will have longer and more stable periods of stratification, which are likely to lead to increasing frequency and worsening impact of cHABs  were in fact composed of an assemblage of different ASVs becoming dominant at different times. These data further suggested that the two most abundant cyanobacterial genera in Lake St. Clair and Lake Erie, Microcystis and Synechococcus, stayed relatively abundant even at lower N and P concentrations than Planktothrix, which dominated in the higher nutrient regimes of the Thames River. Overall, there was still a large proportion of the variation observed in the microbial community structure that was not explained by spatial and environmental factors, demonstrating the importance of unexplored drivers of microbial and cyanobacterial community structure such as biotic interactions and hydrodynamics. The high connectivity and level of dispersion between the upstream, riverine and Lake Erie microbial and cyanobacterial communities highlight the need for watershed scale management to improve the water quality conditions in Lake St. Clair and the Western Basin of Lake Erie.Here we used an integrated approach at the watershed scale to better understand the biological and ecological context shaping Lake Erie’s microbiome, with a special focus on the cyanobacterial community given Lake Erie’s long history of harmful algal blooms. This study showed how spatial and temporal variations, as well as environmental variables, are shaping the microbial communities in the Thames River–Lake St. Clair-Lake Erie continuum. In terms of community composition, gradual changes along the water continuum were observed for the whole microbial community. On a finer taxonomical level, distinct communities of cyanobacteria developed in the Thames River, mostly dominated by 6.https://www.ncbi.nlm.nih.gov/genbank/, PRJNA877648.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: SC, TE, SW, and JC designed study. SC, TE, LW, JC, ND, AD, KD, TF, RM, AZ, and JC collected data. SC and JC analyzed sequencing data, performed statistical analyses, and conceived of the manuscript. SC, TE, LW, SW, CG, and JC supervised the project and performed research. SC took the lead in writing the manuscript with help in editing and correcting from all the other authors. All authors contributed to the article and approved the submitted version.This study was funded under the Canada’s Genomics Research and Development Initiative (GRDI) & Great Lake Protection Initiative (GLPI), and also supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) , the Great Lakes Center for Fresh Waters and Human Health supported by NIEHS (1P01ES02328939–01), and NSF (OCE-1840715).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Introduction: Autoimmune bullous dermatoses (ABD) represent a heterogeneous group of blistering disorders that may be debilitating with high morbidity. Clinical, histological, and direct immunofluorescence (DIF) studies are essential in establishing an accurate diagnosis of ABD, which is essential for its clinical management. Our study objective was to perform a systematic evaluation of ABD cases in a patient population at an academic medical center in Ho Chi Minh City, Vietnam, and determine the degree of concordance of clinical, histological, and DIF findings in ABD. Methodology: A systematic retrospective cross-sectional study was performed on 92 patients diagnosed with ABD by clinical, histological, and DIF studies at the University of Medicine and Pharmacy in Ho Chi Minh City, Vietnam, between September 2019 and September 2021. The clinical histories, H and E stained tissue sections, and DIF stains were evaluated by pathologists at the University of Medicine and Pharmacy. Results: ABD was evaluated as a whole and subdivided into an intraepidermal blister subgroup and a subepidermal blister subgroup. The analysis of paired diagnostic methods  for concordance with the final diagnosis was performed and showed that there were no statistically significant differences between the paired methods . There was moderate concordance between the clinical, histological, and DIF diagnoses among all ABD cases . In the intraepidermal blister subgroup, the diagnostic accuracies of the histology and DIF stains were comparable to each other, and both were more accurate than a clinical diagnosis alone. In the subepidermal blister subgroup, there was no statistically significant difference in each pair of the three diagnostic methods  . The concordance between the clinical, histological, and DIF diagnoses was high for the intraepidermal blister subgroup . However, the concordance between the clinical, histological, and DIF diagnoses was slight for the subepidermal blister subgroup . Conclusion: Histological evaluation is highly accurate in the diagnosis of the intraepidermal blister subgroup, but it is not as accurate in the diagnosis of the subepidermal blister subgroup in the Vietnamese patient cohort in which clinical, histological, and DIF studies were performed. DIF stains are a crucial diagnostic tool for ABD in this patient population. Autoimmune bullous dermatoses (ABD) represent a heterogeneous group of rare blistering disorders characterized by antibody-mediated autoimmune responses against the structural components of the skin and mucosa, resulting in blistering eruptions ,2,3. Bul(a)Adequate clinical history and description of lesions;(b)Skin and/or mucosal biopsies were sent to the pathology laboratory of the University of Medicine and Pharmacy at Ho Chi Minh City with proper preservation and transportation for the DIF assays;(c)Hematoxylin and eosin (H and E) stained slides of the skin biopsies were available for evaluation;(d)DIF-stained slides of the skin biopsies were available for evaluation;(e)Cases with a missing epidermis on the DIF and/or H and E slides were excluded from the study. Also excluded were cases with negative DIF results, including cases with prior treatments, and therefore may have had negative DIF results.A cross-sectional retrospective chart review study was conducted on 92 cases diagnosed with ABD and DIF stains in the Department of Pathology, University of Medicine and Pharmacy in Ho Chi Minh City, Vietnam, from September 2019 to September 2021. The clinical histories and histopathology work-ups were retrospectively collected from patients’ medical records. The inclusion criteria of this study were:The clinical data were collected from patients’ medical records. For each patient, two biopsy specimens were obtained and processed: one biopsy for the routine H and E stains and the other biopsy for the DIF stains. A shave biopsy specimen was obtained from the edge of an intact blister consisting of the edge of a bulla and adjacent non-bullous “normal” skin. The specimen was fixed in 10% neutral-buffered formalin and then processed in paraffin as per standard histological procedures. Four micron-thick tissue sections were cut for hematoxylin and eosin (H and E) staining. Another shave biopsy specimen was taken from non-bullous erythematous skin within 1 cm of a bulla for the DIF stains. This specimen was placed on saline-soaked gauze and transported to the laboratory within 24 h. The specimen was embedded in the Optimal Cutting Temperature (OCT) compound and frozen at −20 °C in a cryostat. Six 4 µm-thick tissue sections of the specimen were cut onto charged glass slides and air-dried for 15 min. The slides were fixed in acetone at −20 °C for 10 min, then air dried for five minutes, and permeabilized with 0.3% Triton X-100/phosphate-buffered saline (PBS) for 10 min before washing in PBS. The slides were then incubated with a fluorescein isothiocyanate (FITC)-labeled primary antibody to IgA, IgG, IgM, C3, and fibrinogen at 37 °C for one hour, then rinsed three times in PBS for five minutes each rinse to remove the unbound antibodies. A negative control slide was prepared in the same manner as the specimen slides without the addition of an antibody. All slides were mounted with buffered glycerin. The DIF-stained slides were examined by a pathologist to determine the split location  and pattern (linear or granular) of the immunoglobulin deposition.The histological diagnoses were based on the presence of classic microscopic features. The microscopic assessment of the H and E slides included the level of split formation , the presence of acantholysis, and the predominant inflammatory cells  ,2,3 Tab. For exaThe DIF diagnoses were based on typical immunoglobulin depositions. The DIF slides were examined to determine the primary sites of immune deposition, classes of immunoglobulin deposition , stain intensity, and patterns of immunoglobulin deposition ,13,14,15Statistical methods: The data analysis was performed using Microsoft Excel and Software for Statistics and Data Science (Stata) version 14.0. The differences between clinical and histopathologic diagnoses, between clinical and DIF diagnoses, and between histopathology and DIF diagnoses were determined using McNemar’s test, which is used to determine if there are differences regarding a dichotomous dependent variable between two related groups. The overall agreement between the clinical, histopathological, and DIF diagnoses was assessed using the Brennan-Prediger coefficient using Kappa statistics. The statistical significance was set at a 95% confidence interval (CI = 95%).We evaluated a total of 92 cases of ABD from 2019 to 2021, consisting of 55 cases of intraepidermal blisters and 37 cases of subepidermal blisters. The microscopic assessment of the H and E slides included the level of split formation , the presence of acantholysis, and the predominant inflammatory cells  [The patients with intraepidermal blisters were between 11 and 82 years of age, with a mean age of 52 years. There were two pediatric cases of intraepidermal blisters: an 11-year-old female with PV and an 11-year-old male with IAP. There was greater than twice the number of females affected than males.The patients with subepidermal blisters were between 10 and 95 years of age, with a mean age of 60 years. There was one pediatric case of subepidermal blisters: a 10-year-old male with BP, a 14-year-old male with LAD, and a 16-year-old female with BSLE. There was an equal ratio of females and males affected. All LAD cases had an onset after puberty, with 3/8 (37.5%) patients younger than 19 years old. We evaluated the extent of concordance between paired diagnostic methods using McNemar’s test to determine if differences existed regarding a dichotomous dependent variable between two paired or related groups. The paired diagnostic methods included clinical diagnosis and histological diagnosis, clinical diagnosis and DIF diagnosis, and DIF diagnosis and histological diagnosis. A result is designated as positive (+) if it is concordant with the final diagnosis. A result is designated as negative (−) if it is discordant with the final diagnosis. The McNemar statistics contingency table comparing the efficacy of the paired diagnostic methods for the intraepidermal bulla and subepidermal bulla subgroups is shown in p-McNemar’s test, α = 0.05) (BP) of 0.522 (CI = 0.95), which indicates a moderate level of agreement.In a total of 92 ABD cases, the differences between the clinical diagnoses and histological diagnoses, between the clinical and DIF diagnoses, and between the histological and DIF diagnoses were not statistically significant (mid- = 0.05) . The agrp-value = 0.021) and between the clinical and DIF diagnoses  were statistically significant. The histological examination and DIF staining provided comparable results  (BP coefficient of 0.758 (CI = 0.95), indicating a substantial level of agreement.Within the intraepidermal blister subgroup, the differences between the clinical diagnosis and histological diagnosis (McNemar’s test mid-= 1.000) . The conp-McNemar’s test (BP of 0.171 (CI = 0.95), which indicates a slight extent of agreement.Within the subepidermal blister subgroup, the in-pair differences of the three pairs of diagnostic methods were not statistically significant according to the mid-r’s test . The conThere were discordant findings in the clinical/DIF pair of diagnostic methods for subepidermal blisters. Examples of such discordant cases are shown in In the Vietnamese patient cohort of this study, pemphigus vulgaris and bullous pemphigoid were the two most prevalent disorders of ABD, with pemphigus vulgaris accounting for 74.5% of the intraepidermal blister subgroup and bullous pemphigoid accounting for 73.0% of the subepidermal blister subgroup. Pemphigus vulgaris was more common than bullous pemphigoid (41 cases of pemphigus vulgaris versus 27 cases of bullous pemphigoid). The findings appear to be comparable with those reported in the literature ,17,18. TThis study shows a marked predilection for females in the intraepidermal blister subgroup with female-to-male ratios of 2.7:1 for pemphigus vulgaris, and 2.2:1 for pemphigus foliaceus. A female predilection for intraepidermal blisters was also reported in other studies in different populations and geographic regions . HoweverWe observed that most patients in the intraepidermal blister subgroup were 30 to 59 years of age, with an average age of 52 years, which is comparable with data reported in the literature . The perBP) of 0.522 (CI = 0.95), which indicates a moderate level of agreement. There was no statistically significant difference between the clinical and histological diagnoses, between the clinical and DIF diagnoses, and between the histological and DIF diagnoses . There were three cases in which the initial clinical diagnosis differed significantly from the final diagnosis. There was a case that had an initial clinical diagnosis of allergic contact dermatitis, which was, in fact, pemphigus foliaceus; a case with a clinical diagnosis of allergic contact dermatitis that turned out to be pemphigus vulgaris; and a case with clinical diagnosis of herpes-associated erythema multiforme that turned out to be bullous pemphigoid. DIF stains performed on these three cases showed immunoglobulin deposition characteristics of immune bullous disorders.We observed that the agreement between the clinical, histological, and DIF diagnoses was statistically significant, with a Brennan-Prediger coefficient . These findings indicate that histological diagnoses have a higher degree of accuracy than clinical diagnoses. Similarly, DIF diagnosis was concordant with the final diagnosis in seven out of nine cases . These findings indicate that DIF diagnoses have a higher degree of accuracy than clinical diagnoses.In the intraepidermal blister subgroup, the observed agreement between the clinical and histological diagnoses was high 81.8% in . Howeverne cases , with a p-McNemar’s test, mid-p-value = 1.000). Moreover, we did not identify any cases in which both the histological and DIF findings were discordant with the final diagnosis. In summary, the utilization of both histological and DIF studies provides the necessary information to derive the final diagnosis in all cases of the intraepidermal blister subgroup in the study.Our study showed that within the intraepidermal blister subgroup, the histological diagnosis was in concordance with the final diagnosis in 96.4% of the cases. The histological diagnosis was based primarily on the plane of split formation and acantholysis. Acantholysis could also be seen in non-autoimmune bullous disorders, such as Hailey-Hailey disease, Darier disease, and Grover’s disease ,2,3,26. p-McNemar’s test (p > 0.05). However, the histological diagnosis was concordant with the final diagnosis in only 64.9% of the subepidermal blister cases, whereas concordance between the clinical diagnosis and final diagnosis was 81.1%, and between DIF diagnosis and the final diagnosis was 83.8%. We based the histological diagnosis of subepidermal disorders on two major findings: the presence of subepidermal blisters and the type of infiltrating inflammatory cells, which may vary according to the age of the lesion. The histological assessment appeared to have lower accuracy in evaluating subepidermal bullous disorders. A possible cause of the discordance is that a number of non-immunobullous disorders, such as drug allergy, hypersensitivity reactions, insect bites, herpetic infection, allergic contact dermatitis, and infectious skin bullae, are relatively common in Vietnam, and they have clinical features that may overlap with subepidermal bullous disorders and may have led to diverse and discordant clinical diagnostic assessments.In the subepidermal blister subgroup, the in-pair difference of the three diagnostic methods was not statistically significant according to mid-BP = 0.17) between the clinical, histological, and DIF findings in the subepidermal group. Similarly, the concordance between the histological and clinical diagnoses, as well as between the histological and DIF diagnoses, was slight, with κBP values of 0.027 and 0.081, respectively. In contrast, there was better concordance between the clinical and DIF diagnoses (κBP = 0.41). These findings suggest that the limited diagnostic accuracy of routine H and E interpretations for classifying subepidermal bullous disorders could influence the overall degree of concordance between the clinical, histological, and DIF diagnoses in this subgroup.The Brennan-Prediger coefficient revealed a slight concordance (κA limitation of our study is that we often lacked comprehensive details of the clinical evaluation of ABD, especially for cases that originated from general practitioners, internists, and other non-dermatologic clinicians. We gathered clinical diagnoses from patients’ medical reports to consider as a reference for formulating the final diagnoses. Without detailed information on the clinical criteria which clinicians utilized for their clinical diagnoses, we were unable to conclude accurate correlations between the clinical diagnosis and histopathologic diagnosis.Other immunological methodologies, such as serologies, ELISA, and indirect immunofluorescent staining with the salt-split skin technique, could improve the diagnostic accuracy of immunobullous disorders. However, many patients in our study did not have access to these assays other than standard H and E, and DIF for diagnostic work-ups. Within the scope of the clinical, histological, and DIF findings in this study, we utilized the classic histological and DIF characteristics of each subtype of bullous disorders to arrive at the final diagnosis. This also reflects the routine and practical approach we use in our daily medical practice in diagnosing bullous disorders in Vietnam. In summary, our study demonstrates that the diagnosis of autoimmune bullous disorders in the Vietnamese population could be accurately formulated based on a combination of clinical, histological, and DIF studies.The assessment of autoimmune bullous dermatoses in Vietnamese patients shows that the clinical, histological, and DIF evaluations had a moderate level of agreement in intraepidermal bullous disorders, while these three diagnostic modalities had a slight level of agreement in subepidermal bullous disorders. The histological and DIF evaluations showed strong concordance in the intraepidermal group, but it appeared to have a limited role in the subepidermal group. In cases with typical clinical and histological features, DIF stains confirmed the diagnosis. However, in cases in which the clinical features and histopathologies were inconclusive, the final diagnosis was concluded based on additional DIF studies. In real-world diagnostic evaluations, a combination of clinical, histological, and DIF studies would provide an optimal diagnostic work-up.


BackgroundUpper gastrointestinal bleeding (GIB) is an important cause of emergency ward admission. Antifibrinolytic agents including tranexamic acid (TXA) have been used for controlling GIB. However, there have been concerns regarding the safety and efficacy of TXA in patients with GIB. Thus, in this study, we aimed to determine the efficacy of TXA in the treatment of massive upper GIB.MethodologyThis double-blind randomized clinical trial was conducted among 86 consecutive patients who were referred to Imam Hossein Hospital in Tehran, Iran from 2018 to 2019 with the chief complaint of massive upper GIB. Patients were chosen to be in the TXA or placebo groups based on a 1:1 allocation using the block randomization method. The rate of rebleeding, need for blood transfusion, hospital stay, adverse effects, and mortality rate were evaluated and compared across the groups.ResultsOf the 86 patients enrolled in this study, 55.8% (n = 48) were males. The mean age of all patients was 53.1 ± 10.6 years . Rebleeding was seen in 11 (25.6%) patients in the TXA group and in 20 (46.5%) patients in the control group, which was statistically significant (p = 0.043). Blood transfusion was carried out in only three (7%) patients in the TXA group compared with 14 (32.6%) patients in the placebo group (p = 0.003). Six (14%) patients experienced a hospital stay of longer than five days in the TXA group and 15 (34.9%) patients in the control group, which was statistically significant (p = 0.024). There were no significant differences in the mortality rate across both groups (p > 0.05).ConclusionsTXA has no effect on mortality associated with severe upper GIB. However, it was associated with a lower rate of rebleeding and hospitalization time, without significant adverse effects. Upper gastrointestinal bleeding (GIB) is an important cause of huge mortality and high health costs. The prevalence is the same in men and women and increases with age . The morTranexamic acid (TXA), a lysine-analog antifibrinolytic agent, inhibits plasminogen activation by binding to its lysin binding site leading to the inhibition of fibrin clot degradation ,9. TXA hStudy designThis double-blind, randomized clinical trial was conducted among 86 consecutive patients who were referred to Imam Hossein Hospital in Tehran, Iran from 2018 to 2019 with the chief complaint of massive upper GIB. All patients aged over 18 years, with an unstable hemodynamic state which was defined as systolic blood pressure under 90 mmHg and heart rate over 110 beats per minute, and fulfillment of informed consent were included in this study. Furthermore, patients under the age of 18 years, pregnant/breastfeeding patients, and those with contraindications for use of TXA  were excluded from the study.Data collectionDemographic data including age, sex, history of smoking, vital signs, and cause of GIB (as determined by upper GI endoscopy) were recorded. Furthermore, standard GIB laboratory data, including hemoglobin (Hb) level, blood group, kidney function tests , prothrombin time (PT), and partial thromboplastin time (PTT), were collected. Indications for blood transfusion were considered as Hb <7 g/dL for patients without any comorbidity. The transfusion threshold was at Hb 9 g/dL for patients with life-threatening comorbidities predisposing the patient to ischemic damage.Rebleeding was defined as hematemesis, hematochezia, significant Hb drop of more than 2 g/dL during the hospital stay, continuous melena, and bright red blood in the nasogastric tube after the treatment was completed.Randomization and interventionPatients were chosen to be in the TXA  or placebo groups based on a 1:1 allocation using the block randomization method and GraphPad software . Both grStatistical analysisData analysis was done by SPSS version 26.0 . Quantitative variables were reported as mean ± SD, and qualitative variables were reported as numerical (percentage) data. The Kolmogorov-Smirnov test was used for assessing the normality of data. Considering the normality of data based on the Kolmogorov-Smirnov test , Fisher’s exact test was used for analyzing the differences between the two study groups, and a p-value under 0.05 was considered statistically significant.Ethical considerationThis study was conducted after obtaining permission from the Medical Ethics Committee of Shahid Beheshti University of Medical Sciences with the registration number IR.SBMU.MSP.RFC.1398.238.Of the 86 patients enrolled in this study, 55.8% (n = 48) were males. There were no significant differences between gender in both groups. The mean age of all patients was 53.1 ± 10.6 years . Moreover, there were no significant differences in age between the two groups. In addition, the most common cause of upper GIB was peptic ulcer disease , followed by malignancy , Mallory-Weiss tear , erosive gastritis , esophageal ulcer , and angiodysplasia . As shown in Table As shown in Table Upper GIB, defined as bleeding proximal to the ligament of Treitz, is a common disease with various etiologies. According to the severity of the bleeding, initial management mainly includes airway management and intravenous hydration. Proton pump inhibitor (PPI) therapy is a non-invasive pharmacologic treatment, which reduces rebleeding, mortality, and the need for endoscopic interventions. Therapeutic endoscopy is considered the cornerstone of diagnosis and treatment of the underlying cause of GIB ,17. AntiOur study aimed to compare the effects of TXA in the management of massive upper GIB versus placebo and to evaluate the role of TXA in bleeding control. According to this trial, it appears that TXA has beneficial effects in the treatment of upper GIB. In addition, it is associated with a significant reduction in the rate of rebleeding, blood transfusion, and hospital stay. Furthermore, the incidence of therapeutic adverse effects was the same across both groups. However, TXA did not reduce the mortality rate from GIB.According to our study, the incidence of GIB was different among males (55.8%) and females (44.2%), which was similar to previous studies reporting a higher frequency of peptic ulcer disease in men . AccordiRegarding the need for blood transfusion, our study showed a significant reduction in blood transfusion in the TXA group compared to the placebo group. von Holstein et al. reported similar results supporting the hypothesis that TXA reduces the need for blood product transfusion (p = 0.018) . AccordiTXA administration has been proven to reduce bleeding-associated death among patients with postpartum hemorrhage and trauma. The CRASH-2, a randomized placebo-controlled trial, evaluated the effects of early TXA administration on mortality and morbidity in trauma patients. They concluded that early TXA administration (beyond three hours) safely reduces mortality among traumatic patients without significant adverse effects . FurtherContrary to our findings, Redeen noted longer hospitalization in patients receiving TXA compared to the placebo group . HoweverFurthermore, TXA administration apparently had no effect on the mortality rate among patients with massive upper GIB. During this trial, only one patient passed away in the placebo group, and myocardial infarction was considered to be the cause. The HALT-IT trial suggested the same results, which was that there is no association between TXA administration and mortality reduction . PreviouDuring our trial, only one patient treated with TXA experienced an adverse effect associated with the medication, which was a skin reaction to TXA. Compared to placebo, it seems that TXA is not associated with significant adverse effects. Previous studies support the fact that TXA is not associated with a significant increase in the risk of adverse effects . In the Notably, the main limitations of this study is the lack of a larger sample size and a short follow-up time. Therefore, we suggest future investigations to evaluate the mid-to-long-term patient outcomes with a more considerable study population. Nevertheless, this study is one of the few prospective clinical trials to assess the safety and efficacy of TXA for the management of massive upper GIB.In summary, we noted that TXA has no effect on mortality associated with severe upper GIB. However, it was associated with a lower rate of rebleeding and hospitalization time, without significant adverse effects. Thus, we encourage physicians to expand the use of TXA in the treatment of GIB outside the context of current standard treatment. Future studies with larger sample populations are required to ascertain other aspects of TXA in the treatment of GIB.


There has been a growing trend of using local anesthesia (LA) compared to general anesthesia (GA) over the last two decades in VR surgery. We aim to answer the following question: what is the institutional benefit of LA versus GA use in operation-room time, anesthesia duration, earlier discharge from an outpatient surgery facility, and the estimated cost savings? We conducted a retrospective analysis of 1476 eyes that underwent vitreoretinal surgery over a 6-year period from a single site; 61.8% of patients received GA and 38.2% received LA for VR surgery. Anesthesia, surgical, and recovery times were significantly shorter with LA  vs. GA . Anesthesia, surgical, and recovery costs were significantly lower for eyes that received LA, with an estimated adjusted cost reduction of USD 1516 per surgery using LA instead of GA. Use of LA for vitreoretinal surgery is associated with better operational efficiency, earlier patient discharge, and significant cost reduction. The number of vitreoretinal (VR) procedures performed in the United States has steadily increased over the past several years, growing from 527,050 procedures in 2000 to more than 3 million procedures in 2014, with the majority of surgeries performed on a one-day (outpatient) surgery basis . There aThe rising cost of health care has necessitated exploring cost utilization strategies. One prior study assessing the cost of a vitrectomy performed under LA versus GA showed that using LA can reduce the total cost burden of the surgery by 46.6% in comparison to GA at two tertiary-care centers in Indonesia . For othWith the previously mentioned limitations of the current literature, we conducted this study to quantify the institutional benefit of using LA versus GA for vitreoretinal surgery. Specifically, we analyzed the operation-room time, anesthesia duration, and time to discharge from the one-day surgery facility. We secondarily compared the cost of the operating room and postoperative anesthesia care unit (PACU) utilization between different methods of anesthesia delivery. We extracted data from the electronic medical record (EMR) system of the University of Arkansas for Medical Sciences (UAMS), a single-site tertiary-care facility. This study was conducted in accordance with the Declaration of Helsinki. An institutional board review exemption was issued by the university, and no patient consent was required. To provide a large data cohort, we selected a study period from January 2015 to September 2021. We focused on a cohort that was 18 years of age or older. We identified an initial database of a total of 2065 eyes that received one-day vitreoretinal surgery. We cleaned the data through a stepwise process that started by organizing data by the date of the first surgery and then filtering out multiple surgeries per eye in each patient. This allowed us to represent only the first surgery in the final cleaned analytical dataset. The final dataset included 1473 eyes, with 635 (43.11%) eyes receiving LA and 838 (56.89%) eyes receiving GA.We collected data pertaining to age, sex, ethnicity, pre-existing systemic comorbidities, body mass index (BMI), smoking status, type of anesthesia administered, type of vitreoretinal procedure, anesthesia time, surgery time, and duration of PACU stay. For analysis, we grouped the data into five categories based on the type of retina surgery : scleral buckle for retinal detachment (67107), pars plana vitrectomy (PPV) for retinal detachment (67108), PPV plus a scleral buckle for retinal detachment (67108), noncomplex PPV including macular surgery, vitreous hemorrhage and opacities, dropped nucleus , and complex PPV (67113). We excluded analysis from extraocular VR procedures that are occasionally done in the operating room and procedures that we could not fit into one of the previous five categories, including the following CPT codes: 67005, 67010, 67027, 67028, 67145, 67141, 67220, 67208, 67210, 67221, 67225, 67227, 67228, 67229, 67550, 67515, 67025, 67101, 67105, 67120, 67250, 67225, 67115, and 67218. The major outcomes of interest in this study were the operating room, anesthesia, and PACU times and the cost for vitreoretinal surgical procedures operated under local anesthesia compared to general anesthesia. Operating-room time was defined from the moment the ophthalmologist makes the initial invasive incision, and this is communicated to the operating-room circulator who documents the procedure start time. Operating-room time ends when the ophthalmologist has made the final closure of the procedure site, which is again documented by the operating-room circulator. Anesthesia time is defined as the time from when the anesthesia provider enters the operating room with the patient and concludes after procedure completion and when the patient has been delivered to the PACU. PACU time was defined as the time the patient has been handed off to the recovery room to the final discharge time from the ambulatory surgery center. Cost was estimated through time-driven activity-based costing (TDABC). We calculated the costs of the operating room and PACU with two different equations that included an initial base charge  plus an additional time charge in 15-minute blocks . Anesthesia cost was calculated by a base unit from the CPT code plus modifying units based upon the American Society of Anesthesiologists (ASA) wellness score plus an additional time factor in 15-minute blocks multiplied by a conversion factor (USD 85.00). All base units from CPT codes for included procedures mapped to the same anesthesia Code (00145 = 6 base units). We initially ran independent-samples t-tests to determine if there were differences in costs between GA and LA categories. Our primary analysis included running three covariate-adjusted multivariate regression models with costs  as the dependent variable and anesthesia type (GA vs. LA) as the independent variable while adjusting for demographics , surgery type, smoking status, BMI, ASA score, and comorbidity score. Comorbidities were included but were not limited to chronic pulmonary disease, congestive heart failure, diabetes, hypertension, liver disease, cancer, renal failure, and alcohol abuse. Age was categorized by decade  to allow for the capture of the expected complex, nonlinear relationship between GA use and age . All significance tests were two-tailed with an alpha of <0.05 to establish statistical significance. Stata 14.0  was utilized for the analysis of data.Our analysis included 1473 eyes that received vitreoretinal surgery between 1 January 2015 and 31 September 2021. Of these surgeries, 635 (43.1%) received LA, while 838 (56.9%) received GA. During the selected period, there was an increasing trend of LA use from 2015–2019  and then a reversal from 2020–2021 (44.66% and 42.61%) . Table 1p < 0.001; OR = 44.18, 95% CI 2.53–76.90, p = 0.009, respectively). Current smoking and increased systemic comorbidities decrease the likelihood of using GA . Regarding the effect of age on the model outcome, we found a decreasing trend in the odds of using GA in patients with age brackets of 40-49 years and older  surgical duration in minutes was 66.47 (34.86) and 100.14 (50.69) for local and general anesthesia, respectively. The mean (SD) anesthesia duration was 100.49 (38.05) for local anesthesia as compared to 145.53 (53.92) for general anesthesia. PACU duration was found to be 53.38 (22.92) and 75.08 (34.82) for local and general anesthesia, respectively . We founp < 0.001). The cost of PACU time for those with LA was found to be USD 886 (USD 130) in the LA group, while in the GA, the cost of PACU time was found to be USD 1000 (USD 260), a mean difference of USD 113 ± USD 11.30 (p < 0.001)  of OR time for the LA group was USD 5393 (USD 1532) lower compared to USD 7236 (USD 2203) in the GA group, with a mean difference (SEM) of USD 1843 (USD 102.20). The cost of anesthesia was also lower for surgeries performed with LA (USD 1141 ± USD 227) compared to those under GA (USD 1383 ± USD 307), with a mean difference of USD 242 ± USD 14.49 (< 0.001) . In totap < 0.001). The use of LA was found to lead to a USD 90.90  decrease in PACU cost. The greatest reduction in price was found to be OR costs, with LA leading to a USD 1251.32  decrease in cost over GA. The total adjusted cost of surgery under LA was lower than GA by approximately USD 1515.63, a cost reduction of 15.76%.We fitted three multivariate regression models to determine the increased costs associated with general anesthesia in the OR, anesthesia, and PACU while adjusting for patient characteristics, surgery type/complexity, and other risk factors that may increase the use of GA . We founIn this single-site study, we analyzed the operational efficiency and cost differences between local and general anesthesia for vitreoretinal surgery anesthesia. We found that surgical time, anesthesia time, and PACU duration were significantly lower in the LA group by approximately 100.41 minutes per surgery. The average cost of OR, anesthesia, and PACU times were substantially lower for the LA group by USD 2199 per surgery compared to the GA group, a 22.86% cost reduction. On adjusted analysis, controlling for covariates that may influence the choice of anesthesia delivery such as patients’ age, complexity of surgery, smoking, and comorbidity score, we found that cost differences were slightly lower, with a total cost reduction of USD 1515.63, a 15.76% cost reduction.With the rising cost of health care, it is imperative to analyze the operational efficiency and cost-reduction strategies of surgery facilities. The costs of the operating room and postoperative anesthesia care unit (PACU) largely depend on the time spent in each area. The time spent in each area also determines the equipment and staffing necessary for each patient. Two essential surgeon-controlled factors include surgical time and the type of anesthesia delivered . We founThere is enhanced operational efficiency with LA use for surgery facilities, with a lower cost burden for patients and surgical facilities. As demonstrated in our study, local anesthesia for vitreoretinal surgery has proven advantages to patients, such as quicker recovery and earlier discharge from the surgery facility. Additionally, LA is less associated with cardiovascular risk, particularly for patients with coexisting comorbidities ,8. HowevIn this study, 38.2% of patients received LA and 61.8% received GA for vitreoretinal surgery. Our data support the prediction of GA for younger patients <40 years of age and for complex vitreoretinal surgery. The use of GA in younger patients may be attributable to the likelihood of choosing to perform a scleral buckle procedure in this patient cohort because of anatomical factors such as lack of posterior vitreous detachment and phakic status. A scleral buckle can be a more painful procedure because of the traction with the handling of extraocular muscles and cryopexy compared to a stand-alone simple pars plana vitrectomy. Additionally, complex PPV and combined PPV and scleral buckles are expected to be prolonged, leading to an increased chance of GA use. Our data also demonstrate that from 2015 to 2019 there was an increasing trend of using LA over GA. From 2020 to 2021, there was a small reversal of this trend, which may be attributable to elective cases at our institution being canceled or postponed because of the international COVID-SARS-2 pandemic. We infer that those cases during this time period were more likely to be urgent and more complex in our tertiary referral center, likely leading to the choice of GA over LA .There are limitations to this study. First, the study is limited by its retrospective, nonrandomized design, which may introduce outcome and selection bias. We did not analyze surgical success or failure rates between the two groups in this study. Additionally, there may be an inherent selection bias from 2020 to 2021 during the pandemic’s closure of elective cases toward the use of GA. In addition, patients in this study may also have more complex vitreoretinal pathologies than those presenting to non-tertiary-care centers where the case mix will be skewed more toward macular, noncomplex vitreoretinal surgery. Furthermore, it is of note that our calculations did not account for medicine or supply expenses and was totally based on the cost of anesthesia, operation room, and perioperative area utilization. General anesthesia drugs have higher acquisition costs than local anesthesia, though the negotiated reimbursement plans for surgery between surgery facilities and insurance companies do not usually differentiate between surgeries performed under local or general anesthesia. We did not analyze cost drivers for MAC and GA use. An important future course would be to analyze the cost drivers in these groups. Finally, given that patients receiving LA receive minimum to no sedation, these patients typically need less supervision by the anesthesia providers after surgery as compared to GA. However, we were not able to measure this variable in the current study.Our study has several strengths. Prior to our report, no contemporary studies have investigated the cost of different types of vitreoretinal surgery anesthesia in Western countries. In addition to presenting the expected benefits in time and cost reduction in using LA, we also provided an adjusted estimate to account for the effect of factors that necessitate the use of GA, such as a young patient’s age and complex retina surgery. Our data are not only relevant to the Western world but can also be helpful to developing countries with limited resources. Our results should aid surgeons and anesthesiologists to understand the operational efficiency and cost effectiveness of anesthesia delivery methods for vitreoretinal surgery.In summary, we provide data on the time-saving and cost differences of the use of LA over GA in the outpatient setting. We found that anesthesia, surgical, and recovery times were significantly lower for eyes that received local anesthesia, and this was associated with an enhanced operational efficiency, rapid turnover, and a cost-reduction estimate of USD 1516 per surgery with using LA. This is a conservative estimate, and we expect the cost savings to increase if the cost of anesthetic medications is also accounted for.


Prospective, double-blind clinical trial comparing tetanus-diphtheria vaccine administration routes, intramuscular (IM) vs. subcutaneous (SC) injection, in patients with oral anticoagulants. ISRCTN69942081.Patients treated with oral anticoagulants, 15 health centers, Vigo (Spain). Sample size, 117 in each group.Safety analysis: systemic reactions and, at the vaccine administration site, erythematic, swelling, hematoma, granuloma, pain.Effectiveness analysis: differences in tetanus toxoid antibody titers.Independent variables: route, sex, age, baseline serology, number of doses administered.Following the CONSORT guidelines, we performed an intention-to-treat analysis. We conducted a descriptive study of the variables included in both groups (117 in each group) and a bivariate analysis. Fewer than 5% of missing values. Imputation in baseline and final serology with the median was performed. Lost values were assumed to be values missing at random. We conducted a descriptive study of the variables and compared routes. For safety, multivariate logistic regression was applied, with each safety criterion as outcome and the independent variables. Odds ratios (ORs) were calculated. For effectiveness, a generalized additive mixed model, with the difference between final and initial antibody titers as outcome. Due to the bimodal distribution of the outcome, the normal mixture fitting with gamlssMX was used. All statistical analyses were performed with the gamlss.mx and texreg packages of the R free software environment.A previously published protocol was used across the 6-year study period. The breakdown by sex and route showed: 102 women and 132 men; and 117 IM and 117 SC, with one dose administered in over 80% of participants. There were no differences between groups in any independent variable. The second and third doses administered were not analyzed, due to the low number of cases. In terms of safety, there were no severe general reactions. Locally, significant adjusted differences were observed: in pain, by sex  and route ; in erythema, by sex  and route ; and in swelling, by sex  and route . In terms of effectiveness, the model selected was the one adjusted for baseline serology. While tetanus is an infrequent disease in Spain, it is nevertheless an important public health problem because, despite its low incidence, the related mortality is very high. Annual case reports show a gradual fall in numbers, with a total of 136 cases being reported in Spain across the period 2009–2015 (a mean of 10 cases per year), 25 of which proved lethal (18.4%) , whether alone or in tandem with passive immunization (anti-tetanus immunoglobulin), depends on the type of wound involved, the probability of its becoming contaminated with tetanus bacilli, and the patient's vaccine record . CurrentMost patients who are anticoagulated in primary care settings and are being treated for atrial fibrillation have a mean age of over 74 years . In antiper se, needle size can also have an influence . Patients were recruited by their family physicians (FPs) at primary care health centers. At the first visit, the physicians determined the patient's vaccination status, by consulting the vaccination records in the patient's medical history or asking the patient in cases where this information was unknown. The FP could then evaluate whether the patient had been adequately vaccinated , or alternatively, whether the patient needed to receive a booster dose, or initiate or complete his/her primary vaccination. The doctor explained the study and requested the patient's consent. Once it was signed, the patient was attended by the nurse, who proceeded to perform the INR, the serology extraction and the entire procedure as established in the protocol. The guidelines used for the pertinent vaccinations were those issued by the Spanish Ministry of Health in 2008 . In addition, a specific database was created for uploading and storing the observations collected.Prior to the study, a training workshop was held for all researchers participating in the clinical trial, covering techniques, data-collection, and the measurement of study variables.The main outcome variables for safety were:Appearance of baseline lesions at the site where the vaccine was administered , axillary lymph nodes, and pain as scored on a visual analog scale , consistAppearance of general symptoms ; and,Occurrence of any serious adverse effect, fatal or life-threatening to the patient, resulting in incapacity or requiring hospitalization.The difference between tetanus antibodies at baseline and post-vaccination was the main outcome variable in the effectiveness analysis. Tetanus antitoxin was analyzed by enzyme immunoassay at a centralized laboratory.As independent variables, route, sex, and age were considered. Initial International Normalized Ratio (INR) were determined by capillary reflectometer technique for clinical control purposes.Assuming that the percentage of local side effects for the IM route was 30%, and that the expected increase in local side effects for the alternative (SC) route using a bilateral approach with a 95% confidence interval was 18%, and a beta risk of 0.20, we calculated that 115 patients for each group would be required. In view of potential data losses of 15%, the final sample size was set at 135 patients for each group. Based on this sample size, we estimated that a mean difference of 3 IU/ml in antibody levels could be detected.The unit of randomization comprised the individuals participating in the trial. Randomization was performed within a 3-level stratification, based on the number of vaccine doses required for successful immunization. Within each level, simple randomization was performed, using a spreadsheet in an attempt to control for the confounding effect of the number of doses. Sampling was performed by the Fundación Galicia Sur (EOXI Vigo), to which all researchers were given telephone access.Data relating to the randomization process were kept confidential until the end of the study. It was each researcher's responsibility to ensure that there was a specific procedure which enabled the code to be opened in case of emergency, with immediate notification of this to the randomization center.The vaccine route was masked in the dataset, to prevent the team tasked with the computer analysis from discovering which route corresponded to each group. Loss masking only occurred in cases of patient emergency and at the end of the study.The physician was blinded to the original administration route at the control visit to detect side effects.In the case of patients with whom contact and follow-up was lost, the researcher documented the steps taken to recontact them. Data contained in each patient's CRF were periodically checked and reviewed, to ensure that they were complete and regularly updated, and that the good clinical practices required by the protocol and follow-up procedures were being maintained. The researchers kept the original documents for each patient who participated in the study, consisting of the notes made at each visit and the original signed informed consent forms.Quantitative data were summarized with the arithmetic mean and standard deviation for parametric variables, and with the median, 25th percentile, and 75th percentile otherwise. For qualitative variables, number and proportions were applied.U-test were used to compare quantitative variables.Considering an alpha error of 0.05, and after checking the necessary conditions, chi-square or Fisher tests were applied to determine the statistical differences between qualitative variables among groups. The t-Student test or Mann-Whitney Intention-to-treat (ITT) analysis was performed in accordance with the CONSORT guidelines .First, we performed a multivariate logistic regression, considering the dichotomous safety variables—pain, erythema, swelling, hematoma, and granuloma—as the target, and adjusting for the independent variables . Odds ratios (ORs) and their confidence intervals were then calculated. We also built suitable generalized additive models for position, scale, and shape, to explain the adjusted outcome for effectiveness (differences in antibody level). Initial serology was considered as independent variable.All analyses were performed using the R Studio statistical software package version 4.1.3. .This study obtained authorization from the Galician Clinical Research Ethics Committee on 07/06/2007 under number 2007/089 (No. EudraCT 2007-001073-29). This authorization was subsequently modified and extended on 13/04/2009, 10/09/2009, and 13/12/2010 to increase patient enrollment.Of the 375 individuals initially considered for participation in the study, 234 were included and 141 declined to participate in the study or were not eligible.The 234 participants were randomized into two groups, by type of route: 117 were vaccinated by the IM route and 117 by the SC route, and of these, 106 and 114 were, respectively, included for study purposes. The flow chart is shown in Recruitment was subsequently extended to 72 months, due to difficulties encountered in achieving the predetermined sample size.The causes for patients' premature abandonment were side effects in the vaccination process, withdrawal of consent, loss to follow-up, administrative problems, and death.A breakdown of the baseline quantitative variables showed that: the initial tetanus antitoxin titers had a median value of 531 ; the median age was 73 years ; and the required dose variable had a median of 1 dose . When it came to the baseline qualitative variables, 50% of the individuals were vaccinated by the SC route, and 56.41% were men.A bivariate analysis was performed, with the non-parametric Mann–Whitney U and chi-square tests being used to ascertain the existence of significant differences between the two groups . The samIn the IM group, 80% of participants had previously received one dose, 8% had received two doses, and 13% had received three doses: in the SC group, 82% of the participants had previously received one dose, 6% had received two doses, and 1% had received three doses.Pain was recoded into a dichotomous variable , with “Yes” defined as any scale score greater than zero. The other elementary lesions  at the vaccine-administration site were recoded as dichotomous variables , with any value greater than 0 mm. being classified as “Yes”.Shown in the Annex  are the via their medians.To reduce any bias due to lack of data during follow-up, an ITT analysis was performed, with the missing values of the initial and final tetanus antitoxin titer variables being imputed The following variables displayed significant differences for dichotomous outcomes: age, with swelling; sex, with erythema and swelling; and route, with erythema and swelling .The safety analysis showed that while no severe side effects were in evidence, there were general reactions, such as fever, headache, and arthralgia in the two routes under study .glm function of the stats package  and sex were significant : patients who were male and had been subcutaneously vaccinated were less likely to experience pain. For erythema, the independent variables that were significant were route  and sex : there was a 5.19 times greater chance of developing erythema when vaccines were given subcutaneously, and women were more likely to develop erythema than were men. For swelling, the independent variables that proved to be significant were route  and sex : patients were 2.74 times more likely to experience swelling, if the vaccine was given subcutaneously, and women were more likely than men to experience swelling. The predictor variable that was significant in the case of granuloma was route .To model the final tetanus antitoxin titration, we considered the increase in antibodies, constructed from the difference between final and baseline tetanus antibodies. We used a multivariate regression model, selected after analyzing the distribution of the outcome variable .In our case, the chosen distribution was a finite mixture of normal distributions and we thus analyzed it with the gamlss.mx package . The parAfter analyzing the behavior of several models by varying the different independent variables, we compared these according to the AIC criteria. The model chosen with the lowest AIC was thus the one that considered the baseline serology variable as a significant influential variable. A detailed summary is shown in The behavior of the residuals associated with the chosen model was analyzed, and only about 5% of the observations were distributed outside the confidence intervals. Their representation is included in the Annex , and indThis study was an independent, double-blind, randomized clinical trial (RCT), designed with the dual aim of comparing the effectiveness and safety of the SC and IM administration routes of DTP vaccine in anticoagulated adults. The outcome variables relate to the comparison of immunogenicity and reactogenicity between the two tetanus vaccine administration routes: SC vs. IM. With respect to safety, there was just one systemic reaction. Locally, there were significant adjusted differences in the following: pain, by sex  and route ; erythema, by sex  and route ; and swelling, by sex  and route . In terms of effectiveness, the model selected was the one adjusted for baseline serology.With respect to immunogenicity, this RCT found a comparable increase in antibody rates for the two routes, but without differences in terms of effectiveness. This finding is in line with other clinical studies published to date, which observe similar immune responses induced by SC and IM immunizations, in various types of vaccines, including: rabies (Kulkarni PS 2013); hepatitis A; hepatitis B ; influenApart from the administration route, other external factors are described which would potentially modify immunogenicity, such as the anatomic site of inoculation , techniqp-value of 0.01 and 0.023, respectively. Other studies on the child population would be consistent with these findings, and describe greater reddening and swelling with administration of Td via the SC route as opposed to the IM route .At the time when the study began, control of anticoagulation was being implemented in primary care and there were not that many anticoagulated patients in the population , 49. ThaThe measure of effectiveness in this RCT was verified by antibody titration, as in almost all RCTs designed to study the immunogenicity of vaccines. This can be considered a limitation, given that small variations in antibody concentrations between groups of persons may not be clinically relevant insofar as vaccine protection is concerned. What is important is the quality of response of the antibodies, since only one subgroup of all those detectable could neutralize pathogens, and, in addition, the innate, cellular and cytokine response would also mediate in the efficacy of vaccines . Yet theOne strength of this study is the undertaking of an RCT in primary care, since this is known to be the setting where RCTs assume greatest relevance, since it is the environment where most treatments are applied and where the effectiveness and iatrogenicity of therapies can be most realistically evaluated , 51. TheMany authors contend that most vaccines should be administered by the IM route, given the fact that there is evidence of a high degree of reduced reactogenicity, and this optimizes immunogenicity , 14. EveIn light of our results, there are no administration-route-related differences in immunogenicity for the TDP vaccine, and the IM route may thus be indicated, given that the risk of hematoma is minimal in patients treated with vitamin K antagonists, which maintain anticoagulation levels in range. While the local reactogenicity of the SC route is higher, there is more pain with the IM injection, with variations by sex, thus making it advisable for patients to be brought into the decision-making process , 52.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Clinical Research Ethics Committee of Galicia. The patients/participants provided their written informed consent to participate in this study.María Teresa Peteiro Rodríguez; A Guarda Health CenterJacintoMosquera Nogueira; Bembrive Health Center (Vigo)Andrés Barreiro Prieto; Chapela Health CenterCarlos Benito Andrade Cochón; Moaña Health CenterJulia Bóveda Fontán; Pintor Colmeiro Health Center (Vigo)María ángeles Charle Crespo; Porriño Health CenterJesús Martínez Barrios; Redondela Health CenterManuel Domínguez Sardiña; Sárdoma Health Center (Vigo)Luis López Vilar; Teis Health Center (Vigo)Reyes Macías Alonso; Tomiño Health CenterSusana Aldecoa Landesa; Beiramar Health Center (Vigo)Félix Tojal del Casero; Doblada Health Center (Vigo)Susana Hernáiz Valero; Val Miñor Health CenterJosé María Sàez de Biteri; Matamà Health Center (Vigo)Isabel Rey Gómez-Serranillos; Xerencia de Atención Primaria de Vigo (Vigo)Carmen Velicia Peñas; Sárdoma Health Center (Vigo)Manuela Fontanillo Fontanillo; Fundación Biomédica del CHUVI (Vigo).FL-D and MM-M conceived, designed the study, and wrote the first draft of the manuscript. FL-D, MM-M, and MV-C organized the database. MV-C and IF-F coordinate the fieldwork. FL-D, MM-M, MV-C, and IF-F conducted the literature search. AC, JR-P, and SR-P performed the statistical analysis. FL-D, MD-F, IF-F, AC, and MM-M interpreted the results. All authors reviewed and approved the final manuscript.


Also, the low performance of chair stand and arm curl tests was associated with poor physical and social dimensions of HRQoL (p < 0.05). In conclusion, a low HRQoL in physically active older people is associated with both morphological and physical fitness factors.This study aimed to associate morphological variables and physical fitness with health-related quality of life (HRQoL) in physically active older people. A cross-sectional study was carried out that evaluated 470 older people  with a mean age of 70.13 ± 6.57 years, residing in two regions of Chile. Morphological variables , physical fitness through the Senior Fitness Test protocol, and HRQoL using the SF-36 questionnaire were obtained. Logistic regression analysis was used to identify risk factors between morphological variables and physical fitness associated with HRQoL. The main results indicated that overweight (OR = 1.52;  Regular physical activity practice produces various benefits in older people ,2, amongIn Chile, only 29.1% of people between 60 and 69 years of age are physically active, which drops to 25.3% for those over 70 years of age . Facts tp < 0.01) [On the other hand, the health-related quality of life (HRQoL) corresponds to the perception of well-being of the person regarding their physical, psychological, and social health . There a < 0.01) . Althoug < 0.01) , there i < 0.01) ,19,20 weThe cross-sectional study evaluated 470 older people  between 60 and 89 years old , selected under an intentional non-probabilistic criterion, residing in two regions of Chile: Araucanía (n = 242) and Maule n = 228). The sample size calculation was made from a population of 686 older people enrolled in a national physical activity program in both regions . The calculation estimate was of 247 participants, where 131 corresponded to Araucanía and 116 to Maule. For this calculation, a confidence level of 95% and a margin of error of 5% were used. These analyses were performed using the GPower software . The inclusion criteria used were: (i) people over 60 years and under 90 years of age; (ii) enrolled in the physical activity government workshops for older people; (iii) regularly practice moderate physical activity (between 150 to 300 min a week) or vigorous physical activity (between 75 to 150 min a week) for a period greater than six months ,21; (iv)8. The saAll participants were informed of the scope of the study and signed an informed consent authorizing the use of information for scientific purposes. The study protocol was reviewed and approved by the Scientific Ethics Committee of the Universidad Autónoma de Chile  and developed following the Declaration of Helsinki.2), and the participants were classified according to their nutritional status as normal weight (<27.9 kg/m2) and overweight (28 or more kg/m2), following to the recommendations of the Pan American Health Organization [Body weight was obtained by wearing minimal clothing and using a mechanical scale , bipedal height was measured with a stadiometer , and WC with a tape measure . Subsequently, the BMI was calculated by dividing the body weight by the squared bipedal height  in the first session, the morphological variables, the HRQoL, and the chair stand and arm curl tests were measured through a single repetition; (ii) in the second session, the two-minute step test (one repetition) was assessed; and (iii) in the third session the chair sit-and-reach, back scratch and timed up-and-go tests were measured, each test was repeated twice, and the best performance of each participant was reported. All measurements were carried out in the respective health centers or beneficiary sports organizations with physical activity government workshops aimed at older people through a level II anthropometrist  of the ISAK and researchers trained in the protocol of the Senior Fitness Test and the SF-36 questionnaire. The characteristics of the sample can be seen in p < 0.05.Data were analyzed with SPSS 25.0 statistical software . Values were reported as mean ± standard deviation. The Kolmogorov–Smirnov test was used to determine the normality of the data, while the Levene’s test was used to determine the homogeneity of variance. Normal distribution was observed for all data. Associated risk factors  with low HRQoL were identified by logistic regression analysis for each of the eight dimensions assessed in the SF-36 questionnaire. These analyses were adjusted for sex, age, and nutritional status and presented as odds ratios (OR) with their respective 95% confidence intervals (95% CI) to present the magnitude of the association. The level of significance was defined as p = 0.001) and vitality . In addition, presenting overweight , WC with risk , and poor performance in the chair stand , arm curl  and back scratch tests  were factors associated with a decrease in HRQoL in physical fitness. On the other hand, poor performance in timed up-and-go test was associated with a decrease in HRQoL in the physical function dimensions , physical role  and body pain .The logistic regression analyses for the physical function, physical role, body pain, and vitality dimensions of HRQoL are summarized in p = 0.014), presenting overweight  and WC with risk  was associated with greater probability of presenting low HRQoL in the social function dimension. On the other hand, being overweight  and WC with risk  was associated with low HRQoL in the general health dimension. Poor performance on the back scratch test was associated with decreased HRQoL in the emotional role dimensions , mental health  and general health . Finally, poor performance on the timed up-and-go test was associated with a higher probability of having a low HRQoL in the social function dimensions , emotional role , health mental  and general health .The study’s main results indicate that some morphological variables and physical fitness factors increase the probability of having a low HRQoL in the different dimensions assessed by the SF-36 questionnaire in physically active older people. Specifically, overweight and WC with the risk increased the probability of presenting a low HRQoL in the dimensions of physical function, social function, and general health. In contrast, low performance in the chair stand and arm curl tests showed a higher probability of low HRQoL in the physical function dimension. Likewise, poor performance on the back scratch test was associated with a higher probability of low HRQoL in physical, emotional, mental, and general health dimensions. Finally, a lower-than-normal performance in the timed up-and-go test was associated with a higher probability of observing a decreased HRQoL in all measured dimensions except vitality.p < 0.001) [p < 0.001) and mental (p < 0.001) aspects [Regarding morphological variables, it has previously been reported that overweight and WC above normal have been related to lower HRQoL scores (< 0.001) . Also, p aspects ,29, bein aspects . HoweverA finding observed in this study revealed that older people with higher body weight and WC were more likely to have a low HRQoL. It has been described that HRQoL corresponds to a subjective and dynamic multidimensional concept that is influenced by different factors that occur throughout life ,30. Amonp < 0.05) [p < 0.05) [p < 0.05) [p < 0.05) [Another interesting study result indicates that low physical fitness increases the probability of having a decreased HRQoL, with the agility and dynamic balance test being the most influential in HRQoL. The timed up-and-go test has been widely recognized as a measure of functional independence in older people , where v < 0.05) , inabili < 0.05) , increas < 0.05) , frailty < 0.05)  and decr < 0.05) . This is < 0.05)  and woulIn addition, it was possible to report that those over 70 years of age are more likely to have a decreased HRQoL in the physical and vitality dimensions. At the same time, the female sex was classified as a risk factor in the social function dimension of the HRQoL. This is related to previous studies showing that HRQoL is perceived more negatively at older ages and that being female has been identified as a risk factor for decreased HRQoL . It has Among the possible limitations of the study are: (i) not including assessments of neurophysiological mechanisms to determine the activation of the flexor-extensor muscles involved in the measurement of physical fitness; (ii) the selection of the sample  that only allows analysis of association; (iii) the low number of male participants; (iv) the geographical context of the older people, which does not allow the results to be extrapolated to other realities. Among the strengths of the study, we could mention: (i) the use of the SF-36 questionnaire, which has been validated in the Chilean context to assess older people and provides situated and reliable information for health professionals; (ii) the simplicity of the morphological and physical fitness assessments, which would allow their use and implementation in physical activity programs focused on older people; (iii) the low costs to carry out these type of activities, which could be replicated in large population groups such as those found in community health centers or neighborhood associations. Given this, public policies could be organized to promote the general health of older people, including regular physical activity programs, nutrition, and psychoeducational lessons in groups, and to develop infrastructure to improve urban mobility. Emerging countries must organize public policies to develop older people’s care and stimulate self-care for all age groups; these countries (emerging countries) are experiencing a change in the age pyramid; thus, many older people will need assistance in medical care in a few years.A low HRQoL in physically active older people is associated with both morphological and physical fitness factors, where overweight, WC with risk, decreased upper and lower limb strength, low upper limb flexibility. Poor agility and dynamic balance performance correspond to risk factors. From a public health perspective, it is essential to consider the factors that impact the HRQoL of older people with the intention of generating preventive and remedial strategies that can benefit the population’s health.