Potentially inappropriate prescriptions and potential prescription omissions in older people living with HIV.

OBJECTIVES: This study aimed to determine the prevalence of potentially inappropriate prescriptions (PIPs) and potential prescription omissions (PPOs) in a Spanish cohort of people living with HIV (PLWH) aged ≥65 years and to identify risk factors for the presence of PIPs and PPOs. METHODS: This retrospective cross-sectional study was conducted across 10 public hospitals in the Autonomous Community of Madrid, Spain. Clinical and demographic data were cross-checked against hospital and community pharmacy dispensation registries. PIPs and PPOs were assessed using the American Geriatrics Society (AGS)/Beers and Screening Tool of Older Persons' Prescriptions (STOPP)/Screening Tool to Alert Doctors to Right Treatment (START) criteria. Risk factors for PIPs and PPOs and agreement between AGS/Beers and STOPP/START criteria were statistically analysed. RESULTS: This study included 313 PLWH (median age 72 years), of whom 80.5% were men. PIP prevalence rates were 29.4% and 44.4% based on the AGS/Beers and STOPP criteria, respectively. The concordance between AGS/Beers and STOPP criteria was moderate. Benzodiazepines and proton pump inhibitors were the chronic comedications most commonly involved in PIPs. PPOs were observed in 61.4% of the patients. The leading omissions were insufficient influenza and pneumococcal vaccine coverage and inadequate bone health-related treatments. The number of chronic comedications, female sex, neuropsychiatric disorders, and cancer diagnosis were risk factors for PIPs, whereas osteopenia and osteoporosis were risk factors for PPOs. CONCLUSIONS: A high prevalence of PIPs and PPOs was observed in our cohort of older PLWH. These findings emphasize the importance of comprehensive medication reviews in this population to reduce inappropriate medication use and address their specific and underserved therapeutic needs.

Effect of High Altitude on the Survival of COVID-19 Patients in Intensive Care Unit: A Cohort Study.

Purpose: The effect of high altitude ( ≥ 1500 m) and its potential association with mortality by COVID-19 remains controversial. We assessed the effect of high altitude on the survival/discharge of COVID-19 patients requiring intensive care unit (ICU) admission for mechanical ventilation compared to individuals treated at sea level. Methods: A retrospective cohort multi-center study of consecutive adults patients with a positive RT-PCR test for COVID-19 who were mechanically ventilated between March and November 2020. Data were collected from two sea-level hospitals and four high-altitude hospitals in Ecuador. The primary outcome was ICU and hospital survival/discharge. Survival analysis was conducted using semi-parametric Cox proportional hazards models. Results: Of the study population (n = 670), 35.2% were female with a mean age of 58.3 ± 12.6 years. On admission, high-altitude patients were more likely to be younger (57.2 vs. 60.5 years old), presented with less comorbidities such as hypertension (25.9% vs. 54.9% with p-value <.001) and diabetes mellitus (20.5% vs. 37.2% with p-value <.001), less probability of having a capillary refill time > 3 sec (13.7% vs. 30.1%, p-value <.001), and less severity-of-illness condition (APACHE II score, 17.5 ± 8.1 vs. 20 ± 8.2, p < .01). After adjusting for key confounders high altitude is associated with significant higher probabilities of ICU survival/discharge (HR: 1.74 [95% CI: 1.46-2.08]) and hospital survival/discharge (HR: 1.35 [95% CI: 1.18-1.55]) than patients treated at sea level. Conclusions: Patients treated at high altitude at any time point during the study period were 74% more likely to experience ICU survival/discharge and 35% more likely to experience hospital survival/discharge than to the sea-level group. Possible reasons for these findings are genetic and physiological adaptations due to exposure to chronic hypoxia.

Biomimetic analyses of interactions between macrophages and palmar fascia myofibroblasts derived from Dupuytren's disease reveal distinct inflammatory cytokine responses.

Dupuytren's disease (DD) is a common and heritable fibrosis of the hand. It is characterized by the shortening and thickening of the palmar fascia into myofibroblastic nodules that can progress to palmar-digital contractures and permanent loss of dexterity. Molecular analyses of DD tissues and the presence of inflammatory cell infiltrates suggest a pathogenesis initiated by a proinflammatory fascial milieu that promotes myofibroblast activation and palmar fascia contractures. However, the relative contributions of vascular and/or tissue derived immune system cells and cytokine-sensitive stromal myofibroblasts to the development of this proinflammatory microenvironment are poorly understood. To gain insights into this process, we have developed and tested a collagen-based 3D tissue biomimetic co-culture system to assess paracrine interactions between THP-1-derived pro-inflammatory macrophages and primary human palmar fascia myofibroblasts (PFMs). We observed significant and reproducible impacts of collagen-adherent macrophage and PFM co-cultures on the cytokine gene expression profiles of these cells compared to their respective monocultures, and significant changes to the resulting cytokine milieu in their shared culture media, notably TNF and IL-6. Our findings are consistent with central roles for PFMs in cytokine production and immunoregulation of the pro-inflammatory milieu hypothesized to promote DD development.

A critical appraisal of the prognostic predictive models for patients with sepsis: Which model can be applied in clinical practice?

BACKGROUND: Sepsis is associated with high mortality and predictive models can help in clinical decision-making. The objective of this study was to carry out a systematic review of these models. METHODS: In 2019, we conducted a systematic review in MEDLINE and EMBASE (CDR42018111121:PROSPERO) of articles that developed predictive models for mortality in septic patients (inclusion criteria). We followed the CHARMS recommendations (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies), extracting the information from its 11 domains (Source of data, Participants, etc). We determined the risk of bias and applicability (participants, outcome, predictors and analysis) through PROBAST (Prediction model Risk Of Bias ASsessment Tool). RESULTS: A total of 14 studies were included. In the CHARMS extraction, the models found showed great variability in its 11 domains. Regarding the PROBAST checklist, only one article had an unclear risk of bias as it did not indicate how missing data were handled while the others all had a high risk of bias. This was mainly due to the statistical analysis (inadequate sample size, handling of continuous predictors, missing data and selection of predictors), since 13 studies had a high risk of bias. Applicability was satisfactory in six articles. Most of the models integrate predictors from routine clinical practice. Discrimination and calibration were assessed for almost all the models, with the area under the ROC curve ranging from 0.59 to 0.955 and no lack of calibration. Only three models were externally validated and their maximum discrimination values in the derivation were from 0.712 and 0.84. One of them (Osborn) had undergone multiple validation studies. DISCUSSION: Despite most of the studies showing a high risk of bias, we very cautiously recommend applying the Osborn model, as this has been externally validated various times.

Properties of Mosquito Repellent-Plasticized Poly(lactic acid) Strands.

Poly(lactic acid) (PLA) is an attractive candidate for replacing petrochemical polymers because it is fully biodegradable. This study investigated the potential of PLA as a sustainable and environmentally friendly alternative material that can be developed into commercially viable wearable mosquito repellent devices with desirable characteristics. PLA strands containing DEET and IR3535 were prepared by twin screw extrusion compounding and simultaneously functioned as plasticizers for the polymer. The plasticizing effect was investigated by thermal and rheological studies. DSC studies showed that the addition of DEET and IR3535 into PLA strands reduced the glass transition temperature consistent with predictions of the Fox equation, thus proving their efficiency as plasticizers. The rheology of molten samples of neat PLA and PLA/repellents blends, evaluated at 200 °C, was consistent with shear-thinning pseudoplastic behaviour. Raman studies revealed a nonlinear concentration gradient for DEET in the PLA strand, indicating non-Fickian Type II transport controlling the desorption process. Release data obtained at 50 °C showed initial rapid release followed by a slower, near constant rate at longer times. The release rate data were fitted to a novel modification of the Peppas-Sahlin desorption model.

Intestinal Immune Dysregulation Driven by Dysbiosis Promotes Barrier Disruption and Bacterial Translocation in Rats With Cirrhosis.

In cirrhosis, intestinal dysbiosis, intestinal barrier impairment, and systemic immune system abnormalities lead to gut bacterial translocation (GBT) and bacterial infection. However, intestinal immune system dysfunction and its contribution to barrier damage are poorly understood. This study correlates immune system dysregulation in the intestines of rats at different stages of CCl4 -induced cirrhosis with barrier function and pathogenic microbiota. The following variables were addressed in the small intestine: intraepithelial lymphocyte (IEL) and lamina propria lymphocyte (LPL) activation status and cytokine production (flow cytometry), cytokine mRNA and protein expression (quantitative real-time PCR and immunofluorescence), microbiota composition of ileum content (16S recombinant DNA massive sequencing), permeability (fecal albumin loss), and epithelial junctions (immunohistochemistry and immunofluorescence). The intestinal mucosa in rats with cirrhosis showed a proinflammatory pattern of immune dysregulation in IELs and LPLs, which featured the expansion of activated lymphocytes, switch to a T helper 1 (Th1) regulatory pattern, and Th17 reduction. In rats with cirrhosis with ascites, this state was associated with epithelial junction protein disruption, fecal albumin loss, and GBT. Direct correlations (P < 0.01) were observed between elevated interferon gamma (IFNγ)-expressing T cytotoxic LPLs and fecal albumin and between inflammatory taxa abundance and IFNγ-producing immune cells in the ileum. Bowel decontamination led to redistributed microbiota composition, reduced proinflammatory activation of mucosal immune cells, normalized fecal albumin levels, and diminished GBT; but there were no modifications in Th17 depletion. Conclusion: The intestinal mucosa of rats with cirrhosis acquires a proinflammatory profile of immune dysregulation that parallels the severity of cirrhosis; this impaired intestinal immune response is driven by gut dysbiosis and leads to disrupted barrier function, promoting GBT.

A Nationwide Study of Incidence and Mortality Due to Traumatic Brain Injury in Ecuador (2004-2016).

OBJECTIVE: Traumatic brain injury (TBI) is a public health problem worldwide. Information regarding TBI from low- and middle-income countries is scarce. The objectives of this study are to determine the incidence, mortality and geodemographic distribution of TBI in Ecuador. METHODS: A population-based analytical study from 2004 to 2016 was conducted in Ecuador. Men and women with a diagnosis of TBI from all ages (0-110 years) were included. Data was obtained from official hospital-discharges records and retrieved from the National Institute of Statistics and Census (INEC) Database. We analyzed data by region, province and canton with a monthly resolution. The incidence, mortality, case fatality rates and the risk of developing TBI within the population were calculated based on the last 13 years of available data. RESULTS: A total of 124,576 hospital admissions and 5,264 deaths due to TBI were registered in Ecuador from 2004 to 2016. The overall TBI-related hospital admission rate was 70.68 per 100,000. The sex- and age-specific rate was 90.1 per 100,000 for men and 64.1 per 100,000 for women. Mestizos' population has the highest adjusted incidence rate of 195.6 per 100,000, followed by the indigenous with 61.4 per 100,000 and Afro-Americans with 14.2 per 100,000. The overall annual mortality rate during the study ranged from 2.11 to 3.35 per 100,000. Case fatality rates were significantly higher in older populations, becoming fatal in up to 27% of men >90 years/old and in 15% of women older than 90 years/old. CONCLUSION: This is the first recorded epidemiological study of the socio-demographic distribution of TBI in Ecuador to date. The study found that young men were almost 4 times more likely to be hospitalized due to TBI than women of this age. Fatalities due to TBI were less likely to occur among younger age groups, increasing significantly among the elderly population. The national incidence rate of TBI has been decreasing since 2011, which coincides with the introduction of stricter alcohol regulation, suggesting that this measure might have played a role in this reduction.

Optimal Piperacillin-Tazobactam Dosing Strategies against Extended-Spectrum-ß-Lactamase-Producing Enterobacteriaceae.

Piperacillin-tazobactam has been proposed as an alternative to carbapenems for the treatment of infections caused by extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae However, limited understanding of optimal dosing strategies for this combination may curtail its utility. In this study, we correlated various exposures of piperacillin-tazobactam to efficacy, using a modified pharmacokinetic/pharmacodynamic index. Using a clinical Klebsiella pneumoniae isolate expressing CTX-M-15, piperacillin MIC values were determined with increasing tazobactam concentrations and fitted to a sigmoid inhibitory maximum effect (Emax) model. A hollow-fiber infection model (HFIM) was used to evaluate the efficacy of escalating tazobactam dosing with a fixed piperacillin exposure. Simulated drug concentrations from the HFIM were incorporated in the Emax model to determine the percentage of free time above instantaneous MIC (%fT>MICi) associated with each experimental exposure. The target %fT>MICi associated with growth suppression was prospectively validated using an SHV-12-producing isolate of Escherichia coli and 2 other CTX-M-15-producing K. pneumoniae isolates. Based on our reference isolate, piperacillin-tazobactam exposures of %fT>MICi of ≥55.1% were associated with growth suppression. Despite underlying differences, these findings were consistent with prospective observations in 3 other clinical isolates. Our modeling approach can be applied relatively easily in the clinical setting, and it appeared to be robust in predicting the effectiveness of various piperacillin-tazobactam exposures. This modified pharmacokinetic/pharmacodynamic index could be used to characterize response to other ß-lactam/ß-lactamase inhibitor combinations.

Determining ß-lactam exposure threshold to suppress resistance development in Gram-negative bacteria.

Objectives: ß-Lactams are commonly used for nosocomial infections and resistance to these agents among Gram-negative bacteria is increasing rapidly. Optimized dosing is expected to reduce the likelihood of resistance development during antimicrobial therapy, but the target for clinical dose adjustment is not well established. We examined the likelihood that various dosing exposures would suppress resistance development in an in vitro hollow-fibre infection model. Methods: Two strains of Klebsiella pneumoniae and two strains of Pseudomonas aeruginosa (baseline inocula of ∼10 8  cfu/mL) were examined. Various dosing exposures of cefepime, ceftazidime and meropenem were simulated in the hollow-fibre infection model. Serial samples were obtained to ascertain the pharmacokinetic simulations and viable bacterial burden for up to 120 h. Drug concentrations were determined by a validated LC-MS/MS assay and the simulated exposures were expressed as C min /MIC ratios. Resistance development was detected by quantitative culture on drug-supplemented media plates (at 3× the corresponding baseline MIC). The C min /MIC breakpoint threshold to prevent bacterial regrowth was identified by classification and regression tree (CART) analysis. Results: For all strains, the bacterial burden declined initially with the simulated exposures, but regrowth was observed in 9 out of 31 experiments. CART analysis revealed that a C min /MIC ratio ≥3.8 was significantly associated with regrowth prevention (100% versus 44%, P = 0.001). Conclusions: The development of ß-lactam resistance during therapy could be suppressed by an optimized dosing exposure. Validation of the proposed target in a well-designed clinical study is warranted.

Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats.

BACKGROUND & AIMS: In advanced cirrhosis, gut bacterial translocation is the consequence of intestinal barrier disruption and leads to bacterial infection. Bile acid abnormalities in cirrhosis could play a role in the integrity of the intestinal barrier and the control of microbiota, mainly through the farnesoid X receptor. We investigated the long-term effects of the farnesoid X receptor agonist, obeticholic acid, on gut bacterial translocation, intestinal microbiota composition, barrier integrity and inflammation in rats with CCl4-induced cirrhosis with ascites. METHODS: Cirrhotic rats received a 2-week course of obeticholic acid or vehicle starting once ascites developed. We then determined: bacterial translocation by mesenteric lymph node culture, ileum expression of antimicrobial peptides and tight junction proteins by qPCR, fecal albumin loss, enteric bacterial load and microbiota composition by qPCR and pyrosequencing of ileum mucosa-attached contents, and intestinal inflammation by cytometry of the inflammatory infiltrate. RESULTS: Obeticholic acid reduced bacterial translocation from 78.3% to 33.3% (p<0.01) and upregulated the expression of the farnesoid X receptor-associated gene small heterodimer partner. Treatment improved ileum expression of antimicrobial peptides, angiogenin-1 and alpha-5-defensin, tight junction proteins zonulin-1 and occludin, and reduced fecal albumin loss and liver fibrosis. Enteric bacterial load normalized, and the distinctive mucosal microbiota of cirrhosis was reduced. Gut immune cell infiltration was reduced and inflammatory cytokine and Toll-like receptor 4 expression normalized. CONCLUSIONS: In ascitic cirrhotic rats, obeticholic acid reduces gut bacterial translocation via several complementary mechanisms at the intestinal level. This agent could be used as an alternative to antibiotics to prevent bacterial infection in cirrhosis.

A propensity score analysis shows that empirical treatment with linezolid does not increase the thirty-day mortality rate in patients with Gram-negative bacteremia.

The role of linezolid in empirical therapy of suspected bacteremia remains unclear. The aim of this study was to evaluate the influence of empirical use of linezolid or glycopeptides in addition to other antibiotics on the 30-day mortality rates in patients with Gram-negative bacteremia. For this purpose, 1,126 patients with Gram-negative bacteremia in the Hospital Clinic of Barcelona from 2000 to 2012 were included in this study. In order to compare the mortality rates between patients who received linezolid or glycopeptides, the propensity scores on baseline variables were used to balance the treatment groups, and both propensity score matching and propensity-adjusted logistic regression were used to compare the 30-day mortality rates between the groups. The overall 30-day mortality rate was 16.0% during the study period. Sixty-eight patients received empirical treatment with linezolid, and 1,058 received glycopeptides. The propensity score matching included 64 patients in each treatment group. After matching, the mortality rates were 14.1% (9/64) in patients who received glycopeptides and 21.9% (14/64) in those who received linezolid, and a nonsignificant association between empirical linezolid treatment and mortality rate (odds ratio [OR], 1.63; 95% confidence interval [CI], 0.69 to 3.82; P = 0.275, McNemar's test) was found. This association remained nonsignificant when variables that remained unbalanced after matching were included in a conditional logistic regression model. Further, the stratified propensity score analysis did not show any significant relationship between empirical linezolid treatment and the mortality rate after adjustment by propensity score quintiles or other variables potentially associated with mortality. In conclusion, the propensity score analysis showed that empirical treatment with linezolid compared with that with glycopeptides was not associated with 30-day mortality rates in patients with Gram-negative bacteremia.

Cardiac rehabilitation and outcome in stable outpatients with recent myocardial infarction.

OBJECTIVE: To compare the mortality rate and the rate of subsequent ischemic events (myocardial infarction [MI], ischemic stroke, or limb amputation) in patients with recent MI according to the use of cardiac rehabilitation or no rehabilitation. DESIGN: Longitudinal observational study. SETTING: Ongoing registry of outpatients. PARTICIPANTS: Patients (N=1043) with recent acute MI were recruited; of these, 521 (50%) participated in cardiac rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Subsequent ischemic events and mortality rates were registered. RESULTS: Over a mean follow-up of 18 months, 50 patients (4.8%) died and 49 (4.7%) developed 52 subsequent ischemic events (MI: n=43, ischemic stroke: n=6, limb amputation: n=3). Both the mortality rate (.16 vs 5.57 deaths per 100 patient-years; rate ratio=.03; 95% confidence interval [CI], 0.0-0.1]) and the rate of subsequent ischemic events (1.65 vs 4.54 events per 100 patient-years; rate ratio=0.4; 95% CI, 0.2-0.7) were significantly lower in cardiac rehabilitation participants than in nonparticipants. Multivariate analysis confirmed that patients in cardiac rehabilitation had a significantly lower risk of death (hazard ratio=.08; 95% CI, .01-.63; P=.016) and a nonsignificant lower risk of subsequent ischemic events (hazard ratio=.65; 95% CI, .30-1.42). CONCLUSIONS: The use of cardiac rehabilitation in patients with recent MI was independently associated with a significant decrease in the mortality rate and a nonsignificant decrease in the rate of subsequent ischemic events.

Deprescribing in older patients with advanced cancer referred to palliative care.

OBJECTIVES: This study aimed to explore the prevalence of potentially inappropriate medications (PIMs) in a cohort of older adults with advanced cancer referred to palliative care. Secondary objectives were to describe the categories of identified PIMs and assess risk factors associated with their presence in this population. METHODS: This retrospective, observational study evaluated patients with advanced cancer admitted to a tertiary university hospital in Madrid, Spain and referred to palliative care between 1 January 2020 and 30 June 2020. Demographic, clinical, and pharmacotherapeutic data were obtained from the electronic medical records and regional databases. PIMs were assessed using the Screening Tool of Older Persons Prescriptions in Frail adults (STOPPFrail) criteria, V1. RESULTS: Among 123 patients (median age 80 years (IQR 73.5-87), 64.2% male), 74% presented at least one PIM according to the STOPPFrail criteria. The most common categories of inappropriate medications were lipid-lowering therapies, proton pump inhibitors, calcium supplements, and oral antidiabetics. The number of chronic comedications was significantly associated with PIM presence. CONCLUSIONS: Our study found a high prevalence of PIM among a cohort of older adults with advanced cancer and short life expectancy. This underlines the need for a comprehensive medication review to optimise pharmacotherapy in this population.

Beyond the acute phase: a comprehensive literature review of long-term sequelae resulting from infectious diseases.

Infectious diseases have consistently served as pivotal influences on numerous civilizations, inducing morbidity, mortality, and consequently redirecting the course of history. Their impact extends far beyond the acute phase, characterized by the majority of symptom presentations, to a multitude of adverse events and sequelae that follow viral, parasitic, fungal, or bacterial infections. In this context, myriad sequelae related to various infectious diseases have been identified, spanning short to long-term durations. Although these sequelae are known to affect thousands of individuals individually, a comprehensive evaluation of all potential long-term effects of infectious diseases has yet to be undertaken. We present a comprehensive literature review delineating the primary sequelae attributable to major infectious diseases, categorized by systems, symptoms, and duration. This compilation serves as a crucial resource, illuminating the long-term ramifications of infectious diseases for healthcare professionals worldwide. Moreover, this review highlights the substantial burden that these sequelae impose on global health and economies, a facet often overshadowed by the predominant focus on the acute phase. Patients are frequently discharged following the resolution of the acute phase, with minimal long-term follow-up to comprehend and address potential sequelae. This emphasizes the pressing need for sustained vigilance, thorough patient monitoring, strategic health management, and rigorous research to understand and mitigate the lasting economic and health impacts of infectious diseases more fully.

Randomized split-mouth clinical trial comparing osteoblastic activity and osteogenic potential of autogenous particle harvesting during implant surgery without irrigation and with irrigation.

OBJECTIVE: To compare the osteoblastic activity and osteogenic potential of autogenous particle harvesting during implant surgery using low-speed drilling without irrigation and high-speed drilling with irrigation. MATERIALS AND METHODS: Thirty patients with bilateral missing teeth of 3.6 and 4.6 were randomized into two groups (Group 1: low-speed drilling without irrigation and Group 2: high-speed drilling with irrigation) and 60 single dental implants were placed. The temperature at the tip of each drill was recorded and the harvested bone was weighed; particle size and Ca and P levels were also analyzed. After osteoblast culture, cell viability, cell cycle assay, cell migration, vascular endothelial growth factor (VEGF) concentration, and mineralized nodule formation were assessed. RESULTS: Although the temperature of the drills was slightly higher in Group 1, no statistically significant differences were observed (p ≤ 0.05); however, the amount of harvested bone was higher (p < 0.001) and the size of the particles was higher (p = 0.019). In relation to osteoblastic activity and osteogenic potential, higher cell proliferation, higher number of cells in G2/M and S phases, higher cell migration capacity, higher VEGF concentration, and higher amount of mineralized nodule formation were observed in Group 1. CONCLUSIONS: Low-speed drilling without irrigation does not result in a significant increase in bone temperature compared to conventional drilling. However, a greater amount of bone is obtained; in addition, osteoblastic activity and osteogenic potential are higher with this technique, but further clinical studies are necessary.

Risk factors for COVID-19 and their association with mortality in Ecuadorian patients admitted to the ICU: A retrospective cohort multicentric study.

Several risk factors were associated with mortality in patients with coronavirus disease 2019 (COVID-19) infection in intensive care units (ICU). We assessed the effect of risk factors related to the characteristics and clinical history of the population, laboratory test results, drug management, and type of ventilation on the probability of survival/discharge from the ICU. A retrospective cohort multicentric study of adults with COVID-19 admitted to the ICU between March 2020 and December 2021. Data were collected from 6 hospitals in 5 cities in Ecuador. The primary outcome was ICU survival/discharge. Survival analysis was conducted using semi-parametric Cox proportional hazards models. Of those admitted to the ICU with COVID-19, (n = 991), mean age was 56.76 ±â€…13.14, and 65.9% were male. Regarding the primary outcome, 51.1% (n = 506) died and 48.9% (n = 485) survived. Of the group that died, their mean age was higher than the survivors (60.7 vs 52.60 years, respectively), and they had a higher prevalence of comorbidities such as arterial hypertension (37.2% vs 20.4%, respectively) and diabetes mellitus (26.9% vs 15.7%, respectively), with P < .001. In ventilatory management, 32.7% of patients used noninvasive ventilation and high-flow nasal cannula, and 67.3% required invasive ventilatory support. After adjusting for confounders, Cox regression analysis showed that patients were less likely to be discharged alive from the ICU if they met the following conditions: arterial hypertension (hazard ratio [HR] = 0.83 95% CI 0.723-0.964), diabetes mellitus (HR = 0.80 95% CI 0.696-0.938), older than 62 years (HR = 0.86 95% CI 0.790-0.956), obese (body mass index ≥ 30) (HR = 0.78 95% CI 0.697-0.887), 1 unit increase in SOFA score (HR = 0.94 95% CI 0.937-0.961), PaO2/FiO2 ratio <100 mm Hg (HR = 0.84 95% CI 0.786-0.914), and the use of invasive mechanical ventilation (HR = 0.68 95% CI 0.614-0.769). Risk factors associated with increased mortality were older age, obesity, arterial hypertension, and diabetes. Factors such as male gender, chronic obstructive pulmonary disease, acute kidney injury, and cancer reported in other investigations did not have the same effect on mortality in our study.

A long-term survey of Serratia spp. bloodstream infections revealed an increase of antimicrobial resistance involving adult population.

Serratia spp. is a well-recognized pathogen in neonates; however, limited data are available in adults. We studied microbiological and clinical characteristics of Serratia spp. causing bloodstream infections (BSI) in our institution (January 2005-July 2020). Overall, 141 BSI episodes affecting 139 patients were identified and medical records reviewed. Antimicrobial susceptibility was recovered from our informatics system and 118 isolates from 116 patients were available for further microbiological studies. Whole genome sequencing (WGS) was completed in 107 isolates. Incidence of Serratia BSI was 0.3/1000 overall admissions (range 0.12-0.60), with maximum prevalence (27 episodes, 19.1%) during 2017-2018. Relevant patients' clinical characteristics were 71.9% ≥60 years (n = 100), with high comorbidity rates (49%, ≥2), 23 (74.2%) of them died within 1 month of the BSI episode. WGS identified all isolates as Serratia marcescens when Kraken bioinformatics taxonomic tool was used despite some which were identified as Serratia nematodiphila (32/118) or Serratia ureilytica (5/118) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Nevertheless, when using MASH distance, Serratia nevei (63/107), S. ureilytica (38/107), and S. marcescens (6/107) were assigned. Carbapenemase (blaVIM-1) and extended-spectrum ß-lactases (ESBL) (blaSHV-12) genes were found in seven and three isolates, respectively, one of them expressing both genes. The worldwide-disseminated IncL/M scaffold plasmid was identified in six VIM producers. Four genotypes were established based on their virulence factors and resistome. Serratia spp. emerged as a relevant nosocomial pathogen causing BSI in elderly patients in our hospital, particularly in recent years with a remarkable increase in antibiotic resistance. ESBL and carbapenemases production related to plasmid dissemination are particularly noteworthy.IMPORTANCESerratia spp. is the third most frequent pathogen involved in outbreaks at neonatal facilities and is primarily associated with bacteremia episodes. In this study, we characterized all causing bloodstream infection (BSI) in patients admitted to our hospital during a 16-year period (2005-2020). Despite having no neonatal intensive care unit in our hospital, this study revealed that Serratia spp. is a relevant pathogen causing BSI in elderly patients with high comorbidity rates. A significant increase of antimicrobial resistance was detected over time, particularly in 2020 and coinciding with the coronavirus disease (COVID-19) pandemic and nosocomial spread of multidrug-resistant Serratia spp. isolates. extended-spectrum ß-lactases and carbapenemases genes associated with plasmid dissemination, typically detected in other Enterobacterales species, were also identified, reinforcing the role of Serratia spp. in the antimicrobial resistance landscape. Additionally, this work highlights the need to reclassify the species of Serratia, since discrepancies were observed in the identification when using different tools.

Mechanisms of linezolid resistance among Staphylococci in a tertiary hospital.

The mechanisms of linezolid resistance among 86 staphylococcal isolates from two intensive care units were investigated. The most frequent was the G2576T mutation in the 23S rRNA (82%). The cfr gene was found in 17% of the isolates, seven S. aureus and eight S. epidermidis isolates. Four of the S. epidermidis isolates had the G2576T mutation and the cfr gene. In four S. haemolyticus isolates, the mechanism could not be identified.

A Relatively Simple Look at the Rather Complex Crystallization Kinetics of PLLA.

This work demonstrates that, despite the existence of a significant number of works on PLA crystallization, there is still a relatively simple way, different from those already described, in which its complex kinetics can be observed. The X-ray diffraction (XRD) results presented here confirm that the PLLA under study crystallizes mostly in the α and α' forms. An interesting observation is that at any temperature in the studied range of the patterns, the X-ray reflections stabilize with a given shape and at a given angle, different for each temperature. That means that both α and α' forms coexist and are stable at the same temperatures so that the shape of each pattern results from both structures. However, the patterns obtained at each temperature are different because the predominance of one crystal form over the other depends on temperature. Thus, a two-component kinetic model is proposed to account for both crystal forms. The method involves the deconvolution of the exothermic DSC peaks using two logistic derivative functions. The existence of the rigid amorphous fraction (RAF) in addition to the two crystal forms increases the complexity of the whole crystallization process. However, the results presented here show that a two-component kinetic model can reproduce the overall crystallization process fairly well over a broad range of temperatures. The method used here for PLLA may be useful for describing the isothermal crystallization processes of other polymers.

[Sleep disorders related to HIV treatment.] / Trastornos en la calidad del sueño asociados a los inhibidores de la integrasa en el tratamiento del VIH.

OBJECTIVE: HIV Clinical Guidelines have positioned integrase inhibitors recently as first-line treatment. However, two of these drugs have also been associated with adverse side effects on the central nervous system, especially with sleep disturbances. The objective was to analyse the influence of bictegravir and dolutegravir on the sleep quality in HIV patients. METHODS: An observational, cross-sectional study was carried out between December 2020 and January 2021 in HIV patients attended in a pharmacy care clinic. Demographic and adherence variables were collected. Sleep quality was measured using the Pittsburgh questionnaire or PSQI. We classified patients into two groups: patients with bictegravir or dolutegravir in their treatment (study group) and the rest (control group). The influence of the variables collected on the PSQI result was analysed using the Chi-Square test for categorical variables and the student t-test or Mann-Whitney U test for continuous variables. RESULTS: One hundred and nineteen patients were included. 64% in the study group and 67% in the control group suffered from sleep disorders according to the PSQI questionnaire (p=0.788). Neither were statistical differences found when the different components of sleep were analysed between the two groups. CONCLUSIONS: A high percentage of patients, regardless of whether their treatment includes bictegravir or dolutegravir, have problems with their sleep quality. We didn't find a correlation between sleep quality and treatment with bictegravir or dolutegravir compared to the other treatments.

OBJETIVO: Los inhibidores de la integrasa se han posicionado recientemente en todas las Guías Clínicas de VIH como tratamiento antirretroviral de primera línea para el VIH. Sin embargo, dos de estos fármacos se han asociado también a efectos adversos a nivel del sistema nervioso central, concretamente con alteraciones del sueño. El objetivo del trabajo fue analizar la influencia de bictegravir y dolutegravir en la calidad del sueño en personas que viven con VIH (PVIH). METODOS: Se realizó un estudio observacional y transversal entre los meses de diciembre de 2020 y enero de 2021 en las PVIH de las consultas de atención farmacéutica del hospital. Se recogieron variables demográficas y de adherencia. La calidad del sueño se midió mediante el Cuestionario de Pittsburgh o PSQI. Las PVIH se clasificaron en 2 grupos: el grupo estudio, constituido por participantes con bictegravir o dolutegravir en su tratamiento, y el grupo control, integrado por el resto de PVIH. Se analizó la influencia de las variables recogidas sobre el resultado del PSQI mediante la prueba de chi cuadrado/odds ratio para variables categóricas y el de t de Student o U de Mann Whitney para variables continuas. RESULTADOS: Se incluyeron 119 PVIH, de las cuales un 64% en el grupo estudio y un 67% en el grupo control sufrían trastornos del sueño según el PSQI (p=0,788). Tampoco hubo diferencias estadísticamente significativas cuando se compararon los diferentes componentes del sueño entre los dos grupos. CONCLUSIONES: Un elevado porcentaje de PVIH, independientemente de si el TAR incluye bictegravir o dolutegravir, tienen problemas relacionados con la calidad del sueño. No se encuentra correlación entre la calidad del sueño y el tratamiento con bictegravir o dolutegravir comparado con el resto de tratamientos.