Sociodemographic and clinical predictors of adherence to antidepressants in depressive disorders: a systematic review with a meta-analysis.

Introduction: Current evidence reveals concerning rates of non-adherence to antidepressant treatment, possibly influenced by various relevant determinants such as sociodemographic factors or those related to the health system and their professionals. The aim of this paper is to review the scientific evidence on sociodemographic and clinical predictors of adherence to pharmacological treatment in patients diagnosed with a depressive disorder. Methods: a systematic review (SR) was conducted. The search for a previous SR was updated and de novo searches were performed in Medline, EMBASE, Web of Science (WoS) and PsycInfo (last 10 years). The risk of bias was assessed using the Cochrane tool for non-randomized studies-of Exposure (ROBINS-E). Meta-analyses were conducted. Results: Thirty-nine studies (n = 2,778,313) were included, 24 of them in the meta-analyses. In the initiation phase, no association of adherence was found with any of the predictors studied. In the implementation and discontinuation phases, middle-aged and older patients had better adherence rates and lower discontinuation rates than younger ones. White patients adhered to treatment better than African-American patients. Discussion: Age and ethnicity are presented as the predictive factors of pharmacological adherence. However, more research is needed in this field to obtain more conclusive results on other possible factors. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023414059], identifier [CRD42023414059].

Cirrhosis-downregulated LSECtin can be retrieved by cytokines, shifts the TLR-induced LSECs secretome and correlates with the hepatic Th response.

BACKGROUND AND AIMS: We evaluated tolerogenic C-type lectin LSECtin loss in cirrhosis and its potential regulation by cytokines. METHODS: Liver tissue from patients with cirrhosis and healthy controls, immortalised and generated LSECtin-CRISPR immortalised LSECs, and murine primary LSECs from the CCl4 model were handled. RESULTS: LSECtin expression was reduced in liver tissue from cirrhotic patients, and it decreased from compensated to decompensated disease. Increased phosphorylation of MAPK, Akt and NFkB was observed upon LSECtin stimulation in LSEC murine cell line, showing a pattern of inflammatory and chemotactic cytokines either restrained (IL-10, CCL4) or unrestrained (TNF-α, IL-1ß, IL-6, CCL2). CD44 attenuated whereas LAG-3 increased all substrates phosphorylation in combination with TLR4 and TLR2 ligands except for NFkB. TNF-α, IL-1 ß, IL-6 and CCL2 were restrained by LSECtin crosslinking on TLRs studied. Conversely, IL-10 and CCL4 were upregulated, suggesting a LSECtin-TLRs synergistic effect. Also, LSECtin was significantly induced after IL-13 stimulation or combined with anti-inflammatory cytokines in cirrhotic and immortalised LSECs. Th17 and regulatory T cells were progressively increased in the hepatic tissue from compensated to decompensated patients. A significant inverse correlation was present between gene expression levels of CLEC4G/LSECtin and RORγT and FOXP3 in liver tissues. CONCLUSION: LSECtin restrains TLR proinflammatory secretome induced on LSECs by interfering immune response control, survival and MAPKs signalling pathways. The cytokine-dependent induction of LSECtin and the association between LSECtin loss and Th17 cell subset expansion in the liver, provides a solid background for exploring LSECtin retrieval as a mechanism to reprogram LSEC homeostatic function hampered during cirrhosis.

The impact of a neuromuscular rehabilitation programme on the quality of life of patients with acute coronary syndrome and its relationship with sexual dysfunction: a randomised controlled trial.

PURPOSE: Many patients with acute coronary syndrome experience problematic or altered sexual function. This aspect of the disease is frequently ignored or overlooked by the healthcare community even though it can strongly influence health-related patient quality of life (HRQoL). Thus, the aim of this study was to compare the effects of a specific cardiac rehabilitation programme focused on aerobic and neuromuscular strength-resistance training to those of a classic rehabilitation programme, both in terms of HRQoL and erectile dysfunction in patients with acute coronary syndrome. METHODS: This study reports both secondary and unregistered outcomes from a double-blinded, randomised, and controlled clinical trial. The proposed intervention was based on the completion of a 20-session (10-week) cardiac rehabilitation programme for patients with cardiovascular disease. The patient cohort had been diagnosed with acute coronary syndrome and was recruited at the Cardiology Service of a private tertiary hospital. The outcomes assessed in this study were HRQoL and erectile disfunction assessed at baseline, after the intervention, and at a 6-month follow-up. RESULTS: A total of 30 participants were randomly allocated to each study arm. The results of the two-way mixed ANOVAs showed significant group × time interactions for all the outcome measures (EQ-5D_index, p = 0.004; EQ-5D_VAS, p = 0.017; QLMI-Q, p ≤ 0.001; and IIEF-5, p = 0.001). CONCLUSION: The neuromuscular strength training programme was more effective than the classic strength training programme in terms of increasing the HRQoL and improving erectile dysfunction in patients following acute coronary syndrome, with differences still remaining between these groups at the 6-month follow-up.

Guillain-Barré Syndrome Post COVID-19 Vaccination with ChAdOx1 nCoV-19 Vaccine: A Colombian Case Report.

Background: Adverse events after vaccination against COVID-19 include rare events, such as Guillain-Barré syndrome. Study Aims. Documentation of clinical and temporary characteristics of the Guillain-Barré syndrome after using anti-COVID-19 ChAdOx1 nCoV-19 vaccine. Case Presentation. An adult, 29-year-old male, without relevant medical history, who developed neuromuscular symptoms nine days after administration of the first dose of anti-COVID-19 ChAdOx1 nCoV-19 vaccine. Results: Symptoms appeared nine days after vaccination, with lower limbs paresthesia. Three days later, paresthesia of upper limbs occurred. The following day, distal weakness of limbs, with standing and gripping difficulties, occurred. The clinical evaluation demonstrated dysarthria, incomplete palpebral closure, bilateral facial, and tongue paresis. The electromyography was compatible with a motor demyelinating polyneuropathy, confirming the diagnosis of the Guillain-Barré syndrome. Management with five sessions of plasma exchange was prescribed, with favorable clinical results. Conclusions: Clinical and laboratory tests confirmed the Guillain-Barré syndrome and the time elapsed from the date of the vaccine administration to the appearance of initial symptoms, added to the absence of other causes, and allowed to establish that the disease was caused by the vaccination.

Carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-haematopoietic stem cell transplant: a retrospective cohort study.

BACKGROUND: Risk factors for carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-HSCT have not been thoroughly explored. METHODS: All children with cancer or post-HSCT who developed Enterobacterales bloodstream infections in two cancer referral centres in major Colombian cities between 2012 and 2021 were retrospectively examined. When the infection episode occurred, carbapenem resistance mechanisms were evaluated according to the available methods. Data were divided in a training set (80%) and a test set (20%). Three internally validated carbapenem-resistant Enterobacterales (CRE) prediction models were created: a multivariate logistic regression model, and two data mining techniques. Model performances were evaluated by calculating the average of the AUC, sensitivity, specificity and predictive values. RESULTS: A total of 285 Enterobacterales bloodstream infection episodes (229 carbapenem susceptible and 56 carbapenem resistant) occurred [median (IQR) age, 9 (3.5-14) years; 57% male]. The risk of CRE was 2.1 times higher when the infection was caused by Klebsiella spp. and 5.8 times higher when a carbapenem had been used for ≥3 days in the previous month. A model including these two predictive variables had a discriminatory performance of 77% in predicting carbapenem resistance. The model had a specificity of 97% and a negative predictive value of 81%, with low sensitivity and positive predictive value. CONCLUSIONS: Even in settings with high CRE prevalence, these two variables can help early identification of patients in whom CRE-active agents are unnecessary and highlight the importance of strengthening antibiotic stewardship strategies directed at preventing carbapenem overuse.

The 3Rs in Experimental Liver Disease.

Patients with cirrhosis present multiple physiological and immunological alterations that play a very important role in the development of clinically relevant secondary complications to the disease. Experimentation in animal models is essential to understand the pathogenesis of human diseases and, considering the high prevalence of liver disease worldwide, to understand the pathophysiology of disease progression and the molecular pathways involved, due to the complexity of the liver as an organ and its relationship with the rest of the organism. However, today there is a growing awareness about the sensitivity and suffering of animals, causing opposition to animal research among a minority in society and some scientists, but also about the attention to the welfare of laboratory animals since this has been built into regulations in most nations that conduct animal research. In 1959, Russell and Burch published the book "The Principles of Humane Experimental Technique", proposing that in those experiments where animals were necessary, everything possible should be done to try to replace them with non-sentient alternatives, to reduce to a minimum their number, and to refine experiments that are essential so that they caused the least amount of pain and distress. In this review, a comprehensive summary of the most widely used techniques to replace, reduce, and refine in experimental liver research is offered, to assess the advantages and weaknesses of available experimental liver disease models for researchers who are planning to perform animal studies in the near future.

Initial opioid prescription characteristics and risk of opioid misuse, poisoning and dependence: retrospective cohort study.

OBJECTIVE: To identify individual and initial prescription-related factors associated with an increased risk for opioid-related misuse, poisoning and dependence (MPD) in patients with non-cancer pain. METHODS: Cohort study linking several databases covering 5 million inhabitants of the region of Valencia, Spain, including all adults initiating prescription opioids in the period 2012-2018. To ascertain the association between the characteristics of the initial prescription choice and the risk of opioid MPD, we used shared frailty Cox regression models. We additionally considered death as a competing risk in sensitivity analyses. RESULTS: 958 019 patients initiated opioid prescription from 2012 to 2018, of which 0.13% experienced MPD. Most patients were prescribed tramadol as initial opioid (76.7%) followed by codeine (16.3%), long-acting opioids (6.7%), short-acting opioids (0.2%) and ultrafast opioids (0.1%). Initiation with ultrafast (HR 7.2; 95% CI 4.1 to 12.6), short-acting (HR 4.8; 95% CI 2.3 to 10.2) and long-acting opioids (HR 1.5; 95% CI 1.2 to 1.9) were associated with a higher risk of MPD when compared with tramadol. Initial prescriptions covering 4-7 days (HR 1.3; 95% CI 1.0 to 1.8), 8-14 days (HR 1.4; 95% CI 1.0 to 1.9), 15-30 days (HR 1.7; 95% CI 1.2 to 2.3) and more than one a month (HR 1.8; 95% CI 1.3 to 2.5) were associated with more MPD risk than initial prescriptions for 1-3 days. Treatments with >120 daily morphine milligram equivalents (MME) increased MPD risk (vs <50 MME, HR 1.6; 95% CI 1.1 to 2.2). Main individual factors associated with increased risk of MPD risk were male sex (HR 2.4; 95% CI 2.1 to 2.7), younger age (when compared with patients aged 18-44 years, patients aged 45-64 years, HR 0.4; 95% CI 0.4 to 0.5; patients aged 65-74 years, HR 0.4; 95% CI 0.3 to 0.5 and patients aged 75 years old and over, HR 0.7; 95% CI 0.6 to 0.8), lack of economic resources (2.1; 95% CI 1.8 to 2.5) and registered misuse of alcohol (2.9; 95% CI 2.4 to 3.5). Sensitivity analyses yielded overall comparable results. CONCLUSIONS: Our study identifies riskier patterns of opioid prescription initiation for non-cancer indications, as well as patient subgroups with higher risk of misuse, poisoning and dependence.

Saturated fatty acid-enriched small extracellular vesicles mediate a crosstalk inducing liver inflammation and hepatocyte insulin resistance.

Background & Aims: Lipotoxicity triggers non-alcoholic fatty liver disease (NAFLD) progression owing to the accumulation of toxic lipids in hepatocytes including saturated fatty acids (SFAs), which activate pro-inflammatory pathways. We investigated the impact of hepatocyte- or circulating-derived small extracellular vesicles (sEV) secreted under NAFLD conditions on liver inflammation and hepatocyte insulin signalling. Methods: sEV released by primary mouse hepatocytes, characterised and analysed by lipidomics, were added to mouse macrophages/Kupffer cells (KC) to monitor internalisation and inflammatory responses. Insulin signalling was analysed in hepatocytes exposed to conditioned media from sEV-loaded macrophages/KC. Mice were i.v. injected sEV to study liver inflammation and insulin signalling. Circulating sEV from mice and humans with NAFLD were used to evaluate macrophage-hepatocyte crosstalk. Results: Numbers of sEV released by hepatocytes increased under NAFLD conditions. Lipotoxic sEV were internalised by macrophages through the endosomal pathway and induced pro-inflammatory responses that were ameliorated by pharmacological inhibition or deletion of Toll-like receptor-4 (TLR4). Hepatocyte insulin signalling was impaired upon treatment with conditioned media from macrophages/KC loaded with lipotoxic sEV. Both hepatocyte-released lipotoxic sEV and the recipient macrophages/KC were enriched in palmitic (C16:0) and stearic (C18:0) SFAs, well-known TLR4 activators. Upon injection, lipotoxic sEV rapidly reached KC, triggering a pro-inflammatory response in the liver monitored by Jun N-terminal kinase (JNK) phosphorylation, NF-κB nuclear translocation, pro-inflammatory cytokine expression, and infiltration of immune cells into the liver parenchyma. sEV-mediated liver inflammation was attenuated by pharmacological inhibition or deletion of TLR4 in myeloid cells. Macrophage inflammation and subsequent hepatocyte insulin resistance were also induced by circulating sEV from mice and humans with NAFLD. Conclusions: We identified hepatocyte-derived sEV as SFA transporters targeting macrophages/KC and activating a TLR4-mediated pro-inflammatory response enough to induce hepatocyte insulin resistance. Impact and Implications: Small extracellular vesicles (sEV) released by the hepatocytes under non-alcoholic fatty liver disease (NAFLD) conditions cause liver inflammation and insulin resistance in hepatocytes via paracrine hepatocyte-macrophage-hepatocyte crosstalk. We identified sEV as transporters of saturated fatty acids (SFAs) and potent lipotoxic inducers of liver inflammation. TLR4 deficiency or its pharmacological inhibition ameliorated liver inflammation induced by hepatocyte-derived lipotoxic sEV. Evidence of this macrophage-hepatocyte interactome was also found in patients with NAFLD, pointing to the relevance of sEV in SFA-mediated lipotoxicity in NAFLD.

Antibiotic resistance and consumption before and during the COVID-19 pandemic in Valle del Cauca, Colombia.

Objective: To assess changes in antibiotic resistance of eight of the World Health Organization priority bug-drug combinations and consumption of six antibiotics (ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, vancomycin) before (March 2018 to July 2019) and during (March 2020 to July 2021) the COVID-19 pandemic in 31 hospitals in Valle del Cauca, Colombia. Methods: This was a before/after study using routinely collected data. For antibiotic consumption, daily defined doses (DDD) per 100 bed-days were compared. Results: There were 23 405 priority bacterial isolates with data on antibiotic resistance. The total number of isolates increased from 9 774 to 13 631 in the periods before and during the pandemic, respectively. While resistance significantly decreased for four selected bug-drug combinations (Klebsiella pneumoniae, extended spectrum beta lactamase [ESBL]-producing, 32% to 24%; K. pneumoniae, carbapenem-resistant, 4% to 2%; Pseudomonas aeruginosa, carbapenem-resistant, 12% to 8%; Acinetobacter baumannii, carbapenem-resistant, 23% to 9%), the level of resistance for Enterococcus faecium to vancomycin significantly increased (42% to 57%). There was no change in resistance for the remaining three combinations (Staphylococcus aureus, methicillin-resistant; Escherichia coli, ESBL-producing; E. coli, carbapenem-resistant). Consumption of all antibiotics increased. However, meropenem consumption decreased in intensive care unit settings (8.2 to 7.1 DDD per 100 bed-days). Conclusions: While the consumption of antibiotics increased, a decrease in antibiotic resistance of four bug-drug combinations was observed during the pandemic. This was possibly due to an increase in community-acquired infections. Increasing resistance of E. faecium to vancomycin must be monitored. The findings of this study are essential to inform stewardship programs in hospital settings of Colombia and similar contexts elsewhere.

Antibiotic resistance and consumption before and during the COVID-19 pandemic in Valle del Cauca, Colombia

[ABSTRACT]. Objective. To assess changes in antibiotic resistance of eight of the World Health Organization priority bug-drug combinations and consumption of six antibiotics (ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, vancomycin) before (March 2018 to July 2019) and during (March 2020 to July 2021) the COVID-19 pandemic in 31 hospitals in Valle del Cauca, Colombia. Methods. This was a before/after study using routinely collected data. For antibiotic consumption, daily defined doses (DDD) per 100 bed-days were compared. Results. There were 23 405 priority bacterial isolates with data on antibiotic resistance. The total number of isolates increased from 9 774 to 13 631 in the periods before and during the pandemic, respectively. While resistance significantly decreased for four selected bug-drug combinations (Klebsiella pneumoniae, extended spectrum beta lactamase [ESBL]-producing, 32% to 24%; K. pneumoniae, carbapenem-resistant, 4% to 2%; Pseudomonas aeruginosa, carbapenem-resistant, 12% to 8%; Acinetobacter baumannii, carbapenem-resis- tant, 23% to 9%), the level of resistance for Enterococcus faecium to vancomycin significantly increased (42% to 57%). There was no change in resistance for the remaining three combinations (Staphylococcus aureus, methicillin-resistant; Escherichia coli, ESBL-producing; E. coli, carbapenem-resistant). Consumption of all anti- biotics increased. However, meropenem consumption decreased in intensive care unit settings (8.2 to 7.1 DDD per 100 bed-days). Conclusions. While the consumption of antibiotics increased, a decrease in antibiotic resistance of four bug-drug combinations was observed during the pandemic. This was possibly due to an increase in commu- nity-acquired infections. Increasing resistance of E. faecium to vancomycin must be monitored. The findings of this study are essential to inform stewardship programs in hospital settings of Colombia and similar contexts elsewhere.

[RESUMEN]. Objetivo. Evaluar los cambios en la resistencia a los antibióticos de ocho de las combinaciones de fármacos y agentes patógenos incluidos en la lista prioritaria de la Organización Mundial de la Salud y el consumo de seis antibióticos (ceftriaxona, cefepima, piperacilina/tazobactam, meropenem, ciprofloxacina, vancomicina) antes de la pandemia de COVID-19 (de marzo del 2018 a julio del 2019) y durante la pandemia (de marzo del 2020 a julio del 2021) en 31 hospitales del Valle del Cauca (Colombia). Métodos. En este estudio se analiza el antes y el después empleando datos recopilados de forma rutinaria. Para el consumo de antibióticos, se compararon las dosis diarias definidas (DDD) por 100 días-cama. Resultados. Hubo 23 405 cepas bacterianas aisladas prioritarias con datos sobre la resistencia a los antibióti- cos. El número total de cepas aisladas aumentó de 9 774 antes de la pandemia a 13 631 durante la pandemia. Si bien la resistencia disminuyó significativamente en las cuatro combinaciones seleccionadas de agentes patógenos y fármacos (Klebsiella pneumoniae, productora de betalactamasa de espectro extendido [BLEE], de 32% a 24%; K. pneumoniae, resistente a los carbapenémicos, de 4% a 2%; Pseudomonas aeruginosa, resistente a los carbapenémicos, de 12% a 8%; Acinetobacter baumannii, resistente a los carbapenémicos, de 23% a 9%), el nivel de resistencia de Enterococcus faecium a la vancomicina aumentó significativamente (de 42% a 57%). No hubo cambios en la resistencia en las tres combinaciones restantes (Staphylococcus aureus, resistente a la meticilina; Escherichia coli, productora de BLEE; E. coli, resistente a los carbapenémi- cos). El consumo de todos los antibióticos aumentó. Sin embargo, el consumo de meropenem disminuyó en los entornos de las unidades de cuidados intensivos (de 8,2 a 7,1 DDD por 100 días-cama). Conclusiones. Aunque el consumo de antibióticos aumentó, se observó una disminución en la resistencia a los antibióticos de cuatro combinaciones de agentes patógenos y medicamentos durante la pandemia, que posiblemente se debió a un aumento en las infecciones adquiridas en la comunidad. Es necesario vigilar el aumento de la resistencia de E. faecium a la vancomicina. Los resultados de este estudio son esenciales para que sirvan de orientación en los programas de optimización del uso de los antibióticos en los entornos hospitalarios de Colombia y en contextos similares en otros lugares.

[RESUMO]. Objetivo. Avaliar as mudanças na resistência a antibióticos em oito das combinações microrganismo/anti- microbiano prioritárias da Organização Mundial da Saúde e o consumo de seis antibióticos (ceftriaxona, cefepima, piperacilina/tazobactam, meropeném, ciprofloxacino, vancomicina) antes (março de 2018 a julho de 2019) e durante (março de 2020 a julho de 2021) a pandemia de COVID-19 em 31 hospitais em Valle del Cauca, Colômbia. Métodos. Este foi um estudo antes/depois utilizando dados coletados rotineiramente. Para avaliar o consumo de antibióticos, foram comparadas doses diárias definidas (DDD) por 100 leitos-dias. Resultados. Havia dados sobre resistência a antibióticos para 23.405 isolados bacterianos prioritários. O número total de isolados aumentou de 9.774 para 13.631 antes e durante a pandemia, respectivamente. Embora a resistência tenha diminuído significativamente para quatro das combinações microrganismo/antimi- crobiano selecionadas (Klebsiella pneumoniae, produtora de betalactamase de espectro estendido [ESBL], 32% a 24%; K. pneumoniae, resistente a carbapenêmicos, 4% a 2%; Pseudomonas aeruginosa, resistente a carbapenêmicos, 12% a 8%; Acinetobacter baumannii, resistente a carbapenêmicos, 23% a 9%), o nível de resistência de Enterococcus faecium a vancomicina aumentou significativamente (42% a 57%). Não houve mudança na resistência para as três combinações restantes (Staphylococcus aureus, resistente a meticilina; Escherichia coli, produtora de ESBL; E. coli, resistente a carbapenêmicos). O consumo de todos os antibióti- cos aumentou. Entretanto, o consumo de meropeném nas unidades de terapia intensiva diminuiu (de 8,2 para 7,1 DDD por 100 leitos-dias). Conclusões. Embora o consumo de antibióticos tenha aumentado, observou-se uma diminuição na resistên- cia a antibióticos de quatro combinações microrganismo/antimicrobiano durante a pandemia. Isso ocorreu possivelmente devido a um aumento nas infecções adquiridas na comunidade. O aumento da resistência de E. faecium à vancomicina deve ser monitorado. Os achados deste estudo são essenciais para guiar os pro- gramas de gerenciamento de antimicrobianos em ambientes hospitalares da Colômbia e em outros contextos similares.

Home Blood Pressure Self-monitoring plus Self-titration of Antihypertensive Medication for Poorly Controlled Hypertension in Primary Care: the ADAMPA Randomized Clinical Trial.

BACKGROUND: Patient empowerment through pharmacological self-management is a common strategy in some chronic diseases such as diabetes, but it is rarely used for controlling blood pressure. OBJECTIVE: This study aimed to assess self-monitoring plus self-titration of antihypertensive medication versus usual care for reducing systolic blood pressure (SBP) at 12 months in poorly controlled hypertensive patients. DESIGN: The ADAMPA study was a pragmatic, controlled, randomized, non-masked clinical trial with two parallel arms in Valencia, Spain. PARTICIPANTS: Hypertensive patients older than 40 years, with SBP over 145 mmHg and/or diastolic blood pressure (DBP) over 90 mmHg, were recruited from July 2017 to June 2018. INTERVENTION: Participants were randomized 1:1 to usual care versus an individualized, pre-arranged plan based on self-monitoring plus self-titration. MAIN MEASURE: The primary outcome was the adjusted mean difference (AMD) in SBP between groups at 12 months. KEY RESULTS: Primary outcome data were available for 312 patients (intervention n=156, control n=156) of the 366 who were initially recruited. The AMD in SBP at 12 months (main analysis) was -2.9 mmHg (95% CI, -5.9 to 0.1, p=0.061), while the AMD in DBP was -1.9 mmHg (95% CI, -3.7 to 0.0, p=0.052). The results of the subgroup analysis were consistent with these for the main outcome measures. More patients in the intervention group achieved good blood pressure control (<140/90 mmHg) at 12 months than in the control group (55.8% vs 42.3%, difference 13.5%, 95% CI, 2.5 to 24.5%, p=0.017). At 12 months, no differences were observed in behavior, quality of life, use of health services, or adverse events. CONCLUSION: Self-monitoring plus self-titration of antihypertensive medication based on an individualized pre-arranged plan used in primary care may be a promising strategy for reducing blood pressure at 12 months compared to usual care, without increasing healthcare utilization or adverse events. TRIAL REGISTRATION: EudraCT, number 2016-003986-25 (registered 17 March 2017) and clinicaltrials.gov , NCT03242785.

Inteligencia emocional y rendimiento académico en estudiantes de Medicina en tiempos de pandemia de COVID-19 / Emotional intelligence and academic performance in medical students in times of the COVID-19 pandemic

Introducción: la enfermedad COVID-19 ha condicionado nuevos escenarios de aprendizaje en el mundo, ha afectado la inteligencia emocional y en consecuencia, el rendimiento académico de grupos poblacionales de estudiantes. Objetivo: indagar, desde varias fuentes de investigación, la relación entre la inteligencia emocional y el rendimiento académico en estudiantes de Medicina en el escenario de la COVID-19, a partir de un estudio en el período de 10 años antes y durante la pandemia. Métodos: se realizó una revisión de fuentes bibliográficas en SciELO, Dialnet y Google académico, comprendidas entre los años 2012 y 2022 con el uso de palabras claves: inteligencia emocional, rendimiento académico, estudiantes, Medicina, COVID-19. Se seleccionaron artículos científicos, tesis de grado y maestría para lograr la pertinencia en el estudio realizado. Desarrollo: se evaluaron en el orden conceptual la inteligencia emocional y el rendimiento académico en estudiantes universitarios, fueron analizadas las investigaciones más relevantes atendiendo al autor (año), el tipo de publicación o estudio realizado. Se aplicaron pruebas estadísticas que permitieron ponderar los criterios y principales regularidades en relación con el tema. Conclusiones: con la revisión de publicaciones se pudo constatar los efectos de la pandemia en la inteligencia emocional y el rendimiento académico. Este nuevo escenario de aprendizaje es todavía un reto para la comprensión de docentes e investigadores.

Introduction: the COVID-19 disease has conditioned new learning scenarios in the world, it has affected emotional intelligence and, consequently, the academic performance of population groups of students. Objective: to investigate, from various research sources, the relationship between emotional intelligence and academic performance in medical students in the COVID-19 scenario, based on a study in the 10-year period before and during the pandemic. Methods: a review of bibliographic sources was carried out in SciELO, Dialnet and Google Scholar, from 2012 to 2022 with the use of keywords: emotional intelligence, academic performance, students, Medicine, COVID-19. Scientific articles, degree and master's theses were selected to achieve relevance in the study carried out. Development: emotional intelligence and academic performance in university students were evaluated in the conceptual order, the most relevant investigations were analyzed according to the author (year), the type of publication or study carried out. Statistical tests were applied that allowed to ponder the criteria and main regularities in relation to the subject. Conclusions: with the review of publications, it was possible to verify the effects of the pandemic on emotional intelligence and academic performance. This new learning scenario is still a challenge for teachers and researchers to understand.

Antibiotic resistance and consumption before and during the COVID-19 pandemic in Valle del Cauca, Colombia / Resistencia antibiótica y consumo de antibióticos antes y durante la pandemia de COVID-19 en el Valle del Cauca, Colombia / Resistência a antibióticos e consumo de antibióticos antes e durante a pandemia de COVID-19 no Valle del Cauca, Colômbia

ABSTRACT Objective. To assess changes in antibiotic resistance of eight of the World Health Organization priority bug-drug combinations and consumption of six antibiotics (ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, vancomycin) before (March 2018 to July 2019) and during (March 2020 to July 2021) the COVID-19 pandemic in 31 hospitals in Valle del Cauca, Colombia. Methods. This was a before/after study using routinely collected data. For antibiotic consumption, daily defined doses (DDD) per 100 bed-days were compared. Results. There were 23 405 priority bacterial isolates with data on antibiotic resistance. The total number of isolates increased from 9 774 to 13 631 in the periods before and during the pandemic, respectively. While resistance significantly decreased for four selected bug-drug combinations (Klebsiella pneumoniae, extended spectrum beta lactamase [ESBL]-producing, 32% to 24%; K. pneumoniae, carbapenem-resistant, 4% to 2%; Pseudomonas aeruginosa, carbapenem-resistant, 12% to 8%; Acinetobacter baumannii, carbapenem-resistant, 23% to 9%), the level of resistance for Enterococcus faecium to vancomycin significantly increased (42% to 57%). There was no change in resistance for the remaining three combinations (Staphylococcus aureus, methicillin-resistant; Escherichia coli, ESBL-producing; E. coli, carbapenem-resistant). Consumption of all antibiotics increased. However, meropenem consumption decreased in intensive care unit settings (8.2 to 7.1 DDD per 100 bed-days). Conclusions. While the consumption of antibiotics increased, a decrease in antibiotic resistance of four bug-drug combinations was observed during the pandemic. This was possibly due to an increase in community-acquired infections. Increasing resistance of E. faecium to vancomycin must be monitored. The findings of this study are essential to inform stewardship programs in hospital settings of Colombia and similar contexts elsewhere.

RESUMEN Objetivo. Evaluar los cambios en la resistencia a los antibióticos de ocho de las combinaciones de fármacos y agentes patógenos incluidos en la lista prioritaria de la Organización Mundial de la Salud y el consumo de seis antibióticos (ceftriaxona, cefepima, piperacilina/tazobactam, meropenem, ciprofloxacina, vancomicina) antes de la pandemia de COVID-19 (de marzo del 2018 a julio del 2019) y durante la pandemia (de marzo del 2020 a julio del 2021) en 31 hospitales del Valle del Cauca (Colombia). Métodos. En este estudio se analiza el antes y el después empleando datos recopilados de forma rutinaria. Para el consumo de antibióticos, se compararon las dosis diarias definidas (DDD) por 100 días-cama. Resultados. Hubo 23 405 cepas bacterianas aisladas prioritarias con datos sobre la resistencia a los antibióticos. El número total de cepas aisladas aumentó de 9 774 antes de la pandemia a 13 631 durante la pandemia. Si bien la resistencia disminuyó significativamente en las cuatro combinaciones seleccionadas de agentes patógenos y fármacos (Klebsiella pneumoniae, productora de betalactamasa de espectro extendido [BLEE], de 32% a 24%; K. pneumoniae, resistente a los carbapenémicos, de 4% a 2%; Pseudomonas aeruginosa, resistente a los carbapenémicos, de 12% a 8%; Acinetobacter baumannii, resistente a los carbapenémicos, de 23% a 9%), el nivel de resistencia de Enterococcus faecium a la vancomicina aumentó significativamente (de 42% a 57%). No hubo cambios en la resistencia en las tres combinaciones restantes (Staphylococcus aureus, resistente a la meticilina; Escherichia coli, productora de BLEE; E. coli, resistente a los carbapenémicos). El consumo de todos los antibióticos aumentó. Sin embargo, el consumo de meropenem disminuyó en los entornos de las unidades de cuidados intensivos (de 8,2 a 7,1 DDD por 100 días-cama). Conclusiones. Aunque el consumo de antibióticos aumentó, se observó una disminución en la resistencia a los antibióticos de cuatro combinaciones de agentes patógenos y medicamentos durante la pandemia, que posiblemente se debió a un aumento en las infecciones adquiridas en la comunidad. Es necesario vigilar el aumento de la resistencia de E. faecium a la vancomicina. Los resultados de este estudio son esenciales para que sirvan de orientación en los programas de optimización del uso de los antibióticos en los entornos hospitalarios de Colombia y en contextos similares en otros lugares.

RESUMO Objetivo. Avaliar as mudanças na resistência a antibióticos em oito das combinações microrganismo/antimicrobiano prioritárias da Organização Mundial da Saúde e o consumo de seis antibióticos (ceftriaxona, cefepima, piperacilina/tazobactam, meropeném, ciprofloxacino, vancomicina) antes (março de 2018 a julho de 2019) e durante (março de 2020 a julho de 2021) a pandemia de COVID-19 em 31 hospitais em Valle del Cauca, Colômbia. Métodos. Este foi um estudo antes/depois utilizando dados coletados rotineiramente. Para avaliar o consumo de antibióticos, foram comparadas doses diárias definidas (DDD) por 100 leitos-dias. Resultados. Havia dados sobre resistência a antibióticos para 23.405 isolados bacterianos prioritários. O número total de isolados aumentou de 9.774 para 13.631 antes e durante a pandemia, respectivamente. Embora a resistência tenha diminuído significativamente para quatro das combinações microrganismo/antimicrobiano selecionadas (Klebsiella pneumoniae, produtora de betalactamase de espectro estendido [ESBL], 32% a 24%; K. pneumoniae, resistente a carbapenêmicos, 4% a 2%; Pseudomonas aeruginosa, resistente a carbapenêmicos, 12% a 8%; Acinetobacter baumannii, resistente a carbapenêmicos, 23% a 9%), o nível de resistência de Enterococcus faecium a vancomicina aumentou significativamente (42% a 57%). Não houve mudança na resistência para as três combinações restantes (Staphylococcus aureus, resistente a meticilina; Escherichia coli, produtora de ESBL; E. coli, resistente a carbapenêmicos). O consumo de todos os antibióticos aumentou. Entretanto, o consumo de meropeném nas unidades de terapia intensiva diminuiu (de 8,2 para 7,1 DDD por 100 leitos-dias). Conclusões. Embora o consumo de antibióticos tenha aumentado, observou-se uma diminuição na resistência a antibióticos de quatro combinações microrganismo/antimicrobiano durante a pandemia. Isso ocorreu possivelmente devido a um aumento nas infecções adquiridas na comunidade. O aumento da resistência de E. faecium à vancomicina deve ser monitorado. Os achados deste estudo são essenciais para guiar os programas de gerenciamento de antimicrobianos em ambientes hospitalares da Colômbia e em outros contextos similares.

Real-world patterns of opioid therapy initiation in Spain, 2012-2018: A population-based, retrospective cohort study with 957,080 patients and 1,509,488 initiations.

Introduction: Europe has seen a steady increase in the use of prescription opioids, especially in non-cancer indications. Epidemiological data on the patterns of use of opioids is required to optimize prescription. We aim to describe the patterns of opioid therapy initiation for non-cancer pain and characteristics of patients treated in a region with five million inhabitants in the period 2012 to 2018. Methods: Population-based retrospective cohort study of all adult patients initiating opioid therapy for non-cancer pain in the region of Valencia. We described patient characteristics at baseline and the characteristics of baseline and subsequent treatment initiation. We used multinominal regression models to identify individual factors associated with initiation. Results: A total of 957,080 patients initiated 1,509,488 opioid treatments (957,080 baseline initiations, 552,408 subsequent initiations). For baseline initiations, 738,749 were with tramadol (77.19%), 157,098 with codeine (16.41%) 58,436 (6.11%) with long-acting opioids, 1,518 (0.16%) with short-acting opioids and 1,279 (0.13%) with ultrafast drugs. When compared to tramadol, patients initiating with short-acting, long-acting and ultrafast opioids were more likely to be older and had more comorbidities, whereas initiators with codeine were more prone to be healthier and younger. Treatments lasting less than 7 days accounted for 41.82% of initiations, and 11.89% lasted more than 30 days. 19.55% of initiators with ultrafast fentanyl received more than 120 daily Morphine Milligram Equivalents (MME), and 16.12% of patients initiating with long-acting opioids were prescribed more than 90 daily MME (p < 0.001). Musculoskeletal indications accounted for 65.05% of opioid use. Overlap with benzodiazepines was observed in 24.73% of initiations, overlap with gabapentinoids was present in 11.04% of initiations with long-acting opioids and 28.39% of initiators with short-acting opioids used antipsychotics concomitantly. In subsequent initiations, 55.48% of treatments included three or more prescriptions (vs. 17.60% in baseline initiations) and risk of overlap was also increased. Conclusion: Opioids are initiated for a vast array of non-oncological indications, and, despite clinical guidelines, short-acting opioids are used marginally, and a significant number of patients is exposed to potentially high-risk patterns of initiation, such as treatments lasting more than 14 days, treatments surpassing 50 daily MMEs, initiating with long-acting opioids, or hazardous overlapping with other therapies.

Predictive Models for Equine Emergency Exploratory Laparotomy in Spain: Pre-, Intra-, and Post-Operative-Mortality-Associated Factors.

The extrinsic and intrinsic characteristics of an equine population may influence the onset of gastrointestinal lesions and affect the survival rate of patients. The equine population in Spain has been the focus of a small number of studies, none of which have involved more than one surgical center. In this retrospective cohort study, we aimed to analyze the survival rate, identify the variables that influenced death, and generate multivariate models using clinical variables. Data were collected from the clinical records of two surgical referral centers in the same region, and a total of 566 horses met the inclusion criteria. The statistical analysis was divided into three parts: The first and second included logistic analysis, in order to identify the variables most closely associated with survival. The third part assessed all previous variables in terms of survival and hospitalization time, using a COX survival analysis. The main risk factors associated with intra-operative mortality were related to seasonality (winter and summer), patient age (older than 9 years), distance from the hospital, the presence of a strangulating lesion, and the bowel segment affected (small intestine). Furthermore, the main factors associated with mortality during hospitalization were the characteristics of the lesions (strangulating) and the differences between surgical centers. The models generated in this study have good predictive value and use only reliable and easily obtainable variables. The most reliable characteristics are those related to the type of colic and the location of the lesion.

Assessing Concurrent Adherence to Combined Essential Medication and Clinical Outcomes in Patients With Acute Coronary Syndrome. A Population-Based, Real-World Study Using Group-Based Trajectory Models.

Aim: Adherence to multiple medications recommended for secondary prevention of cardiovascular conditions represents a challenge. We aimed to identify patterns of concurrent adherence to combined therapy and assess their impact on clinical outcomes in a cohort of patients with acute coronary syndrome (ACS). Methods: Population-based retrospective cohort of all patients discharged after hospitalization for ACS (2009-2011), prescribed ≥3 therapeutic groups within the first month. We assessed monthly concurrent adherence (≥24 days of medication out of 30) to ≥3 medications during the first year, and patterns were identified through group-based trajectory models. A composite clinical outcome during the second year was constructed. The association between adherence patterns and traditional refill adherence metrics [e.g., the proportion of days covered (PDC)], and outcomes were assessed through a multivariable Cox proportional hazards model. Results: Among 15,797 patients discharged alive, 12,057 (76.32%) initiated treatment with ≥3 therapeutic groups after discharge. We identified seven adherence trajectories to ≥3 medications: Adherent (52.94% of patients); Early Gap (6.64%); Middle Gap (5.67%); Late Decline (10.93%); Occasional Users (5.45%); Early Decline (8.79%); Non-Adherent (9.58%). Compared to the Adherent group, patients belonging to Early Gap (HR:1.30, 95%CI 1.07;1.60), Late decline (hazards ratio (HR): 1.31, 95% CI 1.1; 1.56), and Non-Adherent trajectories (HR: 1.36, 95% CI 1.14; 1.63) had a greater risk of adverse clinical outcomes, which was also different to the risk ascertained through concurrent PDC < 80 (HR: 1.13, 95% CI 1.01; 1.27). Conclusion: Overall, seven adherence trajectories to ≥3 drugs were identified, with three distinct adherence patterns being at higher risk of adverse outcomes. The identification of patterns of concurrent adherence, a more comprehensive approach than traditional measurements, may be useful to target interventions to improve adherence to multiple medications.

Predictive Performance of the FRAX Tool Calibrated for Spain vs. an Age and Sex Model: Prospective Cohort Study with 9082 Women and Men Followed for up to 8 Years.

In Spain, the Fracture Risk Assessment Tool (FRAX) was adapted using studies with a small number of patients, and there are only a few external validation studies that present limitations. In this prospective cohort study, we compared the performance of FRAX and a simple age and sex model. We used data from the ESOSVAL cohort, a cohort composed of a Mediterranean population of 11,035 women and men aged 50 years and over, followed for up to 8 years, to compare the discrimination, calibration, and reclassification of FRAX calibrated for Spain and a logistic model including only age and sex as variables. We found virtually identical AUC, 83.55% for FRAX (CI 95%: 80.46, 86.63) and 84.10% for the age and sex model (CI 95%: 80.91, 87.29), and there were similar observed-to-predicted ratios. In the reclassification analyses, patients with a hip fracture that were reclassified correctly as high risk by FRAX, compared to the age and sex model, were -2.86%, using either the 3% threshold or the observed incidence, 1.54% (95%CI: -8.44, 2.72 for the 3% threshold; 95%CI: -7.68, 1.97 for the incidence threshold). Remarkably simple and inexpensive tools that are easily transferable into electronic medical record environments may offer a comparable predictive ability to that of FRAX.

Reinfection by SARS CoV2 in Valle Del Cauca, Colombia: A Descriptive Retrospective Study.

Introduction: In coronavirus cases, reinfection has been associated with short-term immunity and genetic changes in viruses which allow them to escape from immune response, viral genotyping is required to make the precise diagnosis of reinfection, but the suspicion occurs in patients with more than 90 days between the tests and total improvement between them. We made a descriptive retrospective study with the cases of reinfection in Valle del Cauca, Colombia. Results: We found up to June 30, 3249 cases with suspected reinfection, 1.1% of all cases. During the first infection episode, 68% of the patients had symptoms, while at the moment of reinfection, the percentage was 73.4%. 55% of the analyzed cases had symptoms in both infection episodes, hospitalization of reinfection cases was 2% during the first episode and 2.2% in the second one. Conclusion: the reinfection percentage was low, as well as the hospitalization and ICU cases. These results allow to define that in terms of the provision of healthcare services, reinfection defined in this study, does not generate any differences in care required vs the first episode.

Impact of Three Safety Interventions Targeting Off-Label Use of Immediate-Release Fentanyl on Prescription Trends: Interrupted Time Series Analysis.

Background: The Spanish health authorities are concerned by the off-label use of immediate-release formulations of fentanyl (IRF) in noncancer pain and cancer pain in patients with no chronic pain therapy. Aim: To evaluate the impact of different interventions to improve appropriateness of IRF prescription on off-label prescription. Patients and methods: We used interrupted time series (ITS) to estimate immediate and trend changes of IRF prescription for noncancer pain (NCP) and breakthrough cancer pain (BCP) in patients with and without chronic cancer pain therapy associated with two medication reviews (I1 and I2) and the issue of a safety warning letter (I3) with data from a Spanish region with 5 million inhabitants, from 2015 to 2018. Results: The use of IRF for NCP in the region Valencia was reduced from about 1,800 prescriptions per week to around 1,400. The first medication review was followed by an immediate level change of -192.66 prescriptions per week (p < 0.001) and a downward trend change of -6.75 prescriptions/week (p < 0.001), resulting in a post-intervention trend of -1.99 (p < 0.001). I2 was associated with a trend change of -23.07 (p < 0.001) prescriptions/week. After I3, the trend changed markedly to 27.23 additional prescriptions/week, for a final post-intervention trend of 2.17 (p < 0.001). Controlled-ITS provided comparable results. For potentially inappropriate BCP use, the second medication review was followed by a downward, immediate level change of -10.10 prescriptions/week (p = 0.011) and a trend change of 2.31 additional prescriptions/week (p < 0.001) and the issue of the safety warning (I3) was followed by a downward trend change of -2.09 prescriptions/week (p = 0.007). Conclusion: Despite IRF prescription for NCP decreased, the interventions showed modest and temporary effect on off-label prescription. Our results call for a review of the design and implementation of safety interventions addressing inappropriate opioid use.