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The third, stepped-wedge, cluster-randomized, Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3), has shown that a goal-directed multi-faceted Care Bundle incorporating protocols for the management of physiological variables was safe and effective for improving functional recovery in a broad range of patients with acute intracerebral hemorrhage (ICH). The INTERACT3 Care Bundle included time- and target-based protocols for the management of early intensive lowering of systolic blood pressure (SBP, target

Background Knowledge of local contextual sex differences in the profile and outcome for stroke can improve service delivery. We aimed to determine sex differences in the profile of patients with acute stroke and their associations with in‐hospital death in the national hospital database of Chile. Methods and Results We present a retrospective cohort based on the analysis of the 2019 Chilean database of Diagnosis‐Related Groups, which represents 70% of the operational expenditure of the public health system. Random‐effects multiple logistic regression models were used to determine independent associations of acute stroke (defined by main diagnosis International Classification of Diseases, Tenth Revision [ICD‐10] codes) and in‐hospital death, and reported with odds ratios (ORs) and 95% CIs. Of 1 048 575 hospital discharges, 15 535 were for patients with acute stroke (7074 [45.5%] in women), and 2438 (15.6%) of them died during hospitalization. Differences by sex in sociodemographic and clinical characteristics were identified for stroke and main subtypes. After fully adjusted model, women with ischemic stroke had lower in‐hospital death (OR, 0.79 [95% CI, 0.69–0.91]) compared with men; other independent predictors included age per year increase (OR, 1.03 [95% CI, 1.03–1.04]), chronic kidney disease (OR, 1.47 [95% CI, 1.20–1.80]), atrial fibrillation (OR, 1.50 [95% CI, 1.26–1.80]), and other risk factors. Conversely, for intracerebral hemorrhage, women had a higher in‐hospital mortality rate than men (OR, 1.19 [95% CI, 1.02–1.40]); other independent predictors included age per year increase (OR, 1.009 [95% CI, 1.003–1.01]), chronic kidney disease (OR, 1.55 [95% CI, 1.23–1.97]), oral anticoagulant use (OR, 1.88 [95% CI, 1.37–2.58]), and other risk factors. Conclusions Sex differences in characteristics and in‐hospital death of hospitalized patients exist for acute stroke in Chile. In‐hospital death is higher for acute ischemic stroke in men and higher for intracerebral hemorrhage in women. Future research is needed to better identify contributing factors.

Abstract Background The ageing population has increased the prevalence of disabling and high-cost diseases, such as dementia and mild cognitive impairment (MCI). The latter can be considered a prodromal phase of some dementias and a critical stage for interventions to postpone the impairment of functionality. Working memory (WM) is a pivotal cognitive function, representing the fundamental element of executive functions. This project proposes an intervention protocol to enhance WM in these users, combining cognitive training with transcranial electrical stimulation of alternating current (tACS). This technique has been suggested to enhance the neuronal plasticity needed for cognitive processes involving oscillatory patterns. WM stands to benefit significantly from this approach, given its well-defined electrophysiological oscillations. Therefore, tACS could potentially boost WM in patients with neurodegenerative diseases. Methods This study is a phase IIb randomised, double-blind clinical trial with a 3-month follow-up period. The study participants will be 62 participants diagnosed with MCI, aged over 60, from Valparaíso, Chile. Participants will receive an intervention combining twelve cognitive training sessions with tACS. Participants will receive either tACS or placebo stimulation in eight out of twelve training sessions. Sessions will occur twice weekly over 6 weeks. The primary outcomes will be electroencephalographic measurements through the prefrontal theta oscillatory activity, while the secondary effects will be cognitive assessments of WM. The participants will be evaluated before, immediately after, and 3 months after the end of the intervention. Discussion The outcomes of this trial will add empirical evidence about the benefits and feasibility of an intervention that combines cognitive training with non-invasive brain stimulation. The objective is to contribute tools for optimal cognitive treatment in patients with MCI. To enhance WM capacity, postpone the impairment of functionality, and obtain a better quality of life. Trial registration ClinicalTrials.gov NCT05291208. Registered on 28 February 2022. ISRCTN87597719 retrospectively registered on 15 September 2023.

IntroductionThe presence of multiple chronic conditions, also referred to as multimorbidity, is a common finding in adults. Epidemiologic research can help identify groups of individuals with similar clinical profiles who could benefit from similar interventions. Many cross-sectional studies have revealed the existence of different multimorbidity patterns. Most of these studies were focused on the older population. However, multimorbidity patterns begin to form at a young age and can evolve over time following distinct multimorbidity trajectories with different impact on health. In this study, we aimed to identify multimorbidity patterns and trajectories in adults 18–65 years old.MethodsWe conducted a retrospective longitudinal epidemiologic study in the EpiChron Cohort, which includes all inhabitants of Aragón (Spain) registered as users of the Spanish National Health System, linking, at the patient level, information from electronic health records from both primary and specialised care. We included all 293,923 patients 18–65 years old with multimorbidity in 2011. We used cluster analysis at baseline (2011) and in 2015 and 2019 to identify multimorbidity patterns at four and eight years of follow-up, and we then created alluvial plots to visualise multimorbidity trajectories. We performed age- and sex-adjusted logistic regression analysis to study the association of each pattern with four- and eight-year mortality.ResultsWe identified three multimorbidity patterns at baseline, named dyslipidaemia & endocrine-metabolic, hypertension & obesity, and unspecific. The hypertension & obesity pattern, found in one out of every four patients was associated with a higher likelihood of four- and eight-year mortality (age- and sex-adjusted odds ratio 1.11 and 1.16, respectively) compared to the unspecific pattern. Baseline patterns evolved into different patterns during the follow-up.DiscussionWell-known preventable cardiovascular risk factors were key elements in most patterns, highlighting the role of hypertension and obesity as risk factors for higher mortality. Two out of every three patients had a cardiovascular profile with chronic conditions like diabetes and obesity that are linked to low-grade systemic chronic inflammation. More studies are encouraged to better characterise the relatively large portion of the population with an unspecific disease pattern and to help design and implement effective and comprehensive strategies towards healthier ageing.

Abstract Background The progressive ageing of the population is leading to an increase in multimorbidity and polypharmacy, which in turn may increase the risk of hospitalization and mortality. The enhancement of care with information and communications technology (ICT) can facilitate the use of prescription evaluation tools and support system for decision-making (DSS) with the potential of optimizing the healthcare delivery process. Objective To assess the effectiveness and cost-effectiveness of the complex intervention MULTIPAP Plus, compared to usual care, in improving prescriptions for young-old patients (65-74 years old) with multimorbidity and polypharmacy in primary care. Methods/design This is a pragmatic cluster-randomized clinical trial with a follow-up of 18 months in health centres of the Spanish National Health System. Unit of randomization: family physician. Unit of analysis: patient. Population Patients aged 65–74 years with multimorbidity (≥ 3 chronic diseases) and polypharmacy (≥ 5 drugs) during the previous 3 months were included. Sample size n = 1148 patients (574 per study arm). Intervention Complex intervention based on the ARIADNE principles with three components: (1) family physician (FP) training, (2) FP-patient interview, and (3) decision-making support system. Outcomes The primary outcome is a composite endpoint of hospital admission or death during the observation period measured as a binary outcome, and the secondary outcomes are number of hospital admission, all-cause mortality, use of health services, quality of life (EQ-5D-5L), functionality (WHODAS), falls, hip fractures, prescriptions and adherence to treatment. Clinical and sociodemographic factors will be explanatory variables. Statistical analysis The main result is the difference in percentages in the final composite endpoint variable at 18 months, with its corresponding 95% CI. Adjustments by the main confounding and prognostic factors will be performed through a multilevel analysis. All analyses will be carried out in accordance to the intention-to-treat principle. Discussion It is important to prevent the cascade of negative health and health care impacts attributable to the multimorbidity-polypharmacy binomial. ICT-enhanced routine clinical practice could improve the prescription process in patient care. Trial registration ClinicalTrials.gov NCT04147130 . Registered on 22 October 2019

Summary: Background: The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster. Methods: During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n = 87). In parallel, cellular immunity (n = 45) was analyzed in stimulated peripheral mononuclear cells by flow cytometry and ELISPOT. Findings: Although a 2.5-fold increase in neutralization of the ancestral SARS-CoV-2 was observed after the second booster when compared with prior its administration (Geometric mean units p

Este artículo describe el proceso de diseño y las características de un cuestionario y una pauta de observación intradomiciliaria desarrollados para evaluar tanto transversal como longitudinalmente la relación vivienda-barrio-salud en el marco de transformaciones urbanas llevadas a cabo en poblaciones de elevada vulnerabilidad socio-territorial. Los instrumentos se desarrollaron para el estudio longitudinal multimétodos RUCAS (Regeneración Urbana, Calidad de Vida y Salud), un experimento natural cuyo objetivo principal es evaluar el impacto en salud y calidad de vida de un programa de Regeneración de Conjuntos Habitacionales en dos conjuntos de vivienda social en Chile. El diseño de los instrumentos siguió cuatro etapas principales: (1) revisión narrativa de la literatura para definir las dimensiones del estudio, y de instrumentos existentes para identificar ítems apropiados para su medición; (2) validación de contenido con expertos; (3) pre-test; y (4) estudio piloto. El cuestionario resultante, compuesto de 262 ítems, tiene en cuenta las distintas etapas del ciclo vital y cuestiones de género. La pauta de observación intradomiciliaria (77 ítems) es aplicada por el/la encuestadora. Los instrumentos abordan (i) características de la situación residencial actual que sabidamente afectan la salud y serán intervenidas por el programa; (ii) dimensiones de la salud potencialmente afectadas por la situación residencial y/o por la intervención dentro de los plazos del estudio (4 años); (iii) otras condiciones de salud y relacionadas con la salud que sean relevantes, aun cuando no se verán modificadas dentro de los plazos del estudio, y (iv) dimensiones socioeconómicas, ocupacionales y demográficas relevantes. Los instrumentos han mostrado ser una herramienta capaz de abordar la multidimensionalidad de los procesos de transformación urbana en contextos de pobreza urbana en vivienda formal.

Abstract A major risk factor of COVID-19 severity is the patient's health status at the time of the infection. Numerous studies focused on specific chronic diseases and identified conditions, mainly cardiovascular ones, associated with poor prognosis. However, chronic diseases tend to cluster into patterns, each with its particular repercussions on the clinical outcome of infected patients. Network analysis in our population revealed that not all cardiovascular patterns have the same risk of COVID-19 hospitalization or mortality and that this risk depends on the pattern of multimorbidity, besides age and sex. We evidenced that negative outcomes were strongly related to patterns in which diabetes and obesity stood out in older women and men, respectively. In younger adults, anxiety was another disease that increased the risk of severity, most notably when combined with menstrual disorders in women or atopic dermatitis in men. These results have relevant implications for organizational, preventive, and clinical actions to help meet the needs of COVID-19 patients.

Between 2008 and 2009 suicide rates in Chile were higher than those observed before and after, increasing more than in other countries in Latin America. The Great Recession has been suggested as an important factor behind this increase. This study assesses the excess of suicide attributable to the crisis in Chile, a “mature” neoliberal society with a precarious social security system, low salaries, and high levels of indebtedness, and identifies the most relevant economic variables that may contribute to this excess. We pooled data since 2000 on monthly suicide rates, unemployment, economic activity and perception of problematic indebtedness for different sex and age groups. We adopted an interrupted time series design with Poisson regressions models adjusted for monthly variations and non-linear pre-crisis trajectories via restricted cubic splines. We then further controlled for economic variables to evaluate their possible contributions to suicide increase attributable to the economic crisis. Suicide mortality during the crisis period was higher than in the previous period in all sex and age groups. Overall, we estimated that 301 suicides (95% CI: 181 to 422) were attributable to the crisis in Chile. This excess was concentrated among men younger than 65 and women 65 and older. Including unemployment and indebtedness perception in the models reduced the excess of suicides. The increase was concentrated in the first half of the crisis and an early pre-crisis effect could be observed when anticipating the crisis beginning by three months. Results suggest that the Great Recession had an impact on suicide mortality in Chile and that increase in unemployment and indebtedness could be related to this increase. Results by sex and age are consistent with the most vulnerable groups in the context of Chilean neoliberalism. For future crises, improving unemployment insurance, and reinforcing suicide prevention attending to the economic context should be a priority.

Objective. A narrative overview of regional academic research collaborations to address the increasing burden and gaps in care for patients at risk of, and who suffer from, stroke in Latin America (LA). Materials and methods. A summary of experiences and knowledge of the local situation is presented. No systematic literature review was performed. Results. The rapidly increasing burden of stroke poses immense challenges in LA, where prevention and manage­ment strategies are highly uneven and inadequate. Clinical research is increasing through various academic consortia and networks formed to overcome structural, funding and skill barriers. However, strengthening the ability to generate, analyze and interpret randomized evidence is central to further develop effective therapies and healthcare systems in LA. Conclusions. Regional networks foster the conduct of multicenter studies –particularly randomized controlled trials–, even in resource-poor regions. They also contribute to the external validity of international studies and strengthen systems of care, clinical skills, critical thinking, and international knowledge exchange.

In Pamplona, Norte de Santander, strawberry (Fragaria x ananassa Duch) producers face a dual challenge: ensuring the safety of their products and conserving natural resources. Nine farms belonging to the Association of Rural Women (ASMUR) were assessed, representing approximately 20% of the total affiliated production units within the association. The level of implementation of Good Agricultural Practices (GAP) was analysed in accordance with the 2020 Resolution of the Colombian Agricultural Institute (ICA), alongside sustainable soil management as per the Food and Agriculture Organization (FAO) guidelines on good practices for the management and sustainable use of soils in rural areas. Field tests and laboratory analyses were carried out to evaluate soil quality. The results revealed that none of the farms meet the requirements for GAP certification, with notable limitations in infrastructure, training, personnel protection, and traceability. On the other hand, the soils exhibited high organic matter content, acidic pH, and low biological activity. To overcome these limitations and achieve GAP certification, it is crucial to develop a specific action plan, provide advisory and training in GAP and sustainable soil management, make investments in key infrastructure, implement soil monitoring, adjust pH with amendments, encourage agroecological practices, promote the use of bio-inputs, and establish partnerships with entities for access to resources and technical-financial support.

IntroductionKidney transplant recipients showed a weak humoral response to the mRNA COVID-19 vaccine despite receiving three cumulative doses of the vaccine. New approaches are still needed to raise protective immunity conferred by the vaccine administration within this group of high-risk patients. MethodsTo analyze the humoral response and identify any predictive factors within these patients, we designed a prospective monocentric longitudinal study of Kidney transplant recipients (KTR) who received three doses of mRNA-1273 COVID-19 vaccine. Specific antibody levels were measured by chemiluminescence. Parameters related to clinical status such as kidney function, immunosuppressive therapy, inflammatory status and thymic function were analyzed as potential predictors of the humoral response. ResultsSeventy-four KTR and sixteen healthy controls were included. One month after the administration of the third dose of the COVID-19 vaccine, 64.8% of KTR showed a positive humoral response. As predictive factors of seroconversion and specific antibody titer, we found that immunosuppressive therapy, worse kidney function, higher inflammatory status and age were related to a lower response in KTR while immune cell counts, thymosin-a1 plasma concentration and thymic output were related to a higher humoral response. Furthermore, baseline thymosin-a1 concentration was independently associated with the seroconversion after three vaccine doses. DiscussionIn addition to the immunosuppression therapy, condition of kidney function and age before vaccination, specific immune factors could also be relevant in light of optimization of the COVID-19 vaccination protocol in KTR. Therefore, thymosin-a1, an immunomodulatory hormone, deserves further research as a potential adjuvant for the next vaccine boosters.