Explore the vast range of titles available.

Purpose To assess the prevalence of urgent hospitalization due to adverse drug reactions (ADRs) in patients aged ≥65 years, to compare the in-hospital mortality rates between patients admitted for ADRs and those admitted for other causes, and to describe the ADRs, the used and suspected drugs, and the drug-reaction associations. Methods A cross-sectional study was conducted by using the institutional database of the Pharmacovigilance Programme of Bellvitge University Hospital, a 750-bed tertiary care hospital, with information corresponding to a 7-year period. ADR-related admissions of patients aged ≥65 years prospectively identified through a systematic daily review of all admission diagnosis were reviewed. Results ADRs were suspected to be the main reason for urgent admission in 1976 out of 60,263 patients aged ≥65 years (prevalence of ADR-related hospitalization 3.3 % [95 % CI 3.1–3.4 %]). The crude in-hospital mortality rate was 10.2 % in patients with ADR-related admission and 9 % in patients admitted for other causes ( p  = 0.077). Most patients (86 %) were exposed to polypharmacy, and a drug-drug interaction was suspected in 49 % of cases. The most frequent drug-reaction associations were acute renal failure related to renin-angiotensin system inhibitors, gastrointestinal bleeding caused by antithrombotics and/or non-steroidal anti-inflammatories, and intracranial bleeding induced by vitamin K antagonists. Conclusions One out of every 30 urgent admissions of patients aged ≥65 years is ADR-related. These ADRs can be as serious and life-threatening as any other acute pathology that merits urgent hospital admission. Most cases involve patients exposed to polypharmacy and result from well-known reactions of a few commonly used drugs.

Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian DNA had a lower DNA methylation content and a reduced correlation in the methylation status of neighboring cytosine—phosphate—guanine (CpGs) throughout the genome in comparison with the more homogeneously methylated newborn DNA. The more hypomethylated CpGs observed in the centenarian DNA compared with the neonate covered all genomic compartments, such as promoters, exonic, intronic, and intergenic regions. For regulatory regions, the most hypomethylated sequences in the centenarian DNA were present mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. We extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray that reinforced the observation of more hypomethylated DNA sequences in the advanced age group. WGBS and 450,000 analyses of middle-age individuals demonstrated DNA methylomes in the crossroad between the newborn and the nonagenarian/centenarian groups. Our study constitutes a unique DNA methylation analysis of the extreme points of human life at a single-nucleotide resolution level.

BackgroundThe WHO ordinal severity scale has been used to predict mortality and guide trials in COVID-19. However, it has its limitations.ObjectiveThe present study aims to compare three classificatory and predictive models: the WHO ordinal severity scale, the model based on inflammation grades, and the hybrid model.DesignRetrospective cohort study with patient data collected and followed up from March 1, 2020, to May 1, 2021, from the nationwide SEMI-COVID-19 Registry. The primary study outcome was in-hospital mortality. As this was a hospital-based study, the patients included corresponded to categories 3 to 7 of the WHO ordinal scale. Categories 6 and 7 were grouped in the same category.Key ResultsA total of 17,225 patients were included in the study. Patients classified as high risk in each of the WHO categories according to the degree of inflammation were as follows: 63.8% vs. 79.9% vs. 90.2% vs. 95.1% (p<0.001). In-hospital mortality for WHO ordinal scale categories 3 to 6/7 was as follows: 0.8% vs. 24.3% vs. 45.3% vs. 34% (p<0.001). In-hospital mortality for the combined categories of ordinal scale 3a to 5b was as follows: 0.4% vs. 1.1% vs. 11.2% vs. 27.5% vs. 35.5% vs. 41.1% (p<0.001). The predictive regression model for in-hospital mortality with our proposed combined ordinal scale reached an AUC=0.871, superior to the two models separately.ConclusionsThe present study proposes a new severity grading scale for COVID-19 hospitalized patients. In our opinion, it is the most informative, representative, and predictive scale in COVID-19 patients to date.

The aim of this study is to determine prevalence and risk factors of Cognitive Impairment (CI) and its association with Type 2 Diabetes Mellitus (T2DM) in subjects aged 65 years and above. Additionally, we attempt to provide a cognitive profile for T2DM group. A cross-sectional analytical study to assess CI was carried out. We evaluated a sample of community-dwelling residents from Chile. All participants underwent a general interview, lifestyle questionnaires and a comprehensive neuropsychological battery. Regression analyses were performed to evaluate risk of CI with T2DM and influencing factors. Results between groups in the different domains of the neuropsychological assessment were compared by Student's -tests and MANOVA. Among all 358 subjects, overall T2DM prevalence were 17.3%. The prevalence of CI was higher in T2DM group compared to the healthy participants (30.7%, < 0.001). The risk of CI was 2.8 times higher in older people with T2DM compared to older people without the diagnosis. Multiple regression analysis, adjusted for age and gender, demonstrated that age, education, presence of dyslipidemia, and T2DM duration were the predictor variables significantly associated with CI. T2DM group performed worse on global cognitive performance, attention, language, verbal memory, visual memory, visual constructional ability, and executive function. After adjusting for significant covariates from multiple regression analysis, a relationship between \"cognition\" and T2DM is still observed. Amnesic multi-domain impairment was the specific cognitive identified pattern for T2DM group. The present study confirms the high prevalence of CI with T2DM among Chilean older adults in a community-based population. T2DM is significantly associated with a higher risk of CI, and age, education, presence of dyslipidemia, and duration of T2DM are risk factors. T2DM patients with CI are impaired in multiple cognitive domains, even after adjusting covariables, resulting in an amnesic multi-domain cognitive profile.

The prevalence of transthyretin‐associated amyloidosis cardiomyopathy (ATTR‐CM) has grown because of newer non‐invasive diagnosis tools. Detecting the presence of extra‐cardiac ATTR manifestations such as musculoskeletal pathologies considered ‘red flags’, when there is minimal or non‐cardiac clinical involvement is primordial to carry out an early diagnosis. The aim of this systematic review is to examine the prevalence of musculoskeletal, ATTR‐deposition‐related co‐morbidities in patients already diagnosed with ATTR‐CM, specifically carpal tunnel syndrome, ruptured biceps tendon, spinal stenosis, and trigger finger. We performed a systematic review using PRISMA guidelines. Inclusion criteria were all studies in English and Spanish language and participants had to be patients diagnosed with ATTR‐CM, by any diagnostic method, with the musculoskeletal co‐morbidities subject of this review. The quality of the studies was based on the Risk of Bias Tool. This systematic review included 22 studies for final analysis. Carpal tunnel syndrome is reported in 21 studies, brachial biceps tendon rupture is reported in three, and spinal stenosis in eight studies. No articles that accomplished all the inclusion criteria for trigger finger were found. Regarding to the quality of the studies, all of them were categorized as being of high and moderate quality. The frequent association between ATTR‐CM and carpal tunnel syndrome, ruptured biceps tendon, and lumbar spinal is confirmed, and the onset of these co‐morbidities usually precedes the diagnosis of by years. This association defines them as red flags that should be search proactively due to the current treatment possibilities and the severity of the presentation of cardiac amyloidosis.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are two chronic diseases with the greatest adverse impact on the general population, and early detection of their decompensation is an important objective. However, very few diagnostic models have achieved adequate diagnostic performance. The aim of this trial was to develop diagnostic models of decompensated heart failure or COPD exacerbation with machine learning techniques based on physiological parameters. A total of 135 patients hospitalized for decompensated heart failure and/or COPD exacerbation were recruited. Each patient underwent three evaluations: one in the decompensated phase (during hospital admission) and two more consecutively in the compensated phase (at home, 30 days after discharge). In each evaluation, heart rate (HR) and oxygen saturation (Ox) were recorded continuously (with a pulse oximeter) during a period of walking for 6 min, followed by a recovery period of 4 min. To develop the diagnostic models, predictive characteristics related to HR and Ox were initially selected through classification algorithms. Potential predictors included age, sex and baseline disease (heart failure or COPD). Next, diagnostic classification models (compensated vs. decompensated phase) were developed through different machine learning techniques. The diagnostic performance of the developed models was evaluated according to sensitivity (S), specificity (E) and accuracy (A). Data from 22 patients with decompensated heart failure, 25 with COPD exacerbation and 13 with both decompensated pathologies were included in the analyses. Of the 96 characteristics of HR and Ox initially evaluated, 19 were selected. Age, sex and baseline disease did not provide greater discriminative power to the models. The techniques with S and E values above 80% were the logistic regression (S: 80.83%; E: 86.25%; A: 83.61%) and support vector machine (S: 81.67%; E: 85%; A: 82.78%) techniques. The diagnostic models developed achieved good diagnostic performance for decompensated HF or COPD exacerbation. To our knowledge, this study is the first to report diagnostic models of decompensation potentially applicable to both COPD and HF patients. However, these results are preliminary and warrant further investigation to be confirmed.

ObjectivesThe aim of this study was to identify, with soft clustering methods, multimorbidity patterns in the electronic health records of a population ≥65 years, and to analyse such patterns in accordance with the different prevalence cut-off points applied. Fuzzy cluster analysis allows individuals to be linked simultaneously to multiple clusters and is more consistent with clinical experience than other approaches frequently found in the literature.DesignA cross-sectional study was conducted based on data from electronic health records.Setting284 primary healthcare centres in Catalonia, Spain (2012).Participants916 619 eligible individuals were included (women: 57.7%).Primary and secondary outcome measuresWe extracted data on demographics, International Classification of Diseases version 10 chronic diagnoses, prescribed drugs and socioeconomic status for patients aged ≥65. Following principal component analysis of categorical and continuous variables for dimensionality reduction, machine learning techniques were applied for the identification of disease clusters in a fuzzy c-means analysis. Sensitivity analyses, with different prevalence cut-off points for chronic diseases, were also conducted. Solutions were evaluated from clinical consistency and significance criteria.ResultsMultimorbidity was present in 93.1%. Eight clusters were identified with a varying number of disease values: nervous and digestive; respiratory, circulatory and nervous; circulatory and digestive; mental, nervous and digestive, female dominant; mental, digestive and blood, female oldest-old dominant; nervous, musculoskeletal and circulatory, female dominant; genitourinary, mental and musculoskeletal, male dominant; and non-specified, youngest-old dominant. Nuclear diseases were identified for each cluster independently of the prevalence cut-off point considered.ConclusionsMultimorbidity patterns were obtained using fuzzy c-means cluster analysis. They are clinically meaningful clusters which support the development of tailored approaches to multimorbidity management and further research.

Background and Objectives: A COVID-19 model with a viral first-week phase and an inflammatory second phase has been proposed. It has been suggested that immunosuppressive treatment in the first week is harmful. This study aimed to analyze the potential damage of corticosteroids (CS) administered in the first week of COVID-19. Materials and Methods: This study was performed on a large cohort of consecutive COVID-19 patients admitted to Bellvitge University Hospital (Barcelona, Spain) from March 2020 to April 2021. Patients diagnosed with COVID-19 who were treated with 6 mg of dexamethasone a day for 10 days, and whose initiation of administration occurred within the first 2 weeks from symptom onset were included. We divided the cohort into the following two groups: patients for whom CS were initiated within the first 7 days after symptom onset vs. patients for whom CS were initiated between days 8 and 14. The degree of analytical inflammation (based on lymphocyte count, C-reactive protein, ferritin, lactate dehydrogenase, and D-dimer) upon admission was taken into account. The primary outcome was in-hospital mortality. Results: A total of 581 patients met the inclusion criteria. The results included, as follows: differences in age at baseline between groups (70.8 years old vs. 62.7, p < 0.001); moderate-to-severe dependency (11.9% vs. 4.2%, p = 0.003); the lymphocyte count (840 × 106/L vs. 900, p = 0.033); D-dimer (400 ng/mL vs. 309, p < 0.001); and PaO2/FiO2 (290 vs. 311, p < 0.001). In-hospital mortality in patients who received CS in the first week of symptom onset was higher (29% vs. 12.8%, p < 0.001). The following risk factors were associated with higher in-hospital mortality: age (OR = 1.06, p < 0.001); Charlson index (OR = 1.34, p = 0.001); tachypnea > 20 bpm (OR = 2.58, p < 0.001); ≥3 high-risk criteria of inflammation (OR = 1.94, p = 0.012); and CS onset in the first week (OR = 2.17, p = 0.004). A higher PaO2/FiO2 (OR = 0.99, p < 0.001) and the use of remdesivir (OR = 0.53, p = 0.021) were identified as protective factors. However, when stratified by analytical inflammation criteria, the onset of CS in the first week did not reach statistical significance. Conclusions: The early administration of CS did not demonstrate a significant detrimental effect. These results highlight the need for a nuanced approach to CS therapy in COVID-19 that carefully weighs the risks and benefits based on individual patient characteristics and the severity of the inflammation.

Heart failure (HF) is a clinical syndrome characterized by the presence of dyspnea or limited exertion due to impaired cardiac ventricular filling and/or blood ejection. Because of its high prevalence, it is a major health and economic burden worldwide. Several mechanisms are involved in the pathophysiology of HF. First, the renin-angiotensin-aldosterone system (RAAS) is over-activated, causing vasoconstriction, hypertension, elevated aldosterone levels and sympathetic tone, and eventually cardiac remodeling. Second, an endogenous compensatory mechanism, the natriuretic peptide (NP) system is also activated, albeit insufficiently to counteract the RAAS effects. Since NPs are degraded by the enzyme neprilysin, it was hypothesized that its inhibition could be an important therapeutic target in HF. Sacubitril/valsartan is the first of the class of dual neprilysin and angiotensin receptor inhibitors (ARNI). In patients with HFrEF, treatment with sacubitril/valsartan has demonstrated to significantly reduce mortality and the rates of hospitalization and rehospitalization for HF when compared to enalapril. This communication reviews in detail the demonstrated benefits of sacubitril/valsartan in the treatment of patients with HFrEF, including reduction of mortality and disease progression as well as improvement in cardiac remodeling and quality of life. The hemodynamic and organic effects arising from its dual mechanism of action, including the impact of neprilysin inhibition at the renal level, especially relevant in patients with type 2 diabetes mellitus, are also reviewed. Finally, the evidence on the demonstrated safety and tolerability profile of sacubitril/valsartan in the different subpopulations studied has been compiled. The review of this evidence, together with the recommendations of the latest clinical guidelines, position sacubitril/valsartan as a fundamental pillar in the treatment of patients with HFrEF.

Diuretic resistance (DR) is common in patients with decompensated heart failure (HF), and is associated with adverse outcomes. To determine the prevalence of DR and its impact on survival among patients with decompensated HF, we prospectively evaluated the prevalence and influence on prognosis of DR (defined as persistent congestion despite ≥ 80 mg of furosemide per day) in a cohort of elderly patients from the Spanish HF registry (RICA) admitted for an acute decompensation of HF. Patients with new-onset HF were excluded. From the global cohort of 2067 patients, 435 (21%; 95% CI 19.3%–22.7%) patients met criteria for DR. Patients with DR had more comorbidities (hypercholesterolemia, diabetes mellitus, valvular disease, chronic kidney disease, and cancer) and a worse functional status compared to patients without DR. In addition, patients with DR had a higher proportion of ischemic etiology, more advanced functional class and lower left ventricular ejection fraction values. After 1 year of follow-up, all-cause mortality was higher in patients with DR with an adjusted hazard ratio of 1.37 (95% CI 1.06–1.79; p = 0.018). The prevalence of DR in a cohort of elderly patients admitted for acute HF decompensation is 21%. DR is an independent predictor of 1-year mortality.