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BackgroundTwo years since the onset of the COVID-19 pandemic no predictive algorithm has been generally adopted for clinical management and in most algorithms the contribution of laboratory variables is limited.ObjectivesTo measure the predictive performance of currently used clinical laboratory tests alone or combined with clinical variables and explore the predictive power of immunological tests adequate for clinical laboratories. Methods: Data from 2,600 COVID-19 patients of the first wave of the pandemic in the Barcelona area (exploratory cohort of 1,579, validation cohorts of 598 and 423 patients) including clinical parameters and laboratory tests were retrospectively collected. 28-day survival and maximal severity were the main outcomes considered in the multiparametric classical and machine learning statistical analysis. A pilot study was conducted in two subgroups (n=74 and n=41) measuring 17 cytokines and 27 lymphocyte phenotypes respectively.Findings1) Despite a strong association of clinical and laboratory variables with the outcomes in classical pairwise analysis, the contribution of laboratory tests to the combined prediction power was limited by redundancy. Laboratory variables reflected only two types of processes: inflammation and organ damage but none reflected the immune response, one major determinant of prognosis. 2) Eight of the thirty variables: age, comorbidity index, oxygen saturation to fraction of inspired oxygen ratio, neutrophil-lymphocyte ratio, C-reactive protein, aspartate aminotransferase/alanine aminotransferase ratio, fibrinogen, and glomerular filtration rate captured most of the combined statistical predictive power. 3) The interpretation of clinical and laboratory variables was moderately improved by grouping them in two categories i.e., inflammation related biomarkers and organ damage related biomarkers; Age and organ damage-related biomarker tests were the best predictors of survival, and inflammatory-related ones were the best predictors of severity. 4) The pilot study identified immunological tests (CXCL10, IL-6, IL-1RA and CCL2), that performed better than most currently used laboratory tests.ConclusionsLaboratory tests for clinical management of COVID 19 patients are valuable but limited predictors due to redundancy; this limitation could be overcome by adding immunological tests with independent predictive power. Understanding the limitations of tests in use would improve their interpretation and simplify clinical management but a systematic search for better immunological biomarkers is urgent and feasible.

Abstract Objectives The objectives of the present analyses are to estimate the frequency of potentially inappropriate prescribing (PIP) at admission according to STOPP/START criteria version 2 in older patients hospitalised due to chronic disease exacerbation as well as to identify risk factors associated to the most frequent active principles as potentially inappropriate medications (PIMs). Methods A multicentre, prospective cohort study including older patients (≥65) hospitalized due to chronic disease exacerbation at the internal medicine or geriatric services of 5 hospitals in Spain between September 2016 and December 2018 was conducted. Demographic and clinical data was collected, and a medication review process using STOPP/START criteria version 2 was performed, considering both PIMs and potential prescribing omissions (PPOs). Primary outcome was defined as the presence of any most frequent principles as PIMs, and secondary outcomes were the frequency of any PIM and PPO. Descriptive and bivariate analyses were conducted on all outcomes and multilevel logistic regression analysis, stratified by participating centre, was performed on the primary outcome. Results A total of 740 patients were included (mean age 84.1, 53.2% females), 93.8% of them presenting polypharmacy, with a median of 10 chronic prescriptions. Among all, 603 (81.5%) patients presented at least one PIP, 542 (73.2%) any PIM and 263 (35.5%) any PPO. Drugs prescribed without an evidence-based clinical indication were the most frequent PIM (33.8% of patients); vitamin D supplement in older people who are housebound or experiencing falls or with osteopenia was the most frequent PPO (10.3%). The most frequent active principles as PIMs were proton pump inhibitors (PPIs) and benzodiazepines (BZDs), present in 345 (46.6%) patients. This outcome was found significantly associated with age, polypharmacy and essential tremor in an explanatory model with 71% AUC. Conclusions PIMs at admission are highly prevalent in these patients, especially those involving PPIs or BZDs, which affected almost half of the patients. Therefore, these drugs may be considered as the starting point for medication review and deprescription. Trial registration number NCT02830425

Abstract Background Patient access to orphan medicinal products (OMPs) is limited and varies between countries, reimbursement decisions on OMPs are complex, and there is a need for more transparent processes to know which criteria should be considered to inform these decisions. This study aimed to determine the most relevant criteria for the reimbursement of OMPs in Spain, from a multi-stakeholder perspective, and using multicriteria decision analysis (MCDA). Methods An MCDA was developed in 3 phases and included 28 stakeholders closely related to the field of rare diseases (6 physicians, 5 hospital pharmacists, 7 health economists, 4 patient representatives and 6 members from national and regional health authorities). Initially [phase A], a bibliographic review was conducted to identify the potential reimbursement criteria. Then, a reduced advisory board (8 members) proposed, selected, and defined the final list of criteria that could be relevant for reimbursement. A discrete choice experiment (DCE) [phase B] was developed to determine the relevance and relative importance weight of such criteria according to the stakeholders’ preferences by choosing between pairs of hypothetical financing scenarios. A multinomial logit model was fitted to analyze the DCE responses. Finally [phase C], the advisory board review the results using a deliberative process. Results Thirteen criteria were selected, related to 4 dimensions: patient population, disease, treatment, and economic evaluation. Nine criteria were deemed relevant for decision-making and associated with a higher relative importance: Health-related quality of life (HRQL) (23.53%), treatment efficacy (14.64%), availability of treatment alternatives (13.51%), disease severity (12.62%), avoided costs (11.21%), age of target population (7.75%), safety (seriousness of adverse events) (4.72%), quality of evidence (3.82%) and size of target population (3.12%). The remaining criteria had a

Objectives To estimate the frequency of chronic conditions and geriatric syndromes in older patients admitted to hospital because of an exacerbation of their chronic conditions, and to identify multimorbidity clusters in these patients.Design Multicentre, prospective cohort study.Setting Internal medicine or geriatric services of five general teaching hospitals in Spain.Participants 740 patients aged 65 and older, hospitalised because of an exacerbation of their chronic conditions between September 2016 and December 2018.Primary and secondary outcome measures Active chronic conditions and geriatric syndromes (including risk factors) of the patient, a score about clinical management of chronic conditions during admission, and destination at discharge were collected, among other variables. Multimorbidity patterns were identified using fuzzy c-means cluster analysis, taking into account the clinical management score. Prevalence, observed/expected ratio and exclusivity of each chronic condition and geriatric syndrome were calculated for each cluster, and the final solution was approved after clinical revision and discussion among the research team.Results 740 patients were included (mean age 84.12 years, SD 7.01; 53.24% female). Almost all patients had two or more chronic conditions (98.65%; 95% CI 98.23% to 99.07%), the most frequent were hypertension (81.49%, 95% CI 78.53% to 84.12%) and heart failure (59.86%, 95% CI 56.29% to 63.34%). The most prevalent geriatric syndrome was polypharmacy (79.86%, 95% CI 76.82% to 82.60%). Four statistically and clinically significant multimorbidity clusters were identified: osteoarticular, psychogeriatric, cardiorespiratory and minor chronic disease. Patient-level variables such as sex, Barthel Index, number of chronic conditions or geriatric syndromes, chronic disease exacerbation 3 months prior to admission or destination at discharge differed between clusters.Conclusions In older patients admitted to hospital because of the exacerbation of chronic health problems, it is possible to define multimorbidity clusters using soft clustering techniques. These clusters are clinically relevant and could be the basis to reorganise healthcare circuits or processes to tackle the increasing number of older, multimorbid patients.Trial registration number NCT02830425.

The methods and results of a practical exercise based on the movie Love and Other Drugs (2010) by Edward Zwick are presented. The exercise was part of the teaching activities in General Pharmacology, in the third year of the medicine degree. The teaching objectives included to perceive different views on the use of drugs (marketer/prescriber/ patient/society), to obtain critical opinions on promotional activities and to get familiar with the ethical codes controlling advertising activities. Two sessions of 2.5 hours were done, separated by two weeks. During the first one the activity was introduced and organized, and the film was viewed. During the second session the students exposed and discussed work which had been prepared guided by a number of specific questions. The resources present in the film were an excellent vehicle for establishing a strong interaction with students, to guide reflections on the importance of drugs in society, to address the need for ethical codes, the differences between licensed indication and off-label use, and to emphasise the use of the SmPC as key reference information. In conclusion, the exercise served to provide students some tools for ethical consideration on their future responsibilities as decision makers in drug prescribing.