No prior study could be identified that combined qualitative and quantitative methods to analyse the long-term psychosocial and functional state of Idiopathic Scoliosis (IS) patients treated during adolescence. This study aimed to comprehensively evaluate the long-term health status of these patients and to identify and contextualize the key factors influencing it by using a multimethod approach. A multimethod approach was used. Qualitative data included recording, transcription, coding and content analysis of focus groups and semi-structured interviews. For the quantitative analysis, patients completed questionnaires. Fifty-seven patients were recruited. Two focus groups and 44 individual interviews were performed. All of them completed the questionnaires. Quantitative analyses showed significant age-related differences in ODI, SRS22-Function, SRS22-Pain, SRS22-Self Image and trunk deformity perception, with older patients showing poorer results. Trunk deformity perception was the only domain associated with treatment received, with conservatively treated patients scoring worse. Qualitative findings highlighted psychosocial impacts of IS and its treatments during adolescence, particularly related to bracing, which was often associated with discomfort and social stigma. However, these effects generally did not persist into adulthood. In contrast, surgical treatment was generally viewed positively, associated with deformity correction, improved self-image and the elimination of bracing, all contributing to better social integration and overall well-being. Qualitative factors influencing current self-image, self-esteem and overall well-being varied by both age and treatment type. While IS may significantly impact adolescents’ psychosocial health, particularly when it is treated with bracing, the effect tends not to persist into adulthood. In adulthood, age becomes the primary determinant of psychosocial health and general well-being. This multimethod approach revealed distinct factors influencing each domain studied and offered a deeper understanding of their interconnections, highlighting the complex interplay between social, physical, and psychological factors. These findings underscore the importance of a holistic, patient-centered approach in managing IS, with greater emphasis on psychosocial aspects including self-image, self-esteem, and sexual health, throughout treatment planning and long-term follow-up.

Importance:Acute adverse events (AEs) after chimeric antigen receptor (CAR) T-cell infusion are well documented, but less information is available regarding the long-term toxic effects. Objective:To assess the occurrence of late AEs for adult patients with large B-cell lymphoma (LBCL) treated with commercially available CD19-targeted CAR T cells. Design, Setting, and Participants:A prospective, observational, clinical practice cohort study was conducted from September 1, 2018, to December 31, 2022, among 172 adult patients in 6 Spanish hospitals who received CD19-targeted CAR T-cell therapy for relapsed or refractory LBCL and survived at least 3 months after infusion, without subsequent antilymphoma therapy. Exposure:Treatment with tisagenlecleucel or axicabtagene ciloleucel. Main Outcomes and Measures:Data on any late AEs occurring in this patient population were collected until the patients received new antilymphoma therapy, were lost to follow-up, died, or reached 24 months after infusion, whichever occurred first. Data collection for each patient started at the third month after infusion and included new-onset AEs, as well as persistent AEs that started earlier but were still ongoing at that time point. Results:The study enrolled 172 patients (mean [SD] age, 58.5 [13.7] years; 101 men [58.7%]), of whom 135 (78.5%) experienced at least 1 late AE of any grade. Infections were the late AEs with the highest incidence (5.6 per 100 person-months [95% CI, 4.5-7.0 per 100 person-months]), followed by neutropenia (3.6 per 100 person-months [95% CI, 2.9-4.5 per 100 person-months]) and thrombocytopenia (2.2 per 100 person-months [95% CI, 1.7-3.0 per 100 person-months]). The incidence of infectious episodes remained stable during the whole study period, while cytopenias decreased beyond 6 months after infusion. All cases of nonrelapse-related mortality were due to infections (COVID-19 pneumonia in 3 patients and sepsis or bacterial pneumonia in 4 patients). Twenty-three patients (13.4%) experienced 27 dermatologic AEs, all mild, with most of them (88.9% [24 of 27]) starting beyond 3 months after infusion. Fifteen neurologic AEs were reported in 15 patients (8.7%), and 10 patients (5.8%) developed 13 cardiovascular AEs. Five secondary neoplasms were reported in 4 patients (2.3%), with no cases of T-cell malignant neoplasms. Conclusions and Relevance:This cohort study suggests that CAR T-cell therapy has a favorable safety profile. However, continuous follow-up of patients is needed, as serious AEs can occur years after infusion.

Introduction. The need for comprehensive geriatric assessment (CGA) in older adults with cancer is increasing, which makes it necessary to have a screening instrument to identify those who would benefit from this evaluation. This study aimed to investigate diagnostic performance of the Timed Up and Go test (TUG) for identifying vulnerable or frail older adults with cancer who might benefit from CGA. Material and methods. This observational and retrospective study took place at the geriatric center of Almenara Hospital in Lima, Peru. We extracted CGA reports from electronic medical records of outpatients and inpatients aged 60 years and older with cancer, who were evaluated between November 2022 and July 2023. Patients were classified based on SIOG-2 (International Society of Geriatric Oncology) criteria as fit, vulnerable, or frail, based on scales including Activities of Daily Living (ADL), Instrumental ADL, Mini-Nutritional Assessment (MNA), Mini-Mental State Exam (MMSE), Geriatric Depression Scale, and Cumulative Illness Rating Scale-Geriatrics (CIRS-G). For the study, two groups were formed: fit patients and non-fit patients (vulnerable plus frail). We estimated sensitivity, specificity, and positive predictive values of the TUG test. The accuracy of the TUG test was analyzed using the area under the receiver operating characteristic curve (AUC). Results. Among the 283 included patients, 154 were men (54.4%) and 129 women (45.6%), and the mean age was 76.8 ± 15.8 years. The most common neoplasms were colorectal (19.4%), stomach (15.2%), prostate (9.9%), and bile duct cancers (8.1%). The percentage of fit and non-fit patients was 21.9% and 78.1%, respectively. When the TUG test was equal to or greater than 15.5 seconds, sensitivity, specificity, positive predictive value, and AUC were 68.5% (95% CI 61.9–74.5), 88.5% (77.8–95.3), 95.6% (91.1–98.2), and 84.8% (0.80–0.90), respectively. Conclusions. A TUG test result equal to or greater than 15.5 seconds demonstrated good screening properties for identifying older cancer patients who were vulnerable or frail and could benefit from CGA.

Background: Hypersensitivity to beta-lactam (BL) antibiotics is one of the most frequent reported drug allergies. In our population, it is common to find labels of BL allergy in electronic medical records (EMRs) that have not been assessed. The objective of our study was to detect patients with beta-lactam allergy labels in their EMRs and to assess how many of them are false after a correct diagnostic evaluation.Methods: A multicentre prospective study was performed with patients labelled as allergic to BLs in their EMRs in the previous 5 years. Demographical and clinical data, as well as variables regarding the BL allergy label and the characteristics of the index reaction from clinical history and EMRs, were recorded. Then, diagnostic assessments including clinical history, skin tests (STs), and drug provocation tests (DPTs) were conducted in order to confirm or exclude the diagnosis of BL allergy.Results: A total of 249 patients completed the study, of which 160 (64.3%) were women with a median age of 57 years (interquartile range [IQR], 45–68). The most frequent BL allergy labels detected were for penicillin (124), amoxicillin/clavulanic acid (61), and amoxicillin (54). Of the 204 patients who underwent STs, 20.1% were positive. DPTs were performed in 224 patients, showing good tolerance in 87.1% of cases. After the allergy diagnosis work-up, 186 patients (74.7%) were diagnosed as non-allergic to BL antibiotics.Conclusion: In our study population, the number of patients labelled as allergic to BLs in their EMRs was similar to that in previously published studies, with proportions near to 75%–80% being falsely labelled as allergic to BLs.

Introduction. Comprehensive geriatric assessment (CGA) is used to personalize cancer treatments in frail older adults. However, its utility to guide treatments in frail older patients with diffuse large B-cell lymphoma (DLBCL) is not well known. We performed a meta-analysis of evidence published in this area.Material and methods. We searched PubMed and Google Scholar for studies published between January 2000 and January 2023 that included patients aged >_ 65 years with a diagnosis of DLBCL who underwent CGA before treatment (CGA-modulated studies) and who did not (non-CGA-modulated studies). We evaluated clinical outcomes in frail/unfit patients in terms of complete response (CR), incidence of grade >_ 3 toxicity, and 2-year overall survival (OS) in both types of studies.Results. Fifteen studies [8 CGA-modulated (n = 733, median age 76, 54% male, 52% frail/unfit) and 7 non-CGA-mod- ulated (n = 2447, median age 76, 52% male, 32% frail/unfit)] were included. In the CGA-modulated studies, the CR proportion of frail/unfit patients was 34% (95% CI 23-46%) vs. 28% (95% CI 19-38%) in the non-CGA-modulated studies (p = 0.436). Grade 3-4 hematological toxicity in frail/unfit patients was 26% (95% CI 5-55%) vs. 36% (95% CI 13-63%) (p = 0.583), respectively. Two-year OS of frail/unfit patients was 52% (95% CI 38-66%) vs. 27% (95% CI 19-36%) (p = 0.003), respectively.Conclusions. Although the proportion of frail/unfit patients was lower in non-CGA-modulated studies, CGA-mod- ulated studies reported higher OS. CGA could be useful to guide the treatment plan in older patients with DLBCL. Randomized clinical trials with standardized CGA instruments are necessary to confirm these findings.

Aim:The aim of the present study was to conduct a meta-analysis of the frequency of isoniazid-induced liver injury (INH-ILI) in patients receiving isoniazid (INH) preventative therapy (IPT). Background:The frequency of hepatotoxicity (drug-induced liver injury: DILI) of antituberculosis drugs has been studied, especially when INH, rifampin, and pyrazinamide are co-administered. However, little is known about the frequency of DILI in patients with latent tuberculosis infection (LTBI), where IPT is indicated. Methods:We searched PubMed, Google Scholar, and the Cochrane Database of Systematic Reviews for studies reporting the frequency of INH-ILI in patients with IPT using one or more diagnostic indicators included in the criteria of the DILI Expert Working Group. Results:Thirty-five studies comprising a total of 22,193 participants were included. The overall average frequency of INH-ILI was 2.6% (95% CI, 1.7-3.7%). The mortality associated with INH-DILI was 0.02% (4/22193). Subgroup analysis revealed no significant differences in the frequency of INH-ILI in patients older or younger than 50 years, children, patients with HIV, candidates for liver, kidney, or lung transplant, or according to the type of study design. Conclusion:The frequency of INH-ILI in patients receiving IPT is low. Studies on INH-ILI are needed where the current DILI criteria are used.

Background: In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women.Objective: To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription.Methods: An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs.Results: From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9-22.2 years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in >95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively.Conclusion: This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use.

BACKGROUND:Dysphagia is a common symptom in multiple sclerosis that can occur even early in the disease course and can lead to serious complications. Early recognition and treatment can promote comfort, safety and optimal nutritional status. Few dysphagia rating scales are available in Spanish. The aim of this study was to translate the Dysphagia in Multiple Sclerosis Questionnaire (DYMUS) into Spanish and to validate it.METHODS:Forward and backward translation method was used to translate the original English version of DYMUS into Spanish. A pilot-study with 10 PwMS was carried on in order to improve the intelligibility of the instrument, comprehensibility and content validity of the questionnaire. The questionnaire was filled out by 100 PwMS who were asked a dichotomous question on their swallowing ("Do you have swallowing troubles?"). Descriptive data are presented as median and quartiles for continuous variables and frequency and percentage for categorical ones. Internal consistency reliability was estimated by Cronbach's alfa. Test-retest reliability was estimated by intraclass correlation coefficient. Concurrent validity with a speech and language therapy assessment (SLT-A) was measured with the weighted kappa statistic for the concordance for both dysphagia type and degree categories. Confirmatory factor analysis by means of structural equation models was used to verify the two-factor (solids and liquids) structure of the DYMUS questionnaire. As the goodness of fit evaluation was poor, an additional exploratory factor analysis was carried out.RESULTS:Internal consistency was high. The globus sensation question and the weight loss questions (item 3 and 10) are the least specific with dysphagia symptomatology so they are worst correlated with the sum of the others (item-rest correlation, 0.243 and 0.248, respectively). The test-retest reliability of the DYMUS among 40 patients using ICC was 0.75 (95% CI 0.57 - 0.86). Concurrent validity with SLT-A was poor (weighted kappa 0.37 for dysphagia type and 0.38 for dysphagia degree). The DYMUS questionnaire detected three times more dysphagia (53% versus 17%) than the dichotomous question. Confirmatory factors analysis failed to confirm the bidimensional structure (solid and liquid items) often reported in other validation studies. The subsequent exploratory factor analysis also identified two factors, but with poor interpretability.CONCLUSION:DYMUS-SP scale is not a sufficiently useful scale to detect dysphagia in PwMS due to the poor concurrent validity and the probable overdiagnosis of the condition; however, it can be helpful as a screening tool when combined with other measures.

Background Interindividual genetic variations contribute to differences in patients' response to drugs as well as to the development of certain disorders. Patients who use non-steroidal anti-inflammatory drugs (NSAIDs) may develop serious gastrointestinal disorders, mainly upper gastrointestinal haemorrhage (UGIH). Studies about the interaction between NSAIDs and genetic variations on the risk of UGIH are scarce. Therefore, we investigated the effect of 16 single nucleotide polymorphisms (SNPs) involved in drug metabolism on the risk of NSAIDs-induced UGIH. Materials and methods We conducted a multicenter case-control study of 326 cases and 748 controls. Participants were sub-grouped into four categories according to NSAID exposure and genetic profile. We estimated odds ratios (ORs) and their 95% confidence intervals (CI) using generalized linear mixed models for dependent binomial variables and then calculated the measures of interaction, synergism index (S), and relative excess risk due to interaction (RERI). We undertook stratified analyses by the type of NSAID (aspirin, non-aspirin). Results We observed an excess risk of UGIH due to an interaction between any NSAID, non-aspirin NSAIDs or aspirin and carrying certain SNPs. The greatest excess risk was observed for carriers of: rs2180314:C>G [any NSAID: S = 3.30 (95%CI: 1.24-8.80), RERI = 4.39 (95%CI: 0.70-8.07); non-aspirin NSAIDs: S = 3.42 (95%CI: 1.12-10.47), RERI = 3.97 (95%CI: 0.44-7.50)], and rs4809957:A>G [any NSAID: S = 2.11 (95%CI: 0.90-4.97), RERI = 3.46 (95%CI: -0.40-7.31)]. Aspirin use by carriers of rs6664:C>T is also associated with increased risk of UGIH [ORaspirin(+),wild-type: 2.22 (95%CI: 0.69-7.17) vs. ORaspirin(+),genetic-variation: 7.72 (95%CI: 2.75-21.68)], yet larger sample size is needed to confirm this observation. Conclusions The joint effect of the SNPs s2180314:C>G and rs4809957:A>G and NSAIDs are more than three times higher than the sum of their individual effects. Personalized prescriptions based on genotyping would permit a better weighing of risks and benefits from NSAID consumption. KEY MESSAGES Multicenter case-control study of the effect of genetic variations involved in drug metabolism on upper gastrointestinal haemorrhage (UGIH) induced by NSAIDs (aspirin and non-aspirin). There is a statistically significant additive synergism interaction between certain genetic polymorphisms and NSAIDs on UGIH: rs2180314:C>G and rs4809957:A>G. The joint effect of each of these single nucleotide polymorphisms and NSAIDs on UGIH is more than three times higher than the sum of their individual effects. Genetic profiling and personalized prescriptions would be useful in managing the risks and benefits associated with NSAIDs.

OBJECTIVES:To assess the efficacy and safety of hydroxychloroquine (HCQ) compared with no treatment in healthcare workers with mild SARS-CoV-2 infection.METHODS:Prospective, non-randomized study. All health professionals with confirmed COVID-19 between April 7 and May 6, 2020, non-requiring initial hospitalization were asked to participate. Patients who accepted treatment were given HCQ for five days (loading dose of 400mg q12h the first day followed by200mg q12h). Control group included patients with contraindications for HCQ or who rejected treatment. Study outcomes were negative conversion and viral dynamics of SARS-CoV-2, symptoms duration and disease progression.RESULT:Overall, 142 patients were enrolled: 87 in treatment group and 55 in control group. The median age was 37 years and 75% were female, with few comorbidities. There were no significant differences in time to negative conversion of PCR between both groups. The only significant difference in the probability of negative conversion of PCR was observed at day 21 (18.7%, 95%CI 2.0-35.4). The decrease of SARS-CoV-2 viral load during follow-up was similar in both groups. A non significant reduction in duration of some symptoms in HCQ group was observed. Two patients with HCQ and 4 without treatment developed pneumonia. No patients required admission to the Intensive Care Unit or died. About 50% of patients presented mild side effects of HCQ, mainly diarrhea.CONCLUSIONS:Our study failed to show a substantial benefit of HCQ in viral dynamics and in resolution of clinical symptoms in health care workers with mild COVID-19.

The cause of structural valve deterioration (SVD) is unclear. Therefore, we investigated oxidative stress markers in sera from patients with bioprosthetic heart valves (BHVs) and their association with SVD. Blood samples were taken from SVD (Phase A) and BHV patients during the first 24 (Phase B1) and >48 months (Phase B2) after BHV implantation to assess total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrotyrosine (NT). The results show that MDA levels increased significantly 1 month after surgery in all groups but were higher at 6 months only in incipient SVD patients. NT levels increased gradually for the first 24 months after implantation in the BHV group. Patients with transcatheter aortic valve implantation (TAVI) showed even higher levels of stress markers. After >48 months, MDA and NT continued to increase in BHV patients with a further elevation after 60–72 months; however, these levels were significantly lower in the incipient and established SVD groups. In conclusion, oxidative stress may play a significant role in SVD, increasing early after BHV implantation, especially in TAVI cases, and also after 48 months’ follow-up, but decreasing when SVD develops. Oxidative stress potentially represents a target of therapeutic intervention and a biomarker of BHV dysfunction.

Background: Antidepressant drug consumption has increased, mainly in the elderly. This trend could be explained by the use for indications other than depression. We aimed to describe the indications related to antidepressant drug new users in two primary care settings. Methods: A longitudinal study of new antidepressant users aged >= 65 was conducted, with data from the NivelPCD (The Netherlands) and SIDIAP (Catalonia) databases (2010-2015). As a proxy for indication, diagnoses registered around the 3 months of antidepressant prescribing were collected. Indications were classified in seven categories and an additional one of non-selected indications. The percentage and incidence calculated over the total population registered was described. Results: A total of 16,537 and 199,168 new antidepressant users were identified in the Nivel-PCD and SIDIAP databases, respectively (women aged 65-69 were the most prevalent). Depression was the most frequent indication (24.0% and 31.3%), followed by anxiety (12.5% and 19.5%) and sleep disorders (10.2% and 26.4%). Tricyclic antidepressants were the most commonly prescribed in Nivel-PCD (48.7%), mainly associated with neuropathic pain, and selective serotonin reuptake inhibitor antidepressants in SIDIAP (63.1%), associated with depression. The non-selected indications category showed an upward trend in the Nivel-PCD database while in the SIDIAP database it decreased. Limitations: It is not mandatory for physicians to register a diagnosis with each prescription. Conclusions: Depression was the most common prescribing indication in The Netherlands and Spain, followed by anxiety and sleep disorders. The most commonly prescribed antidepressant differed between the countries and is likely explained by differences in local guidelines.

In SLE, underlying immune dysregulation and immunosuppression may increase the susceptibility to COVID-19 and impair the humoral and adaptive response. We aimed to characterize COVID-19 infection, identifying susceptibility and severity risk factors, assessing the presence of SARS-CoV-2 IgG antibodies and analyzing the cellular response. We established a prospective cohort of lupus patients to estimate the COVID-19 incidence compared to the reference general population. Data were collected via telephone interviews and medical record review. SARS-CoV-2 IgG antibodies were measured cross-sectionally as part of routine surveillance. Longitudinal changes in antibody titers and immunological profile from convalescent COVID-19 patients were evaluated at 6, 12 and 24 week after symptom onset. From immunological studies, PBMCs from convalescent patients were extracted and analyzed by flow cytometry and gene expression analysis. We included 725 patients, identifying 29 with PCR-confirmed COVID-19 infection and 16 with COVID-19-like symptoms without PCR-testing. Of the 29 confirmed cases, 7 had severe disease, 8 required hospital admission (27.6%), 4 intensive care, and 1 died. COVID-19 accumulated incidence was higher in lupus patients. Health care workers and anti-SSA/Ro52 antibody positivity were risk factors for COVID-19 susceptibility, and hypocomplementemia for severity. SARS-CoV-2 IgG antibodies were detected in 8.33% of patients. Three fourths of confirmed COVID-19 cases developed antibodies. High prednisone doses were associated with lack of antibody response. Antibody titers declined over time (39%). Convalescent patients at week 12 after symptom onset displayed a CD8 + T cell reduction and predominant Th17 with a mild Th2 response, more pronounced in severe COVID-19 disease. Longitudinal immune response analysis showed a progressive sustained increase in CD8 + T and B memory cells with a decrease of Th17 signaling. Lupus patients are at higher risk of COVID-19 infection and new susceptibility and severity risk factors were identified. Lupus patients were able to mount humoral and cellular responses despite immunosuppressive therapy.

Aims: To describe and compare the adherence to different direct oral anticoagulants (DOACs) in eight European databases representing six countries. Methods: Longitudinal drug utilization study of new users (≥18 years) of DOACs (dabigatran, rivaroxaban, apixaban) with a diagnosis of non-valvular atrial fibrillation (2008–2015). Adherence was examined by estimating persistence, switching, and discontinuation rates at 12 months. Primary non-adherence was estimated in BIFAP and SIDIAP databases. Results: The highest persistence rate was seen for apixaban in the CPRD database (81%) and the lowest for dabigatran in the Mondriaan database (22%). The switching rate for all DOACs ranged from 2.4 to 13.1% (Mondriaan and EGB databases, respectively). Dabigatran had the highest switching rate from 5.0 to 20.0% (Mondriaan and EGB databases, respectively). The discontinuation rate for all DOACs ranged from 16.0 to 63.9% (CPRD and Bavarian CD databases, respectively). Dabigatran had the highest rate of discontinuers, except in the Bavarian CD and AOK NORDWEST databases, ranging from 23.2 to 64.6% (CPRD and Mondriaan databases, respectively). Combined primary non-adherence for examined DOACs was 11.1% in BIFAP and 14.0% in SIDIAP. There were differences in population coverage and in the type of drug data source among the databases. Conclusion: Despite the differences in the characteristics of the databases and in demographic and baseline characteristics of the included population that could explain some of the observed discrepancies, we can observe a similar pattern throughout the databases. Apixaban was the DOAC with the highest persistence. Dabigatran had the highest proportion of discontinuers and switchers at 12 months in most databases (EMA/2015/27/PH).

BACKGROUND: Direct oral anticoagulants (DOACs) are widely used for the prevention of stroke in nonvalvular atrial fibrillation (NVAF); however, real-world primary nonadherence (failing to collect the first prescription) has been measured in very few studies. OBJECTIVE: To report primary nonadherence in NVAF patients who are newly prescribed DOACs and identify associated factors. METHODS: This observational retrospective cohort study used a large primary care database in Catalonia. Patients with NVAF who were newly prescribed a DOAC between January 2009 and December 2015 were identified, and primary nonadherence was measured by comparing prescribing records to pharmacy claims data. Multivariable logistic regression was used to determine associated factors. RESULTS: A total of 12,257 patients met the inclusion and exclusion criteria; of these, 1,276 (10.4%) were primary nonadherent. Primary nonadherence was found to be 12.8% for apixaban, 8.6% for dabigatran, and 10.8% for rivaroxaban. Multivariable logistic regression indicated higher odds of primary nonadherence with apixaban and rivaroxaban compared to dabigatran (apixaban: OR = 1.61, 95% CI = 1.39-1.87; rivaroxaban: OR = 1.28, 95% CI = 1.11-1.47). Patients aged at least 80 years showed lower odds of primary nonadherence compared to those aged less than 65 years (OR = 0.78, 95% CI = 0.66-0.93). A diagnosis of chronic kidney disease was associated with primary nonadherence (OR = 1.27, 95% CI = 1.08-1.50). Whereas, diabetes (OR = 0.85, 95% CI = 0.74-0.97), hypertension (OR = 0.79, 95% CI = 0.70-0.91), and stroke/transient ischemic attack (OR = 0.70, 95% C I =0.59-0.82) were inversely associated with primary nonadherence. CONCLUSIONS: Overall, 10.4% of patients prescribed DOACs were primary nonadherent, failing to collect the first prescription. The percentage could have serious implications for patient outcomes and the real-world cost-effectiveness of prescribing DOACs in NVAF. Rates of primary nonadherence and associated factors may provide useful information for the design and evaluation of adherence interventions. DISCLOSURES: No outside funding was received for this study. The data for this study came from the European Medicines Agency PE-PV project (Grant/Award Number EMA/2015/27/PH). The authors have nothing to disclose. A preliminary version of this work was presented at the European Drug Utilisation Research Group (EuroDURG) Conference, Szeged, Hungary, March 5, 2020.

Background Covid-19 vaccines may increase the risk of venous thromboembolism (VTE), thrombocytopenia (TCP), and VTE associated with TCP. We aimed at estimating this risk by age and sex, after the first dose of both adenovirus vector-based and mRNA-based Covid-19 vaccines, and after the second dose of m-RNA vaccines. Methods In this population-based retrospective cohort study, we examined three groups: 1 662 719 people 10 years of age and over vaccinated with the first dose of a Covid-19 vaccine, 622 778 with the second dose, and 190 616 diagnosed of Covid-19 in the same period (between1 January 2021 and 18 April 2021). The rates of various clinical presentations of VTE and TCP were compared with those in the reference population (7 013 040 people served by the health care system in 2919). The two primary outcomes were the observed 21 day rate of a composite variable of cerebral venous sinus thrombosis, mesenteric thrombosis, portal vein thrombosis, or any venous thromboembolism (VTE) associated with thrombocytopenia (TCP), and the rate of any VTE associated with TCP (VTE+TCP). Analyses were standardised by age and sex. Findings The 21 day rate per 100 000 of the primary composite variable was 2.15 in the reference population, 5.65 following the first vaccine dose (standardised difference, 2.53 (95 percent confidence interval, 1.04-4.00), and 7.23 following the second dose (standardised difference, 4.07 (95 percent confidence interval, 1.43-6.70). The event rates of VTE+TCP and of all the secondary variables showed the same patterns. Excess event rates were higher in men than in women, and they were not especially increased in any particular age group. All Covid-19 vaccines were associated with increased rates of the outcome variables. Excess event rates were many-fold higher in the Covid-19 cohort. Interpretation We observed small increases of rates of venous thromboembolism in usual and unusual anatomical sites and of thrombocytopenia in recipients of both adenovirus vector and mRNA vaccines against Covid-19. Excess rates were higher in men than in women and they were not particularly elevated in any specific age group.

Background: It has been postulated that metformin could have anti-SARS-CoV-2 action. This raises the hypothesis that people who take metformin may have lower SARS-CoV-2 severity and/or mortality. Objective To conduct a meta-analysis of the association between the use of Metformin and risk of severity and mortality in SARS-CoV-2 infection. Data Sources We searched PubMed, EMBASE, Google scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv and Research Square) for studies published between December 2019 and January 2021. Data was extracted on study location, year of publication, design, number of participants, sex, age at baseline, body mass index, and exposure and outcome definition. Effect statistics were pooled using random effects models with 95% confidence intervals (CI). The quality of included studies was assessed with the Newcastle–Ottawa Scale (NOS). Results Thirty-two observational studies were included, combining to a total sample of 44306 participants. The mean NOS score of included studies was 7.9. Results suggested that metformin use was associated with a reduced risk of SARS-CoV-2 mortality (OR= 0.56, 95% CI: 0.46-0.68, p<0.001; 22 studies) but not to disease severity (OR=0.85, 95% CI: 0.71-1.02, p=0.077; 15 studies). In the subgroup analysis, metformin reduces the risk of mortality (OR = 0.69, 95% CI: 0.55-0.88; p=0.002) and severity (OR = 0.83, 95% CI: 0.70-0.97, p=0.023) in patients aged 70 and above. Conclusions The use of metformin was associated to lower risk of mortality from SARS-CoV-2 infection. This association does not imply causation and further research is required to clarify potential mechanisms.

Current evidence on antidepressant‐related stroke or mortality risk is inconsistent. Because the elderly have the highest exposure to antidepressants, the aim was to quantify their association with stroke and mortality risks in this vulnerable population.