The role of traditional NSAIDs and selective COX-2 inhibitors on COVID-19 outcomes: a real-world data study.

The relation between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and severity of COVID-19 has been the subject to debate since the outbreak of the pandemic. Despite speculations about the possible harmful or protective effects, the position currently most supported by the scientific community is that there is no association between use of NSAIDs and COVID-19 outcomes. With the aim of contributing to increase the body of evidence on this issue, we conducted a case-control study using real-world data to investigate the association between prior use of NSAIDs, by active ingredient and type (traditional NSAIDs and selective COX-2 inhibitors), and important COVID-19-related outcomes, including susceptibility, PCR + patient progression, and hospitalisation. Our findings suggest that, in general, the use of traditional NSAIDs is not associated with any adverse COVID-19 outcome. However, we observed a possible association between diclofenac and a higher risk of PCR + patient progression. Our results also suggest that selective COX-2 inhibitors might be related with a reduction in the risk of PCR + patient progression. These results suggest that, with the possible exception of diclofenac, the use of NSAIDs should not be advised against for relief of symptoms in patients with COVID-19. In addition, they support the importance of continue to investigate the treatment potential of selective COX-2 inhibitors in the management of COVID-19, something that could have significant implications for the treatment of this disease and other viral infections.

Validity and Reliability of a Questionnaire on Attitudes, Knowledge, and Perceptions of Pharmacy Students Regarding the Training Received on Antibiotics and Antimicrobial Resistance during Their University Studies.

BACKGROUND: Antimicrobial resistance is a major public health issue today. Therefore, it is essential to focus on the education of pharmacists as future dispensers. The objective of this study was to validate a questionnaire that assesses the knowledge, attitudes, and perceptions of pharmacy students regarding the education received during their university degree on the use and dispensation of antibiotics, as well as bacterial resistance. METHODS: An online questionnaire was developed and distributed via RedCap v.13.7.1 to pharmacy students at the University of Santiago de Compostela using the WhatsApp social network. The questionnaire consisted of 28 items evaluating 5 dimensions: "quality of care", "communication skills", "antibiotic resistance", "teaching methodology", and "education on antibiotics at the faculty". The questionnaire validation was conducted in 2 steps: Step 1 involved content and appearance validation, and Step 2 involved reliability analysis. RESULTS: A total of 61 completed questionnaires were received. The mean age was 21.82 ± 3.81 years, with 20 males (32.8%) and 41 females (67.2%). Content validation was performed through a nominal group of 5 experts, and appearance validation was conducted by a focus group of 6 university pharmacy students. The questionnaire demonstrated a Cronbach's alpha value of 0.80 and adequate item discrimination capability. Confirmatory factor analysis was performed to assess construct validity, confirming the 5 predefined dimensions. CONCLUSIONS: A questionnaire has been developed and validated with high reliability and validity. Its use will help identify areas for improvement in the university education of pharmacy students, ultimately contributing to better use and dispensation of antibiotics and thereby improving antimicrobial resistance.

Antibiotic Use and Antimicrobial Resistance: A Global Public Health Crisis.

The discovery of antibiotics revolutionized modern medicine, effectively treating bacterial infections that were once fatal [...].

Liquid Biopsies Based on Cell-Free DNA Integrity as a Biomarker for Cancer Diagnosis: A Meta-Analysis.

Liquid biopsies have been identified as a viable source of cancer biomarkers. We aim to evaluate the diagnostic accuracy of cell-free DNA integrity (cfDI) in liquid biopsies for cancer. A comprehensive literature search was conducted through PubMed, Embase, Web of Science, and Cochrane Library up to June 2024. Seventy-two study units from forty-six studies, comprising 4286 cancer patients, were identified and evaluated. The Quality Assessment for Studies of Diagnostic Accuracy-2 (QUADAS-2) was used to assess study quality. Meta-regression analysis was employed to investigate the underlying factors contributing to heterogeneity, alongside an evaluation of publication bias. The bivariate random-effect model was utilized to compute the primary diagnostic outcomes and their corresponding 95% confidence intervals (CIs). The pooled sensitivity, specificity, and positive and negative likelihood ratios of cfDI in cancer diagnosis were 0.70 and 0.77, 3.26 and 0.34, respectively. The overall area under the curve was 0.84, with a diagnostic odds ratio of 10.63. This meta-analysis suggested that the cfDI index has a promising potential as a non-invasive and accurate diagnostic tool for cancer. Study registration: The study was registered at PROSPERO (reference No. CRD42021276290).

Outpatient glucocorticoid use and COVID-19 outcomes: a population-based study.

INTRODUCTION: Owing to controversy information surrounds effect of glucocorticoids on the evolution of COVID-19, we evaluate the effects of outpatient glucocorticoid use on the severity and progression of COVID-19 and risk of infection and analyse the effect of window of exposure and dose. METHODS: We conducted a population-based case - control study, involving 4 substudies: (i) Hospitalisation; (ii) Mortality, using subjects hospitalised with a PCR + as cases and subjects without a PCR + as controls; (iii) Progression, including subjects with a PCR + (hospitalised versus non-hospitalised); and (iv) Susceptibility, with all subjects with a PCR + and subjects without a PCR + . Adjusted odds ratios (ORa) and their 95% confidence intervals (95% CI) were calculated. RESULTS: The outpatient glucocorticoid use was associated with an increased risk of hospitalisation (aOR 1.79; 95% CI 1.56-2.05), mortality (aOR 2.30; 95% CI 1.68-3.15), progression (aOR 1.69; 95% CI 1.43-2.00) and susceptibility (aOR 1.29, 95% CI 1.19-1.41). Furthermore, the effects was observed to be greater at higher doses and the closer that drug use approached the outcome date, with an almost fourfold increase in mortality among users in the previous month (aOR 3.85; 95% CI 2.63-5.62). CONCLUSIONS: According to the results of this real-world data study, outpatient glucocorticoid use should be considered in making decisions about intrahospital treatment.

Outpatient Antipsychotic Use and Severe COVID-19: Avoiding the Impact of Age in a Real-World Data Study.

BACKGROUND: The association between use of antipsychotics and COVID-19 outcomes is inconsistent, which may be linked to use of these drugs in age-related diseases. Furthermore, there is little evidence regarding their effect in the nongeriatric population. We aim to assess the association between antipsychotic use and risk of disease progression and hospitalization due to COVID-19 among the general population, stratifying by age. METHODS: We conducted a population-based, multiple case-control study to assess risk of hospitalization, with cases being patients with a PCR(+) test who required hospitalization and controls being individuals without a PCR(+) test; and risk of progression to hospitalization, with cases being the same as those used in the hospitalization substudy and controls being nonhospitalized PCR(+) patients. We calculated adjusted odds-ratios (aOR) and 95% confidence intervals (CI), both overall and stratified by age. RESULTS: Antipsychotic treatment in patients younger than 65 years was not associated with a higher risk of hospitalization due to COVID-19 (aOR 0.94 [95%CI = 0.69-1.27]) and disease progression among PCR(+) patients (aOR 0.96 [95%CI = 0.70-1.33]). For patients aged 65 years or older, however, there was a significant, increased risk of hospitalization (aOR 1.58 [95% CI = 1.38-1.80]) and disease progression (aOR 1.31 [95% CI = 1.12-1.55]). CONCLUSIONS: The results of our large-scale real-world data study suggest that antipsychotic use is not associated with a greater risk of hospitalization due to COVID-19 and progression to hospitalization among patients younger than 65 years. The effect found in the group aged 65 years or older might be associated with off-label use of antipsychotics.

Impact of prior antihypertensive treatment on COVID-19 outcomes, by active ingredient.

OBJECTIVES: To assess the impact of prior chronic treatment with angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs), both as a group and by active ingredient, on severity (risk of hospitalization and mortality), progression of and susceptibility to COVID-19. METHODS: We conducted a multiple population-based case-control study in Galicia (north-west Spain). The study data were sourced from medical, administrative and clinical databases. We assessed: (1) risk of hospitalization, by selecting all patients hospitalized due to COVID-19 with PCR + as cases, and a random sample of subjects without a PCR + as controls; (2) COVID-19 mortality risk; (3) risk of disease progression; and (4) susceptibility to SARS-CoV-2, considering all patients with PCR + as cases, and the same subjects used in the previous model as controls. Adjusted odds ratios (aORs) were calculated. RESULTS: ACEIs and ARBs were shown to decrease the risk of hospitalization (aOR = 0.78 [95%CI 0.69-0.89] and aOR = 0.80 [95%CI 0.72-0.90] respectively), risk of mortality (aOR = 0.71 [95%CI 0.52-0.98] and aOR = 0.69 [95%CI 0.52-0.91] respectively), and susceptibility to the virus (aOR = 0.88 [95%CI 0.82-0.94] and aOR = 0.92 [95%CI 0.86-0.97] respectively). By active ingredient: use of enalapril was associated with a significantly lower risk of hospitalization (aOR = 0.72 [95%CI 0.61-0.85]), mortality (aOR = 0.59 [95%CI 0.38-0.92]) and susceptibility to COVID-19 (aOR = 0.86 [95%CI 0.79-0.94]); and use of candesartan was associated with a decreased risk of hospitalization (aOR = 0.76 [95%CI 0.60-0.95]), mortality (aOR = 0.36 [95%CI 0.17-0.75]) and disease progression (aOR = 0.73 [95%CI 0.56-0.95]). CONCLUSION: This large-scale real-world data study suggest that enalapril and candesartan are associated with a considerable reduction in risk of severe COVID19 outcomes.

Impact of prior use of antiplatelets on COVID-19 susceptibility, progression, and severity: a population-based study.

INTRODUCTION AND OBJECTIVES: Hypercoagulability and thromboembolism are processes that arise from severe acute respiratory syndrome coronavirus 2 infection and are responsible for a high degree of coronavirus disease 2019 (COVID-19)-related morbidity and mortality. This study sought to assess the effect of antiplatelet drugs on COVID-19 severity (risk of hospitalization and mortality), susceptibility to severe acute respiratory syndrome coronavirus 2 infection, and progression to severe COVID-19. METHODS: We conducted a population-based case-control study in a northwestern region of Spain in 2020. The study involved 3060 participants with a positive polymerase chain reaction test who were hospitalized, 26 757 participants with a positive polymerase chain reaction test who were not hospitalized, and 56 785 healthy controls. RESULTS: Triflusal seemed to be associated with a significant increase in risk of hospitalization (aOR, 1.97; 95%CI, 1.27-3.04) and susceptibility to infection (OR, 1.45; 95%CI, 1.07-1.96). It also appeared to lead to a nonsignificant increase in the risk of mortality (OR, 2.23; 95%CI, 0.89-5.55) and/or progression to more severe disease stages (OR, 1.42; 95%CI, 0.8-2.51). Aspirin seemed to be associated with a statistically significant decrease in susceptibility to severe acute respiratory syndrome coronavirus 2 infection (OR, 0.92; 95%CI, 0.86-0.98). CONCLUSIONS: Triflusal use appears to increase the risk of susceptibility to COVID-19 infection and an even higher risk of hospitalization, whereas the other antiplatelets could be associated with a reduction in the risk of the various outcomes or have no effect on risk. These findings could support reconsideration of triflusal prescription in COVID-19 pandemic situations.

Protein Plasma Levels of the IGF Signalling System Are Altered in Major Depressive Disorder.

The Insulin-like growth factor 2 (IGF-2) has been recently proven to alleviate depressive-like behaviors in both rats and mice models. However, its potential role as a peripheral biomarker has not been evaluated in depression. To do this, we measured plasma IGF-2 and other members of the IGF family such as Binding Proteins (IGFBP-1, IGFBP-3, IGFBP-5 and IGFBP-7) in a depressed group of patients (n = 51) and in a healthy control group (n = 48). In some of these patients (n = 15), we measured these proteins after a period (19 ± 6 days) of treatment with antidepressants. The Hamilton Depressive Rating Scale (HDRS) and the Self-Assessment Anhedonia Scale (SAAS) were used to measure depression severity and anhedonia, respectively. The general cognition state was assessed by the Mini-Mental State Examination (MMSE) test and memory with the Free and Cued Selective Reminding Test (FCSRT). The levels of both IGF-2 and IGFBP-7 were found to be significantly increased in the depressed group; however, only IGF-2 remained significantly elevated after correction by age and sex. On the other hand, the levels of IGF-2, IGFBP-3 and IGFBP-5 were significantly decreased after treatment, whereas only IGFBP-7 was significantly increased. Therefore, peripheral changes in the IGF family and their response to antidepressants might represent alterations at the brain level in depression.

Effect of dapagliflozin on COVID-19 infection and risk of hospitalization.

BACKGROUND: Dapagliflozin has been proposed as a potential treatment for coronavirus disease 2019 (COVID-19) by reducing cytokine production and inflammation. However, there are limited data on its effectiveness. We aimed to evaluate the impact of dapagliflozin on COVID-19 severity (including hospitalization risk, ICU admission, in-hospital death and progression to severe COVID-19) and its potential on susceptibility to COVID-19 infection. METHODS: We conducted a population-based case-control study. For aim 1, we assessed COVID-19 severity in cases (positive PCR patients requiring hospitalization) and matched controls (negative PCR patients or positive PCR patients not requiring hospitalization). For aim 2, we compared positive PCR cases (hospitalized and non-hospitalized) with controls. Adjusted odds ratios (aORs) were calculated using a generalized linear mixed model. RESULTS: We analysed 86 602 subjects: 3060 were hospitalized cases, 26 757 were non-hospitalized cases and 56 785 were controls. Among the hospitalized COVID-19 patients, 228 were admitted to the ICU and 413 died. Dapagliflozin had no effect on the risk of hospitalization (aOR 0.98; 95% CI 0.65-1.48; P = 0.915), ICU admissions (aOR 1.21; 95% CI 0.34-4.25; P = 0.767) or in-hospital death (aOR 1.33; 95% CI 0.53-3.30; P = 0.543). Dapagliflozin reduced the risk of progression to severe COVID-19 by 35%, but this was not statistically significant (aOR 0.65; 95% CI 0.40-1.06; P = 0.086). Dapagliflozin was associated with a 30% increased risk of susceptibility to COVID-19 infection (aOR 1.31; 95% CI 1.05-1.62; P = 0.015). CONCLUSIONS: Use of dapagliflozin prior to SARS-CoV-2 infection was not associated with an increased risk of hospitalization, ICU admission, mortality or progression to severe COVID-19. However, it was associated with an increased risk of susceptibility to COVID-19 infection.