Trends in urinary tract infection hospitalization in older adults in Spain from 2000-2015

Objective: To analyze trends in urinary tract infection hospitalization (cystitis, pyelonephritis, prostatitis and non-specified UTI) among patients over 65 years in Spain from 2000-2015. Methods: We conducted a retrospective observational study using the Spanish Hospitalization Minimum Data Set (CMBD), with codifications by the International Classification of Diseases (ICD-9). We collected data on sex, age, type of discharge, main diagnosis, comorbid diagnosis, length of stay, and global cost. All the hospitalizations were grouped by age into three categories: 65-74 years old, 75-84 years old, and 85 years old and above. In the descriptive statistical analysis, crude rates were defined as hospitalizations per 1,000 inhabitants aged ≥65. To identify trends over time, we performed a Joinpoint regression. Results: From 2000-2015, we found 387,010 hospitalizations coded as UTIs (54,427 pyelonephritis, 15,869 prostatitis, 2643 cystitis and 314,071 non-specified UTI). The crude rate of hospitalization for UTIs between 2000 and 2015 ranged from 2.09 in 2000 to 4.33 in 2015 Rates of hospitalization were higher in men than in women, except with pyelonephritis. By age group, higher rates were observed in patients aged 85 years or older, barring prostatitis-related hospitalizations. Joinpoint analyses showed an average annual percentage increase (AAPC) in incidence rates of 4.9% (95% CI 3.2;6.1) in UTI hospitalizations. We observed two joinpoints, in 2010 and 2013, that found trends of 5.5% between 2000 and 2010 (95% CI 4.7;6.4), 1.5% between 2010 and 2013 (95% CI -6.0;9.6) and 6.8% between 2013 and 2015 (95% CI -0.3;14.4). Conclusions: The urinary infection-related hospitalization rate in Spain doubled during the period 2000-2015. The highest hospitalization rates occurred in men, in the ≥85 years old age group, and in non-specified UTIs. There were increases in all types of urinary tract infection, with non-specified UTIs having the greatest growth. Understanding these changing trends can be useful for health planning.This study has been funded by Instituto de Salud Carlos III through the project “PI19/01700”, as part of the Plan Estatal de I+D+I 2017-2020 co-funded by European Regional Development Fund (ERDF) “A way of shaping Europe”. In addition, the principal investigator JRS received support to increase his research activities and to publish this manuscript from the 2020 funding program of the Fundación de Investigación e Innovación Biosanitaria en Atención Primaria (FIIBAP), Community of Madrid.S

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease