IntroductionUncomplicated lower urinary tract infections (uLUTI) are a common problem in primary care. Current local guidelines recommend the use of a single 3 g dose of fosfomycin. However, most ...general practitioners (GP) prefer short-course therapies to single-dose therapy. No study has compared head-to-head short-course antimicrobial agents for uLUTIs. Therefore, the aim of this randomised clinical trial is to compare three different short-course antibiotic therapies with a single-dose of fosfomycin for these infections.Methods and analysisThis will be a pragmatic, multicentre, parallel group, open trial. Women aged 18 or older and with symptoms of uLUTI and a positive urine dipstick analysis will be randomised to one of the following four groups: a single dose of 3 g of fosfomycin, 2 days of 3 g of fosfomycin o.d., 3 days of pivmecillinam 400 mg three times per day (t.i.d) or 5 days of nitrofurantoin 100 mg t.i.d. A total sample of 1120 patients was calculated. The primary endpoint is clinical effectiveness at day 7, defined as cure of symptoms reported by the patients in a diary including four symptoms: dysuria, urgency, frequency and suprapubic pain, which will be scored on a 4-point severity scale (not present/mild/moderate/severe). Follow-up visits are scheduled at days 7 (phone call), 14 and 28 for assessing evolution. Urine samples will be collected in the three on-site visits and urine cultures performed. If positive, antibiograms for the three antibiotics studied will be performed. Bacterial eradication will be measured at days 14 and 28.Ethics and disseminationThe study was approved by the Ethical Board of IDIAP Jordi Gol (reference number: 21/173-AC) and Spanish Agency of Medicines and Medical Devices. The findings of this trial will be disseminated through research conferences and peer-review journals.Trial registration numberNCT04959331; EudraCT Number: 2021-001332-26.Time scheduleJanuary 2022 to April 2023.
Rationale and objectives
Late diagnosis of HIV infection is a public health problem. Framed by the international guidelines for improving HIV testing, in 2014, the Spanish Ministry of Health ...published a guide of recommendations to promote early diagnosis of HIV in health care settings. In the Community of Madrid, in order to implement these recommendations, we defined 3 new HIV testing strategies in primary health care. The objectives of this study were to know the interest of professionals and the acceptability for patients towards these strategies.
Methods
We performed a quasi‐experimental study to assess the feasibility of the implementation of new strategies (indicator condition, risk based, and universal offer) to promote early detection of HIV infection in the framework of the ESTVIH project. The centres participating in this project were randomly chosen among centres located in the health areas with the highest incidence of HIV infection. The feasibility was assessed in 6 centres. We considered outcomes by strategy in relation to the participation of professionals (family physician and nursing) and patients.
Results
Overall, 56.9% of eligible professionals agreed to take part in the study; however, the percentage of professionals who recruited patients was 25.9%. This percentage was higher in the indicator condition strategy (47.2%, versus 18.5% in the universal offer and 14.3% in the risk‐based strategy, P‐value < 0.05). The test uptake percentage was greater than 80%, and there were no statistically significant differences between strategies.
Conclusion
Different strategies promoting HIV testing in primary care had different acceptability among professionals and similar among patients. At the end of the ESTVIH project, these results will be complemented with others related to the contribution of each strategy to improving the early diagnosis of HIV infection.
In the context of the COVID‐19 pandemic, this paper provides recommendations for medical eye care during the easing of control measures after lockdown. The guidelines presented are based on a ...literature review and consensus among all Spanish Ophthalmology Societies regarding protection measures recommended for the ophthalmologic care of patients with or without confirmed COVID‐19 in outpatient, inpatient, emergency and surgery settings. We recommend that all measures be adapted to the circumstances and availability of personal protective equipment at each centre and also highlight the need to periodically update recommendations as we may need to readopt more restrictive measures depending on the local epidemiology of the virus. These guidelines are designed to avoid the transmission of SARS‐CoV‐2 among both patients and healthcare staff as we gradually return to normal medical practice, to prevent postoperative complications and try to reduce possible deficiencies in the diagnosis, treatment and follow‐up of the ophthalmic diseases. With this update (5th) the Spanish Society of Ophthalmology is placed as one of the major ophthalmology societies providing periodic and systematized recommendations for ophthalmic care during the COVID‐19 pandemic.
Evaluation of Electron Density Shifts in Noncovalent Interactions Iribarren, Iñigo; Sánchez-Sanz, Goar; Alkorta, Ibon ...
The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory,
06/2021, Letnik:
125, Številka:
22
Journal Article
Recenzirano
Odprti dostop
In the present paper, we report the quantitative evaluation of the electron density shift (EDS) maps within different complexes. Values associated with the total EDS maps exhibited good correlation ...with different quantities such as interaction energies, E int, intermolecular distances, bond critical points, and LMOEDA energy decomposition terms. Besides, EDS maps at different cutoffs were also evaluated and related with the interaction energies values. Finally, EDS maps and their corresponding values are found to correlate with E int within systems with cooperative effects. To our knowledge, this is the first time that the EDS has been quanitatively evaluated.
The aim of this study was to assess the diagnostic performance of an autoantibody battery in patients receiving immune checkpoint inhibitors who experienced immune-related adverse events (irAEs).
We ...retrospectively analyzed several variables potentially related to irAEs, namely, demographic, clinical, and laboratory characteristics, including an autoantibody battery (antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor).
Sixty-nine patients (48 men; 61.8 ± 10.9 years at baseline) diagnosed with stage-4 solid-organ cancer and treated with nivolumab were followed up for 12 ± 10.3 months. Thirty-two irAEs were detected in 26 patients (37.5%). Adverse events occurred more commonly in women (62% vs. 27%, p = .006), and younger patients (irAEs: 58.1 ± 9.8, no irAEs: 64.1 ± 10.9 years, p = .024). Autoantibody battery results were available for 26 patients and were more frequently positive in patients with irAEs (87% vs. 30%, p = .009). The positive predictive value, negative predictive value, and diagnostic accuracy of the battery were 82.3%, 77.8%, and 80.8%, respectively. Among the 64 patients with an evaluable response, 23 (38.5%) experienced tumour progression, this being less frequent in patients with irAEs (19% vs. 48.5%, p = .03). Overall survival was higher in patients developing irAEs (HR = 1.88, p = .05).
Positivity in a readily available autoantibody battery may be associated with the occurrence of irAEs.
KEY MESSAGES
Positivity in an accessible and inexpensive autoantibody battery including antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor may be associated with the occurrence of immune-related adverse events.
Patients with cancer on immune checkpoint inhibitors experiencing immune-related adverse events showed a lower risk of progression and better overall survival than patients not experiencing this type of adverse effect.
Sex‐related differences in mortality are widespread in the animal kingdom. Although studies have shown that sex determination systems might drive lifespan evolution, sex chromosome influence on aging ...rates have not been investigated so far, likely due to an apparent lack of demographic data from clades including both XY (with heterogametic males) and ZW (heterogametic females) systems. Taking advantage of a unique collection of capture–recapture datasets in amphibians, a vertebrate group where XY and ZW systems have repeatedly evolved over the past 200 million years, we examined whether sex heterogamy can predict sex differences in aging rates and lifespans. We showed that the strength and direction of sex differences in aging rates (and not lifespan) differ between XY and ZW systems. Sex‐specific variation in aging rates was moderate within each system, but aging rates tended to be consistently higher in the heterogametic sex. This led to small but detectable effects of sex chromosome system on sex differences in aging rates in our models. Although preliminary, our results suggest that exposed recessive deleterious mutations on the X/Z chromosome (the “unguarded X/Z effect”) or repeat‐rich Y/W chromosome (the “toxic Y/W effect”) could accelerate aging in the heterogametic sex in some vertebrate clades.
A computational study of the iodide discrimination by different neutral and cationic iodotriazole halogen bonding hosts was carried out by means of Density Functional Theory. The importance of the ...size of the scaffold was highlighted and its impact observed in the binding energies and intermolecular X···I distances. Larger scaffolds were found to reduce the electronic repulsion and increase the overlap between the halide electron lone pair and the corresponding I-C antibonding orbital, increasing the halogen bonding interactions. Additionally, the planarity plays an important role within the interaction, and can be tuned using hydroxyl to perform intramolecular hydrogen bonds (IMHB) between the scaffold and the halogen atoms. Structures with IMHB exhibit stronger halogen bond interactions, as evidenced by the shorter intramolecular distances, larger electron density values at the bond critical point and more negative binding energies.
This paper presents a theoretical analysis the effect of non-covalent interactions (NCI) in three different S
N
2 reactions (X
–
:CH
3
X → XCH
3
:X
–
, X = Cl, Br and I) has been theoretically ...analysed in the pre-reactive complexes, TS and products. A total of eighteen Lewis acids (LAs: FH, ClH, FCl, I
2
, SeHF, SeF
2
, PH
2
F, PF
3
, SiH
3
F, SiF
4
, BH
3
, BF
3
, BeH
2
, BeF
2
, LiH, LiF, Au
2
and AgCl) interact with the halogen atom of the CH
3
X molecule. To analyse the strength of the non-covalent interactions, both the independent gradient model tool and electron density maps have been employed. The results reveal that in all cases, the interaction between the anion and the Lewis acid leads to an increase in the transition barriers compared to the parental reaction.
Monkeypox is the most prevalent Orthopoxvirus zoonosis infection since the eradication of smallpox. The current multi-country outbreak involves five WHO regions affecting mainly Europe. Accurate ...clinical and virological aspects of the disease outside endemic areas are needed.
We performed an observational study of cases diagnosed in Madrid (Spain) (May/June 2022). Confirmation from vesicular lesions swabs, Orthopoxvirus real-time PCR, sequencing, phylogenetic analysis, and direct detection by Electron microscopy was performed. In addition, a structured epidemiological questionnaire was completed systematically to gather sociodemographic, clinical, and behavioral data from all confirmed cases.
We extracted data from 48 patients, all cisgender men. The median age was 35 years (IQR 29 - 44), and 87.5% were MSM. The most prevalent symptoms were the presence of vesicular-umbilicated and pseudo-pustular skin lesions (93.8%), asthenia (66.6%), and fever (52.1%). In addition, the location of the lesions in the genital or perianal area was related to the role in sexual intercourse (p<0.001). Sequencing analysis indicated the virus circulating in Spain belongs to the western African clade. Like the other European cases in the outbreak, the Spanish isolates are a direct descendant of viruses previously detected in Nigeria, the UK, Singapore, and Israel in 2017-2018.
Monkeypox is an emerging infectious disease in Europe where community transmission is reported, mainly in MSM. The first symptom was skin lesions instead of classical fever and rash. The disease follows a self-limited course, and there have been no cases with a serious presentation or severe complications.
Early recognition of sepsis is a key factor to improve survival to this disease in surgical patients, since it allows prompt control of the infectious source. Combining pro-inflammatory and ...immunosupression biomarkers could represent a good strategy to improve sepsis detection. Here we evaluated the combination of procalcitonin (PCT) with gene expression levels of HLA-DRA to detect sepsis in a cohort of 154 surgical patients (101 with sepsis and 53 with no infection). HLA-DRA expression was quantified using droplet digital PCR, a next-generation PCR technology. Area under the receiver operating curve analysis (AUROC) showed that the PCT/HLA-DRA ratio outperformed PCT to detect sepsis (AUROC CI95%, p): PCT: 0.80 0.73-0.88, <0.001; PCT/HLA-DRA: 0.85 0.78-0.91, <0.001. In the multivariate analysis, the ratio showed a superior ability to predict sepsis compared to that of PCT (OR CI 95%, p): PCT/HLA-DRA: 7.66 1.82-32.29, 0.006; PCT: 4.21 1.15-15.43 0.030. Multivariate analysis was confirmed using a new surgical cohort with 74 sepsis patients and 21 controls: PCT/HLA-DRA: 34.86 1.22-995.08, 0.038; PCT: 5.52 0.40-75.78, 0.201. In conclusion, the combination of PCT with HLA-DRA is a promising strategy for improving sepsis detection in surgical patients.
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