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Crimean-Congo hemorrhagic fever (CCHF) is a viral infectious disease for which distribution of the main vector, Hyalomma spp. ticks, is expanding. We analyzed all 10 cases of CCHF diagnosed in Spain during 2013-2021; case-patient median age was 56.5 years, and 7 were men. We identified CCHF virus genotypes III and V. Six case-patients acquired the infection in urban areas. Sixty percent of patients were infected in summer and 40% in spring. Two patients met criteria for hemophagocytic syndrome. Seven patients survived. The epidemiologic pattern of CCHF in Spain is based on occasional cases with an elevated mortality rate. Genotype III and, to a less extent also genotype V, CCHF circulates in humans in a common geographic area in Spain. Those data suggest that the expansion pathways are complex and may change over time. Physicians should remain alert to the possibility of new CCHF cases.

Efficient and early triage of hospitalized Covid-19 patients to detect those with higher risk of severe disease is essential for appropriate case management. We trained, validated, and externally tested a machine-learning model to early identify patients who will die or require mechanical ventilation during hospitalization from clinical and laboratory features obtained at admission. A development cohort with 918 Covid-19 patients was used for training and internal validation, and 352 patients from another hospital were used for external testing. Performance of the model was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity and specificity. A total of 363 of 918 (39.5%) and 128 of 352 (36.4%) Covid-19 patients from the development and external testing cohort, respectively, required mechanical ventilation or died during hospitalization. In the development cohort, the model obtained an AUC of 0.85 (95% confidence interval [CI], 0.82 to 0.87) for predicting severity of disease progression. Variables ranked according to their contribution to the model were the peripheral blood oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio, age, estimated glomerular filtration rate, procalcitonin, C-reactive protein, updated Charlson comorbidity index and lymphocytes. In the external testing cohort, the model performed an AUC of 0.83 (95% CI, 0.81 to 0.85). This model is deployed in an open source calculator, in which Covid-19 patients at admission are individually stratified as being at high or non-high risk for severe disease progression. This machine-learning model, applied at hospital admission, predicts risk of severe disease progression in Covid-19 patients.

Ethanol consumption triggers oxidative stress by generating reactive oxygen species (ROS) through its metabolites. This process leads to steatosis and liver inflammation, which are critical for the development of alcoholic liver disease (ALD). Autophagy is a regulated dynamic process that sequesters damaged and excess cytoplasmic organelles for lysosomal degradation and may counteract the harmful effects of ROS-induced oxidative stress. These effects include hepatotoxicity, mitochondrial damage, steatosis, endoplasmic reticulum stress, inflammation, and iron overload. In liver diseases, particularly ALD, macroautophagy has been implicated as a protective mechanism in hepatocytes, although it does not appear to play the same role in stellate cells. Beyond the liver, autophagy may also mitigate the harmful effects of alcohol on other organs, thereby providing an additional layer of protection against ALD. This protective potential is further supported by studies showing that drugs that interact with autophagy, such as rapamycin, can prevent ALD development in animal models. This systematic review presents a comprehensive analysis of the literature, focusing on the role of autophagy in oxidative stress regulation, its involvement in organ–organ crosstalk relevant to ALD, and the potential of autophagy-targeting therapeutic strategies.

[This corrects the article DOI: 10.1371/journal.pone.0240200.].

IntroductionNon-initiation is defined as the refusal to start a medication prescribed for the first time to the patient. In the adult population, the non-initiation prevalence ranges between 6% and 28%, and it is associated with higher costs for the public system and worsen health outcomes. To the best of our knowledge, there is no evidence on the prevalence of non-initiation in the paediatric population. The study seeked to estimate the prevalence of paediatric non-initiation of the most prescribed pharmacotherapeutic groups and to determine its explanatory factors.MethodsThis was a cross-sectional study based on real word data in Catalonia. Data on the paediatric patients was obtained from the PADRIS dataset (2011-2018); which uses data from the electronic medical record of public providers that cover the entire population in Catalonia. Data was collected from all paediatric patients who were prescribed a new medicine (a previous drug-free period of at least 3 months was established).Non-initiation was estimated crossing data from prescription and dispensing databases. Prescriptions that were not filled after 1 month of the prescription date were considered not initiated. Sensitivity analyses allowed for 2 and 3 months. To determinate explanatory factors, a multivariate multilevel logistic regression was performed. Factors related to the patient (sociodemographic and clinical), the medication, the prescriber and the primary care centres were explored.ResultsThe prevalence of paediatric non-initiation in Catalonia was 20.1%. Non-initiation of treatments for pain-related disorders was around 28% and around 20% for antihistaminic treatments and corticosteroids. On treatments for severe mental disorders, such as depression and schizophrenia, non-initiation was about 14%. In diabetes, non-initiation ranged from 18% (insulins) to 23% (oral antidiabetics). Non-initiation of treatments for infectious diseases depended on the pharmaceutical form, being higher in topical (≈15%) than oral (≈7%) forms.Some medication, patient and physician-related factors explained non-initiation, such as the prescription of a generic brand medication, the patient’s socioeconomical status and the specialty of the prescriber.Conclusion/ DiscussionPaediatric non-initiation is highly prevalent and could be affecting the effectiveness of treatments and clinical outcomes. In this study, a series of explanatory factors were identified that should be taken into account by paediatricians and decision-makers to design interventions to improve paediatric initiation.LimitationsPatients who withdrawn the medication might have not started the treatment. On the other hand, some patients who did not withdraw the medication prescribed may have taken the treatment if they had oversupplies from previous prescriptions at home.Current databases in Catalonia do not link children to their relatives. The impact on non-initiation of factors related to fathers, mothers and/or caregivers could not be assessed.Suggestions For Future ResearchIn the future, the impact on clinical outcomes and costs of non-initiation should be assessed in the paediatric population. In order to fully understand the decision-making process, qualitative studies should be conducted to explore the motivations of carers and patients and factors that determine the decision not to initiate the pharmacological treatments prescribed to minors. The information gathered in these studies would enhance the development support strategies.

IntroductionMedication adherence and health results are highly improved by the use of collaborative care including primary and secondary care and community pharmacist. Treatment non-initiation is a prevalent behaviour that increases the expenditure of the health systems. Non-initiation not only delays the access to treatment, but it can also cause inadequate care in the follow-up.Among other factors, the patients’ decision to initiate a prescription medication is influenced by their interaction with the healthcare providers and by the coordination of the levels of care. Discordant discourses between primary and secondary care physicians or with the pharmacists can lead to non-initiation.MethodsThe project seeks to design a multidisciplinary intervention to manage a potentially harmful behaviour using a patient-centred approach and involving stakeholders. The design of the intervention was based on the Theoretical Model on Medication Non-initiation.A review of the literature was conducted to identify the evidence and theory relevant to the behaviour. A first version of the IMA intervention, which focuses on new treatments for cardiovascular disease and diabetes, was designed.In order to increase the acceptability and transferability of the intervention, discussion groups were conducted with general practitioners, community pharmacists, nurse practitioners, social workers and other medical doctors (cardiologists, endocrines and internists). After describing the motivations for non-initiation and the rationale for the IMA intervention, the participants were asked to make suggestions for optimisation and to describe the limitations of the intervention and the anticipated barriers for its implementation.ResultsThe results of the discussion groups were used to optimize the design of IMA intervention. The intervention provides healthcare professionals with the knowledge, skills and tools to help the patient make an informed decision. A brief and flexible intervention is proposed to facilitate the scalability and transferability of the intervention. The intervention has several components that try to harmonize and standardize the interventions of primary care professionals including the training of healthcare professionals and technical support tools such as leaflets, warnings in the e-prescription system and web resources.Conclusion/DiscussionDeveloping a multidisciplinary intervention would enhance synergies between these services, strengthen cohesion among health professionals and improve the integration of health care levels of the national health system. The IMA intervention has the potential to improve medication initiation. It will improve the excellence of the system, improving its efficiency by promoting a rational use of resources and the effectiveness of treatments.LimitationsIn the focus groups, there could be distortion of the information due to the judgment of the rest of the participants.Suggestions For Future ResearchThe final design of IMA intervention is being piloted. A trial will be performed to assess the effectiveness and cost-effectiveness of the IMA intervention. If proven effective and efficient, the implementation of the intervention in Primary Care will be pursued.

Background and Aims Osteoporosis is a systemic skeletal disease characterized by low bone mass and microstructural deterioration of bone tissues, resulting in bone fragility and increased fracture risk. It is the most common bone‐related disease in the population. However, the proportion of patients who start treatment but discontinue it during the first year is very high (around 50%). Endeavors are made to promote patient participation in treatment by implementing patient decision aids (PDA), whose function is to help the patient make disease‐related decisions. We aim to summarize the characteristics of the currently available PDA for osteoporosis, as well as deciding factors. Methods Comprehensive review of the literature. Results Currently, eleven PDAs can be found for osteoporosis. These PDA have different characteristics or options such as information about treatments tailored to patient needs, graphic information of the results (to facilitate understanding), personal histories (learning), tests to check the knowledge acquired, provision of evidence, clinical practice guidelines or a final summary to share with their doctor. Only five of these PDAs can be considered complete since they provide relevant disease information and therapeutic options to the patient, promote patient's reflection and foment patient‐physician discussion. Conclusions This study provides an update on the current state of decision making on osteoporosis and available PDA, which can help engage the patient through shared decision‐making by considering, among other things, patient preferences. Physicians should consider PDA, as it may promote adherence and effectiveness of treatment.

The aim was to assess the associations between morphine, fentanyl and adverse events in primary care patients. A retrospective, propensity-score-weighted cohort study using a primary-care database covering >75% population of Catalonia, Spain was conducted. Patients aged ≥18 years with ≥1 year of available data and incident dispensation of morphine or fentanyl, were included from 1st January 2007 to 31st December 2017. Outcomes were all-cause mortality, cardiac arrhythmias, fractures (hip, pelvis, vertebra, wrist, humerus), constipation, delirium, falls, opioid abuse/dependence, and sleep disorders while on treatment. Risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using cause-specific Cox models. A total of 12,632 patients (3,040 with morphine and 9,695 with fentanyl) were included (median [IQR] age, 78.4 [63.8; 86.1] years; 63.6% female). Compared with morphine, fentanyl dispensation was associated with a higher risk of fractures (incidence: 6.92 vs. 4.13 per 1,000 dispensations-month; HR, 1.63 [95% CI, 1.15-2.32]; RR, 1.78 [95% CI, 1.25-2.53]), especially in men and in those <65 and over >80 years old. No difference was observed for the rest of outcomes. Among outpatients, a new prescription dispensation of fentanyl, compared with morphine, was associated with a higher risk of fractures. The findings should be interpreted cautiously given the potential for residual confounding.

Excessive alcohol consumption impairs the immune system, induces oxidative stress, and triggers the activation of peripheral blood (PB) monocytes, thereby contributing to alcoholic liver disease (ALD). We analyzed the M1/M2 phenotypes of circulating classical monocytes and macrophage-derived monocytes (MDMs) in excessive alcohol drinkers (EADs). PB samples from 20 EADs and 22 healthy controls were collected for isolation of CD14+ monocytes and short-term culture with LPS/IFNγ, IL4/IL13, or without stimulation. These conditions were also used to polarize MDMs into M1, M2, or M0 phenotypes. Cytokine production was assessed in the blood and culture supernatants. M1/M2-related markers were analyzed using mRNA expression and surface marker detection. Additionally, the miRNA profile of CD14+ monocytes was analyzed. PB samples from EADs exhibited increased levels of pro-inflammatory cytokines. Following short-term culture, unstimulated blood samples from EADs showed higher levels of soluble TNF-α and IL-8, whereas monocytes expressed increased levels of surface TNF-α and elevated mRNA expression of pro-inflammatory cytokines and inducible nitric oxide synthase. MDMs from EADs showed higher levels of TNF-α and CD206 surface markers and increased IL-10 production. LPS/IFNγ induced higher mRNA expression of Nrf2 only in the controls. miRNA analysis revealed a distinctive miRNA profile that is potentially associated with liver carcinogenesis and ALD through inflammation and oxidative stress. This study confirms the predominantly pro-inflammatory profile of PB monocytes among EADs and suggests immune exhaustion features in MDMs.