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Digestive Diseases and Sciences May 2024Infliximab and vedolizumab are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC). (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative Efficacy of Subcutaneous and Intravenous Infliximab and Vedolizumab for Maintenance Treatment of TNF-naive Adult Patients with Inflammatory Bowel Disease: A Systematic Literature Review and Network Meta-analysis.
BACKGROUND
Infliximab and vedolizumab are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC).
AIMS
This systematic review and network meta-analysis evaluated comparative efficacy of various regimens for intravenous or subcutaneous infliximab and vedolizumab during maintenance treatment in CD and UC.
METHODS
Parallel-group randomized controlled trials (RCTs) were identified by a systematic literature review (CRD42022383401) and included if they evaluated therapeutics of interest for maintenance treatment of adults with moderate-to-severe luminal CD or UC and assessed clinical remission between Weeks 30 and 60. Clinical remission rates in CD or UC and mucosal healing rates in UC were analyzed in a Bayesian network meta-analysis model. Endoscopic outcomes in CD were synthesized by proportional meta-analysis.
RESULTS
Overall, 13 RCTs were included in the analyses. All vedolizumab studies randomized induction responders to maintenance treatment; infliximab studies used a treat-through design. Subcutaneous infliximab 120 mg every 2 weeks had the highest odds ratio (OR) [95% credible interval] versus placebo for clinical remission during the maintenance phase (CD: 5.90 [1.90-18.2]; UC: 5.45 [1.94-15.3]), with surface under the cumulative ranking curve (SUCRA) values of 0.91 and 0.82, respectively. For mucosal healing in UC, subcutaneous infliximab 120 mg every 2 weeks showed the highest OR (4.90 [1.63-14.1]), with SUCRA value of 0.73, followed by intravenous vedolizumab 300 mg every 4 weeks (SUCRA value, 0.70). Endoscopic outcomes in CD were better with subcutaneous infliximab 120 mg every 2 weeks than intravenous infliximab 5 mg/kg every 8 weeks.
CONCLUSIONS
Subcutaneous infliximab showed a favorable efficacy profile for achieving clinical remission and endoscopic outcomes during maintenance treatment in CD or UC.
Topics: Humans; Infliximab; Antibodies, Monoclonal, Humanized; Injections, Subcutaneous; Gastrointestinal Agents; Colitis, Ulcerative; Crohn Disease; Administration, Intravenous; Treatment Outcome; Adult; Randomized Controlled Trials as Topic; Remission Induction; Network Meta-Analysis; Maintenance Chemotherapy
PubMed: 38499736
DOI: 10.1007/s10620-023-08252-1 -
Critical Care Medicine Jul 2024To conduct a systematic review and meta-analysis assessing whether the use of antipsychotic medications in critically ill adult patients with delirium impacts... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To conduct a systematic review and meta-analysis assessing whether the use of antipsychotic medications in critically ill adult patients with delirium impacts patient-important outcomes.
DATA SOURCES
A medical librarian searched Ovid MEDLINE, EMBASE, APA PsycInfo, and Wiley's Cochrane Library as well as clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform up to November 2023.
STUDY SELECTION
Independently and in duplicate, reviewers screened abstracts and titles for eligibility, then full text of qualifying studies. We included parallel-group randomized controlled trials (RCTs) that included critically ill adult patients with delirium. The intervention group was required to receive antipsychotic medications at any dose, whereas the control group received usual care or placebo.
DATA EXTRACTION
Reviewers extracted data independently and in duplicate using a piloted abstraction form. Statistical analyses were conducted using RevMan software (version 5.4).
DATA SYNTHESIS
Five RCTs ( n = 1750) met eligibility criteria. The use of antipsychotic medications compared with placebo did not increase the number of delirium- or coma-free days (mean difference 0.90 d; 95% CI, -0.32 to 2.12; moderate certainty), nor did it result in a difference in mortality, duration of mechanical ventilation, ICU, or hospital length of stay. The use of antipsychotics did not result in an increased risk of adverse events (risk ratio 1.27; 95% CI, 0.71-2.30; high certainty). Subgroup analysis of typical versus atypical antipsychotics did not identify any subgroup effect for any outcome.
CONCLUSIONS
In conclusion, our systematic review and meta-analysis demonstrated with moderate certainty that there is no difference in delirium- or coma-free days when delirious critically ill adults are treated with antipsychotic medications. Further studies in the subset of patients with hyperactive delirium may be of benefit.
Topics: Humans; Delirium; Antipsychotic Agents; Critical Illness; Randomized Controlled Trials as Topic
PubMed: 38488422
DOI: 10.1097/CCM.0000000000006251 -
Journal of Clinical Nursing Jul 2024To synthesise evidence from studies that explored the impact of electronic and self-rostering systems to schedule staff on healthcare organisations and healthcare... (Review)
Review
AIM
To synthesise evidence from studies that explored the impact of electronic and self-rostering systems to schedule staff on healthcare organisations and healthcare workers.
DESIGN
Mixed-method systematic review.
METHODS
Studies were screened by two independent reviewers and data were extracted using standardised data extraction tables. The quality of studies was assessed, and parallel-results convergent synthesis was conducted.
DATA SOURCES
Academic Search Complete, CINAHL, ERIC, MEDLINE, PsycINFO and PsycARTICLES were searched on January 3, 2023.
RESULTS
Eighteen studies were included (10 quantitative descriptive studies, seven non-randomised studies and one qualitative study). Studies examined two rostering interventions including self-rostering (n = 12) and electronic rostering (n = 6). It was found that the implementation of electronic and self-rostering systems for staff scheduling impacted positively on both, healthcare workers and healthcare organisations. Benefits included enhanced roster efficiency, staff satisfaction, greater control and empowerment, improved work-life balance, higher staff retention and reduced turnover, decreased absence rates and enhanced healthcare efficiency. However, self-rostering was found to be less equitable than fixed rostering, was associated with increased overtime, and correlated with a higher frequency of staff requests for shift changes.
CONCLUSION
The impact of electronic and self-rostering systems to schedule staff on healthcare organisations and healthcare workers' outcomes was predominantly positive. Further randomised controlled trials and longitudinal studies are warranted to evaluate the long-term impact of various rostering systems, including electronic and self-rostering systems.
IMPLICATIONS FOR HEALTHCARE
Rostering is a multifaceted responsibility for healthcare administrators, impacting patient care quality, workforce planning and healthcare expenditure.
IMPACT
Given that healthcare staffing costs constitute a substantial portion of global healthcare expenditure, efficient and strategic resource management, inclusive of healthcare staff rostering, is imperative.
REPORTING METHOD
The 27-item Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist.
PATIENT OR PUBLIC CONTRIBUTION
No Patient or Public Contribution.
Topics: Humans; Health Personnel; Personnel Staffing and Scheduling; Job Satisfaction
PubMed: 38481071
DOI: 10.1111/jocn.17114 -
The Cochrane Database of Systematic... Mar 2024New strategies in immunotherapy with specific antigens that trigger an anti-tumour immune response in people with lung cancer open the possibility of developing... (Review)
Review
BACKGROUND
New strategies in immunotherapy with specific antigens that trigger an anti-tumour immune response in people with lung cancer open the possibility of developing therapeutic vaccines aimed at boosting the adaptive immune response against cancer cells.
OBJECTIVES
To evaluate the effectiveness and safety of different types of therapeutic vaccines for people with advanced non-small cell lung cancer.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, Wanfang Data, and China Journal Net (CNKI) up to 22 August 2023.
SELECTION CRITERIA
We included parallel-group, randomised controlled trials evaluating a therapeutic cancer vaccine, alone or in combination with other treatments, in adults (> 18 years) with advanced non-small cell lung cancer (NSCLC), whatever the line of treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival, progression-free survival, and serious adverse events; secondary outcomes were three- and five-year survival rates and health-related quality of life.
MAIN RESULTS
We included 10 studies with 2177 participants. The outcome analyses included only 2045 participants (1401 men and 644 women). The certainty of the evidence varied by vaccine and outcome, and ranged from moderate to very low. We report only the results for primary outcomes here. TG4010 The addition of the vector-based vaccine, TG4010, to chemotherapy, compared with chemotherapy alone in first-line treatment, may result in little to no difference in overall survival (hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.65 to 1.05; 2 studies, 370 participants; low-certainty evidence). It may increase progression-free survival slightly (HR 0.74, 95% CI 0.55 to 0.99; 1 study, 222 participants; low-certainty evidence). It may result in little to no difference in the proportion of participants with at least one serious treatment-related adverse event, but the evidence is very uncertain (risk ratio (RR) 0.70, 95% CI 0.23 to 2.19; 2 studies, 362 participants; very low-certainty evidence). Epidermal growth factor vaccine Epidermal growth factor vaccine, compared to best supportive care as switch maintenance treatment after first-line chemotherapy, may result in little to no difference in overall survival (HR 0.82, 95% CI 0.66 to 1.02; 1 study, 378 participants; low-certainty evidence), and in the proportion of participants with at least one serious treatment-related adverse event (RR 1.32, 95% CI 0.88 to 1.98; 2 studies, 458 participants; low-certainty evidence). hTERT (vx-001) The hTERT (vx-001) vaccine compared to placebo as maintenance treatment after first-line chemotherapy may result in little to no difference in overall survival (HR 0.97, 95% CI 0.70 to 1.34; 1 study, 190 participants). Racotumomab Racotumomab compared to placebo as a switch maintenance treatment post-chemotherapy was assessed in one study with 176 participants. It may increase overall survival (HR 0.63, 95% CI 0.46 to 0.87). It may make little to no difference in progression-free survival (HR 0.73, 95% CI 0.53 to 1.00) and in the proportion of people with at least one serious treatment-related adverse event (RR 1.03, 95% CI 0.15 to 7.18). Racotumomab versus docetaxel as switch maintenance therapy post-chemotherapy was assessed in one study with 145 participants. The study did not report hazard rates on overall survival or progression-free survival time, but the difference in median survival times was very small - less than one month. Racotumomab may result in little to no difference in the proportion of people with at least one serious treatment-related adverse event compared with docetaxel (RR 0.89, 95% CI 0.44 to 1.83). Personalised peptide vaccine Personalised peptide vaccine plus docetaxel compared to docetaxel plus placebo post-chemotherapy treatment may result in little to no difference in overall survival (HR 0.80, 95% CI 0.42 to 1.52) and progression-free survival (HR 0.78, 95% CI 0.43 to 1.42). OSE2101 The OSE2101 vaccine compared with chemotherapy, after chemotherapy or immunotherapy, was assessed in one study with 219 participants. It may result in little to no difference in overall survival (HR 0.86, 95% CI 0.62 to 1.19). It may result in a small difference in the proportion of people with at least one serious treatment-related adverse event (RR 0.95, 95% CI 0.91 to 0.99). SRL172 The SRL172 vaccine of killed Mycobacterium vaccae, added to chemotherapy, compared to chemotherapy alone, may result in no difference in overall survival, and may increase the proportion of people with at least one serious treatment-related adverse event (RR 2.07, 95% CI 1.76 to 2.43; 351 participants).
AUTHORS' CONCLUSIONS
Adding a vaccine resulted in no differences in overall survival, except for racotumomab, which showed some improvement compared to placebo, but the difference in median survival time was very small (1.4 months) and the study only included 176 participants. Regarding progression-free survival, we observed no differences between the compared treatments, except for TG4010, which may increase progression-free survival slightly. There were no differences between the compared treatments in serious treatment-related adverse events, except for SRL172 (killed Mycobacterium vaccae) added to chemotherapy, which was associated with an increase in the proportion of participants with at least one serious treatment-related adverse event, and OSE2101, which may decrease slightly the proportion of people having at least one serious treatment-related adverse event. These conclusions should be interpreted cautiously, as the very low- to moderate-certainty evidence prevents drawing solid conclusions: many vaccines were evaluated in a single study with small numbers of participants and events.
Topics: Adult; Female; Humans; Male; Carcinoma, Non-Small-Cell Lung; Docetaxel; EGF Family of Proteins; Lung Neoplasms; Mycobacteriaceae; Quality of Life; Vaccines; Randomized Controlled Trials as Topic
PubMed: 38470132
DOI: 10.1002/14651858.CD013377.pub2 -
General Hospital Psychiatry 2024Long COVID can include impaired cognition ('brain fog'; a term encompassing multiple symptoms) and mental health conditions. We performed a systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Long COVID can include impaired cognition ('brain fog'; a term encompassing multiple symptoms) and mental health conditions. We performed a systematic review and meta-analysis to estimate their prevalence and to explore relevant factors associated with the incidence of impaired cognition and mental health conditions.
METHODS
Searches were conducted in Medline and PsycINFO to cover the start of the pandemic until August 2023. Included studies reported prevalence of mental health conditions and brain fog in adults with long COVID after clinically-diagnosed or PCR-confirmed SARS-CoV-2 infection.
FINDINGS
17 studies were included, reporting 41,249 long COVID patients. Across all timepoints (3-24 months), the combined prevalence of mental health conditions and brain fog was 20·4% (95% CI 11·1%-34·4%), being lower among those previously hospitalised than in community-managed patients(19·5 vs 29·7% respectively; p = 0·047). The odds of mental health conditions and brain fog increased over time and when validated instruments were used. Odds of brain fog significantly decreased with increasing vaccination rates (p = ·000).
CONCLUSIONS
Given the increasing prevalence of mental health conditions and brain fog over time, preventive interventions and treatments are needed. Research is needed to explore underlying mechanisms that could inform further research in development of effective treatments. The reduced risk of brain fog associated with vaccination emphasizes the need for ongoing vaccination programs.
Topics: Adult; Humans; Post-Acute COVID-19 Syndrome; Mental Health; Prevalence; COVID-19; SARS-CoV-2; Mental Fatigue
PubMed: 38447388
DOI: 10.1016/j.genhosppsych.2024.02.009 -
International Urology and Nephrology Jul 2024The present systematic review and meta-analysis aimed at evaluating the effect of low dialysate sodium concentration on interdialytic weight gain (IDWG) in chronic... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The present systematic review and meta-analysis aimed at evaluating the effect of low dialysate sodium concentration on interdialytic weight gain (IDWG) in chronic hemodialysis patients.
METHODS
Studies were eligible for inclusion if they were English language papers published in a peer-reviewed journal and met the following inclusion criteria: (1) studies in adult patients (over 18 years of age), (2) included patients on chronic hemodialysis since at least 6 months; (3) compared standard (138-140 mmol/l) or high (> 140 mmol/l) dialysate sodium concentration with low (< 138 mmol/l) dialysate sodium concentration; (4) Included one outcome of interest: interdialytic weight gain. Medline, PubMed, Web of Science, and the Cochrane Library were searched for the quality of reporting for each study was performed using the Quality Assessment Tool of Controlled Intervention Studies of the National Institutes of Health. The quality of reporting of each cross-over study was performed using the Revised Cochrane Risk of Bias (RoB) tool for cross-over trials as proposed by Ding et al. RESULTS: Nineteen studies (710 patients) were included in the analysis: 15 were cross-over and 4 parallel randomized controlled studies. In cross-over studies, pooled analysis revealed that dialysate sodium concentration reduced IDWG with a pooled MD of - 0.40 kg (95% CI - 0.50 to - 0.30; p < 0.001). The systematic review of four parallel, randomized, studies revealed that the use of a low dialysate sodium concentration was associated with a significant reduction of the IDWG in two studies, sustained and almost significant (p = 0.05) reduction in one study, and not significant reduction in one study.
CONCLUSION
Low dialysate sodium concentration reduces the IDWG in prevalent patients on chronic hemodialysis.
Topics: Humans; Renal Dialysis; Sodium; Weight Gain; Dialysis Solutions; Kidney Failure, Chronic; Hemodialysis Solutions
PubMed: 38446246
DOI: 10.1007/s11255-024-03972-3 -
Diseases of the Colon and Rectum Jun 2024Restorative proctocolectomy with IPAA improves the quality of life in patients with ulcerative colitis by the removal of diseased large bowel and preservation of the...
BACKGROUND
Restorative proctocolectomy with IPAA improves the quality of life in patients with ulcerative colitis by the removal of diseased large bowel and preservation of the natural route of defecation. Although the surgery may improve preexisting extraintestinal manifestations in the joints, skin, and eyes, extraintestinal manifestations, particularly primary sclerosing cholangitis, can persist after colectomy.
OBJECTIVES
A systematic review of diagnosis and treatment of liver, joint, skin, and eye manifestations in patients with restorative proctocolectomy and IPAA for ulcerative colitis.
DATA SOURCES
PubMed, Google Scholar, and Cochrane database.
STUDY SELECTION
Relevant articles on primary sclerosing cholangitis and extraintestinal manifestations in ileal pouches published between January 2001 and July 2023 in English were included on the basis of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
INTERVENTION
Diagnosis and treatment of primary sclerosing cholangitis and extraintestinal manifestations in patients with restorative proctocolectomy and IPAA were included.
MAIN OUTCOME MEASURES
Association between primary sclerosing cholangitis, extraintestinal manifestations, and inflammatory disorders of the pouch and their management.
RESULTS
Primary sclerosing cholangitis and extraintestinal manifestations are associated with pouchitis, particularly chronic pouchitis. Primary sclerosing cholangitis is associated with chronic pouchitis, enteritis, and possible pouch neoplasia. However, the disease severity and course of primary sclerosing cholangitis and pouchitis do not appear to be parallel. Despite the fact that oral vancomycin or budesonide have been used to treat primary sclerosing cholangitis-associated pouchitis, their impact on the disease course of primary sclerosing cholangitis is not known. Biological therapy for chronic inflammatory disorders of the pouch may also be beneficial for the concurrent extraintestinal manifestations of the joints, skin, and eyes. However, studies on the correlation between the severity of inflammatory pouch disorders and the severity of joint, skin, and eye diseases are lacking.
LIMITATIONS
This is a qualitative, not quantitative, review of case series and case reports.
CONCLUSIONS
Primary sclerosing cholangitis and extraintestinal manifestations of the joints, skin, and eyes appear to be associated with inflammatory disorders of the ileal pouch. Although the treatment of pouchitis does not seem to affect the disease course of primary sclerosing cholangitis, effective therapy of inflammatory pouch disorders, particularly with biologics, likely benefits concurrent disorders of the joints, skin, and eyes. See video from the symposium .
Topics: Cholangitis, Sclerosing; Humans; Proctocolectomy, Restorative; Pouchitis; Colitis, Ulcerative; Colonic Pouches; Eye Diseases; Skin Diseases
PubMed: 38411984
DOI: 10.1097/DCR.0000000000003231 -
Pediatric Pulmonology Jun 2024Elective flexible bronchoscopy (FB) is now widely available and standard practice for a variety of indications in children with respiratory conditions. However, there is...
INTRODUCTION
Elective flexible bronchoscopy (FB) is now widely available and standard practice for a variety of indications in children with respiratory conditions. However, there is limited evidence regarding the utility of elective FB in children. This systematic review (SRs) aimed to determine the utility of FB on its impact in clinical decision making and quality of life (QoL).
METHODS
We searched Pubmed, Cochrane central register of controlled trials, Embase, World Health Organization Clinical Trials Registry Platform and Cochrane database of SRs from inception to April 20, 2023. We included SRs and randomized controlled trials (RCTs) that used parallel group design (comparing use of elective FB vs. no FB, or a wait-list approach [early FB vs. usual wait FB]) in children aged ≤ 18 years. Our protocol was prospectively registered and used Cochrane methodology for systemic reviews of interventions.
RESULTS
Our search identified 859 articles; 102 duplicates were removed, and 753 articles were excluded by title and abstract. Four full text articles were reviewed and subsequently excluded, as none met the inclusion criteria outlined in our patient, intervention, comparator, outcome measures framework.
CONCLUSIONS
There is a paucity of high-quality RCT evidence to support the routine use of elective FB in children with respiratory conditions. However, available retrospective and a single prospective study demonstrate the high utility of FB in the elective pediatric setting.
REGISTRATION
PROSPERO CRD42021291305.
Topics: Humans; Bronchoscopy; Quality of Life; Child; Elective Surgical Procedures; Adolescent; Clinical Decision-Making; Child, Preschool
PubMed: 38411339
DOI: 10.1002/ppul.26940 -
Systematic Reviews Feb 2024Evidence on the effects of bovine colostrum (BC) supplementation on gastrointestinal (GI) diseases is conflicting.
BACKGROUND
Evidence on the effects of bovine colostrum (BC) supplementation on gastrointestinal (GI) diseases is conflicting.
OBJECTIVES
This systematic review summarized the findings of clinical trials (CTs) on the effects of BC supplementation on GI diseases.
METHODS
A systematic search was conducted in online databases, including PubMed, ISI Web of Science, and Scopus, until March 2021 and updated until December 2023. CTs investigated BC's effect on any measurable symptomatic change in terms of GI health as the primary outcome variable or as one of the outcomes in any population eligible for this systematic review.
RESULTS
Out of 6881 records, 22 CTs (uncontrolled = 4, cross-over = 1, and parallel = 17) with 1427 patients were enrolled in the systematic review. Diarrhea, the most frequently evaluated symptom (20 interventional arms), was decreased in frequency with BC supplementation in 15 of these arms. However, most studies reported no change in its duration. BC supplementation consistently reduced stool frequency across all seven studies. Abdominal pain relief was noted in four interventional arms but showed no improvement in five others. Assessment of other GI symptoms was limited, yielding inconclusive results.
CONCLUSIONS
There is limited evidence on the effects of BC on GI diseases, with mixed findings. More well-designed controlled clinical trials are required to explore its effects.
Topics: Female; Pregnancy; Humans; Animals; Cattle; Colostrum; Gastrointestinal Diseases; Diarrhea; Feces
PubMed: 38409162
DOI: 10.1186/s13643-024-02489-1 -
European Neuropsychopharmacology : the... Apr 2024Sleep medications often carry residual effects potentially affecting driving safety, warranting network meta-analysis (NMA).... (Meta-Analysis)
Meta-Analysis
Residual effects of medications for sleep disorders on driving performance: A systematic review and network meta-analysis of randomized controlled trials: NMA driving and hypnotics.
Sleep medications often carry residual effects potentially affecting driving safety, warranting network meta-analysis (NMA). PubMed/EMBASE/TRID/Clinicaltrials.gov/WHO-ICTRP/WebOfScience were inquired for randomized controlled trials of hypnotic driving studies in persons with insomnia and healthy subjects up to 05/28/2023, considering the vehicle's standard deviation of lateral position - SDLP (Standardized Mean Difference/SMD) and driving impairment rates on the first morning (co-primary outcomes) and endpoint. Risk-of-bias, global/local inconsistencies were measured, and CINeMA was used to assess the confidence in the evidence. Of 4,805 identified records, 26 cross-over RCTs were included in the systematic review, of which 22 entered the NMA, focusing on healthy subjects only. After a single administration, most molecules paralleled the placebo, outperforming zopiclone regarding SDLP. In contrast, ramelteon 8 mg, daridorexant 100 mg, zolpidem 10 mg bedtime, zolpidem middle-of-the-night 10 mg and 20 mg, mirtazapine 15-30 mg, and triazolam 0.5 mg performed significantly worse than placebo. Lemborexant 2.5-5 mg, suvorexant 15-20 mg, and zolpidem 3.5 mg middle-of-the-night associated with lower impairment than zopiclone. Repeated administration (maximum follow-up time of ten days) caused fewer residual effects than acute ones, except for flurazepam. Heterogeneity and inconsistency were negligible. Confidence in the evidence was low/very low. Sensitivity analyses confirmed the main analyses. Most FDA-approved hypnotics overlapped placebo at in-label doses, outperforming zopiclone. Repeated administration for 15 days or less reduced residual effects, warranting further research on the matter.
Topics: Humans; Hypnotics and Sedatives; Zolpidem; Network Meta-Analysis; Automobile Driving; Psychomotor Performance; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Piperazines; Azabicyclo Compounds
PubMed: 38401406
DOI: 10.1016/j.euroneuro.2024.01.011