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Antimicrobial resistance (AMR) poses a significant threat to global health, leading to increased deaths from drug-resistant infections and escalates healthcare costs. Often termed a “silent pandemic,” AMR occurs when pathogens become resistant to antimicrobial drugs, enabling their proliferation and spread. Inappropriate antibiotic usage is a major contributor to this phenomenon, which also extends to fungal infections. In particular, the duration of antibiotic therapy is a crucial aspect, with evidence suggesting that prolonged use can heighten bacterial resistance and harm the human microbiota. In fact, studies comparing short-term versus long-term antibiotic therapies show no significant difference in traditional treatments. In addition, therapeutic drug monitoring allows personalized antibiotic regimens, optimizing dosage and duration to minimize resistance and adverse effects. As a result, clinicians should regularly reassess treatment effectiveness, utilizing techniques like antibiotic timeout and de-escalation therapy to avoid prolonged antibiotic use and mitigate resistance. All these strategies are crucial to prevent and counter the phenomenon of antimicrobial resistance.

An updated meta-analysis incorporating nine randomized trials ( n  = 816) investigating low-to-moderate dose prolonged glucocorticoid treatment in acute respiratory distress syndrome (ARDS) show moderate-to-high quality evidence that glucocorticoid therapy is safe and reduces (i) time to endotracheal extubation, (ii) duration of hospitalization, and (iii) mortality (number to treat to save one life = 7), and increases the number of days free from (i) mechanical ventilation, (ii) intensive care unit stay, and (iii) hospitalization. Recent guideline suggests administering methylprednisolone in patients with early moderate-to-severe (1 mg/kg/day) and late persistent (2 mg/kg/day) ARDS (conditional recommendation based on moderate quality of evidence).

IntroductionIt is known that early withdrawal can lead to a worsening of mental health. This is particularly relevant for depressive patients with clinical high-risk for psychosis (CHR) for whom the recommended duration of treatment has not been established.ObjectivesAnalyze the actual treatment duration of depressive patients at CHR after their discharge from hospital and compare it with the group of depressive patients without CHR.MethodsA comparative study of 124 depressive patients with CHR and 27 depressive patients without CHR was conducted within a year after discharge from hospital to assess the therapy duration and treatment compliance.ResultsWithin a year after discharge only 12.1% depressive patients with CHR and 29.6% ones without CHR continued to receive the therapy. The average duration of treatment after discharge was 7.4 months in the first group and 11.7 months in the second group. The majority of patients stopped treatment for the following reasons (in descending order of importance): lack of awareness of their mental condition (51.9% vs 40.3%), side effects (38.7% vs 11.1%), and negative attitudes towards the treatment on the part of patients’ immediate family members (8.9% vs 7.4%).ConclusionsIt has been found out that depressive patients with CHR are less likely to follow medical prescriptions than ones without CHR, they are more likely to have the lack of awareness of their mental condition, they are more likely to have side effects of the therapy. These findings require the development of a universal approach to the treatment of such patients after discharge from hospital.DisclosureNo significant relationships.

Atezolizumab plus bevacizumab (Atez/BV) as first-line therapy and lenvatinib (LEN) as second-line therapy are the recommended treatments for patients with unresectable hepatocellular carcinoma. Adverse immune events caused by immune checkpoint inhibitors (such as Atez) generally only occur several months after administration; therefore, the potential influence of the first-line treatment on second-line treatment is not clear. The present study investigated the safety of second-line LEN treatment (2nd LEN) by comparing the adverse events (AEs) of 2nd LEN after first-line Atez/BV treatment for unresectable liver cancer, with those of first-line LEN treatment (1st LEN). Patients who received Atez/BV as first-line therapy and 2nd LEN, or those who received 1st LEN at Ogaki Municipal Hospital (Ogaki, Japan) between April 2018 and September 2023 were retrospectively evaluated for treatment duration and AEs. The median treatment duration for patients in the 1st LEN (n=39) and 2nd LEN (n=13) groups was 151.0 days [95% confidence interval (CI) 77-303 days] and 128.5 days (95% CI 68-270 days), respectively (P=0.385). A greater proportion of patients showed elevated aspartate aminotransferase/alanine aminotransferase levels in the 2nd LEN group (76.9%) compared with those in the 1st LEN group (46.2%) (P=0.016). Hypothyroidism was more common in those receiving 2nd LEN (46.2%) than 1st LEN (12.8%) (P=0.016). In addition, grade 1 (three patients) and grade 2 (three patients) hypothyroidism was observed in patients receiving 2nd LEN. For these six patients, during first-line Atez/BV treatment, four patients had grade 0 hypothyroidism and two patients had grade 1 hypothyroidism (P=0.025). In conclusion, patients receiving 2nd LEN after treatment with Atez/BV are at an increased risk of hypothyroidism. Key words: hypothyroidism, AE, duration of treatment, HCC, LEN, Atez/BV

Background: Several narrative reports document long-term responses to regorafenib treatment in patients with metastatic colorectal cancer (mCRC). However, no large-scale study has assessed long-term responses and there are no established predictors of potential long-term benefit. We carried out an observational study of characteristics of patients treated in real-world clinical practice in the USA using duration of treatment (DoT) as a surrogate for treatment response. Patients and Methods: This retrospective cohort study used a de-identified electronic health record-derived database and included patients aged ≥18 years with mCRC who initiated regorafenib monotherapy between 1 July 2013 and 30 June 2023. Patient cohorts were defined by DoT ≥4 months (LTR4), ≥5 months (LTR5), or ≥6 months (LTR6) and are not mutually exclusive. Results: Of 2444 patients who initiated regorafenib monotherapy during the study, those with long-term response were analyzed: 544 had LTR4 (22%), 367 had LTR5 (15%), and 250 had LTR6 (10%). Most patients with long-term responses had left-sided tumors (65–70%), Eastern Cooperative Oncology Group performance status of 0/1 (67–68%), and liver metastases (55–61%) and had received prior bevacizumab treatment (60–67%). The median age in each group was 66 years, and patients most frequently initiated regorafenib as third-line treatment (31–33%). Median time to regorafenib discontinuation was 6.0–9.3 months among long-term responders. Conclusions: Most patients with long-term responses to regorafenib had favorable performance status at treatment initiation, left-sided tumors, and liver metastases and had received prior bevacizumab treatment. The study highlights that patients in the real-world setting were able to tolerate and maintain long-term responses to regorafenib treatment.

The evaluation of staging and activity of invasive fungal infection (IFI) is used to adjust the type and duration of antifungal therapy (AT). Typically anatomy-based imaging is used. Positron emission tomography/CT with F-fluorodeoxyglucose ( F-FDG PET/CT) not only evaluates more than one body area in one session, but adds functional information to the anatomic data provided by usual imaging techniques and can potentially improve staging of IFI and monitoring of the response to therapy. Our objective is to analyse the impact of the systematic use of F-FDG PET/CT in IFI diagnostic and therapeutic management. Multicentre prospective cohort study of IFI with performance of systematic F-FDG PET/CT at diagnosis and follow-up that will be carried out in 14 Spanish tertiary hospitals. It is planned to include 224 patients with IFI over a 2-year study period. Findings and changes in management before and after F-FDG PET/CT will be compared. Additionally, the association of initial quantitative F-FDG PET/CT parameters with response to therapy will be evaluated.The primary endpoint is to compare the yield of F-FDG PET/CT with standard management without F-FDG PET/CT in IFI at initial assessment (staging) and in monitoring the response to treatment.The impact of the results of F-FDG PET/CT on the diagnostic-therapeutic management of patients with IFI (added value), as well as the prognostic ability of different quantification parameters of F-FDG PET/CT will be secondary endpoints. The Clinical Research Ethics Committee of Puerta de Hierro-Majadahonda University Hospital approved the protocol of the study at the primary site. We plan to publish the results in high-impact journals. NCT05688592.

In recent years, the Geriatric Nutritional Risk Index (GNRI) has been reported as a predictor of prognosis in many patients with cancer. This study investigated the association of preoperative GNRI with the occurrence of adverse events and duration of treatment with capecitabine plus oxaliplatin (CAPOX), a postoperative adjuvant chemotherapy, in 59 patients with colorectal cancer from September 2019 to April 2022. A cut-off value of 100.9 was used to categorize patients into high and low GNRI groups. The incidence of grade ≥2 leukopenia (p=0.03), and all grades peripheral neuropathy (p=0.04) were significantly more frequent in the low GNRI group. Analysis of factors influencing treatment duration by univariate and multivariate Cox regression proportional hazards models showed a significant difference in GNRI (p=0.0097). GNRI, a nutritional indicator assessed before the start of treatment, influences the occurrence of adverse events and duration of treatment with CAPOX as adjuvant chemotherapy. To complete CAPOX therapy, preoperatively, it is important to assess the patients' nutritional status using the GNRI and to actively intervene in nutritional therapy.

Diagnostic tools for the management of acute osteomyelitis (OM) and septic arthritis (SA) have improved over the last decade. To investigate the influence and availability of magnetic resonance imaging (MRI) and nucleic acid testing (NAT), a retrospective cohort study was done. Patients admitted with acute OM or SA between 2005 and 2014 were identified using ICD-10 discharge codes. Ninety-six children were identified: OM, n = 45; SA, n = 42; and OM + SA, n = 9. Diagnostic imaging was performed in 100% of OM or OM + SA and 95% of SA patients. MRI was performed in 85% of OM patients, 26% of SA patients and 100% OM + SA patients. In patients with OM or SA, concomitant joint/bone involvement was detected in 24 and 36% of patients, respectively. In 58% of patients, a pathogen was detected (Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae being most common). Blood and tissue culture were positive in 41 and 86% for OM patients and in 14 and 41%, respectively, for SA patients. In 42% of patients, no pathogen was identified, of which 40% had no material for blood or tissue culture/NAT taken. Conclusion: Optimal use of imaging modalities including MRI and systematic pathogen detection including NAT should be advocated to limit use of broad spectrum antibiotics and treatment duration.

Lenvatinib (LEN), a multitarget tyrosine kinase inhibitor, is a standard therapeutic agent for hepatocellular carcinoma, but the high incidence of adverse events (AEs) related to LEN treatment often necessitates treatment discontinuation. The present study aimed to clarify the therapeutic efficacy and tolerability of modified LEN dosing methods, such as alternate-day dosing, necessitated by AEs of LEN. A total of 66 patients who received LEN at Ogaki Municipal Hospital (Ogaki, Japan) between April 2018 and January 2022 were retrospectively evaluated. These patients were divided into those who completed treatment with the standard administration method (standard LEN, n=48) and those who changed from the standard administration method to a modified administration method in the middle of treatment [modified LEN (weekends off/alternate days), n=18]. The treatment duration and reasons for discontinuation of LEN treatment were analysed. The discontinuation rate due to AEs in the modified LEN group (1 patient) was less compared with that in the standard LEN group (16 patients) (P=0.022). The median treatment duration for patients in the standard LEN (n=48), modified LEN (weekends off, n=6) and modified LEN (alternate days, n=12) groups was 71 [95% confidence interval (CI) 55-134], 483 (95% CI: 193-644) and 222 (95% CI: 98-303) days, respectively (P=0.044). Modification of the administration method ensured fewer AE-related treatment discontinuations. However, weekends off dosing showed a longer treatment duration compared with standard dosing, whereas alternate day dosing showed no difference from standard dosing.

Increasing numbers of patients are being referred to specialised palliative care (SPC) which, in order to be beneficial, is recommended to last more than three months. This cohort study aimed to describe time to end-of-life after initiating SPC treatment and to explore potential regional variations. We used national register data from all Danish hospital SPC teams. We included patients who started SPC treatment from 2015–2018 to explore if time to end-of-life was longer than three months. Descriptive statistics were used to summarise the data and a generalised linear model was used to assess variations among the five Danish regions. A total of 27,724 patients were included, of whom 36.7% (95% CI 36.2–37.1%) had over three months to end-of-life. In the Capital Region of Denmark, 40.1% (95% CI 39.0–41.3%) had over three months to end-of-life versus 32.5% (95% CI 30.9–34.0%) in North Denmark Region. We conclude that most patients live for a shorter period of time than the recommended three months after initiating SPC treatment. This is neither optimal for patient care, nor the healthcare system. A geographical variation between regions was shown indicating different practices, patient groups or resources. These results warrant further investigation to promote optimal SPC treatment.