UNASSIGNED: Streptococcus pneumoniae is a common pathogen associated with bloodstream infections, respiratory infections, peritonitis, infective endocarditis, and meningitis. Literature assessing duration of antibiotic therapy for a S pneumoniae bacteremia secondary to common infection is scarce, leading to variability in practice. Therefore, this study evaluated the effectiveness of short (5-10 days) versus long (11-16 days) antibiotic durations for S pneumoniae bacteremia.
UNASSIGNED: This retrospective, single-center cohort study assessed hospitalized patients with S pneumoniae-positive blood cultures, who received active antibiotics within 48 hours of first positive blood culture collection and achieved clinical stability by day 10 of the first positive blood culture collection. Exclusion criteria included treatment duration <5 or >16 days, death before completion of 10 days of therapy, polymicrobial bloodstream infection, and invasive infection. Rates of clinical failure (composite of 30-day hospital readmission, bacteremia recurrence, and mortality) were compared between the groups.
UNASSIGNED: A total of 162 patients were included, with 51 patients in the short- and 111 patients in the long-duration group. Pneumonia was the suspected source of bacteremia in 90.1% of patients. Rates of clinical failure were not significantly different between the 2 groups. Patients received a median antibiotic course of 7 days in the short group compared to 14 days in the long group; however, there was no significant difference observed in the median hospital length of stay, median intensive care unit length of stay, or rate of Clostridioides difficile infection.
UNASSIGNED: Shorter antibiotic courses may be appropriate in patients with S pneumoniae bacteremia secondary to community-acquired pneumonia.

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.

OBJECTIVE: To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens.
METHODS: This retrospective real-world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first-line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib-based induction therapy, followed by an ixazomib-based oral regimen for 2 year or until disease progression or intolerable toxicity.
RESULTS: The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence in situ hybridization (M-FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib-based treatment spanning 6 months. At the 20-month median follow-up, 53% of patients remained on therapy. The 24-month PFS rate was 84.3% from the initiation of bortezomib-based induction and 83.4% from the start of ixazomib-based treatment. Overall response rate (ORR) was 100% post-bortezomib induction and 90% following 6 cycles of the ixazomib-based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib\'s safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia.
CONCLUSIONS: In the real-world Chinese MM population, NDMM and FRMM patients responded favorably to PI-based continuous therapy, demonstrating substantial response rates. The ixazomib-based iCT allows for sustained PI-based treatment, offering promising efficacy and tolerable AEs.

OBJECTIVE: 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.
METHODS: A cut-off value of 100.9 was used to categorize patients into high and low GNRI groups.
RESULTS: 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).
CONCLUSIONS: 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.

The aim was to analyse the costs and duration of orthodontic-surgical treatment with mandibular advancement in the public health care sector in Finland.
The study was conducted as a retrospective registry study in a public district hospital on all nonsyndromic patients that were ethnic Finns and treated with full fixed appliances and mandibular advancement surgery in 2016-2020.
The mean treatment duration of the included 45 patients was 28.1 months, including 18.9 months pre and 9.2 months postoperative orthodontics. The median number of visits was 27, including 17 visits before and 9 visits after surgery. The mean total treatment time was 14.5 h. The mean total direct costs per course of treatment were 7574 € to the municipality and 947 € to the patient. The costs positively correlated with the duration of the treatment (rho = 0.71, P = .000), but were not associated to gender or age of patient. The mean surgery time was 78 minutes, and significantly less with an experienced surgeon (P = .002). It was calculated that the mean minimum treatment costs would be 45% of the present total, achievable with a patient with optimum dental arches at the start of treatment.
The major limitation of the study is the relatively small number of study subjects.
A 55% share of the costs is influenced by case- and operator-dependent factors. This indicates that the complexity and performance of the orthodontic phases of treatment are important determinants in the cost structure.

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 18F-fluorodeoxyglucose (18F-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 18F-FDG PET/CT in IFI diagnostic and therapeutic management.
Multicentre prospective cohort study of IFI with performance of systematic 18F-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 18F-FDG PET/CT will be compared. Additionally, the association of initial quantitative 18F-FDG PET/CT parameters with response to therapy will be evaluated.The primary endpoint is to compare the yield of 18F-FDG PET/CT with standard management without 18F-FDG PET/CT in IFI at initial assessment (staging) and in monitoring the response to treatment.The impact of the results of 18F-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 18F-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.

BACKGROUND: The duration of treatment (DOT) of the initial intervention and subsequent treatment is the key to determining the accuracy of anticancer-drug budget impact analysis (BIA) calculations. However, existing studies only use simple assumptions as a proxy for DOT, resulting in a high degree of bias.
OBJECTIVE: To enhance the accuracy and reliability of anticancer-drug BIA and solve the problem regarding DOT, we propose an alternative individual patient data (IPD)-based approach that reconstructs IPD from the published Kaplan Meier survival curves to estimate DOT.
METHODS: We developed a four-step methodological framework for this new approach, taking the use of pembrolizumab in treating microsatellite-instability-high (MSI-H) advanced colorectal cancer as an example: (1) reconstructing the IPD; (2) calculating the total DOT of the initial intervention and subsequent treatment for each patient; (3) assigning a randomized time and DOT; and (4) multiple replacement sampling and calculation of the mean value.
RESULTS: Using this approach, the average DOT for the initial intervention and subsequent treatment in each year of the BIA time horizon can be calculated and used to calculate the resources consumed and costs in each year. In our example, the average DOT for the initial intervention with pembrolizumab from the first to the fourth year was 4.90, 6.60, 5.24, and 5.06 months, respectively, while the average DOT for subsequent treatment was 0.75, 2.84, 2.99, and 2.50 months, respectively.
CONCLUSIONS: The reconstructed IPD-based approach can improve the accuracy and reliability of anticancer-drug BIA compared with conventional methods, and can be widely used, especially for anticancer drugs with excellent efficacy.

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.

UNASSIGNED: High-dose glucocorticoids are associated with improved recovery of deficits in primary autoimmune hypophysitis (PAH), but optimal dosing, route, and duration are unclear.
UNASSIGNED: We reviewed literature for first-line glucocorticoid treatment in PAH until December 2021 and performed an individual patient data meta-analysis to analyze clinical, hormonal, and radiological outcomes with respect to route, dose, and duration (<6.5 vs 6.5-12 vs >12 weeks) of glucocorticoid treatment according to disease severity.
UNASSIGNED: A total of 153 PAH patients from 83 publications were included. The median age at presentation was 41 (32.5-48) years with a female preponderance (70.3%). Visual field recovery was significantly better with i.v. (91.7%) as compared to oral (54.5%) route and high dose (100%) and very high dose (90.9%) as compared to medium dose (20%) of glucocorticoids. Corticotroph axis recovery was greater in i.v. (54.8% vs 28.1% oral, P = 0.033) route and increasing glucocorticoid dose group (0% vs 38.1% vs 57.1%), attaining statistical significance (P = 0.012) with very high-dose. A longer duration of treatment (>6.5 weeks) was associated with better corticotroph and thyrotroph recovery. The need for rescue therapy was lower with i.v. route (38% vs 17.5%, P = 0.012) and with increasing glucocorticoid doses (53.3% vs 34.3% vs 17.3%, P = 0.016). In severe disease, visual field and corticotroph axis recovery were significantly higher with i.v. route and very high-dose steroids. The adverse effects of glucocorticoids were independent of dose and duration of treatment.
UNASSIGNED: Very high-dose glucocorticoids by i.v. route and cumulative longer duration (>6.5 weeks) lead to better outcomes and could be considered as first-line treatment of severe PAH cases.

Background Different techniques have been used to reduce functional treatment time including low-level laser therapy (LLLT), and the majority of studies have been conducted on animals. Therefore, the aim of the current study was to evaluate the effects of LLLT on improving orthodontic functional treatment using the Twin-Block (TB) appliance. Materials and methods This study was a three-arm, parallel-group randomized controlled trial. Patients were selected using the following inclusion criteria: skeletal Class II Division 1 malocclusion resulting from mandibular retrognathia (angle between the anterior cranial base and the NB plane (i.e., SNB angle): 73°-78°), the sagittal skeletal discrepancy angle (ANB angle) between 4° and 9°, and overjet between 5 and 9 mm. Forty-eight patients were randomly allocated into three equal groups. In the LLLT-TB group, the low-level laser device was used with a wavelength of 808 nm and power of 250 mW in addition to functional treatment with a Twin-Block appliance. The laser was applied on the skin at the bilateral temporomandibular joint (TMJ) regions, at five points, each point received 5 J of the laser for 20 seconds. The laser course was twice a week in the first month, every two weeks in the second month, and every three weeks up to the end of the treatment. The second group (the TB group) received functional treatment with a Twin-Block appliance, while patients in the third group (the untreated control group (UCG)) were observed for nine months without any intervention. Results There were statistically significant differences in treatment periods between the LLLT-TB group and the TB group (129 days and 235 days, respectively, P-value<0.001). The change in the effective mandibular length (Co-Gn) was the highest in the LLLT-TB group compared with the TB and the UCG groups (4.41 mm, 3.66 mm, and 1.07 mm, respectively; P-value<0.001). Conclusions The application of low-level laser therapy on the condylar regions accelerated the functional treatment in skeletal Class II malocclusion patients by approximately 45% and increased the bone growth and mandibular length. The improvement in the SNB angle was similar in both interventional groups. Irradiation of low-level laser stimulated bone growth at the condyles and did not cause anterior movement of the temporomandibular joint following functional orthopedic correction.