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The treatment landscape for relapsing forms of multiple sclerosis (RMS) has expanded considerably over the last 10 years with the approval of multiple new disease-modifying therapies (DMTs), and others in late-stage clinical development. All DMTs for RMS are believed to reduce central nervous system immune-mediated inflammatory processes, which translate into demonstrable improvement in clinical and radiologic outcomes. However, some DMTs are associated with long-lasting effects on the immune system and/or serious adverse events, both of which may complicate the use of subsequent therapies. When customizing a treatment program, a benefit–risk assessment must consider multiple factors, including the efficacy of the DMT to reduce disease activity, the short- and long-term safety and immunologic profiles of each DMT, the criteria used to define switching treatment, and the risk tolerance of each patient. A comprehensive benefit–risk assessment can only be achieved by evaluating the immunologic, safety, and efficacy data for DMTs in the controlled clinical trial environment and the postmarketing clinical practice setting. This review is intended to help neurologists make informed decisions when treating RMS by summarizing the known data for each DMT and raising awareness of the multiple considerations involved in treating people with RMS throughout the entire course of their disease.

Previously treated TB patients still pose a serious threat to global control of TB, yet new re-treatment therapies were little studied. This study aimed to examine the therapeutic effects of new re-treatment regimens, and explore risk factors associated with recurrence after successful treatment. We conducted a cohort study in nine regions of China and enrolled previously treated TB patients from October, 2008 to December, 2010. Patients were randomly divided into four treatment regimen groups including standard, high-dose, long-course, and individualized treatment. After treatment, those with successful treatment outcomes were followed up to 7 years. The effects of different regimens and the information of recurrence were recorded. Risk factors to poor treatment outcomes were calculated using logistic regression model, while risk factors to recurrence or death were calculated using Cox model. Four hundred ninety-two participants were enrolled during the study time and 419 patients were included in our analysis of treatment effects. Overall, the treatment success rate is 75.9%, and the recurrence and death rate is 6.9% and 3.8%, respectively. Reduced risks of poor outcomes were observed in patients who were treated with high-dose and individualized regimen compared with standard regimen, and the adjusted ORs were 0.3 (0.1–0.6), 0.2 (0.1–0.5), respectively. In our analysis of factors associated with recurrence, all documented variables were not significant. Revised re-treatment regimen has better therapeutic effects compared to standard regimen, but it was not associated with lower risk of TB recurrence. Further studies are warranted to evaluate the role of other revised re-treatment regimens in recurrence risk. Trial registration: chictr.org Identifier: ChiCTR1800017441.

Polyadenosine 5'-diphosphoribose polymerase inhibitors (PARP-Is) are novel, effective agents for treating newly diagnosed epithelial ovarian cancer (EOC). However, the effect of PARP-I on the progression of recurrent EOC has not yet been determined. In particular, there is limited evidence regarding retreatment with PARP-I for recurrent EOC that has progressed on PARP-I in the short term. A 69-year-old woman with a BRCA1 mutated EOC relapsed five months after starting olaparib maintenance following neoadjuvant chemotherapy and interval debulking surgery. Although the platinum-free interval was within six months, secondary cytoreductive surgery was performed because the tumor was locoregional. Following two cycles of weekly nedaplatin, niraparib induced a complete response, and the patient maintained a progression-free status for 15 months. Even with short-term progression on PARP-I, local control combined with different platinum agents and PARP-I can be used to achieve good responses.

Background: Despite significant advancements in treatment, patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) continue to face the challenge of drug resistance, highlighting the need to develop new drugs and treatment strategies. Pyrotinib has exhibited notable efficacy in managing HER2-positive MBC, especially in individuals with brain metastasis (BM). However, real-world evidence on the effectiveness of pyrotinib re-treatment remains limited. Objectives: This study aims to assess the efficacy of pyrotinib re-treatment—including treatment beyond progression (TBP) and rechallenge—in patients with HER2-positive MBC, particularly those with BMs, in a real-world clinical setting. Design: A retrospective, multicenter, real-world study. Methods: Patients with HER2-positive MBC who experienced progression during pyrotinib treatment and subsequently continued or resumed pyrotinib-based regimens were enrolled. Patients were divided into two groups according to the re-treatment pattern: the pyrotinib TBP group and the pyrotinib rechallenge group. The endpoints were progression-free survival (PFS) and overall survival (OS). Results: A total of 226 participants received pyrotinib TBP, whereas 33 received pyrotinib rechallenge. The median PFS of pyrotinib re-treatment (7.2 vs 6.3 months, p = 0.31) and the median OS, measured from the start of pyrotinib re-treatment (31.6 vs 21.0 months, p = 0.062), were comparable between the two groups. Among patients with BMs before pyrotinib re-treatment, the median PFS for pyrotinib re-treatment was 7.2 months, and the median OS was 25.2 months. Conclusion: Pyrotinib TBP and pyrotinib rechallenge both demonstrate potential benefits for patients with HER2-positive MBC, including those with BM. Plain Language Summary Reusing pyrotinib after cancer progression may still help patients with HER2-positive breast cancer and brain spread Patients with HER2-positive metastatic breast cancer (MBC), especially those whose cancer has spread to the brain, often face drug resistance after a period of treatment. Pyrotinib is a targeted drug that has shown benefits in treating HER2-positive MBC, but what happens after the cancer progresses on this drug is unclear. In this study, researchers looked at real-world outcomes from 259 patients who continued using pyrotinib even after their cancer had progressed. Some continued the drug immediately (called “treatment beyond progression”), while others paused and then reused it later (called “rechallenge”). The goal was to understand whether these re-treatment strategies still help. Researchers found that both approaches offered meaningful benefits: patients lived a median of 7.2 and 6.3 months without further disease worsening, and had overall survival times of 31.6 and 21.0 months, respectively. These differences were not statistically significant but suggest that continuing or reusing pyrotinib could still help in some cases. Importantly, patients who had brain metastases also benefited, and those who had longer benefit during their first use of pyrotinib were more likely to do well with re-treatment. This study highlights the potential of pyrotinib as a treatment option even after progression, especially in real-world clinical settings. Further research is needed to identify which patients are most likely to benefit.

Background Tuberculosis retreatment is a major challenge in Ethiopia. Notwithstanding its considerable ramifications, there is a paucity of empirical evidence concerning the phenomenon of tuberculosis retreatment in highly populated city, Addis Ababa. Thus, this study aimed to determine the magnitude of tuberculosis retreatment and its determinants among tuberculosis patients receiving care at selected public health institutions in Addis Ababa, Ethiopia. Methods A five-year (from July 2017 to 7th July 2022) retrospective chart review of 876 TB patients’ registers was conducted in 12 public health centers in Addis Ababa. The data were meticulously coded and inputted using Epi-Data version 3.0 and subsequently analyzed using SPSS version 26. A multivariable binary logistic regression model was employed to ascertain the relationship between dependent and independent variables. The results are presented using a combination of narrative descriptions, tabular formats, and graphical representations. Findings The prevalence of tuberculosis retreatment was 20.1% (95% CI: 16.75–23.0). Patients who were male (AOR = 1.68; 95% CI: 1.04–2.71), had a body weight below 50 kg at enrollment (AOR = 5.56; 95% CI: 3.04–10.18) had a significantly higher odds of requiring tuberculosis retreatment. In contrast, individuals aged 15–29 years (AOR = 0.23; 95% CI: 0.15–0.37) and those with a normal body mass index (AOR = 0.12; 95% CI: 0.06–0.26) exhibited a lower odds of developing tuberculosis retreatment. Interpretation Higher retreatment rates among underweight patients and males underscore the importance of integrating nutritional assessment and gender-responsive interventions into TB programs. Conversely, younger age and individuals with a normative body mass index appeared to have reduced odds. Early nutritional and gender-specific strategies within tuberculosis treatment programs can mitigate retreatment and enhance patient outcomes. Clinical trial number Not applicable.

Objectives This retrospective study aimed to evaluate the effect of titration-guided focal selective retina therapy (SRT) for chronic central serous chorioretinopathy (cCSCR) and determine the need and effectiveness of re-treatment. Methods SRT was performed in 60 eyes of 57 patients with cCSCR, targeting focal leakage points (FLP) using a Nd:YLF-Laser at 527 nm (R:GEN®, Lutronic, South Korea) titration-guided at 80% threshold, with 140 ms irradiation time, 100 Hz frequency, 1.7 µs pulse duration, 200 µm spot size. Best documented visual acuity (BDVA), peak height of subretinal fluid (SRF), height of SRF at the fovea, central retinal thickness (cRT) and total macular retinal volume (tRV) were measured. Results A significant improvement in BDVA was observed up to 1 year compared to baseline ( p  < 0.02). A limited analysis due to the small sample size showed no significant difference between the BDVA at baseline and 2-year ( n  = 15) and 3-year ( n  = 10) follow-ups. A significant decrease in the height of the SRF at the highest point and fovea and total retinal volume up to the 3-year follow-up was observed compared to the baseline ( p  < 0.03). Thirty (50%) eyes of 30 patients required re-treatment, on average 9.2 ± 9.6 months after the initial SRT. This study found no predictors for the need of re-treatment. Conclusions The study concludes that SRT is safe and shows anatomical and functional benefits for treating cCSCR. We recommend performing regular check-ups every three months and following a zero-fluid tolerance policy for re-treatment. Trial registration German Clinical Trials Register ID: DRKS00031038, registration date: 2023-01-16

This study sought to evaluate the efficacy of SWEEPS in the removal of epoxy-resin-based and calcium-silicate-containing endodontic sealer combined with single-cone and carrier-based obturation techniques through a micro-CT analysis. Seventy-six single-rooted extracted human teeth with single root canal were instrumented with Reciproc instruments. Specimens were randomly divided into four groups (n = 19) according to the root canal filling material and obturation technique: (1) AH Plus sealer + Reciproc gutta-percha, (2) TotalFill BC sealer + TotalFill BC Points, (3) AH Plus sealer + Guttafusion obturator, and (4) MTA Fillapex + Guttafusion obturator. All specimens were re-treated one week later using Reciproc instruments. Following re-treatment, root canals were additionally irrigated using the Auto SWEEPS modality. The differences in the root canal filling remnants were analyzed by micro-CT scanning of each tooth after root canal obturation, after re-treatment, and after additional SWEEPS treatment. Statistical analysis was performed using an analysis of variance (p < 0.05). The additional treatment with SWEEPS significantly reduced the volume of the root canal filling materials in all experimental groups compared to the removal of root canal filling using only reciprocating instruments (p < 0.05). However, the root canal filling was not removed completely from any of the samples. SWEEPS can be used to enhance the removal of both epoxy-resin-based and calcium-silicate-containing sealers, in combination with single-cone and carrier-based obturation techniques.

Objectives: We analyzed tuberculosis (TB)-related costs according to treatment adherence, as well as the association between treatment adherence, treatment outcomes, and costs related to drug-susceptible TB in South Korea. Methods: Patients who had newly treated TB in South Korea between 2006 and 2015 were selected from nationwide sample claims data and categorized into adherent and non-adherent groups using the proportion of days TB drugs covered. Patients were followed-up from the initiation of TB treatment. The mean five-year cumulative costs per patient were estimated according to adherence. Moreover, we evaluated the relative ratios to identify cost drivers such as adherence, treatment outcomes, and baseline characteristics using generalized linear models. Four treatment outcomes were included: treatment completion, loss to follow-up, death, and the initiation of multidrug-resistant TB treatment. Results: Out of the 3,799 new patients with TB, 2,662 were adherent, and 1,137 were non-adherent. Five years after initiating TB treatment, the mean TB-related costs were USD 2,270 and USD 2,694 in the adherent and non-adherent groups, respectively. The TB-related monthly cost per patient was also lower in the adherent than in the non-adherent (relative ratio = 0.89, 95% CI 0.92–0.98), while patients who were lost to follow-up spent more on TB-related costs (2.52, 2.24–2.83) compared to those who completed the treatment. Conclusion: Non-adherent patients with TB spend more on treatment costs while they have poorer outcomes compared to adherent patients with TB. Improving patient adherence may lead to effective treatment outcomes and reduce the economic burden of TB. Policymakers and providers should consider commitment programs to improve patient’s adherence.