Shorter Treatment Duration Research Articles

Achievement of deep molecular response and treatment-free remission with asciminib treatment in CML.

We evaluated the possibility of treatment-free remission (TFR) and durability of deep molecular response (DMR) with asciminib treatment by monitoring major BCR::ABL mRNA on the International Scale (BCR::ABL-IS) in 4 patients who needed to reduce or discontinue asciminib due to adverse event concerns, intolerance, or personal circumstances. IS increased in all 4 patients after discontinuation of asciminib, but 3 patients who resumed asciminib achieved DMR again. None of the patients achieved TFR with asciminib, but DMR could be achieved again by restarting asciminib after TFR failure. As this was a retrospective study in a small number of patients, no conclusions can be drawn regarding the possibility of TFR with asciminib. However, this study included patients with short treatment duration and DMR maintenance periods, so strict conditioning may be necessary. Safe dose reduction or TFR with asciminib may need to be considered in more cases.

Barriers and facilitators to the implementation of personalised medicine at the micro-, meso- and macro-regional levels

Abstract Background/Introduction Personalised Medicine (PM) involves tailoring treatment to a patient's characteristics, needs and preferences. It classifies patients based on their disease risk or response to treatment using diagnostic markers and aims to improve treatment control, precision and disease prediction. An organised approach is crucial for the integration of PM into European healthcare systems in order to shape the future of health and social care. PM's dynamic evolution, which takes into account individual factors in disease progression and drug efficacy, allows for more accurate and tailored care. Despite its emergence, the economic focus on specific interventions has neglected a comprehensive theoretical framework, potentially hindering the progress of PM in clinical practise. [1] Purpose The purpose of the study was to identify barriers and facilitators to the implementation of innovative interventions and to identify best practises that are applicable across European countries and support the implementation of e-health, m-health and PM interventions at micro-, meso- and macro-regional levels. The research was funded and carried out as part of the international Regions4PerMed (H2020) project. Methods The methodology of the study consisted of a combination of desk research and qualitative research methods. Desk research involved analysing existing articles, with a focus on the literature related to barriers and facilitators in e-health and m-health. Following the desk research, a semi-structured questionnaire entitled "Barriers and facilitators of Personalised Medicine implementation - qualitative study under Regions4PerMed (H2020) project" was developed. In addition, three focus groups were organised to explore the topic of the study in greater depth. Results The findings on potential support for adapting e-health, m-health and PM to citizens' needs were categorised into different areas of need, including education, funding, dissemination, data protection/data sharing, data analysis, system changes, integrated care policies, cooperation, healthcare providers, physicians, public and patient engagement. The barriers and facilitators were categorised according to the primary stakeholders involved in the implementation challenges. Conclusion(s) The implementation of technological solutions improves diagnostic procedures and decision making in health and social care, leading to more precisely tailored treatments, lower costs and shorter treatment durations. PM plays a crucial role in rationalising the diagnosis, prevention and treatment of diseases. The overall aim is to break down barriers between healthcare providers such as public authorities and hospitals in order to promote closer collaboration. However, PM faces challenges, including incongruent legislation, bureaucratic procedures and lengthy legislative processes. Obstacles also include the approach to physician education and the lack of social awareness of PM.

Antimicrobial use practices in canine and feline patients with co-morbidities undergoing dental procedures in primary care practices in the US.

This study aimed to investigate how the presence of co-morbid conditions influenced antimicrobial usage as presumptive prophylaxis for suspected bacteremia in dogs and cats undergoing dental treatments at primary care veterinary clinics in the United States. In 2020, data was collected from 1076 veterinary clinics across 44 US states. A total of 681,541 general anesthesia dental procedures were conducted on 592,472 dogs and 89,069 cats. This revealed that systemic antimicrobials were administered in 8.8% of dog procedures and 7.8% of cat procedures in the absence of concurrent periodontal disease or extractions. Cefpodoxime, clindamycin, and amoxicillin-clavulanate were the most frequently used antimicrobials in dogs, while cefovecin, amoxicillin-clavulanate, and clindamycin topped the list for cats. Dogs with cardiovascular, hepato-renal, and endocrine co-morbidities, as well as those undergoing concurrent removal of cutaneous or subcutaneous neoplasia, displayed higher antimicrobial use. Similarly, cats with endocrine or hepato-renal disease, retroviral infection (i.e., feline leukemia virus (FeLV), feline immunodeficiency virus (FIV)), and concurrent removal of cutaneous or subcutaneous neoplasia exhibited increased antimicrobial use. Dogs with hepato-renal abnormalities had longer treatment durations compared to those without (10.1 vs. 9.6 days). Conversely, cats with concurrent removal of cutaneous or subcutaneous neoplasia had shorter durations of treatment as compared to those that did not have this procedure performed (8.4 vs 9.2 days). The findings of this study underscore the necessity for further research and collaboration within the veterinary community to develop evidence-based guidelines, promoting responsible antimicrobial use, and advancing the field of veterinary dentistry for enhanced patient outcomes.

Targeting mycobacterial efflux system to enhance tuberculosis therapy

The worldwide health epidemic of tuberculosis (TB) persists. It still claims millions of lives each year despite medical breakthroughs. Long-term therapies, drug-resistant TB strains, and co-infections with conditions like HIV necessitate novel approaches. The use of Mycobacterium tuberculosis (Mtb) efflux pumps, which actively expel drugs and decrease their effectiveness, is one such approach. EPIs (Efflux Pump Inhibitors) have the potential to treat tuberculosis. This review offers insights into Mtb's immune evasion mechanisms, including its strong cell wall, granuloma formation, immunological modulation, and dormancy, as well as TB epidemiology, worldwide eradication efforts, and those processes. Dissecting Efflux Pumps highlights their significance in drug resistance, particularly against first-line TB medications. Efflux pumps are notorious for causing antibiotic resistance. EPIs may have benefits such as increased drug efficacy, resistance reversal, shortened treatment durations, less toxicity, improved adherence, and targeting of latent TB. The effectiveness of various EPI classes, including phenylalkylamines, protonophores, phenothiazines, and plant-derived derivatives, against Mtb growth and efflux pumps is evaluated. The creation of effective EPIs, a clearer understanding of efflux pump control, and essential clinical trials for validation remain obstacles.

Prevalence of vitamin D deficiency and the effect of vitamin D3 supplementation on response to anti-tuberculosis therapy in patients with extrapulmonary tuberculosis

BackgroundWe aimed to assess serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations in extrapulmonary tuberculosis (EPTB) patients and to evaluate the effect of vitamin D3 supplementation on their treatment course.MethodsSerum 25(OH)D3concentrations were measured in 47 newly diagnosed EPTB patients and 42 controls. Vitamin D-deficient EPTB patients were randomly assigned to receive 50,000 IU of vitamin D3 (cholecalciferol) orally once a week for 6 weeks (total 300,000 IU), followed by maintenance doses of 1000 IU a day besides anti-TB drugs or the first line anti-TB treatment only. Follow up serum 25(OH)D3 concentrations were measured after 3 months of starting vitamin D3 supplementation. Both groups were evaluated for clinical, laboratory, and radiological outcomes after treatment.ResultsSerum 25(OH)D3 concentrations were significantly lower among TB cases (17.1 ± 5.5 nmol/L) compared to healthy controls (51.8 ± 27.3 nmol/L), and vitamin D deficiency was observed in all EPTB patients (n = 47). Patients in VD3 supplementation group had significantly higher weight gain and serum albumin level at 2 months and end of treatment, higher hemoglobin concentration at the end of treatment, significantly lower CRP and ESR at 2 months and at the end of treatment. In cases with TB pleurisy, a significant higher rate of full resolution of pleural fluid after 6 months of anti-TB treatment and shorter treatment duration were noted compared to the other group.ConclusionsVitamin D deficiency is prevalent in EPTB patients, in whom, vitamin D supplementation is a useful adjunctive therapy to anti-TB drugs and improves treatment course.

Real-world experience of immune checkpoint inhibitors in patients with solid tumours in the Top End of the Northern Territory, Australia from 2016 to 2021: a retrospective observational cohort study.

Use of immune checkpoint inhibitors is growing, but clinical trial data may not apply to Indigenous patients or patients living in remote areas. To provide real-world incidence of immune-related adverse events (irAE) in the Top End of the Northern Territory and compare incidence between demographic subgroups. This retrospective, observational, cohort study collected data from electronic records of patients living in the Top End with solid organ cancer treated with immunotherapy between January 2016 and December 2021. The primary outcome was cumulative incidence of any-grade and severe irAE. Secondary outcomes were overall survival, treatment duration and reason for treatment discontinuation. Two hundred and twenty-six patients received immunotherapy. Forty-eight (21%) lived in a remote or very remote area, and 36 (16%) were Indigenous. Cumulative incidence of any-grade irAE was 54% (122/226 patients); incidence of severe irAE was 26% (59/226 patients). Rates were similar between Indigenous and non-Indigenous patients of any-grade (42% vs 56%, P = 0.11) and severe (11% vs 18%, P = 0.29) irAE. However, Indigenous patients had shorter treatment duration, more frequently discontinued treatment due to patient preference and appeared to have shorter median overall survival than non-Indigenous patients (17.1 vs 30.4 months; hazard ratio (HR) = 1.5, 95% confidence interval (CI) = 0.92-2.66). There was no difference in mortality between remote and urban patients (median overall survival 27.5 vs 30.2 months; HR = 1.1, 95% CI = 0.7-1.7). Rates of irAE in our cohort are comparable to those in the published literature. There was no significant difference in any-grade or severe irAE incidence observed between Indigenous and non-Indigenous patients.

Safety and Efficacy of Directly Acting Antivirals (Sofosbuvir & Daclatasvir) in Treatment of Chronic HCV

Abstract Background The introduction of direct-acting antiviral agents, has revolutionized the treatment for chronic HCV with higher cure rates, shorter duration of treatment and more tolerability have been achieved. Aim of the Work The aim of our study is to estimate the efficacy and safety of DAAs in treatment of chronic HCV in patients co-infected with HIV. Patients and Methods This study of previously untreated HCV infection in patients with HCV and HIV co-infection conducted at Abbasia Fever Hospital, from July 2019 to February 2020. Patients included are chronic HCV infection and were receiving antiretroviral therapy for the HIV with a CD4 T-lymphocyte count of 200 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed during treatment by combination of daclatasvir 90mg and sofosbuvir 400mg+/- ribavirin 800mg daily for 12 weeks. Results In this study, the rate of a sustained virologic response (SVR) at post-treatment week 12 (SVR 12) were high (29/30, 96.67%). The most common adverse events were fatigue (73.33%), headache (46.67%), and there was a high safety profile on using DAAs. No patient discontinued treatment because of adverse events. No serious adverse events or mortality were reported. In this study, AST & ALT were significantly decreased at end of treatment and 12 weeks after treatment, CD4 count was significantly increased. Otherwise there are no significant changes in both hematological and biochemical laboratory results. Conclusion Combination of daclatasvir and sofosbuvir have showed 96.67% sustained virologic response at 12 weeks after treatment (SVR 12) among HIV/HCV co-infected patients, with a very good safety profile. Moreover, the treated patients showed a significant increase in CD4 count. Accordingly, HIV/HCV co-infected patients should be treated with sofosbuvir and daclatesvir containing regimens.

A Nationwide Target Trial Emulation Assessing the Risk of Antidepressant-Induced Mania Among Patients With Bipolar Depression.

Antidepressants are commonly used to treat bipolar depression but may increase the risk of mania. The evidence from randomized controlled trials, however, is limited by short treatment durations, providing little evidence for the long-term risk of antidepressant-induced mania. The authors performed a target trial emulation to compare the risk of mania among individuals with bipolar depression treated or not treated with antidepressants over a 1-year period. The authors emulated a target trial using observational data from nationwide Danish health registers. The study included 979 individuals with bipolar depression recently discharged from a psychiatric ward. Of these, 358 individuals received antidepressant treatment, and 621 did not. The occurrence of mania and bipolar depression over the following year was ascertained, and the intention-to-treat effect of antidepressants was analyzed by using Cox proportional hazards regression with adjustment for baseline covariates to emulate randomized open-label treatment allocation. The fully adjusted analyses revealed no statistically significant associations between treatment with an antidepressant and the risk of mania in the full sample (hazard rate ratio=1.08, 95% CI=0.72-1.61), in the subsample concomitantly treated with a mood-stabilizing agent (hazard rate ratio=1.16, 95% CI=0.63-2.13), and in the subsample not treated with a mood-stabilizing agent (hazard rate ratio=1.16, 95% CI=0.65-2.07). Secondary analyses revealed no statistically significant association between treatment with an antidepressant and bipolar depression recurrence. These findings suggest that the risk of antidepressant-induced mania is negligible and call for further studies to optimize treatment strategies for individuals with bipolar depression.

A 10-year review of isoniazid-resistant TB management in Uzbekistan 2009-2020.

Isoniazid (INH, H) resistance is the most common drug-resistant TB pattern, with treatment success rates lower than those in drug-susceptible TB. The WHO recommends a 6-month regimen of rifampicin (RIF, R), ethambutol (EMB, E), pyrazinamide (PZA, Z), and levofloxacin (Lfx) (6REZLfx) for INH-resistant, RIF-susceptible TB (HRRS-TB). Uzbekistan has a high burden of TB (62/100,000 population) and multidrug-resistant TB (12/100,000 population). We conducted a retrospective, descriptive study of microbiologically confirmed HRRS-TB using routinely collected programmatic data from 2009 to 2020. We included 854 HRRS-TB cases. Treatment success was 80.2% overall. For REZLfx, the treatment success rate was 92.0% over a short treatment duration, with no amplifications to RIF or second-line anti-TB drug resistance. We documented 46 regimens with REZLfx plus linezolid (success 87.0%) and 539 regimens using kanamycin or capreomycin (success 76.6%). We identified 37 treatment failures (4.3%), 30 deaths (3.5%), 25 resistance amplifications (2.9%), including eight to RIF (0.9%), and 99 lost to follow-up (LTFU) cases (11.6%). Unsuccessful outcomes were more common with older age, diabetes, chest X-ray cavities, smear positivity, smear-positive persistence, and male sex. LTFU was more common with injection-containing regimens. REZLfx is a safe and effective first-line treatment for INH-resistant, RIF-susceptible TB. Treatment success was lower and LTFU was higher for injection-containing regimens.

A unifying model to explain frequent SARS-CoV-2 rebound after nirmatrelvir treatment and limited prophylactic efficacy

In a pivotal trial (EPIC-HR), a 5-day course of oral ritonavir-boosted nirmatrelvir, given early during symptomatic SARS-CoV-2 infection (within three days of symptoms onset), decreased hospitalization and death by 89.1% and nasal viral load by 0.87 log relative to placebo in high-risk individuals. Yet, nirmatrelvir/ritonavir failed as post-exposure prophylaxis in a trial, and frequent viral rebound has been observed in subsequent cohorts. We develop a mathematical model capturing viral-immune dynamics and nirmatrelvir pharmacokinetics that recapitulates viral loads from this and another clinical trial (PLATCOV). Our results suggest that nirmatrelvir’s in vivo potency is significantly lower than in vitro assays predict. According to our model, a maximally potent agent would reduce the viral load by approximately 3.5 logs relative to placebo at 5 days. The model identifies that earlier initiation and shorter treatment duration are key predictors of post-treatment rebound. Extension of treatment to 10 days for Omicron variant infection in vaccinated individuals, rather than increasing dose or dosing frequency, is predicted to lower the incidence of viral rebound significantly.

Recurrence and Pain Analysis in the Treatment Outcomes of Acromioclavicular Joint Dislocation Following Hook Plate Removal

Background: The treatment of acute dislocation of the acromioclavicular joint, specifically types III to V, involves various methods, each with its own advantages and disadvantages. Objectives: This study aims to investigate the treatment outcomes of acromioclavicular joint dislocation after hook plate removal, focusing on the recurrence of dislocation and pain in the affected area. Methods: A retrospective statistical study was conducted on 40 patients (18 - 40 years old) who presented with acromioclavicular joint dislocation and received treatment at Golestan and Imam Khomeini (RA) hospitals in Ahvaz between 2013 and 2021. Among the patients, 28 were male and 12 were female, and all were treated using the hook plate method. A follow-up was conducted on all patients after an average duration of one year. Patient data were collected through radiographic analysis and completion of relevant questionnaires to assess the specific objectives of this research. Results: None of the patients treated with the hook plate method required additional surgery due to reduction loss. All patients who underwent re-surgery had their hook plates removed after an average of six months. There were no cases of plate breakage or recurrence after the operation. However, four cases (10% of all patients) reported partial dislocation. The average duration of the hook plate procedure was estimated to be 45 minutes, with an estimated blood loss of 100 cc. Furthermore, complete immobilization after the hook plate procedure lasted between three days and one week. Conclusions: The hook plate method exhibits favorable outcomes, including lower complication rates, reduced postoperative pain, minimal blood loss, shorter treatment duration, and lower surgical costs. Therefore, it is considered a preferred and economically viable treatment option.

Evidence for the use of cannabis-based medicines in osteoarthritis: a scoping review.

The purpose of this study was to conduct a scoping review to describe the evidence on the efficacy and safety of using cannabis-based medicines for osteoarthritis. The review was conducted following the framework proposed by Arksey and O'Malley and reported following PRISMA extension for scoping reviews guidelines. We conducted a comprehensive search across various databases including MEDLINE, Embase, Cochrane Library, CINAHL, Scopus, and Proquest, spanning from inception of each database to March 2023. We retrieved 2533 citations, and after deduplication, title and abstract screening, and full-text screening, 10 articles were included for analysis. These studies were composed of randomized-controlled trials (n = 4/10), cross-sectional surveys (n = 3/10), case studies (n = 2/10), and a cohort study (n = 1/10). Evidence for using cannabis-based medicines was mixed, with just 60% (n = 6/10) of included studies reporting statistically significant improvements in pain. Studies with larger samples sizes and longer durations of exposure did not find significant benefits for pain. The few adverse effects reported were generally mild and affected a minority of participants. Several studies also discovered that cannabis-based medicines were associated with a reduction in opioid use. Currently available data on the use of cannabis-based medicines in osteoarthritis is insufficient to make recommendations. Future research should address concerns regarding small sample sizes and short treatment durations to provide a more robust evidence base. Key Points • Current evidence remains mixed; studies that found a positive benefit with using cannabis-based medicines had limitations with small sample sizes and short durations of exposure • The use of cannabis-based medicines in osteoarthritis appears to be generally well tolerated, adverse effects are mild and experienced by a minority of participants • Cannabis-based medicines may decrease the use of opioids in patients with osteoarthritis • Future research should address the gaps in long-term efficacy and safety data.

The Effects of Longer Use of Teriparatide on Clinical and Radiographic Outcomes after Spinal Fusion in Geriatric Patients.

Background: Teriparatide is an anabolic agent for osteoporosis and is believed to improve the bone healing process. Previous studies showed that teriparatide could enhance not only fracture healing but also spine fusion. It has been reported that use of teriparatide could promote the spine fusion process and decrease mechanical complications. However, there was no consensus regarding optimal treatment duration. The purpose of this study was to compare surgical outcomes between short-duration and long-duration teriparatide treatment after lumbar fusion surgery in elderly patients. Materials and Methods: All consecutive patients older than 60 years who underwent 1-level lumbar fusion surgery for degenerative diseases between January 2015 and December 2019 were retrospectively reviewed. Based on the duration of teriparatide treatment (daily subcutaneous injection of 20 µg teriparatide), patients were subdivided into two groups: a short-duration (SD) group (<6 months) and a long-duration (LD) group (≥6 months). Mechanical complications, such as screw loosening, cage subsidence, and adjacent vertebral fractures, were investigated. Postoperative 1-year union rate was also evaluated on computed tomography. Clinical outcomes were recorded using visual analog scale (VAS) and Oswestry Disability Index (ODI). Between-group differences for these radiographic and clinical outcomes were analyzed. Results: Ninety-one patients were reviewed in this study, including sixty patients in the SD group and thirty-one patients in the LD group. Their mean age was 72.3 ± 6.2 years, and 79 patients were female. Mean T-score was -3.3 ± 0.8. Cage subsidence (6.7% vs. 3.2%), screw loosening (28.3% vs. 35.5%), and adjacent vertebral fracture (6.7% vs. 9.7%) were not significantly different between the SD and LD groups. Union rate at 1-year postoperative was 65.0% in the SD group and 87.1% in the LD group (p = 0.028). Both groups showed improvement in VAS and ODI after surgery. However, the differences of VAS from preoperative to 6 months and 1 year postoperative were significantly higher in the LD group. Conclusions: Longer teriparatide treatment after lumbar fusion surgery resulted in a higher union rate at 1-year postoperative than the shorter treatment. Also, it could be more beneficial for clinical outcomes.

Simultaneous integrated boost on pathologic lymph nodes safely improves clinical outcomes compared to sequential boost in locally advanced cervical cancer: a multicenter retrospective study.

This multicenter study aimed to retrospectively evaluate the impact of high boost simultaneous integrated boost (SIB) to pathologic lymph nodes compared to Sequential boost (Seq) in patients with locally advanced cervical cancer (LACC). 97 patients with pelvic and/or para-aortic (PAo) node-positive LACC treated by definitive chemoradiation were included. Two groups were analyzed: Sequential boost group and simultaneous integrated boost (SIB) group. Endpoints were Distant Recurrence Free Survival (DRFS), Recurrence Free Survival (RFS), Overall Survival (OS), locoregional pelvic and PAo control and toxicities. 3-years DRFS in SIB and Seq groups was 65% and 31% respectively (log-rank p < 0.001). 3-years RFS was 58% and 26% respectively (log-rank p = 0.009). DRFS prognostic factors in multivariable analysis were SIB, PAo involvement and maximum pelvic node diameter ≥ 2cm. Adenocarcinoma histology and absence of brachytherapy tended to be prognostic factors. SIB provided the best pelvic control at first imaging with 97%. There was no significant difference in terms of toxicities between groups. Nodal SIB seems to be unavoidable in the treatment of node-positive LACC. It provides the best DRFS, RFS and pelvic control without additional toxicity, with a shortened treatment duration.

Air Plasma Modification of Graphite-Based Electrode for Improved Performance of Aqueous Redox Flow Batteries

Graphite felt is widely utilized as a porous carbon electrode in aqueous redox flow batteries (RFBs). However, its inherent hydrophobic nature and limited electrochemical activity present challenges. While the correlation between RFB performance and electrode properties has been extensively studied for vanadium chemistry and other inorganic redox active materials, it remains scarce in literature for organic systems. In this study, we employ air plasma treatment, known for its controllability, solvent-free nature, and short treatment duration, to modify commercially available graphite felt for RFB applications. A comprehensive analysis is conducted to establish correlations between plasma treatment, physical properties, electrochemical characteristics, and overall cell performance in aqueous RFBs. Comparative evaluation reveals a significant enhancement, with treated graphite felt exhibiting an 85% increase in capacity at 140 mA cm−2 compared to its pristine counterpart. By intentionally utilizing authentic RFB electrodes and employing state-of-the-art ferrocyanide posolyte, this study underscores the crucial role of the interface, even for rapid (reversible) redox-active materials utilized in AORFBs.

Clinical outcomes after adjuvant anti-PD1 therapy for high-risk resectable melanoma and predictors of response.

e21502 Background: Adjuvant anti-PD1 is the standard of care for high-risk resectable melanoma but many still suffer recurrence. We report a single institution observational study of patients who received adjuvant anti-PD1 with a particular focus on those who recurred. Methods: Through an approved protocol by Huntsman Cancer Institute IRB, patients with resected high-risk melanoma who first received anti-PD1 in the adjuvant setting were consented and followed. Clinical outcomes were assessed per RECIST 1.1, progression free survival (PFS), and overall survival (OS). Results: 186 eligible patients were included, 105 male and 81 females, median age at C1D1 58 (22-93), 12/161/7 at stage II/III/IV and 5 unstageable. Subtypes included 79 (43%) superficial spreading, 50 (27%) nodular, 16 (9%) lentigo/nevoid, 13 (7%) non-acral skin (NOS), 10 (5%) acral, 4 (2%) mucosal, and 14 (7%) others. With median follow up of 708 days (23-9599), 66 (35.5%) had progressive disease (PD), including 33 (50%) early PD and 33 (50%) late PD. Statistically significant predictors of worse outcome included age &gt; 50 (OS p = 0.043), acral subtype (PFS p = 0.023), PD-L1 IHC &lt; = 1% (OS p = 0.052, PFS p = 0.002), duration of treatment &lt; 3 months (OS p = 0.005, PFS p = 1.8E-07), early PD (OS p = 0.003, PFS p = 1.5E-6) and distant recurrence (OS p = 0.002). Trends that were not significant included: male gender (worse OS), BRAF mutation (better PFS), NF1 mutation (better PFS). No correlation between outcomes and TMB, NRAS, TERT mutation, and primary location. In the early/late PD groups, median age was 57/55 (range 28-79 / 25-84), 64/61% male, 1/0, 29/31, 3/2 stage II, III, IV. 17/13 were superficial spreading, 6/10 nodular, 2/5 acral, 2/2 lentigo, 1/0 mucosal and 4/3 other non-acral skin. Primary site was 12/12 head/neck, 9/5 trunk, 4/7 upper limb, 8/9 lower limb. BRAF was 9/11 wildtype, 15/9 mutant and 9/13 unknown. PD-L1 &gt; = 1% by IHC was 4/2. TMB mut/mb &gt; 10 was 6/5. Sites of recurrence included 6/12 local, 7/7 regional LN, 20/14 distal (3/1 in brain) relapses. For unresectable PD (13/13 early/late) response to next line systemic therapy is shown in Table 1. Conclusions: One third of patients developed PD after adjuvant anti-PD1 for high-risk melanoma. PD-L1 negativity and short duration of treatment was associated with worse outcome. Early PD corresponded to more distant metastasis, poorer OS and response to subsequent systemic therapy. Importantly most late PD can still have a favorable response by resuming anti-PD1 therapy. Further molecular study is ongoing to investigate mechanisms of resistance. [Table: see text]

Phase 1 study of BDTX-1535, an oral 4th generation covalent EGFR inhibitor, in patients with recurrent glioblastoma: Preliminary dose escalation results.

2068 Background: Epidermal growth factor receptor ( EGFR) gene is the most frequently altered oncogenic driver in glioblastoma (GBM). In-frame deletion alterations (e.g., EGFRvIII) and missense mutations co-occur in the setting of EGFR gene amplification and are characterized as a hallmark of disease pathogenesis in GBM. BDTX-1535 is an oral, highly potent, brain penetrant, selective, irreversible 4th generation tyrosine kinase inhibitor that targets EGFR alterations in GBM and NSCLC. Preliminary results of the Phase 1 dose escalation study (NCT05256290) of patients with recurrent GBM (rGBM) are presented here. Methods: BDTX-1535-101 is a first-in-human study that enrolled patients with either rGBM harboring EGFR alterations following standard of care or patients with locally advanced or metastatic EGFR mutated NSCLC that progressed on prior EGFR TKIs. Using an adaptive Bayesian optimal interval design in the Phase 1 part, patients were enrolled at increasing dose cohorts and were treated daily for 21-day cycles until treatment discontinuation. The primary objective was to determine the BDTX-1535 recommended Phase 2 dose based on the overall safety, PK, pharmacodynamics, and preliminary antitumor activity. Results: Twenty-seven patients with rGBM were enrolled in the Phase 1 cohort that consisted of 54 patients in total including 27 patients with NSCLC. Patients were treated across seven dose levels (15mg – 400mg QD). The mean age of patients with rGBM was 58.7 years (range 41-85) with 96% of patients with previous temozolomide (TMZ) treatment and a median of 2 lines of prior therapy (range 1-4). The most common all-grade treatment-related AEs across all cohorts were rash (78%), diarrhea (41%), fatigue (15%), stomatitis (11%), decreased appetite (11%), nausea (11%) and paronychia (11%). Gr 3 TRAEs ≥ 10% included rash (19%) reported at 300 or 400 mg QD doses. Plasma exposure of BDTX-1535 increased dose proportionally and had a half-life of ~15h, supporting once daily dosing. The maximum tolerated dose (MTD) is 300 mg QD. Among 19 evaluable patients for response based on RANO criteria, 1 confirmed partial response was observed and 8 patients achieved stable disease. Five patients remained on BDTX-1535 with stable disease for an extended period (&gt;5 months) who previously performed poorly on TMZ with short treatment duration, and 1 patient continues on BDTX-1535 after 16 months of treatment. Conclusions: BDTX-1535 was well-tolerated up to 300mg daily, which is the MTD, and promising preliminary clinical activity was observed in patients with rGBM after relapse on standard of care treatment. Given the inability to reconfirm EGFR status at the time of treatment with BDTX-1535 in this Phase 1 trial, further exploration of BDTX-1535 in a “window of opportunity” study is ongoing (NCT06072586). Clinical trial information: NCT05256290 .

Evaluating a Reduction in Treatment Duration of Ivermectin Diet for Fur Mite (Radfordia affinis) Eradication in Mice.

Murine fur mites are commonly excluded in modern research animal programs, yet infestations continue to persist due to challenges in detection and control. Because all diagnostic methods and treatment options have limitations, programs must make many operational decisions when trying to eradicate these ectoparasites. The primary aim of this study was to assess various durations of treatment time with an ivermectin-compounded diet in eliminating Radfordia affinis in mice as determined by PCR testing and pelt examination. A shorter treatment duration would be highly advantageous as compared with the current regimen of 8 wk as it would minimize cost and time for animal management programs, impediments to research, and ivermectin drug effects on infested animals. Five experimental groups of R. affinis -positive mice received dietary ivermectin for 0, 2, 4, 6, or 8 wk. A fur mite-negative, naïve mouse was added to each group every 8 wk to perpetuate the infestation and amplify any remaining populations of fur mites. At 16 wk after the respective treatment end, PCR testing was performed for all treated groups in conjunction with the positive control group (no treatment). Visual examination of pelts for mites and eggs via direct microscopy was also performed at each time point. All treated mice were free of R. affinis at 16 wk after the end of treatment as confirmed by both PCR testing and pelt examination. These findings indicate that a dietary ivermectin treatment duration of as little as 2 wk is effective in eliminating R. affinis, making successful eradication initiatives more achievable.

Shortening treatment duration for uncomplicated community acquired pneumonia to align with best practice guidelines in a large academic paediatric emergency department

Recommendations for antibiotic therapy for community acquired pneumonia recently changed from 10-day to 5-day duration. This quality improvement project aimed to change the practice of providers in an urban, free-standing children's hospital paediatric emergency department in the United States to match the updated recommendations. Improvement interventions included educational outreach, data sharing, on-site reminders, and audit-and-feedback. The project included analysis of ED return visits to monitor possible treatment failure. Interventions successfully increased 5-day antibiotic prescription rate from 3% to 85% within 12 months.

Combination treatment of WHO standard drugs and Artemisia Afra for pulmonary tuberculosis - a Pilot study of 25 multi resistant patients

Introduction: Tuberculosis is one of the leading infectious causes of death worldwide. The WHO estimates that 1.7 billion people close to one quarter of the humanity are infected with Mycobacterium Tuberculosis the bacteria that causes TB. Last year, 10.6 million fell ill from TB and 1.6 million died.1 Moreover, multi resistance to the current anti-tuberculosis drugs is growing thus causing a serious challenge in controlling the spread of the disease worldwide. Fortunately, as we demonstrated on previous studies that Artemisia Afra infusions given with the WHO approved drugs can shorten treatment duration and resistance from 9 months to 52 days maximum2 and out of the 102 patients 95 were cured in 30 days and 7 in 52 days. Most recently we also demonstrated that 25 patients of regular tuberculosis completely recovered after 30 days or less by combining Artemisia Afra infusions whereby the other 25 patients who took the WHO treatment ALONE either abandoned their treatment and if they continued it, they were still sick on day 30.3 The objective of this pilot study is to demonstrate that 25 patients with multi resistant tuberculosis when given Artemisia Afra infusions combined with second line anti tb drugs were able to recover in 35 days maximum instead of 90 days or more. Methods: This case study involved 25 patients who were all multi resistant or recidivist to the tuberculosis and have failed the first line treatment. Moreover, they were confirmed by a GeneXpert test to be resistant to Rifampicin and or Isoniazid. All patients were hospitalized at Ijenda Hospital in Bujumbura rural Province, Burundi between February, and April 2024. They were given the second line treatment at the regular dose + Artemisia Afra infusion at 330 ml three times a day. The patients were also fed with a protein rich meal and nurses made sure that medications were taken regularly according to DOT [Directly Observed Technique]. Results: All the 25 patients recovered in 35 days maximum (see details in the Tables below). Conclusion: The combination therapy [Artemisia Afra infusions+ WHO protocol] has a lot of potential in curing tuberculosis but more studies on a larger cohort [300 patients] will be carried out and there will also be a third leg with multi resistant cases that failed first line treatment with many months of sickness.