Treatment Dose Research Articles (Page 1)

Background: The impact of atogepant, an oral calcitonin gene-related peptide receptor antagonist used for migraine prevention, was evaluated on participants reporting best possible quality of life (QoL) based on Migraine-Specific Quality of Life Questionnaire among responders and non-responders to Patient Global Impression of Change (PGIC). Methods: ADVANCE, ELEVATE, and PROGRESS were phase 3, multicenter, randomised, double-blind, placebo-controlled, 12-week trials that included adults with episodic migraine (EM), EM with prior inadequate responses to 2-4 oral preventive treatments, and chronic migraine (CM), respectively. This post hoc analysis evaluated the proportion of participants who achieved a score of 100 for all 3 MSQv2.1 domain scores at Week 12 based on their PGIC response (responders and non-responders). PGIC is a 7-point single question scale measuring participants impression of change in migraine symptoms since first dose of treatment. MSQv2.1 is a 3-domain questionnaire composed of 14 items designed to assess how migraine limits social and work activities, prevents social and work activities, and emotions associated with migraine. A score of 100 indicates the best possible QoL, with less disruption from migraine. Results: In PGIC responders, a higher proportion of EM participants treated with atogepant 60mg once daily achieved MSQv2.1 scores of 100 in all 3 domains compared with placebo [ADVANCE(P≤.05); ELEVATE(P≤.001)], and numerically higher proportion in CM atogepant-treated participants [PROGRESS(P≥.05)]. Conclusion: A greater proportion of atogepant-treated EM and CM participants who are PGIC responders reported best possible QoL with lower disruption from migraine, compared with placebo. Note: This individual (Martina Martini) has been added to this publication author by-line, with the permission of the original authors, for the express purpose of conducting the presentation at a local congress or in a local language. She did not contribute to the content of the publication.

Linezolid serum concentrations in critically ill patients show high variability. In this retrospective study, we analysed the linezolid plasma through levels (Cmin) in patients on intensive care units (ICUs) under extracorporeal membrane oxygenation (ECMO) support. The aim was to evaluate if patients' clinical or demographic characteristics influence drug concentrations and if these are within the therapeutic range. In total, 156 linezolid trough plasma concentrations from 52 ICU ECMO patients were analysed. Linezolid trough levels were correlated with the following clinical and demographic characteristics: Age, sex, body mass index (BMI), dosage per day, creatinine clearance (CrCl), and requirement for renal replacement therapy (RRT). Drug concentrations were quantified by liquid chromatography with tandem mass spectrometry. The European Committee on Antimicrobial Susceptibility Testing susceptibility breakpoints of 4mg/L of linezolid for staphylococci and enterococci and of 2mg/L for streptococci and other Gram-positive rods were used as minimum target concentration. Patients were treated with standard linezolid dosage (2 × 600mg iv per day; n = 88 Cmin, 56.4%) or by adjusted dosing regimens (n = 68 Cmin, 43.6%). The total amount of the drug ranged from 600 to 2400mg per day (median 1200, IQR 1200-1800mg). The mean of all trough levels measured among the cohort was 2.32mg/L (median 1.55mg/L, IQR 0.61-3.07). In total, 84.0% of all measurements were below the 4mg/L breakpoint (62.2% below the 2mg/L breakpoint), with 90.4% (78.8%) of patients showing inadequate levels in at least one measurement and 63.5% (36.5%) of patients below the threshold in every measurement. This result was irrespective of a standard or an adjusted dosing regimen. Female sex (p = 0.022), RRT (p = 0.047), increased CrCl (p = 0.012), and BMI (p = 0.023) were significantly correlated with lower Cmin levels. Patients' individual linezolid trough levels and outcomes did not display conclusive patterns, irrespective of dosing or duration of treatment. Both standard and increased dosing regimens of linezolid showed potentially inadequate linezolid plasma levels in the large majority of critically ill ECMO patients of our study. Future TDM studies with optimized dosing and application regimens in ECMO patients are warranted.

Background: Eptinezumab is a monoclonal antibody (mAb) targeting the CGRP recently approved for migraine prevention. This study aimed to assess the rates of responders and super-responders to eptinezumab, and to identify clinical predictors of treatment response and dose escalation over a 9-month period. Methods: Fifty-eight adult patients with migraine, attending the Headache Clinic at San Raffaele Hospital (Milan), were enrolled. Demographic data and clinical parameters, including monthly headache (MHD) and migraine (MMD) days, acute medication use in terms of pills (AMP) and days (AMD), headache intensity (NRS), disability (MIDAS), impact (HIT-6), and allodynia symptoms (ASC-12) scores, were recorded at baseline and after 3 (M3), 6 (M6), and 9 (M9) months of treatment. Adverse events were assessed at all time-points. Responders and super-responders were defined by a ≥50% or ≥75% reduction in MMD from baseline, respectively. All patients initially received 100 mg of intravenous eptinezumab; for those with a suboptimal response based on the clinician’s judgment, the dose was escalated to 300 at M3 or M6. Results: The cohort was predominantly female (92%), with a median age of 50 years (IQR 36–56). Chronic migraine was present in 76% of patients. Participants had failed a median of five prior preventives (IQR 3–6) and 47% had prior anti-CGRP mAb exposure. The median MHD e MMD values at baseline were 20 and 16 respectively. At M3, responders were 40%, including 21% super-responders. At M6 responders were 23%, including 5% super-responders. At M9 responders were 46%, including 17% super-responders. A significant predictor of non-response to treatment at M3 was prior therapy with mAb (p = 0.0137). Patients who increased the eptinezumab dosage to 300mg were 72% at M3 and 87% at M6. Factors associated with dose escalation included higher MHD and MMD at baseline (p<0.05), and a prior failure to anti-CGRP mAb (p < 0.04). Only two patients reported mild adverse events. Conclusion: Eptinezumab is effective and well-tolerated in patients with high-frequency and treatment-refractory migraine. Prior anti-CGRP mAb failure and higher baseline migraine burden predict the need for early dose escalation. Initiating therapy at 300 mg may be advantageous in selected difficult-to-treat cases.

Helminthic therapy, as an emerging strategy for Diabetes Mellitus (DM), demonstrates significant clinical benefits by modulating host immune and metabolic systems. Studies have shown that this approach effectively enhances insulin sensitivity, reduces chronic inflammation, and restores metabolic homeostasis through the regulation of gut microbiota. However, certain diabetic patients undergoing helminthic therapy may encounter risks such as infections or metabolic disturbances, necessitating the development of safer and more precise therapeutic methods. This review, conducted following the PRISMA guidelines, systematically retrieved and analyzed 163 high-quality studies from PubMed, Web of Science, and Scopus databases. It comprehensively evaluates the mechanisms, clinical outcomes, and safety improvement strategies associated with helminthic therapy. To ensure the safe application of this treatment, we propose strategies including genetic editing, real-time monitoring, targeted therapeutics, and helminth-derived molecules, along with a detailed clinical decision-making framework. This framework encompasses the matching of host health status with helminth species selection, guidance on dose optimization and treatment duration, and the application of modern intelligent technologies for real-time monitoring of therapeutic processes and potential adverse effects. Helminthic therapy has demonstrated success in alleviating hyperglycemia, chronic inflammation, and insulin resistance in diabetic patients, offering substantial health benefits through its immunomodulatory and metabolic regulatory effects. These findings suggest that helminthic therapy holds the potential to become a revolutionary approach in the field of DM.

Evidence and clinical guidelines on methylphenidate dosing in different weight status groups are limited. This study aimed to evaluate real-world methylphenidate dosing practices and treatment discontinuation rates in children and adolescents in relation to weight status. We used data from the BMI Epidemiology Study Gothenburg cohort, which includes weight and height measurements linked to national registers. Exposures included body weight, standardised body mass index (zBMI), and body mass index (BMI) status. The main outcome was the dose and weight-adjusted dose of methylphenidate for the baseline and follow-up prescriptions. We used a logistic regression model to evaluate treatment discontinuation in relation to weight status, sex, and age. The study included 1741 children and adolescents who initiated methylphenidate treatment and had BMI available. Among them, 612 had a follow-up prescription with BMI available. Children and adolescents with overweight and obesity received slightly higher absolute doses of methylphenidate at baseline prescriptions, but lower weight-adjusted doses. Children and adolescents with underweight received higher weight-adjusted doses. Absolute dose increases between treatment initiation and follow-up were highest in children and adolescents with obesity and lowest in children and adolescents with underweight. Girls received higher absolute and weight-adjusted doses than boys at follow-up, while children over 12 years of age received higher absolute but lower weight-adjusted doses than children under 12 years. A significantly higher proportion of children and adolescents with baseline underweight discontinued treatment during the first year, compared with the normal weight group. Beside lower baseline zBMI, female sex and higher age were also significantly associated with treatment discontinuation during the first year. Our findings suggest that weight status, sex, and age are significantly associated with differential methylphenidate dosing and treatment discontinuation in children and adolescents.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), affects approximately 4.9 million individuals globally. Advanced therapies have significantly improved IBD management; however, maintenance doses commonly exceed labeled recommendations for optimal efficacy. This study aimed to estimate the financial impact of introducing Risankizumab (RISA) for CD and Upadacitinib (UPA) for UC treatment in Saudi Arabia (KSA), incorporating adjusted dosing practices rather than label doses alone. Cost-calculation model (CCM) was developed to estimate average monthly costs per patient, capturing complexities like induction, maintenance adjustments, discontinuation, switching, re-induction, and death. Data on adjusted dosing were collected via two expert interviews. The CCM compared scenarios "with" and "without" UPA for UC, and "with" and "without" RISA for CD, analyzing financial impacts over a 5-year horizon, from the payer's perspective. Adjusted UC treatment doses increased five-year costs by 22% compared to label doses. Introducing UPA with adjusted dosing resulted in a 6.7% higher cost versus scenarios without UPA, based on tender prices. For CD, adjusted dosing increased treatment costs by 24.5% compared to label doses. However, adding RISA with adjusted dosing slightly reduced the total drug cost by 0.35%. Expert interviews and detailed patient pathway modeling indicated substantial cost increases for UC and CD treatments in KSA when adjusted doses were considered. The introduction of UPA and RISA under adjusted dosing yielded minor financial differences, with potential implications for economic evaluations in other regions.

The diagnosis and treatment of schistosomiasis among migrants in nonendemic countries are still challenging. An online questionnaire was sent to adult and pediatric infectious disease specialists through the French infectious disease societies' mailing lists to assess attitudes and practices toward the disease. We included all individuals who responded to the online questionnaire but excluded from analysis residents and doctors with dual practices (adults and children) from the analysis. The questionnaire consisted of 19 questions about professional status, screening practices, diagnostic methods, treatment protocols, and follow-up. The response rate was 10.5% (n = 102/970); four respondents were excluded, including two medical residents and two respondents with dual practices. Adult and pediatric infectious disease specialists participated in the study. Serology was the most frequently used diagnostic method among asymptomatic patients. The preferred imaging examination was ultrasound, especially among pediatricians. Praziquantel treatment dose schemes were heterogeneous; 55 of 98 respondents prescribed more than one dose. Serology was still used by 23% (n = 23/98) of the respondents as a follow-up tool despite its irrelevance. The management of chronic schistosomiasis in nonendemic countries is heterogeneous even among infectious disease specialists. New guidelines need to consider the diversity of nosological frameworks.

Treating older patients with cutaneous neoplasms (CN) can be challenging as oncological resection and definitive external beam radiotherapy (EBRT) can both have limitations in terms of their therapeutic ratio at critical anatomical sites. Here, we present the cohort study results of high-dose-rate (HDR) mould-based brachytherapy (MbBT) for CN focusing on oncological outcomes and patient-reported outcome measures (PROMs), using custom or three-dimensional-printed moulds. Between January 2019 and March 2024, 64 patients underwent MbBT. All patients were either deemed unsuitable for radical resection or definitive EBRT or refused them. Patients were prospectively enrolled in a database and underwent clinical evaluation at the end of treatment as well as after 30 and 90days to assess acute and late toxicity. In addition, oncological follow-up and documentation of their quality of life and subjective cosmetic assessment was performed every 6months thereafter. The median age was 80years. Histology revealed 19 squamous cell carcinomas, 27 basal cell carcinomas, 2 lesions with both histologies, 9 melanocytic tumours and 7 lesions of other histologies. The median treatment dose was 39Gy (range 30-45Gy) at 3Gy per fraction (range 3-4Gy), administered once daily at 5 days per week. After a median follow-up of 679days (interquartile range 361-1049days), there were seven local recurrences (11%). Thirty-sevenpatients (58%) rated the cosmetic result as at least good, 23 (36%) rated the treatment as more tolerable than expected, while 16 (25%) rated it as at least bothersome. Apart from one grade 4 cataract, no other grade 4 late toxicity was documented. High-dose-rate MbBT for CN is an effective and well-tolerated treatment option for older and frail patients who are not eligible for radical surgery or definitive EBRT.

Background: Children whose cancer is treated with anthracycline chemotherapy and/or chest directed radiation (RT) are at risk for premature cardiovascular disease including cardiomyopathy. Echocardiography screening is recommended every 2 to 5 years, depending on the cumulative dose of cardiotoxic treatment and modalities received. We previously developed and validated an AI model using ECG as a sole input (ECG-AI) that can predict 5-year risk for cardiomyopathy with moderate accuracy. Goal: The goal of this study was to compare ECG-AI accuracy to a baseline clinical model and assess whether incorporation of clinical variables increase accuracy. Methods: The original ECG-AI model (Model 1) was an attention-based encoder-decoder deep neural network using 10 second 12-lead ECGs as an input to predict 5-year cardiomyopathy risk. It was trained and validated on 80% of data from the St Jude Lifetime Cohort Study (SJLIFE) then it was tested internally on 20% holdout of SJLIFE and externally on the Dutch Childhood Cancer Survivor Study (DCCSS-LATER) cohort. Both SJLIFE and DCCSS are prospective cohorts of five-year survivors of childhood cancer. Most participants had exposure to prior cardiotoxic treatments such as anthracycline chemotherapy and/or chest RT. We built two additional models on the 20% SJLIFE holdout data of the previous study and validated models in DCCSS-LATER including clinical variables available in both cohorts. Model 2 used stepwise logistic regression including variables listed in Table 1. Model 3 used stepwise logistic regression incorporating the ECG-AI (Model 1) outcomes and the clinical variables in Table 1. Results: SJLIFE holdout data included 1,515 ECGs from 959 participants and DCCSS-LATER included 667 ECGs from 330 participants (Table 1). Results obtained from the models are reported in Table 2. Model 1 (ECG-AI) outperforms Model 2 (clinical model) in SJLIFE derivation cohort while Model 2 is failing to generalize to DCCSS-LATER cohort. Combining ECG-AI results with other clinical data result only in a marginal increase in accuracy. Conclusions: ECG-AI provides generalizable cardiomyopathy risk prediction relying solely on electrocardiogram as an input while additional clinical data resulted in marginal increase in accuracy. Future studies are needed to incorporate more comprehensive clinical and genetic risk factors to obtain higher accuracy.

Liraglutide, an analog of glucagon-like peptide-1, is prescribed for managing weight in obese people. This meta-analysis investigated whether liraglutide was suitable for younger children with obesity, and to evaluate the efficacy and safety of varying treatment durations and dosage regimens. Randomized controlled trials published up to March 20, 2025 were retrieved from in PubMed, Embase, Scopus, Cochrane library, Web of Science, and Google Scholar. Seven trials involving 575 patients were included in the analysis. Liraglutide significantly decreased body mass index (BMI) (WMD: -0.57; P = 0.007), BMI z-score (WMD: -0.45; P < 0.00001), body weight (WMD: -0.31; P = 0.0004), HbA1c (WMD: -0.43; P = 0.004), fasting plasma glucose (WMD: -1.23; P = 0.003) and systolic blood pressure (WMD: -0.20; P = 0.03) compared with placebos in obese children and adolescents. Subgroup analyses found that children 6-12 years of age did not have a significantly different BMI z-score (z = 1.76; P = 0.08) and body weight (z = 1.75; P = 0.08) versus adolescents. Fifty-six weeks of liraglutide treatment (z = 4.60; P < 0.00001) significantly reduced the BMI z-score versus the short-term treatment group (<13 weeks) (z = 1.20; P = 0.23). Liraglutide was an effective and safe option for managing overweight and obesity in children and adolescents. Liraglutide was more suitable for adolescents and is endorsed for long-term use. This is the first meta-analysis to explore the suitability of liraglutide for younger children with obesity and to evaluate its efficacy and safety across varying treatment durations and dosage regimens. Earlier meta-analyses did not include children under 12 years, and neither dosage nor treatment duration was specifically addressed. Our result shows liraglutide is an effective and safe option for managing overweight and obesity in children and adolescents aged 6 to 18 years. Liraglutide was more suitable for adolescents and is endorsed for long-term use.

Radiotherapy-free pembrolizumab combined with chemotherapy for locally advanced non-small-cell lung cancer with PD-L1 tumour proportion score of 50% or higher (Evolution trial): a multicentre, single-arm, phase 2 study.

Dual regulation of FZD1/7 by IGF2BP3 enhances stem-like properties and carboplatin resistance in triple-negative breast cancer.

Mood stabilizers: Insights from users' perceptions.

Abstract Introduction Idiopathic inflammatory myopathies (IIMs) are a heterogeneous disease group characterised by a subacute course of muscle weakness and inflammatory muscle changes that are presumed to be caused by autoimmune mechanisms. Immune-mediated necrotising myopathy (IMNM) is a distinct subgroup of inflammatory myopathy characterised by myofibre necrosis with minimal inflammatory infiltrates on muscle biopsy, highly elevated creatine kinase levels, and infrequent extra-muscular involvement. We will discuss a case of a 36-year-old lady presenting with nonspecific joint pains with mildly raised CK and anti-CCP positivity without clinical evidence of inflammatory arthritis eventually re-presenting two years later with significant muscle weakness. Case description A 36-year-old morbidly obese female patient initially presented with an episode of self-limited inflammatory arthralgia. There were no features of inflammatory arthritis despite significantly positive anti-CCP antibodies and rheumatoid factor. CRP was elevated at 14 mg/L. LFTs were noted to be deranged with ALT of 100 u/l and AST of 95 u/l. Creatine kinase (CK) was mildly raised at 279. She re-presented two years later with worsening mobility resulting in a fall and a hip dislocation. On examination, there was significant weakness particularly in the lower limbs with leg hip extensors and flexors having significantly reduced power at 2/5 with diminished reflexes in lower limbs. CRP was raised at 60 mg/l and CK was found to be 14000u/l. EMG showed myopathic changes; however, it was a difficult study due to high BMI. There were no extra muscular manifestations. Inflammatory myopathy was suspected and high dose steroids were commenced with DMARD therapy (methotrexate). Extended myositis panel showed anti-SRP positivity with the muscle biopsy identifying necrotising myopathy. Her immunosuppression was therefore augmented with the addition of rituximab. There was slow clinical and biochemical improvement after two doses of rituximab treatment. After initial response, CK remained elevated at 885u/l with clinical improvement having plateaued and the patient still having difficulty standing from a lying position and performing simple daily tasks. Therefore, through collaboration between the neurology and rheumatology team, treatment was augmented by addition of monthly IVIG which resulted in significant improvement in muscle function and CK levels improving to 265u/l. She was also reviewed and managed by the rehabilitation team of physiotherapists and occupational therapist throughout her treatment. The patient has recently expressed her strong wish to pursue pregnancy in the near future which currently poses a therapeutic dilemma around adjustment of immunosuppression to support her, having only just achieved disease remission on combination of immunomodulatory therapies. Discussion IMNM can be classified based on the proposed European Neuromuscular Centre (ENMC) criteria. It can also be characterised by myositis-associated antibodies which guides treatment. Preserving and maximising functional status is the major aim and desirable outcome of treatment. Corticosteroids are the first line of management for quick response. Steroid sparing agents are recommended; however, there are no specific clinical trials to support a specific agent of choice. For anti-SRP disease, rituximab instead or in addition to methotrexate is recommended. Early rituximab is often favoured in anti-SRP disease, as per the ENMC guidelines. Despite early introduction of combination of rituximab and methotrexate, together with corticosteroid, our patient demonstrated active disease both clinically and biochemically, with further improvement following addition of monthly courses of IVIG therapy. Having recently achieved disease stability, the patient is keen to pursue her first pregnancy, which poses several therapeutic dilemmas. Given the severity of her disorder, which requires combined immunosuppression, we need to carefully consider a suitable switch in her treatment which would be safe in pregnancy without jeopardising her prognosis. Other medications used in IMNM include azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine, and cyclophosphamide, though evidence on individual agent efficacy remains limited. Azathioprine is an attractive replacement for methotrexate and IVIG are considered safe in pregnancy. However, we need to ensure disease stability for several months after changing immunosuppression. There are few data available on outcomes of pregnancy in patients with idiopathic inflammatory myopathies (IIM) and the influence of pregnancy on the activity of inflammatory muscle disease. Key learning points 1. Anti-SRP-associated IMNM is associated with significant muscle weakness and disability. 2. Young age of onset is a poor prognosticating factor. 3. Subtle biochemical changes (mildly raised CK and deranged liver function tests) can be picked up earlier in the disease course prior to clinical presentation of actual muscle weakness as in this case. 4. There are no clinical trials to guide management, and treatment is largely based on ENMC guidelines along with expert opinion and clinical observations. 5. An MDT approach is paramount in long-term management. 6. There are very limited data available on outcomes of pregnancy in patients with IIM and the influence of pregnancy on the activity of inflammatory muscle disease.

This study aimed to evaluate the accuracy of the 6-month evaluation to accept treatment failure after a single dose of radioactive iodine (RAI) for Graves' disease and to decide whether to repeat the dose. This study retrospectively analyzed 104 patients who received a single dose of RAI between 2003 and 2022, had regular follow-up for at least 2 years, and did not have extrathyroidal symptoms. The study group was divided into two groups: patients who developed hypothyroidism within the first 6 months and patients who developed hypothyroidism after 6 months, and statistically analyzed. The mean administered dose of RAI was 10.6 ± 4.4 mCi, and the average duration of hypothyroidism was 5.5 ± 5.4 months. In patients with late-onset hypothyroidism (>6 months), the 2-h iodine uptake values were significantly higher, and post-RAI thyroid-stimulating hormone levels were significantly lower. While 58.5% of patients with early-onset hypothyroidism (<6 months) required antithyroid drug (ATD) therapy after RAI, all patients who developed hypothyroidism after 6 months received supportive ATD treatment. The 24-h iodine uptake values were significantly higher in the hypothyroid group compared with the euthyroid group. During follow-up, 26.9% of patients were hypothyroid at 0-3 months, 62.5% at 3-6 months, and 77.9% at 12 months. While 20.2% of patients remained hyperthyroid at 6 months, this rate declined to 3.8% at 12 months. This study suggests that the 6 th month following RAI treatment in patients with Graves' disease may not be sufficient to assess treatment response, as hypothyroidism tends to develop cumulatively over time. Iodine uptake values at 2 and 24 h may serve as useful indicators for predicting the development of early or late hypothyroidism, while also helping to guide the maintenance of a euthyroid state.

Patient-reported outcomes with belantamab mafodotin, pomalidomide, and dexamethasone versus bortezomib, pomalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-8): a phase 3, open-label, randomised controlled trial.

Neuropeptide S system mediates nicotine-induced reward-facilitatory behavior.

Compensated biological effective dose in extended radiotherapy course via a time-modified linear quadratic model for biological adaptive radiotherapy.

TeleHealth Resistance exercise Intervention to preserve dose intensity and Vitality in Elder Breast Cancer Patients (THRIVE 65).

Pathophysiological mechanisms underlying diarrhea across generations of EGFR-TKIs: The role of ERBB signaling and potential therapies.