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1. Less frequent dosing of GLP ‐1 receptor agonists as a viable weight maintenance strategy

   https://doi.org/10.1002/oby.24302  

   Wu, Calvin C; Cengiz, Anıl; Lawley, Sean D (July 2025, Obesity)

   Abstract ObjectiveIncretin mimetics are revolutionizing obesity treatment, but high prices and supply shortages limit patient access. Some clinicians have suggested less frequent dosing as an off‐ramping strategy to maintain weight loss, but this approach lacks published evidence regarding its weight loss efficacy. We aim to provide such clinical evidence and to rationalize these results with mathematical modeling. MethodsWe present a real‐world case series of two patients who took their incretin mimetic less frequently than recommended. We complement this case report with a pharmacokinetic‐pharmacodynamic model of virtual patients that simulates long‐term weight change with semaglutide and tirzepatide administered at various frequencies. ResultsBoth real‐world and virtual patients maintained significant weight loss under reduced dosing frequencies. Our results indicate that reducing frequency does not commensurately reduce efficacy. The majority of weight loss persists even when patients wait 2, 3, or perhaps even 4 weeks between doses. ConclusionsOur findings support the hypothesis that less frequent administration of incretin mimetics can be a viable and cost‐saving long‐term weight maintenance strategy in conjunction with sustained lifestyle modification. Further research is warranted to validate the effectiveness of this off‐label approach, define optimal dosing regimens to meet individual patient needs, and evaluate the cost–benefit implications. 

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2. Alternative dosing regimens of GLP ‐1 receptor agonists may reduce costs and maintain weight loss efficacy

   https://doi.org/10.1111/dom.16229  

   Cengiz, Anıl; Wu, Calvin C; Lawley, Sean D (April 2025, Diabetes, Obesity and Metabolism)

   Abstract AimsTo discover alternative dosing regimens of incretin mimetics that simultaneously reduce costs and maintain weight loss efficacy. As a secondary objective, we used our results to explore how allocating a limited incretin mimetics budget could affect public health on a national scale. Materials and MethodsWe used mathematical modelling and simulation of semaglutide and tirzepatide to investigate dosing regimens which have not yet been studied clinically. For semaglutide, we used a recent pharmacokinetic (PK) and pharmacodynamic (PD) model. For tirzepatide, we used a recent PK model and modelled PD by reparameterizing the semaglutide PD model to fit tirzepatide clinical data. ResultsReducing dose frequency does not commensurately reduce weight loss. For example, merely switching from one dose per week (q1wk) to one dose every 2 weeks (q2wk) maintains roughly 75% of the weight loss. Furthermore, if the decrease in dose frequency involves an appropriate increase in dose size, then approximately 100% of the weight loss is maintained. In addition, we compared offering incretin mimetics to (1) a fraction of obese US adults with q1wk dosing versus (2) twice as many obese US adults with q2wk dosing. Though scenarios (1) and (2) require the same budget, our analysis suggests that (2) reduces national obesity and mortality to a much greater degree. ConclusionOur study highlights the potential utility of alternative dosing regimens of incretin mimetics. Compared with standard once‐weekly dosing, costs can be halved and weight loss maintained. These cost‐saving results have implications for patients, physicians, insurers, and governments. 

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3. How Many Patients Do You Need? Investigating Trial Designs for Anti-Seizure Treatment in Acute Brain Injury Patients

   https://doi.org/10.1101/2023.08.21.23294339  

   Parikh, Harsh; Sun, Haoqi; Amerineni, Rajesh; Rosenthal, Eric S; Volfovsky, Alexander; Rudin, Cynthia; Westover, M Brandon; Zafar, Sahar F (August 2023, medRxiv)

   Abstract ObjectivesEpileptiform activity (EA) worsens outcomes in patients with acute brain injuries (e.g., aneurysmal subarachnoid hemorrhage [aSAH]). Randomized trials (RCTs) assessing anti-seizure interventions are needed. Due to scant drug efficacy data and ethical reservations with placebo utilization, RCTs are lacking or hindered by design constraints. We used a pharmacological model-guided simulator to design and determine feasibility of RCTs evaluating EA treatment. MethodsIn a single-center cohort of adults (age >18) with aSAH and EA, we employed a mechanistic pharmacokinetic-pharmacodynamic framework to model treatment response using observational data. We subsequently simulated RCTs for levetiracetam and propofol, each with three treatment arms mirroring clinical practice and an additional placebo arm. Using our framework we simulated EA trajectories across treatment arms. We predicted discharge modified Rankin Scale as a function of baseline covariates, EA burden, and drug doses using a double machine learning model learned from observational data. Differences in outcomes across arms were used to estimate the required sample size. ResultsSample sizes ranged from 500 for levetiracetam 7 mg/kg vs placebo, to >4000 for levetiracetam 15 vs. 7 mg/kg to achieve 80% power (5% type I error). For propofol 1mg/kg/hr vs. placebo 1200 participants were needed. Simulations comparing propofol at varying doses did not reach 80% power even at samples >1200. InterpretationOur simulations using drug efficacy show sample sizes are infeasible, even for potentially unethical placebo-control trials. We highlight the strength of simulations with observational data to inform the null hypotheses and assess feasibility of future trials of EA treatment. 

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4. Development and Implementation of a Personal Virtual Assistant for Patient Engagement and Communication in Postsurgical Cancer Care: Feasibility Cohort Study

   https://doi.org/10.2196/64145  

   Bargas-Ochoa, Miguel; Zulbaran-Rojas, Alejandro; Finco, M G; Costales, Anthony B; Flores-Camargo, Areli; Bara, Rasha O; Pacheco, Manuel; Phan, Tina; Khichi, Aleena; Najafi, Bijan (February 2025, JMIR Cancer)

   Abstract BackgroundCancer-care complexity heightens communication challenges between health care providers and patients, impacting their treatment adherence. This is especially evident upon hospital discharge in patients undergoing surgical procedures. Digital health tools offer potential solutions to address communication challenges seen in current discharge protocols. We aim to explore the usability and acceptability of an interactive health platform among discharged patients who underwent oncology-related procedures. MethodsA 4-week exploratory cohort study was conducted. Following hospital discharge, a tablet equipped with an integrated Personal Virtual Assistant (PVA) system was provided to patients who underwent oncology-related procedures. The PVA encompasses automated features that provide personalized care plans, developed through collaboration among clinicians, researchers, and engineers from various disciplines. These plans include guidance on daily specific assignments that were divided into 4 categories: medication intake, exercise,symptom surveys, and postprocedural specific tasks. The aim was to explore the acceptability of the PVA by quantification of dropout rate and assessing adherence to each care plan category throughout the study duration. The secondary aim assessed acceptability of the PVA through a technology acceptance model (TAM) questionnaire that examined ease of use, usefulness, attitude toward use, and privacy concerns. ResultsIn total, 17 patients were enrolled. However, 1 (5.8%) patient dropped out from the study after 3 days due to health deterioration, leaving 16/17 (94.2%) completing the study (mean age 54.5, SD 12.7, years; n=9, 52% Caucasian; n=14, 82% with a gynecological disease; n=3, 18% with a hepatobiliary disease). At the study end point, adherence to care plan categories were 78% (SD 25%) for medications, 81% (SD 24%) for exercises, 61% (SD 30%) for surveys, and 58% (SD 44%) for specific tasks such as following step-by step wound care instructions, managing drains, administering injectable medications independently, and performing pelvic baths as instructed. There was an 80% patient endorsement (strongly agree or agree) across all TAM categories. ConclusionThis study suggests the potential acceptability of the PVA among patients discharged after oncology-related procedures, with a dropout rate of less than 6% and fair-to-good adherence to tasks such as medication intake and exercise. However, these findings are preliminary due to the small sample size and highlight the need for further research with larger cohorts to validate and refine the system. 

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5. Spatiotemporal fractionation schemes for stereotactic radiosurgery of multiple brain metastases

   https://doi.org/10.1002/mp.16457  

   Torelli, Nathan; Papp, Dávid; Unkelbach, Jan (August 2023, Medical Physics)

   Abstract BackgroundStereotactic radiosurgery (SRS) is an established treatment for patients with brain metastases (BMs). However, damage to the healthy brain may limit the tumor dose for patients with multiple lesions. PurposeIn this study, we investigate the potential of spatiotemporal fractionation schemes to reduce the biological dose received by the healthy brain in SRS of multiple BMs, and also demonstrate a novel concept of spatiotemporal fractionation for polymetastatic cancer patients that faces less hurdles for clinical implementation. MethodsSpatiotemporal fractionation (STF) schemes aim at partial hypofractionation in the metastases along with more uniform fractionation in the healthy brain. This is achieved by delivering distinct dose distributions in different fractions, which are designed based on their cumulative biologically effective dose () such that each fraction contributes with high doses to complementary parts of the target volume, while similar dose baths are delivered to the normal tissue. For patients with multiple brain metastases, a novel constrained approach to spatiotemporal fractionation (cSTF) is proposed, which is more robust against setup and biological uncertainties. The approach aims at irradiating entire metastases with possibly different doses, but spatially similar dose distributions in every fraction, where the optimal dose contribution of every fraction to each metastasis is determined using a new planning objective to be added to the BED‐based treatment plan optimization problem. The benefits of spatiotemporal fractionation schemes are evaluated for three patients, each with >25 BMs. ResultsFor the same tumor BED₁₀and the same brain volume exposed to high doses in all plans, the mean brain BED₂can be reduced compared to uniformly fractionated plans by 9%–12% with the cSTF plans and by 13%–19% with the STF plans. In contrast to the STF plans, the cSTF plans avoid partial irradiation of the individual metastases and are less sensitive to misalignments of the fractional dose distributions when setup errors occur. ConclusionSpatiotemporal fractionation schemes represent an approach to lower the biological dose to the healthy brain in SRS‐based treatments of multiple BMs. Although cSTF cannot achieve the full BED reduction of STF, it improves on uniform fractionation and is more robust against both setup errors and biological uncertainties related to partial tumor irradiation. 

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