Citations

Background: Platelet-rich plasma (PRP) is an emerging therapy that demonstrates potential benefits for knee osteoarthritis (OA); however, the accessibility of PRP remains limited, in part, because its use is not covered by insurance. Purpose: To identify factors contributing to health disparities in PRP treatment for knee OA using machine learning models. Study Design: Cross-sectional study; Level of evidence, 3. Methods: The authors collected data from electronic medical records at 2 upper Midwest medical centers (Mayo Clinic and Detroit Medical Center) from 2022 to 2023 encompassing demographic, socioeconomic, and clinical factors. Data collection encompassed age, sex, race, ethnicity, area deprivation index, marital status, income, rurality, insurance, employment, language, religion, treatment site, and region. Logistic regression and random forest models were applied to 3667 samples (80% training, 20% testing), comparing PRP recipients against a standard care group. Models were evaluated using 10-fold cross-validation to ensure robust performance assessment. Results: Logistic regression revealed that increased age, widowed status, lower income, rural residence, unemployment/disability, and Medicaid/Medicare insurance were associated with lower odds of receiving PRP. Upper-middle income, contracted insurance, and treatment at the Mayo-Arizona and Mayo-Florida sites were associated with higher odds. The model achieved areas under the curve of 0.83 (training set) and 0.82 (testing set). Random forest analysis identified distance to care, age, area deprivation index, income, and treatment site as top predictors, with areas under the curve of 0.92 (training) and 0.87 (testing). Conclusion: The current study demonstrated that both models discerned key barriers (income, distance to care, retirement status) and facilitators (regional differences) affecting PRP accessibility. These findings provide potential policy initiatives aimed at improving PRP access for underserved demographics, offering a quantitative blueprint to foster equitable access to regenerative therapies for knee OA.

Abstract Background An accurate discrete spot scanning (DSS) beam delivery time (BDT) model is essential, particularly as 4D dynamic dose accumulation calculations rely on machine‐specific time models for reliable interplay evaluation. Purpose To derive a BDT model for a synchrotron‐based Hitachi Probeat PBS proton system from oscilloscope measurements of key BDT structures, including multi‐energy extraction (MEE) characteristics. Methods Key BDT structures were characterized using oscilloscope measurements, supplemented by delivery log files where appropriate. Spot‐to‐spot scanning trajectories were visualized using a CROSSmini 2D strip ionization chamber (Liverage Biomedical Inc, Taiwan) via the dose‐driven continuous scanning (DDCS) mode. The MEE design and MEE charge recapture efficiencies were also characterized. In addition, the impact of the number of delivered spots on both the extractable fraction of charge and MEE recapture efficiency was investigated. Results An improved synchrotron‐based BDT model was derived that incorporates dead times between radiofrequency knockout (RFK) and high‐speed steering magnet (HSST) signals. Spot‐to‐spot movement follows a “hockey‐stick”‐like behavior where the effective spot‐to‐spot move time is governed by the slower axis. An energy‐dependent variation in the number of MEE layers deliverable per spill was also observed, with fewer MEE layers per spill (1–3) was observed in low and high energy ranges compared to the mid‐energy range (4–5), deviating from the nominal vendor value of five MEE layers per spill per block. A reduction in the extractable fraction of charge was observed with an increasing number of spots per spill, while increasing the number of delivered spots in the preceding layer significantly reduced the MEE recapture efficiency. Conclusion MEE characteristics should be incorporated into synchrotron‐based time models for accurate beam delivery modeling. The methodology presented here also provides a framework for centers seeking to derive machine‐specific delivery time models for their proton systems.

Introduction The unproven stem cell intervention (SCI) industry markets stem cell products to patients navigating chronic and serious conditions who seek alternative options when conventional treatments no longer offer relief or improvement. This market is often characterized by providers using deceptive advertising to misinform potential consumers to seek stem cells that have not been shown to be safe and/or effective through clinical studies. Objective This study examines how patients describe interpersonal and institutional trust in relation to their interest in and decisions about unproven SCIs among two distinct and divergent chronic disease patient groups: patients with little or no interest in unproven SCIs (low seekers) and those with high interest or have undertaken an unproven SCI (high seekers). Methods A semi-structured interview guide was developed deductively and modified inductively based on the Unified Theory of Health Behavior. Qualitative interviews among 36 patients and carers were conduct and transcripts were analyzed using constant comparison based on the principles of grounded theory. Results Trust varies across social contexts as low seekers expressed strong reservations about the commercialization elements of the SCI industry placing greater confidence in conventional medicine. In contrast, high seekers questioned the advice of conventional providers and motives of medical regulators. Across both, personal relationships were commonly described as influential in how participants evaluated unproven SCIs. Conclusion These findings suggest that communication efforts in clinical settings should account for the relational and emotional dimensions of trust. Interventions aimed at countering misleading information and promoting informed choices should engage trusted messengers and address the broader social and psychological contexts in which patients may seek unproven SCIs.

Abstract Background Dose‐driven continuous scanning (DDCS) is a type of beam delivery in Hitachi pencil beam scanning (PBS) particle therapy system. Particle beam is irradiated continuously between spots to achieve a higher effective dose rate and a shorter beam delivery time. The beam is only turned off at break spots, the end of a treatment layer and during spill change. The break spot is a unique feature of the DDCS introduced by the treatment planning system (TPS) to interrupt continuous scanning. DDCS separates the dose delivery of a spot into a move dose and stop dose components. The move dose is controlled by the scanning speed and beam current, while the stop dose delivers the remaining monitor units (MUs). Hence, rigorous quality assurance (QA) of the scanning speed and functionality of break spot are required to ensure safe and successful DDCS delivery. Purpose We aim to report for the first time the QA methodology and result for DDCS, focusing on the scanning speed and break spot validation. Methods A rectangular spiral irradiation pattern with different degree of break spots were irradiated on a 2D strip ionization chamber (CROSSmini) detector using 50 time resolution to validate the break spots. Four methods of measuring scanning speeds were proposed. Using a spiral irradiation pattern, methods one and two applied linear regression to the scanning time measured by the CROSSmini for different inter‐spot distances, with measurements taken at sampling rates of 5 and 20 kHz, respectively. Methods three and four measured the scanning time of single inter‐spot distances in the X and Y directions. Method three measured the scanning time with the CROSSmini while method four measured the rise and fall time of the scanning magnet (SCM) current. All measurements were performed with 70.2, 150.2 and 228.7 MeV proton beam energies and three different beam currents of 8, 14 and 20 MU/s. Lastly, the scanning speed tolerance limit was calculated analytically under the requirement of avoiding a beam abort when the stop dose was less than zero. Results The data recorded by the CROSSmini under the spiral irradiation patterns with break spots was reconstructed into a 2D dose, and the break spots’ operations were visually validated for all the energies and beam currents. There were no statistically significant difference in the measured X and Y scanning speeds across the four methods. However, the last method involving the SCM current yielded the largest type A uncertainty of up to 25% () due to the noisy signal. The first method with the linear regression and 5 kHz acquisition rate was preferred due to a smaller type A uncertainty of up to 2.0% and a lower false negative rate in detecting the rising and falling edges during scanning. The calculated tolerance limit based on our current DDCS setting was found to be 0.50 times of the expected scanning speed. Conclusion We have introduced QA protocols for DDCS, designed to ensure complete and safe beam delivery without interruptions caused by move doses exceeding planned spot doses.

Abstract Regenerative medicine is a rapidly advancing field, particularly within the field of physical medicine and rehabilitation. While orthobiologics are currently being used in clinical practice, there remains a need for high-quality clinical trials and translational research to standardize treatments and improve patient outcomes. Education is vital for streamlining development of evidence-based, practical, and effective treatments. In this article, we highlight the need for a 1-yr advanced fellowship in translational orthobiologics aiming to create a standardized core curriculum targeting physicians involved in treating musculoskeletal diseases. The fellowship’s objectives include advancing translational orthobiologics research, ethical considerations, and promoting effective communication regarding orthobiologic therapies. Such a program would serve as a foundation for physicians interested in conducting clinically oriented orthobiologics research for musculoskeletal disorders while improving the development of safe and effective therapeutics related to musculoskeletal disorders.

Abstract Introduction Most US businesses offering unproven stem cell interventions (SCIs) are run by physicians, many of whom operate outside their scope of training. To date, little effort has been made to educate practicing physicians about SCIs. To circumvent the need, several businesses have begun advertising training opportunities for physicians. Objective To understand the current training landscape for physicians, we undertook a systematic content analysis of stem cell courses advertised on the internet. Methods We conducted Google searches using keywords and included onsite, online, and hybrid training programs targeting physicians or other clinicians. We systematically examined all information and identified 14 courses (6 onsite, 4 online, and 4 hybrid) offered by 11 different organizations. Courses ranged from single-day workshops to year-long programs with an average cost of $4,919 and ranged from $500 to $22,000. Results Nine courses listed a practicum component and ten courses listed 63 affiliated clinics, companies, and non-profit institutions. Eight organizations included learner testimonials as text and/or video with most authored by physicians and all expressed a positive tone. We analyzed marketing language used by training organizations that 6 of 14 explicitly mentioned offering assistance in marketing and/or revenue growth to learners. We also examined the backgrounds of physician faculty among organizations. Of the 7 businesses which listed faculty, a total of 172 faculty were found ranging from 4 to 71 individuals. Among the 172 faculty, 121 were physicians where we were able to determine whether they provided unproven, questionable or proven treatments within their practice. The majority of physician faculty (66%) were associated with unproven treatments, 21% offered proven treatments, and 13% offered questionable treatments. Nearly half the faculty (48%) provided 3-5 unproven therapies, 35% provided 1-2 unproven therapies, and 17% provided 6 or more unproven therapies. Conclusions Our results indicate that current pedagogical offerings for physicians interested in SCIs are likely to offer questionable training that is not rooted in evidence. Physicians interested in SCIs should seek training from nationally accredited organizations. The scientific community should invest in physician training surrounding SCIs. Disclosure No.

Abstract Introduction . Dispersion in an accelerator quantifies the deviation of the proton trajectory when there is a momentum deviation. We present for the first time a safe method of measuring dispersion in the clinic, using a scintillator detector and the momentum deviations within a spill. This is an important accelerator quantity as we found that this is the reason behind the large dose fluctuation in our absolute dosimetry measurement. Methods . Dispersions are measured for nine energies in a Hitachi ProBeat system at three locations (isocenter and at two profile monitors) and at two gantry angles (0 and 90 degrees) by first measuring the spot position and momentum drift within a spill. The spot position drift is measured by the XRV-4000 at the isocenter, and by the two profile monitors located at 0.57 and 2.27 m from the isocenter. The momentum drift is calculated from the intra-spill range drift which is measured using the Ranger accessory. The dispersion at isocenter and its gradient are calculated using the weighted least square regression on the measured dispersions at the three locations. A constraint is formulated on the dispersion and its gradient to ensure minimal intra-spill spot position deviation around the isocenter. Results . The measured intra-spill range and spot positional drift at isocenter are less than 0.25 mm and 0.7 mm respectively. The momentum spread calculated from the range drift are less than 0.08%. The dispersion at the isocenter ranged from 0.50 to 4.30 m and the zero-crossing happens upstream of isocenter for all energies. 2 of the 9 energies (168.0 and 187.5 MeV) violated the constraint and has an intra-spill spot positional deviation greater than 1.0 within 5 cm from the isocenter. Conclusion . This measurement is recommended as part of commissioning and annual quality assurance for accelerator monitoring and to ensure intra-spill spot deviations remain low.

AbstractBackgroundAbsolute dosimetry measurement is an integral part of Treatment Planning System (TPS) commissioning and it involves measuring the integrated absorbed dose to water for all energies in a pencil beam scanning delivery system. During the commissioning of Singapore's first proton therapy center, a uniform scanned field with an Advanced Markus chamber method was employed for this measurement, and a large dose fluctuation of at least 5% was observed for 10% of the energy layers during repeated measurements.PurposeThis study aims to understand the root cause of this fluctuation by relating the actual delivered spot information in the log file with the charge measurement by the ion chambers.MethodsA dedicated pencil beam dose algorithm was developed, taking into account the log file parameters, to calculate the dose for a single energy layer in a homogeneous water phantom. Three energies, 70.2, 182.7, and 228.7 MeV were used in this study, with the 182.7 MeV energy exhibiting large dose fluctuation. The dose fluctuation was investigated as a function of detector's sizes (pinpoint 3D, Advanced Markus, PTW 34070, and PTW 34089) and water depth (2 , 6, and 20 cm). Twelve ion chambers measurements were performed for each chamber and depth. The comparison of the theoretically predicted integrated dose and the charge measurement served as a validation of the algorithm.ResultsAbout 5.9% and 9.6% dose fluctuation were observed in Advanced Markus and pinpoint 3D measurements at 2 cm depth for 182.7 MeV, while fluctuation of 1.6% and 1.1% were observed in Advanced Markus with 228.7 and 70.2 MeV at similar depth. Fluctuation of less than 0.1% was observed for PTW34070 and PTW 34089 for all energies. The fluctuation was found to diminish with larger spot size at 20 cm depth to 1.3% for 182.7 MeV. The theoretical and measured charge comparison showed a high linear correlation of for all datasets, indicating the fluctuation originated from the delivered spot characteristics. The cause of fluctuation was identified to be due to the spill change occurring close to the detector, and since the spot positional deviation profiles were different between two spills, this resulted in local hot spots between columns of spots. The actual position of spill change varies randomly during measurement, which led to a random occurrence of hot spot within the detector's sensitive volume and a fluctuating dose measurement.ConclusionThis is the first report of a dose fluctuation greater than 5% in absolute dosimetry measurement with a uniform scanned field and the cause of the fluctuation has been conclusively determined. It is important to choose the MU and scanning pattern carefully to avoid spill change happening when the spot delivery is near the detector.

Abstract Background For gravely ill patients who have no treatment options and who are ineligible for clinical trials, the US Food and Drug Administration (FDA) established the Expanded Access Program (EAP). Motivated by efforts to weaken FDA regulation and sold as providing greater access to experimental drugs, the federal Right to Try Act (RTT) was passed in 2017. It reduces FDA oversight by not requiring physicians to report safety data and foregoes approval of protocols by local institutional review boards. Methods This study explored the views of 17 neuro-oncologists from 15 different academic medical centers with varying experience with EAP and RTT using convenience sampling. We conducted semi-structured interviews and qualitative analysis to identify emerging themes. Results Most oncologists were confused between the two pathways, had little familiarity with RTT, and had little knowledge about experimental medicine available through either pathway. Oncologists reported a preference of enrolling patients in clinical trials over off-trial preapproval pathways with scant data. As a result, oncologists revealed concerns over properly evaluating risks for their patients. Conclusion Our findings suggest that neuro-oncologists need better resources and clearer mechanisms at their institutions to help navigate EAP and RTT in order to counsel patients interested in experimental medicine.