Clinical Protocols Research Articles

Sex Differences in Aging-related Myocardial Stiffening Quantitatively Measured with MR Elastography.

Purpose To investigate the feasibility of using quantitative MR elastography (MRE) to characterize the influence of aging and sex on left ventricular (LV) shear stiffness. Materials and Methods In this prospective study, LV myocardial shear stiffness was measured in 109 healthy volunteers (age range: 18-84 years; mean age, 40 years ± 18 [SD]; 57 women, 52 men) enrolled between November 2018 and September 2019, using a 5-minute MRE acquisition added to a clinical MRI protocol. Linear regression models were used to estimate the association of cardiac MRI and MRE characteristics with age and sex; models were also fit to assess potential age-sex interaction. Results Myocardial shear stiffness significantly increased with age in female (age slope = 0.03 kPa/year ± 0.01, P = .009) but not male (age slope = 0.008 kPa/year ± 0.009, P = .38) volunteers. LV ejection fraction (LVEF) increased significantly with age in female volunteers (0.23% ± 0.08 per year, P = .005). LV end-systolic volume (LVESV) decreased with age in female volunteers (-0.20 mL/m2 ± 0.07, P = .003). MRI parameters, including T1, strain, and LV mass, did not demonstrate this interaction (P > .05). Myocardial shear stiffness was not significantly correlated with LVEF, LV stroke volume, body mass index, or any MRI strain metrics (P > .05) but showed significant correlations with LV end-diastolic volume/body surface area (BSA) (slope = -3 kPa/mL/m2 ± 1, P = .004, r2 = 0.08) and LVESV/BSA (-1.6 kPa/mL/m2 ± 0.5, P = .003, r2 = 0.08). Conclusion This study demonstrates that female, but not male, individuals experience disproportionate LV stiffening with natural aging, and these changes can be noninvasively measured with MRE. Keywords: Cardiac, Elastography, Biological Effects, Experimental Investigations, Sexual Dimorphisms, MR Elastography, Myocardial Shear Stiffness, Quantitative Stiffness Imaging, Aging Heart, Myocardial Biomechanics, Cardiac MRE Supplemental material is available for this article. Published under a CC BY 4.0 license.

Adaptation to ex vivo culture reduces human hematopoietic stem cell activity independently of cell cycle.

Loss of long-term hematopoietic stem cell (LT-HSC) function ex vivo hampers the success of clinical protocols reliant on culture. However, the kinetics and mechanisms by which this occurs remain incompletely characterized. Here, through time-resolved scRNA-Seq, matched in vivo functional analysis and the use of a reversible in vitro system of early G1 arrest, we define the sequence of transcriptional and functional events occurring during the first ex vivo division of human LT-HSCs. We demonstrate that the sharpest loss of LT-HSC repopulation capacity happens early on, between 6 and 24 hours of culture, before LT-HSCs commit to cell cycle progression. During this time window, LT-HSCs adapt to the culture environment, limiting global variability in gene expression and transiently upregulating gene networks involved in signaling and stress responses. From 24 hours, LT-HSC progression past early G1 contributes to the establishment of differentiation programmes in culture. However, contrary to current assumptions, we demonstrate that loss of HSC function ex vivo is independent of cell cycle progression. Finally, we show that targeting LT-HSC adaptation to culture by inhibiting early activation of JAK/STAT signaling improves HSC long-term repopulating function ex vivo. Collectively, our study demonstrates that controlling early LT-HSC adaptation to ex vivo culture, for example via JAK inhibition, is of critical importance to improve HSC gene therapy and expansion protocols.

Data-driven identification and comparison of full multivariable models for propofol–remifentanil induced general anesthesia

In this paper, we present results with clinical data to enable a 2x2 input–output multivariable patient model for hypnosis and analgesia. Nonlinear multi-drug interaction models are identified from data recorded from 70 patients undergoing surgery during total intravenous anesthesia (TIVA) with several medical monitors for variables such as Bispectral Index, Nociception level (Medasense), skin conductance (Medstorm) and advanced spectral analysis conductance (AnspecPro). Bispectral index measures the depth of hypnosis (lack of consciousness), while nociception related indices from Medasense, Medstorm, and AnspecPro devices measure levels related to analgesia (lack of reaction to noxious stimuli). A comparison is given among three response surface model (RSM) structures – Minto, Greco, and Reduced Greco – for hypnotic and analgesic states during Propofol–Remifentanil interaction. The identified models capture the pharmacodynamic properties of dose–effect concentrations of Propofol/Remifentanil while the pharmacokinetic part of the patient model is calculated from patient’s biometric values using Schnider/Minto (SM), and Eleveld/Eleveld (EE) models. In presence of strict clinical protocols delivering data under poor identifiability conditions, we propose two methods of identification: (i) based on steady-state gains, and (ii) using all available data which includes part of the dynamic transient. The model parameters are optimized with Genetic Algorithm based on a goodness of fit performance measure complemented with root mean square error. The results suggest that the EE model combination is advantageous for Bispectral index pharmacokinetic modeling at the cost of numerical complexity, therefore reducing the uncertainty left to be identified in the pharmacodynamic part of the patient model. By contrast, the SM model combination is less computationally demanding and provides some improvement in the RSM accuracy for nociception level indicators. The comparison of three devices for nociception levels evaluation suggests that clinical data captured with the Medasense monitor provides best fitted RSMs with the Reduced Greco RSM structure, despite having fewer parameters.

Efficacy and safety of carrimycin in ten patients with severe pneumonia following solid organ transplantation

BACKGROUND The number of patients undergoing solid organ transplantation has increased annually. However, infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of immunosuppressants. Carrimycin is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4’’-O-isovaleryltransferase gene (ist) from streptomyces thermotoleran. Carrimycin has good antibacterial and antiviral effects. However, no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia (SP) after solid organ transplantation. AIM To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical treatment. METHODS In March 2022, ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March 2022. When the condition was critical and difficult to control with other drugs, carrimycin was administered. These ten patients' clinical features and treatment protocols were retrospectively analyzed, and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were evaluated. RESULTS All ten patients were included in the analysis. Regarding etiological agent detection, there were three cases of fungal pneumonia, two cases of bacterial pneumonia, two cases of Pneumocystis pneumonia, and three cases of mixed infections. After treatment with carrimycin, the disease in seven patients significantly improved, the course of the disease was significantly shortened, fever was quickly controlled, chest computed tomography was significantly improved, and oxygenation was significantly improved. Finally, the patients were discharged after curing. One patient died of acute respiratory distress syndrome, and two patients discontinued treatment. CONCLUSION Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation. Carrimycin may have antibacterial and antiviral effects in patients with SP following solid organ transplantation.

Understanding tightened muscle in knee osteoarthritis and the impacts of Fu's subcutaneous needling: A pilot trial with shear-wave elastography and near-infrared spectroscopy.

Given the scarce reports on the interplay between Fu's subcutaneous needling (FSN), tightened muscle, and therapeutic effects, we developed a clinical research protocol to synchronously collect data on clinical efficacy and muscle characteristics in patients with knee osteoarthritis, exploring the mechanism of FSN action. The primary aim was to assess the feasibility and safety of this protocol, guiding future trials and their sample size calculations. In this prospective, single-blind, self-controlled study, 19 patients with early to mid-stage unilateral knee osteoarthritis underwent FSN therapy on both knees over 1 week (4 sessions, every other day). We measured local elastic modulus, muscle thickness, blood flow volume, and oxygen consumption rate of bilateral vastus lateralis muscles using shear-wave elastography and near-infrared spectroscopy (NIRS) before and after the first and fourth treatments. Additionally, real-time NIRS indicators (oxygenated hemoglobin [O2Hb], deoxyhemoglobin [HHb], total hemoglobin [THb], and tissue saturation index [TSI]) were recorded during these treatments. Pain intensity (visual analogue scale [VAS]), functional status (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), and active range of motion were evaluated before these treatments. All 19 participants completed the trial without serious adverse events. After 3 FSN treatments, significant changes were observed in VAS and WOMAC scores (VAS: P < .001; WOMAC: P < .001), and knee flexion (P < .001) and external rotation (P = .02), except for internal rotation. No meaningful significant differences were observed in muscle characteristics at baseline or between pre- and post-treatment periods. NIRS results during treatments indicated significant increases in local O2Hb and THb post-FSN therapy (First treatment: O2Hb: P = .005; THb: P = .006. Fourth treatment: O2Hb: P = .002; THb: P = .004); however, no significant increases were observed for HHb (First treatment: P = .06; Fourth treatment: P = .28). No linear correlation was found between therapeutic effects and changes in tightened muscle indices. FSN reduces pain and improves joint function in knee osteoarthritis, while also enhancing blood flow and oxygenation in the vastus lateralis muscle of the affected side. Further revisions of this protocol are warranted based on our insights.

Is the Mediterranean Low Fodmap Diet Effective in Managing Irritable Bowel Syndrome Symptoms and Gut Microbiota? An Innovative Research Protocol

Introduction: Irritable bowel syndrome (IBS) symptoms can be effectively managed with the low FODMAP diet. However, its efficacy in reducing inflammation is not yet proven. On the contrary, the Mediterranean diet has anti-inflammatory properties with proven efficacy in treating chronic low-grade inflammation-related diseases. Aim: To publicly share our protocol evaluating the efficacy of the Mediterranean low-FODMAP (MED-LFD) versus NICE recommendations (British National Institute for Health and Care Excellence) diet in managing IBS symptoms and quality of life. Materials and Methods: Participants meeting the Rome IV criteria will be randomly assigned to MED-LFD or NICE recommendations and they will be followed for six months. Efficacy, symptom relief, quality of life and mental health will be assessed using validated questionnaires. In addition, fecal samples will be analyzed to assess gut microbiota, and to measure branched and short-chain fatty acids, and volatile organic compounds (metabolic byproducts from bacteria). Expected results and discussion: By publicly sharing this clinical study protocol, we aim to improve research quality in the field of IBS management by allowing for peer review feedback, preventing data manipulation, reducing redundant research efforts, mitigating publication bias, and empowering patient decision-making. We expect that this protocol will show that MED-LFD can effectively alleviate IBS symptoms and it will provide pathophysiology insights on its efficacy. The new dietary pattern that combines the LFD and the MED approaches allows for the observation of the synergistic action of both diets, with the MED’s anti-inflammatory and prebiotic properties enhancing the effects of the LFD while minimizing its limitations. Identifier in Clinical Trials: NCT03997708

#1321 Long term outcomes in people with fluctuating criteria for the diagnosis of chronic kidney disease

Abstract Background and Aims The diagnostic criteria for chronic kidney disease (CKD) recognise that measures of kidney function may fluctuate in the short term by requiring that abnormalities must persist for at least 90 days to support the diagnosis. Nevertheless, studies have reported that even people who meet the diagnostic criteria may have transient or prolonged improvement in kidney function in the absence of specific treatment. In this study we used the opportunity afforded by long term follow-up of a cohort recruited from primary care to assess the impact on outcomes of fluctuations in CKD diagnostic criteria. Method Participants with confirmed CKD stage 3 were recruited from primary care practices in 2008-2010. Clinical assessment and protocol laboratory tests were performed at baseline, 1 and 5 year study visits. In 2019-20, information on deaths and latest available outpatient estimated GFR (eGFR) and urine albumin to creatinine ratio (UACR) values was obtained from electronic records. Participants with eGFR ≥60 ml/min/1.73 m2 and UACR &amp;lt;3 mg/mmol were regarded as being in “remission” at each time point. CKD progression was defined as a decline in eGFR of ≥25% and progression to a more advanced stage (KDIGO definition). Results The cohort included 1741 participants with median (IQR) age 74 (67-79) years, eGFR 53.8 (45.3-61.7) ml/min/1.73 m2 and UACR 0.3 (0.001-1.5) mg/mmol at baseline. During a median observation period of 9.8 (9.2-10.0) years, 680 participants (39.1%) died and CKD progression was observed in 430 of 1402 (30.6%) but only 24 (1.4%) progressed to CKD stage 5. The prevalence of remission was 495/1737 (28.5%) at baseline, 424/1618 (26.2%) at year 1, 335/1236 (27.1%) at year 5 and 176/1190 (14.8%) at year 10. Remission was present at all three visits in 15.4%, two visits in 13.0% and one visit in 15.8%. Participants with diabetes and those treated with a renin-angiotensin system inhibitor evidenced a lower prevalence of remission at all time points. Blood pressure control to &amp;lt;130/80 mmHg was not associated with remission. Evidence of remission at 1, 2 or 3 study visits was associated with progressively lower incidence of persistent CKD, CKD progression and death at 10 years (Table, p &amp;lt; 0.001 for all trends). No participants with an episode of remission had progressed to CKD stage 5 at 10 years. Conclusion A substantial minority of people diagnosed with CKD in primary care exhibit fluctuating diagnostic criteria. People with one or more episodes of remission appear to have a better prognosis than those with persistent CKD but remain at risk of CKD progression. They can therefore be reassured that an episode of remission is associated with an improved prognosis but long-term monitoring of kidney function is still warranted.

Enhancing Physicians' Autonomy through Practical Trainings.

In medical emergencies adherence to standardized clinical protocols is crucial to ensure a better outcome for patients. Newly qualified physicians may play several roles in serving the National Health Service (substituting general practitioners, on-call duty, working in emergency rooms, etc.) in Italy. In these situations, the physician may have to manage critical patients autonomously. Moreover, newly qualified physicians may show a considerable deficiency in routine medical activities. In fact, many universities do not provide a practical simulation training programme, which is why a substantial number of students only face clinical emergencies when they start working after graduation. A cross-sectional study was performed by engaging medical doctors. Both experienced physicians and newly licensed physicians (graduated less than 24 months ago) were included in the study. A questionnaire was distributed to each participant during SIMED's Courses from June 2021 to December 2022. The questionnaire consisted of two sections. The first one analyzed participation in standardized practical courses on medical emer gencies (Basic Life Support, Advanced Cardiac Life Support, International Trauma Life Support and a course on Advanced Airway Management). The second section analyzed the perceived autonomy of health professionals in the management of five different work settings, using a 5-point likert scale. 2,168 questionnaires were analyzed, of which 68.7% were from newly qualified doctors and 31.3% from more experienced doctors The highest rate of physicians who undertook training courses was achieved for the basic life support course (77.5%) and the lowest rate for the advanced trauma course (15.9%). Physicians perceive themselves the highest autonomy in Primary Care setting (63.1%), while in the Emergency Department they perceive themselves with less autonomy (24.0%). In the analyzed sample, experienced physicians show a higher percentage of autonomy than newly qualified doctors (31.4% vs 8.1%) in all scenarios. Our analysis shows a possible correlation between the self-perceived autonomy of physicians and attending practical simulation courses. Although the role of training through practical courses is relevant, the percentage of trained professionals is insufficient and therefore the implementation of practical training projects has to be encouraged.

Targeting the tumor microenvironment for treating double refractory chronic lymphocytic leukemia

The introduction of BTK inhibitors and BCL2 antagonists to the treatment of chronic lymphocytic leukemia has revolutionized therapy and improved patient outcomes. These agents have replaced chemoimmunotherapy as standard of care. Despite this progress, a new group of patients is currently emerging, which has become refractory or intolerant to both classes of agents, creating an unmet medical need. Here, we propose that the targeted modulation of the tumor microenvironment provides new therapeutic options for this group of "double refractory" patients. Furthermore, we outline a sequential strategy for tumor microenvironment-directed combination therapies in CLL that can be tested in clinical protocols.

Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea.

Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Barriers to diverse clinical trial participation in Duchenne muscular dystrophy: Engaging Hispanic/Latina caregivers and health professionals

BackgroundDespite the increasing availability of clinical trials in Duchenne muscular dystrophy, racial/ethnic minorities and other populations facing health disparities remain underrepresented in clinical trials evaluating products for Duchenne. We sought to understand the barriers faced by Hispanic/Latino families specifically and underrepresented groups more generally to clinical trial participation in Duchenne.MethodsWe engaged two participant groups: Hispanic/Latino caregivers of children with Duchenne in the US, including Puerto Rico, and health professionals within the broader US Duchenne community. Caregiver interviews explored attitudes towards and experiences with clinical trials, while professional interviews explored barriers to clinical trial participation among socio-demographically underrepresented families (e.g., low income, rural, racial/ethnic minority, etc.). Interviews were analyzed aggregately and using a thematic analysis approach. An advisory group was engaged throughout the course of the study to inform design, conduct, and interpretation of findings generated from interviews.ResultsThirty interviews were conducted, including with 12 Hispanic/Latina caregivers and 18 professionals. We identified barriers to clinical trial participation at various stages of the enrollment process. In the initial identification of patients, barriers included lack of awareness about trials and clinical trial locations at clinics that were less likely to serve diverse patients. In the prescreening process, barriers included ineligibility, anticipated non-compliance in clinical trial protocols, and language discrimination. In screening, barriers included concerns about characteristics of the trial, as well as mistrust/lack of trust. In consent and recruitment, barriers included lack of timely decision support, logistical factors (distance, time, money), and lack of translated study materials.ConclusionsNumerous barriers hinder participation in Duchenne clinical trials for Hispanic/Latino families and other populations experiencing health disparities. Addressing these barriers necessitates interventions across multiple stages of the clinical trial enrollment process. Recommendations to enhance participation opportunities include developing clinical trial decision support tools, translating prominent clinical trials educational resources such as ClinicalTrials.gov, fostering trusting family-provider relationships, engaging families in clinical trial design, and establishing ethical guidelines for pre-screening potentially non-compliant patients.

Keratoconus in the West Region of Cameroon: Stakeholder knowledge and management

Background: Adequate knowledge and skills by eyecare personnel and administrators are essential for the early diagnosis and prompt management of keratoconus (KC).Aim: This study aimed to determine the knowledge and skills of key stakeholders on KC management in eyecare facilities of Bafoussam, West Region of Cameroon.Setting: Eyecare facilities in the West Region of Cameroon.Methods: A qualitative study, using a purposive (non-probability) sampling technique, was applied to collect data relevant to this study. In-depth interviews were used to collect data from eyecare personnel and administrators. Eyecare personnel in this study comprised optometrists, ophthalmic nurses and optometric technicians, who are trained to World Council of Optometry (WCO) competency level one or two. There were no ophthalmologists working at the study sites. Data obtained were captured, de-identified and stored in a password-protected electronic file. Data were coded and analysed applying a deductive thematic analysis approach.Results: There were 21 participants (five administrators and 16 eyecare professionals) from five facilities. Fourteen (66.6%) were males; 10 (47.6%) had 11–20 years of work experience. The majority of the participants had limited or no knowledge of KC. They reported an undersupply of KC diagnostic equipment and consumables at facilities, resulting in poor diagnosis and management of KC patients.Conclusion: The study revealed inadequate knowledge, training and skills of eyecare practitioners and administrators on KC. Deficiencies in KC diagnosis and management could cause visual impairment with a potential negative impact on the quality of life (QoL) of KC patients.Contribution: This study illustrates the need to procure basic equipment, capacitate eyecare workers with knowledge of KC and establish standard clinical protocols for the diagnosis and management of KC, including referral pathways.

Uniportal video-assisted thoracic surgery versus open thoracotomy for chronic pain after surgery: a prospective cohort study.

The potential of uniportal video-assisted thoracic surgery (U-VATS) to reduce chronic pain after thoracic surgery (CPTS) compared to open thoracotomy (OT) remains unexplored. This prospective study aims to assess the incidence of CPTS following U-VATS or OT and identify associated risk factors. Patients undergoing thoracic surgery were recruited from March 2021 to March 2022, categorized by surgical approach (U-VATS vs. OT). Standard clinical protocols for surgery, anesthesia, and analgesia were followed. Pain symptoms were assessed using the Short-form McGill Pain Questionnaire, with follow-ups up to 6months. Perioperative factors influencing CPTS at 3months were analyzed through univariate and multivariate methods. A total of 694 patients were analyzed. Acute pain after thoracic surgery (APTS) was significantly less severe in the U-VATS group (p < 0.001). U-VATS patients exhibited a lower incidence of CPTS at 3months (63.4% vs. 80.1%, p < 0.001), with reduced severity among those experiencing CPTS (p = 0.007) and a decreased occurrence of neuropathic pain (p = 0.014). Multivariate analysis identified OT incision, moderate to severe APTS (excluding moderate static pain at 24h postoperative), nocturnal surgery, and lung surgery as risk factors for CPTS. This study underscores the potential of U-VATS to reduce both the incidence and severity of CPTS at 3months compared to OT. Furthermore, it highlights risk factors for CPTS, including OT incision, inadequately managed APTS, lung surgery, and nocturnal surgery. These findings emphasize the importance of considering surgical approach and perioperative pain management strategies to mitigate the burden of CPTS.

Antibacterial therapy in patients with acute sinusitis

The prevalence of the acute sinusitis in ENT practice is very high. The current prevalence in Russian Federation is roughly estimated at 6 to 15%, and accounts for about 10 million cases a year. The incidence of acute sinusitis increases in autumn and early spring and decreases in the summer. Most cases of acute sinusitis are of a viral etiology, but it can also arise from bacterial infection, allergies, or injuries. The disease is characterized by swelling of the nasal mucous membrane, nasal blockage and discharge. Typically, the duration of acute inflammation of the paranasal sinuses averages about 4 weeks. In case of the inappropriate treatment, the inflammatory process can spread to adjacent anatomical structures – to the orbit, ear, or brain, resulting in serious, sometimes life-threatening complications. Over the last 10 years, the resistance of pathogenic flora to antimicrobial agents has greatly increased due to the unjustifiability and irrationality of their use. The purpose of this review was to analyze the effectiveness and safety of the antibiotic therapy for acute rhinosinusitis. The paper discusses the etiology, pathogenesis, and characteristics of the acute sinusitis. It presents the features of the most used drugs, with special attention to the comparative assessment of their therapeutic effectiveness compared to other antibiotics, as well as determining the optimal schemes for their use within the framework of modern clinical protocols. A description of a clinical case of acute sinusitis and a treatment regimen with Cefixime EXPRESS is presented.

Towards retrospective motion correction and reconstruction for clinical 3D brain MRI protocols with a reference contrast.

In a typical MR session, several contrasts are acquired. Due to the sequential nature of the data acquisition process, the patient may experience some discomfort at some point during the session, and start moving. Hence, it is quite common to have MR sessions where some contrasts are well-resolved, while other contrasts exhibit motion artifacts. Instead of repeating the scans that are corrupted by motion, we introduce a reference-guided retrospective motion correction scheme that takes advantage of the motion-free scans, based on a generalized rigid registration routine. We focus on various existing clinical 3D brain protocols at 1.5 Tesla MRI based on Cartesian sampling. Controlled experiments with three healthy volunteers and three levels of motion are performed. Radiological inspection confirms that the proposed method consistently ameliorates the corrupted scans. Furthermore, for the set of specific motion tests performed in this study, the quality indexes based on PSNR and SSIM shows only a modest decrease in correction quality as a function of motion complexity. While the results on controlled experiments are positive, future applications to patient data will ultimately clarify whether the proposed correction scheme satisfies the radiological requirements.

Adherence-Promoting Design Features in Pediatric Neurostimulators for ADHD Patients.

The emergence of remote health monitoring and increased at-home care emphasizes the importance of patient adherence outside the clinical setting. This is particularly pertinent in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients, as the population inherently has difficulty remembering and initiating treatment tasks. Neurostimulation is an emerging treatment modality for pediatric ADHD and requires strict adherence to a treatment regimen to be followed in an at-home setting. Thus, to achieve the desired therapeutic effect, careful attention must be paid to design features that can passively promote and effectively monitor therapeutic adherence. This work describes instrumentation designed to support a clinical trial protocol that tests whether choice of color, or color itself, can statistically significantly increase adherence rates in pediatric ADHD patients in an extraclinical environment. This is made possible through the development and application of an internet-of-things approach in a remote adherence monitoring technology that can be implemented in forthcoming neurostimulation devices for pediatric patient use. This instrumentation requires minimal input from the user, is durable and resistant to physical damage, and provides accurate adherence data to parents and physicians, increasing assurance that neurostimulation devices are effective for at-home care.

Impact of breath sample collection method and length of storage of breath samples in Tedlar bags on the level of selected volatiles assessed using gas chromatography-ion mobility spectrometry (GC-IMS)

The analysis of volatile organic compounds (VOCs) in exhaled air has attracted the interest of the scientific community because it provides the possibility of monitoring physiological and metabolic processes and non-invasive diagnostics of various diseases. However, this method remains underused in clinical practice as well as in research because of the lack of standardized procedures for the collection, storage and transport of breath samples, which would guarantee good reproducibility and comparability of results. The method of sampling, as well as the storage time of the breath samples in the polymer bags used for sample storage and transport, affect the composition and concentration of VOCs present in the breath samples. The aim of our study was to compare breath samples obtained using two methods with fully disposable equipment: a Haldane sampling tube intended for direct breath collection and breath samples exhaled into a transparent Tedlar bag. The second task was to monitor the stability of selected compounds of real breath samples stored in a Tedlar bag for 6 h. Gas chromatography coupled with ion mobility spectrometry (GC-IMS) implemented in the BreathSpec® device was used to analyse exhaled breath. Our results showed a significant difference in the signal intensity of some volatiles when taking a breath sample with a Haldane tube and a Tedlar bag. Due to its endogenous origin, acetone levels were significantly higher when the Haldane tube sampler was used while elevated levels of 2-propanol and unidentified VOC (designated as VOC 3) in the Tedlar bag samples likely originated from contamination of the Tedlar bags. The VOC stability study revealed compound-specific signal intensity changes of the selected VOCs with storage time in the Tedlar bags, with some volatiles showing increasing signal intensity during storage in Tedlar bags. This limits the use of Tedlar bags only for very limited time and carefully selected purpose. Our results highlight the importance of careful design and implementation of experiments and clinical protocols to obtain relevant and reliable results.

How quickly does FLASH need to be delivered? A theoretical study of radiolytic oxygen depletion kinetics in tissues

Purpose. Radiation delivered over ultra-short timescales (‘FLASH’ radiotherapy) leads to a reduction in normal tissue toxicities for a range of tissues in the preclinical setting. Experiments have shown this reduction occurs for total delivery times less than a ‘critical’ time that varies by two orders of magnitude between brain (∼0.3 s) and skin (⪆10 s), and three orders of magnitude across different bowel experiments, from ∼0.01 to ⪆(1–10) s. Understanding the factors responsible for this broad variation may be important for translation of FLASH into the clinic and understanding the mechanisms behind FLASH. Methods. Assuming radiolytic oxygen depletion (ROD) to be the primary driver of FLASH effects, oxygen diffusion, consumption, and ROD were evaluated numerically for simulated tissues with pseudorandom vasculatures for a range of radiation delivery times, capillary densities, and oxygen consumption rates (OCR’s). The resulting time-dependent oxygen partial pressure distribution histograms were used to estimate cell survival in these tissues using the linear quadratic model, modified to incorporate oxygen-enhancement ratio effects. Results. Independent of the capillary density, there was a substantial increase in predicted cell survival when the total delivery time was less than the capillary oxygen tension (mmHg) divided by the OCR (expressed in units of mmHg/s), setting the critical delivery time for FLASH in simulated tissues. Using literature OCR values for different normal tissues, the predicted range of critical delivery times agreed well with experimental values for skin and brain and, modifying our model to allow for fluctuating perfusion, bowel. Conclusions. The broad three-orders-of-magnitude variation in critical irradiation delivery times observed in in vivo preclinical experiments can be accounted for by the ROD hypothesis and differences in the OCR amongst simulated normal tissues. Characterization of these may help guide future experiments and open the door to optimized tissue-specific clinical protocols.

Implementation Barriers Encountered During a Universal Suicide Screening Program in Pediatric Emergency Departments.

Because understanding barriers to universal suicide risk screening in pediatric emergency departments (PEDs) may improve both identification and management of suicidal behaviors and ideation, this study assessed barriers to a quality improvement initiative examining the use of a novel computerized adaptive test (CAT), the Kiddie-CAT, in 2 PEDs. Research assistants (RAs) trained in Rapid Assessment Procedures-Informed Clinical Ethnography methods documented barriers related to the environment, individuals, and workflow as encountered during screening shifts, categorizing the barriers' impacts as either general to a screening shift or related to screening an individual youth/caregiver dyad. Using thematic content analysis, investigators further categorized barriers based on type (eg, workflow, language/comprehension, clinician attitudes/behaviors) and relationship to the limited integration of this initiative into clinical protocols. Reasons for refusal and descriptive data on barriers are also reported. Individual screen barriers were most often related to workflow (22.9%) and youth/caregiver language/comprehension challenges (28%). Similarly, workflow issues accounted for 48.2% of all general shift barriers. However, many of these barriers were related to the limited integration of the initiative, as RAs rather than clinical staff conducted the screening. Although this study was limited by a lack of complete integration into clinical protocols and was complicated by the COVID-19 pandemic impacts on PEDs, the findings suggest that considerable attention needs to be directed both to physician education and to workflow issues that could impede universal screening efforts.

Efficacy of Continuous Lateral Rotation Therapy in Mechanically Ventilated Critically Ill Adults on Clinical Outcomes.

Background: This PICO-guided systematic review assessed continuous lateral rotation therapy (CLRT) versus conventional position changes in mechanically ventilated critically ill adults, evaluating mortality, intensive care unit (ICU) and hospital stay duration as primary outcomes, and respiratory function, mechanical ventilation duration, pulmonary complications, and adverse events, as secondary outcomes. Methods: A systematic review followed PRISMA criteria (PROSPERO CRD42022384258). Searches spanned databases: MEDLINE/PubMed, EMBASE, Scopus, ScienceDirect, Cochrane, CINAHL and Web of Science, without language or publication year restrictions. Inclusion criteria involved randomized (RCT) and quasi-randomized trials, comparing CLRT (intervention) with conventional position changes (control). Risk of bias and quality of evidence for RCTs were assessed using the Cochrane collaboration and GRADE tools. For the quasi-randomized trials, the ROBINS-I tool was used. Results: In 18 studies with 1.466 participants (intervention, n= 700, 47.7%; control, n= 766, 52.2%), CLRT was predominantly used for prophylactic purposes, with protocols varying from 10 to 24 hours/day. Meta-analysis (16 RCTs) favored CLRT for reduced mechanical ventilation duration (SMD -0.17 days, CI -0.29 to -0.04, p=0.008) and lower nosocomial pneumonia incidence (OR 0.39, CI 0.29 to 0.52, p<0.00001). CLRT showed no significant impact on mortality (OR 1.04, CI 0.80 to 1.34, p= 0.77), ICU stay (SMD -0.11 days, CI -0.25 to 0.02, p= 0.11), hospital stay (SMD -0.10 days, CI -0.31 to 0.11, p= 0.33) and incidence of pressure ulcers (OR 0.73, CI 0,34 to 1.60, p= 0.44). Conclusions: CLRT showed no significant difference in primary outcomes (mortality, ICU, and hospital stay duration) but revealed significant differences in secondary outcomes (consistently reduced nosocomial pneumonia, with a minor effect on MV duration), supported by moderate certainty. Very low certainty for other outcomes highlights the need for current studies in diverse clinical settings and protocols to assess CLRT effectiveness.