Adequate Dose Research Articles

Mavorixafor; CXCR4 antagonist a novel treatment for whim syndrome, first FDA approval 2024 (Editorial)

WHIM syndrome is a rare autosomal dominant disorder characterized by gain-of-function mutations in the Chemokine receptor type-4 (CXCR4 receptor). The acronym WHIM stands for Warts, Hypogammaglobulinemia, recurrent bacterial Infections, and Myelokathexis. Traditionally, WHIM syndrome has been managed with intravenous immunoglobulin (IVIG) and filgrastim (Granulocyte Colony-Stimulating Factor, G-CSF). IVIG is used to provide passive immunity to counteract hypogammaglobulinemia, while filgrastim stimulates the production and release of neutrophils from the bone marrow to address neutropenia. However, these treatments have limited efficacy, require frequent administration, and involve significant costs and patient burden. The recent Food and Drug Administration (FDA) approval of Mavorixafor, a small molecule CXCR4 antagonist, marks a significant advancement in the management of WHIM syndrome. Mavorixafor enhances white blood cell mobilization from the bone marrow, directly targeting the underlying cause of the disease. In a pivotal Phase-3 trial conducted by Badalato R et al. (2024), involving 30 participants randomized to receive Mavorixafor 400 mg daily or placebo for 52 weeks, Mavorixafor demonstrated a statistically significant increase in absolute neutrophil count (ANC) (p<0.01) and a notable reduction in annual infection frequency compared to placebo. Additionally, a Phase-2 study reported a 75% reduction in cutaneous warts and an annual infection rate of 2.27 occurrences with adequate dosing. Mavorixafor maintained a favorable safety profile and required fewer administration complexities than IVIG and filgrastim, with 78% of patients achieving an overall response compared to 10% in the placebo group. These findings underscore the potential of Mavorixafor to significantly improve clinical outcomes for patients with WHIM syndrome, offering a more effective and targeted treatment option. The approval of Mavorixafor not only enhances current therapeutic strategies but also paves the way for future research into CXCR4 antagonists, potentially revolutionizing the management of WHIM syndrome and similar immunodeficiencies.

Derivation of Best-Practice Scan Speeds and Excess Scan Durations for CT Pulmonary Angiography: Analysis Using Registry Data for 166,769 Examinations Across 121 Sites.

Background: Radiology practices' potential use of a fixed scan speed results in scanning some patients more slowly than necessary for the clinical scenario. For CT pulmonary angiography (CTPA), use of fixed scan speeds can lead to prolonged breath-hold requirements and potentially lower image quality from motion artifact. Objective: To develop best-practice scan speeds for CTPA examinations as well as to assess the extent of variation from these speeds and resulting excess scan durations in real-world clinical practice. Methods: This retrospective study included 192,779 acquisitions from 166,769 CTPA examinations performed in adult patients (97,649 male, 68,925 female; median age, 60 years) from January 1, 2016 to January 1, 2021, at 121 sites using 277 physical scanners representing 28 scanner models from four vendors. The examinations were identified from an international CT dose registry. Acquisition characteristics were extracted from the registry and used to calculate scan speeds and durations. Acquisitions were stratified into five equally size radiation dose categories using CTDIvol values. For each combination of scanner model and dose category, best-practice scan speed was calculated as the 95th-percentile actual speed, although a higher dose category's best-practice speed was assigned if faster. Excess scan durations were calculated with respect to hypothetical durations if acquisitions used best-practice speeds. Results: The acquisitions had speeds that, on average, were 30% slower than the best-practice scan. A total of 87% of acquisitions were slower than the best-practice speed; 62% were >20% slower than the best-practice speed. Acquisitions had a median scan duration of 4.8 seconds; use of best-practice scan speeds would have saved a median of 1.2 seconds. The 95th-percentile excess scan duration was 7.1 seconds, which was exceeded by at least one examination for 58% of sites. Conclusion: CTPA commonly uses speeds slower than the proposed best-practice speeds for a given scanner's capabilities, potentially leading to greater motion artifact, suggesting widespread opportunity for improvement. Simple protocol modifications can decrease scan duration while still allowing adequate radiation dose. Clinical Impact: The findings indicate widespread opportunity for CTPA protocol improvement through simple adjustments designed to shorten scan speeds at a maintained dose output that preserves image quality.

Are contemporary antifungal doses sufficient for critically ill patients? Outcomes from an international, multicenter pharmacokinetics study for Screening Antifungal Exposure in Intensive Care Units-the SAFE-ICU study.

Appropriate antifungal therapy is a major determinant of survival in critically ill patients with invasive fungal disease. We sought to describe whether contemporary dosing of antifungals achieves therapeutic exposures in critically ill patients. In a prospective, open-label, multicenter pharmacokinetic study, intensive care unit (ICU) patients prescribed azoles, echinocandins, or polyene antifungals for treatment or prophylaxis of invasive fungal disease were enrolled. Blood samples were collected on two occasions, with three samples taken during a single dosing interval on each occasion. Total concentrations were centrally measured using validated chromatographic methods. Pharmacokinetic parameters were estimated using noncompartmental methods. Antifungal dosing adequacy was assessed using predefined PK/PD targets. We included 339 patients from 30 ICUs across 12 countries. Median age 62 (interquartile range [IQR], 51-70) years, median APACHE II score 22 (IQR, 17-28), and 61% males. Antifungal therapy was primarily prescribed for treatment (80.8%). Fluconazole was the most frequently prescribed antifungal (40.7%). The most common indication for treatment was intra-abdominal infection (30.7%). Fungi were identified in 45% of patients, of which only 26% had a minimum inhibitory concentration available. Target attainment was higher for patients receiving prophylaxis (> 80% for most drugs). For patients receiving treatment, low target attainment was noted for voriconazole (57.1%), posaconazole (63.2%), micafungin (64.1%) and amphotericin B (41.7%). This study highlights the varying degrees of target attainment across antifungal agents in critically ill patients. While a significant proportion of patients achieved the predefined PK/PD targets, wide variability and subtherapeutic exposures persist. ClinicalTrials.gov Identifier: NCT03136926, 2017-04-21.

Brain-targeting drug delivery systems: The state of the art in treatment of glioblastoma.

Glioblastoma (GBM) is the most prevalent primary malignant brain tumor, characterized by a high mortality rate and a poor prognosis. The blood-brain barrier (BBB) and the blood-tumor barrier (BTB) present significant obstacles to the efficacy of tumor-targeted pharmacotherapy, thereby impeding the therapeutic potential of numerous candidate drugs. Targeting delivery of adequate doses of drug across the BBB to treat GBM has become a prominent research area in recent years. This emphasis has driven the exploration and evaluation of diverse technologies for GBM pharmacotherapy, with some already undergoing clinical trials. This review provides a thorough overview of recent advancements and challenges in targeted drug delivery for GBM treatment. It specifically emphasizes systemic drug administration strategies to assess their potential and limitations in GBM treatment. Furthermore, this review highlights promising future research directions in the development of intelligent drug delivery systems aimed at overcoming current challenges and enhancing therapeutic efficacy against GBM. These advancements not only support foundational research on targeted drug delivery systems for GBM but also offer methodological approaches for future clinical applications.

Deep unsupervised clustering for prostate auto-segmentation with and without hydrogel spacer

Abstract Introduction. Clinical datasets for training deep learning (DL) models often exhibit high levels of heterogeneity due to differences such as patient characteristics, new medical techniques, and physician preferences. In recent years, hydrogel spacers have been used in some prostate cancer patients receiving radiotherapy to separate the prostate and the rectum to better spare the rectum while achieving adequate dose coverage on the prostate. However, this substantially affects the computed tomography image appearance, which downstream reduced the contouring accuracy of auto-segmentation algorithms. This leads to highly heterogeneous dataset. Methods. To address this issue, we propose to identify underlying clusters within the dataset and use the cluster labels for segmentation. We collected a clinical dataset of 909 patients, including those with two types of hydrogel spacers and those without. First, we trained a DL model to locate the prostate and limit our field of view to the local area surrounding the prostate and rectum. We then used Uniform Manifold Approximation and Projection (UMAP) for dimensionality reduction and employed k-means clustering to assign each patient to a cluster. To leverage this clustered data, we propose a text-guided segmentation model, contrastive language and image pre-training (CLIP)-UNet, which encodes the cluster information using a text encoder and combines the encoded text information with image features for segmentation. Results. The UMAP results indicated up to three clusters within the dataset. CLIP-UNet with cluster information achieved a Dice score of 86.2% compared to 84.4% from the baseline UNet. Additionally, CLIP-UNet outperforms other state-of-the-art models with or without cluster information. Conclusion. Automatic clustering assisted by DL can reveal hidden data clusters in clinical datasets, and CLIP-UNet effectively utilizes clustered labels and achieves higher performance.

Congenital hypothyroidism and associated visual-motor and intellectual development.

Congenital hypothyroidism's sequelae include visuomotor and intellectual developmental deficits. Visual-motor perception is a cognitive function related to academic performance. Intellect is the ability to learn and use acquired knowledge to solve and achieve goals. Our objective was to evaluate visual-motor and intellectual development in children with late initiation of treatment for congenital hypothyroidism enrolled in a developmental follow-up and intervention program. We evaluated the visual-motor and intellectual development of 75 infants with congenital hypothyroidism, 34 with athyrosis, and 41 with ectopia using the Bender Visual-Motor Development Test and the Weschler Intelligence Scale at eight and nine years of age. Children with ectopia had a visual-motor delay of -2 years and an Intelligence Quotient (IQ)greater than 98 points. Children with athyrosis had a visual-motor delay equivalent to -3.2 years and an IQ below 90 points. Better performance on Bender's test was positively correlated with IQ. Attending more than 80% of Developmental Intervention Program appointments had a positive impact on intellectual development. Timely diagnosis and early treatment with the appropriate dose of levothyroxine are determining factors; however, attendance to a development follow-up and intervention program could further support the cognitive development of children with congenital hypothyroidism. Visuomotor development influences cognitive functions related to school performance. Deficits in the ability to learn and use acquired knowledge to solve problems and achieve goals are characteristic of children with congenital hypothyroidism. Delayed treatment is associated with more severe sequelae in both visual-motor and intellectual development. Here, we show that treatment with adequate doses of levothyroxine and inclusion in a follow-up and developmental program are highly recommended for patients with delayed treatment. A better understanding of these factors will allow clinicians to target therapeutic interventions.

High-intensive physical rehabilitation approach in children and adolescents with acquired brain injury during subacute phase (REHABILITY): a feasibility study protocol

IntroductionWhile principles of neuroplasticity and motor learning emphasise the potential of high dosage of physical rehabilitation in children and adolescents with acquired brain injury (ABI) during the subacute phase, we...

Impact of seasonal malaria chemoprevention timing on clinical malaria incidence dynamics in the Kedougou region, Senegal.

Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine is recommended by the World Health Organization since 2012 for clinical malaria prevention in children in the Sahelian region of Africa. In Senegal, SMC implementation began in 2013 and is given to children under 10 years old. This study aimed to describe clinical malaria incidence in the general population during routine SMC implementation and to analyse how SMC timing impacted clinical malaria dynamics in eligible children. We conducted an ecological study in the Kedougou region of Senegal in 27 villages included in the Bandafassi Health and Demographic Surveillance System (HDSS). We calculated weekly Plasmodium falciparum malaria incidence by age group using malaria case data recorded by community health workers and health-posts, and population denominators obtained from Bandafassi Health and Demographic Surveillance System. We used negative binomial generalized additive multilevel models to analyse the incidence of clinical episodes in children under 10 years during the expected SMC prophylactic period and at the end of the transmission period. Malaria incidence was strongly seasonal with a high transmission period starting in June. Children under SMC presented an overall lower incidence compared to older children and young adults. Among children eligible for SMC, the incidence was lowest for approximately 3 weeks after treatment administration and increased subsequently, suggesting a gradual loss of protection. At the end of the high transmission period, a higher malaria incidence was recorded from the 3rd to 6th week after the week of administration of the fourth (final) SMC round. While protecting children under 10 years, SMC warrants adjustment to reduce exposure before the next round, to increase protection of 5-9 years, and to cover the high transmission period completely. The addition of a 5th round of SMC in 2023 was necessary to cover the end of the transmission season, but individual-level studies are required to ensure that drug efficacy and adequate dosing are maintained.

Clinical Pharmacokinetics of Antitubercular Drugs in the Overweight and Obese Population: Implications for Dosage Adjustments.

The rise in global obesity prevalence has increased the need to understand the pharmacokinetics of drugs in overweight and obese individuals. Tuberculosis remains a significant health challenge, and its treatment outcomes can be influenced by the pharmacokinetic profiles of antitubercular agents. This literature review aims to point out the clinical pharmacokinetics of antitubercular drugs in the overweight and obese patient population, highlighting considerations for potential dosage adjustments. We conducted a comprehensive search of the PubMed US National Library of Medicine from inception to January 2024. Articles focusing on the pharmacokinetics of antitubercular agents used for both drug-susceptible and multidrug-resistant tuberculosis in overweight and obese adults were included. In total, 349 scientific articles were identified and examined for human pharmacokinetic parameters. Of these, 19 were included in this article. To highlight potential differences, pharmacokinetic data for normal-weight tuberculosis patients are also presented, albeit selectively. In general, pharmacokinetic studies of antitubercular agents in overweight and obese individuals are lacking. Fixed-dose combinations often used in the treatment of drug-susceptible tuberculosis are not recommended when treating these population groups. Rather, individual dosing based on therapeutic drug monitoring and the known solubility of the substance should be considered. To improve the management of tuberculosis in overweight and obese patients, there is an urgent need for pharmacokinetic studies and, ultimately, adequate dosing in this patient population, especially given the increasing prevalence of obesity.

Bacteriological Profile and Antibiotic Sensitivity Pattern of Urinary Tract Infection

Introduction:Urinary tract infection (UTI) is a common infection that may occur in any part of the urinary system - kidneys, ureters, bladder and urethra. UTIs are caused by a wide range of pathogens, and recurrence rates of UTIs are high. Antibiotic resistance to microorganism is a burning issue all over the world due to inappropriate antibiotic use. Antibiotic resistance leads to morbidity, mortality and overall, the economic burden. Therefore, surveillance of antimicrobial resistance of UTI is essential to see its impact on population health and local treatment practices. Objective: This study was conducted to identify the bacterial agents of urinary tract infections and determine antibiogram patterns. Methods: A cross-sectional study was conducted at the outpatient service. The study included all patients who presented with UTIs and the symptoms included urinary frequency, urgency, hematuria, dysuria, and suprapubic discomfort. Those patients with clinical manifestations but are on antibiotics or antibiotics completed within the past five days were excluded. Results: The prevalence of UTI is high among females (88.67%) than males (13.33%). Among 30 samples, the pathogens implicated were Escherichia coli (E. coli) 24 (80%), Klebsiella 3. Organisms showed higher sensitivity toward Meropenem and Imipenem (100%) followed by Amikacin and Nitrofurantoin (96.6%). Isolates organisms showed high resistance levels to betalactamaes ampicillin (60%) and cephalosporines groups. According to the sensitivity profiles, the most effective oral antibiotics were Nitrofurantoin (96%) followed by Ciprofloxacin (90%). Conclusion:This study findings emphasize the significance of local antibiotic resistance patterns in urinary tract infection. More studies can be done to create local and national guidelines and physicians should use rational and adequate dose of antibiotics to avoid the emergence of antibiotic resistance. EWMCJ Vol. 13, No. 1, January 2025: 23-27

Resistant and Apparently Resistant Hypertension in Peritoneally Dialyzed Patients.

Hypertension in chronic kidney disease patients is very common. The definition of resistant hypertension in the general population is as follows: uncontrolled blood pressure (BP) on three or more hypotensive agents in adequate doses, or when patients are on four or more hypotensive agent categories irrespective of the BP control, with diuretics included in the therapy. However, these resistant hypertension definitions do not apply to the setting of end-stage kidney disease. True resistant hypertension is diagnosed when adherence to treatment and uncontrolled values of BP by ambulatory blood pressure measurement or home blood pressure measurement are confirmed. Due to these limitations, apparent treatment-resistant hypertension (ATRH) is now defined as an uncontrolled blood pressure on three or more antihypertensive medication classes or the introduction and use of four or more medications regardless of blood pressure level. Concerning dialysis patients, data are very limited on hypertension, its epidemiology, and the prevalence of apparent treatment-resistant hypertension in peritoneal dialysis. In this review, therefore, we discuss the hypertension definitions, targets of the therapy in patients on peritoneal dialyses, and their biases and limitations. We present the pathophysiology, diagnosis, and management of high blood pressure in the peritoneally dialyzed population together with published data on the apparent treatment-resistant hypertension prevalence in this population. Peritoneally dialyzed patients represent a unique population of dialyzed subjects; therefore, studies should be conducted on a larger population with a higher quality of drug adherence and target blood pressure values. The definition of resistant hypertension and apparent resistant hypertension in this group should be redefined, which should also consider residual kidney function in relation to both subclinical and clinical endpoints.

A study of association between maternal tetanus toxoid immunization and neonatal mortality in the context of Bangladesh.

Maternal tetanus toxoid (MTT) vaccination during pregnancy remains an important factor for reducing infant mortality globally, especially in developing nations, including Bangladesh. Despite commendable progress in reducing child mortality through widespread MTT vaccination during pregnancy, the issue still exists. This analysis explores the impact of MTT vaccination on neonatal mortality in Bangladesh and identifies associated factors. This research utilizes data from the 2019 Bangladesh Multiple Indicator Cluster Survey (MICS). The dataset consists of 23,402 cases; among them, 587 cases resulted in infant death. The outcome variable was infant mortality, which was binary. The independent variables identified as potential contributors to the cause of death included tetanus toxoid vaccination status, mode of delivery (cesarean section or not), and mother's education level, among others. The Poisson model was employed to analyze the data. The analyses showed that the neonatal mortality rate was 2.51%. Notably, 45.90% of mothers received the MTT vaccination during pregnancy. Among them, 23.07% received a single dose, and 22.82% took adequate doses (receiving more than two doses) and adhered to WHO guidelines. The adjusted incidence rate ratio (IRR) was 1.36, which indicates that there was a 36% higher risk of neonatal mortality for those children whose mothers did not take TT (IRR = 1.36, p = 0.081). We also found that women from middle-class households (IRR = 1.58, 95% CI = 0.98, 2.54) and women with higher parity (IRR = 1.96, 95% CI = 0.95, 4.03) also had a higher risk of newborn fatalities. A comparable trend has been observed regarding the correlation between the number of tetanus doses administered and neonatal mortality, where it also emphasizes the importance of receiving adequate doses (a minimum of 2 doses of tetanus vaccine) to mitigate neonatal mortality (adjusted IRR = 0.54, 95% CI = 0.29, 1.01) in comparison to no doses received. Administering a minimum of one maternal tetanus dose significantly lowers the risk of neonatal mortality. Other than Maternal Tetanus Toxoid vaccination, the analyses underscore various contributors to neonatal mortality, encompassing maternal healthcare, delivery procedures, socio-economic status, and education. Targeted interventions addressing these factors have the potential to efficiently decrease neonatal mortality rates and improve overall maternal and child health.

Examining the association between fentanyl use and perceived adequacy of methadone dose: A retrospective cohort study.

People exposed to fentanyl may report that the dose of methadone in the commonly accepted therapeutic range feels too low. We examined self-reported methadone dose adequacy. We conducted a retrospective cohort study of individuals prescribed methadone at a dose of at least 60mg daily using data from three community-recruited prospective cohort studies of people who use drugs in Vancouver, Canada from December 2016 through March 2020. We used multivariable generalized estimating equations to estimate the relationship between type of opioid exposure - measured using urine drug tests and categorized as: (1) fentanyl-positive, (2) fentanyl-negative opioid-positive, and (3) fentanyl- and opioid-negative, and report of their methadone dose being too low. In total, 1732 observations from 616 participants were included, of which 914 (52.8 %) observations had a fentanyl-positive, 178 (10.3 %) had a fentanyl-negative opioid-positive, and 640 (37.0 %) had a fentanyl- and opioid-negative urine drug test. Compared with those with a fentanyl-positive urine drug test, in the adjusted model those with a fentanyl- and opioid-negative urine drug test were significantly less likely to report their methadone dose as too low (adjusted odds ratio [AOR]=0.57, 95 % CI 0.41-0.81), while there was no significant association among those with a fentanyl-negative opioid-positive urine drug test (AOR=0.92, 95 % CI 0.59-1.43). We found that exposure to non-fentanyl opioids while on methadone was not associated with feeling the dose was too low compared with individuals exposed to fentanyl. Our findings support adequate titration of methadone for individuals with continued exposure to unregulated opioids including fentanyl.

Effects of Ketamine and Esketamine on Cognitive Functions in Treatment-Resistant Depression

Major depressive disorder is a public health issue that negatively impacts quality of life and leads to cognitive impairments, causing significant disruptions in work, education, and social life. Treatment-resistant depression is defined as the failure to achieve improvement in depressive symptoms despite the use of at least two different antidepressant medications at adequate doses and durations. Current pharmacological approaches are inadequate for about half of treatment-resistant depression patients, and the effects of these medications on cognitive impairments are limited. Therefore, there is a need for new and effective treatment methods. This review aims to evaluate the effects of ketamine and esketamine on cognitive functions in the treatment of treatment-resistant depression patients. Relevant literature has been reviewed and recent studies have been evaluated. The results of randomized controlled trials indicate that ketamine is effective in treating treatment-resistant depression and can improve specific cognitive domains. Significant improvements in cognitive functions such as visual memory, processing speed, working memory, and attention have been recorded in patients responding to 0.5 mg/kg ketamine infusion. However, long-term use of ketamine may have negative effects on spatial working memory. Esketamine, an NMDA receptor antagonist, has shown rapid and effective antidepressant outcomes, providing stability or improvement in cognitive functions. Additionally, its intranasal administration offers practical advantages. However, findings suggest that high doses of esketamine may have neurotoxic effects and negatively impact cognitive functions. The effects of both drugs on depressive symptoms and cognitive functions vary depending on dose, duration of use, and frequency of administration. In conclusion, while ketamine and esketamine show significant potential in the treatment of treatment-resistant depression and improvement of cognitive symptoms, further research is needed regarding their long-term effects and safety.

Antibiotic-associated dysbiosis: modern strategy for microbiota restoration. A review

Antibiotic-associated dysbiosis is a disorder of the intestinal microbiota caused by antibiotics, which can contribute to the development of antibiotic-associated diarrhea and other complications. Disorder of a previously stable, functionally complete microbiota can lead to adverse health effects in both the short and long term, with a potential increase in the risk of various non-communicable diseases, as well as neurological, behavioral, and psychological disorders. Current microbiota recovery strategies include specific probiotics such as Saccharomyces boulardii CNCM I-745 and Lactobacillus rhamnosus GG. Systematic reviews and meta-analyses of clinical studies confirm the strain-specific efficacy of these probiotics in the treatment and prevention of antibiotic-associated diarrhea in both children and adults and also demonstrate that timely administration of an adequate dose of a probiotic (from day 1 of antibiotic therapy) can help prevent or eliminate the consequences of antibiotic-associated dysbiosis and contribute to the preservation of the resilience of the intestinal microbiota, returning it to the state preceding the use of antibiotics.

Second-step strategies in antidepressant pharmacotherapy : Results of current meta-analyses

Antidepressant pharmacotherapy often does not result in the desired effect despite adequate duration and dose. Better evidence on second-step strategies is needed. Overview of the current evidence for various pharmacological second-step strategies after nonresponse to antidepressant monotherapy. Summary of recent systematic reviews with meta-analyses of the group of authors on pharmacological second-step treatment. Ameta-analysis showed no advantage of switching to asecond antidepressant compared with continuing the previously ineffective monotherapy. Another two meta-analyses showed no benefit of increasing the dose of selective serotonin reuptake inhibitors (SSRI). For serotonin and noradrenaline reuptake inhibitors (SNRI) and tricyclic antidepressants (TCA) in each case ameta-analysis showed no clear advantage of increasing the dose. Another two meta-analyses showed asuperiority of acombination therapy consisting of areuptake inhibitor (SSRI, SNRI, TCA) with apresynaptic alpha‑2 autoreceptor antagonist (e.g., mirtazapine) compared with an antidepressant monotherapy. In accordance with the recommendations of the German national treatment guideline, in the event of nonresponse to antidepressant monotherapy, the combination of two antidepressants is preferable to repeated switching of the antidepressant.

Accelerated Low-Dose Total Skin Electron Beam Therapy Using the Modified Stanford Technique: An In Vivo Dosimetry Confirmation Study.

Purpose Low-dose total skin electron beam therapy (LD-TSEBT) has recently gained popularity in treating mycosis fungoides (MF) due to its reduced toxicity and favorable response rates. Combining accelerated LD-TSEBT with the modified Stanford technique (mST), a condensed cycling approach, offers a promising and convenient option. However, in vivo dosimetry data confirming the effectiveness of this approach is limited. We retrospectively analyzed in vivo data from patients who received accelerated LD-TSEBT using the mST for MF. Methods Patients treated with accelerated LD-TSEBT using the mST for MF were identified. Optically stimulated radiation dosimeters (OSLDs) were used to measure doses at 10 anatomical sites: vertex, larynx, right shoulder, right forearm, right hip, umbilicus, left medial thigh, right knee, left dorsal foot, and left dorsal hand. Measurements were aggregated and compared to the prescribed dose, using the European Organisation For Research And Treatment Of Cancer (EORTC) homogeneity tolerance criteria, whichaccountfor the American Association of Physicians in Medicine (AAPM) TG023 setup variability: ±20% of the prescribed dose. Patient characteristics, demographics, and disease details were also collected. Descriptive statistics were performed to evaluate clinical and dosimetric characteristics. Results Thirty-six patients were identified, and 360 OSLD measurements were recorded. The median of all OSLD measurements relative to the prescribed dose at all sites was 97.4%. The highest median delivered dose was recorded at the umbilicus (106%)and the lowest at the left dorsal hand (79%). After accounting for deviation at the left dorsal hand, 85.8% of all OSLD measurements met the homogeneity criteria at the other anatomic sites. Other patient metrics, such as height and BMI, did not impact the median delivered OSLD dose or number of anatomical sites per patient meeting the EORTC tolerance criteria. Conclusion Accelerated LD-TSEBT using the mST delivers accurate doses, with most subjects meeting the EORTC tolerance criteria. This study supports the use of OSLDs for in vivo dosimetry in patients undergoing this regimen, ensuring adequate dosing despite the truncated cycling approach.

Virtual Reality Therapy for Chronic Pain: A Scoping Review on Indications, Mechanisms of Action, and Effectiveness

Background: The application of virtual reality (VR) technology as a nonpharmacologic treatment option for chronic pain has been increasingly studied. However, the mechanisms underlying this treatment modality's potential positive effects and appropriate indications are not well understood or summarized in the literature. Objectives: This scoping review aims to better understand the chronic pain populations best indicated for head-mounted display-based VR interventions, explore their efficacy on pain score reduction, and characterize the mechanisms of action underlying their efficacy. Methods: PubMed database systematic searches were conducted including articles from January 2010 to August 2023 with primary qualifying criteria including but not limited to use of head-mounted display VR and adequate VR treatment dosage. Mechanisms of action(s) were deduced via an exploratory approach whereby characteristics of VR treatment interventions were analyzed and categorized. Results: Fourteen studies met qualifying criteria, representing a total treatment group of 327. Study data extracted were solely relative to VR treatment group participants. VR intervention mechanisms of action were best characterized via 2 broad but distinct categories: addressing kinesiophobia and psychobehavioral modulation. Three studies investigating chronic neck pain used addressing kinesiophobia as a mechanism of action and demonstrated a significant improvement [weighted average numerical rating scale (NRS): 4.6 at baseline, 2.5 post-intervention, and 2.5 3 months post-intervention]. Six studies investigated chronic low back pain, for which 5 studies, representing 99% of the subgroup, used psychobehavioral modulation. Each demonstrated significant reduction in pain (weighted average NRS: 5.1 baseline and 3.2 post-intervention). Conclusion: This large-scale within-group analysis review proposes 2 broad mechanisms of action underlying the efficacy of VR interventions for chronic pain indications. VR interventions addressing kinesiophobia seem to be significantly effective in nontraumatic chronic neck pain patients. Psychobehavioral VR interventions demonstrate significant efficacy in the chronic low back pain population. Studies with interventions targeting nonspecific chronic pain populations did not show significant results.

Evaluating the Impact of a Peer Support Program on Participants' Well-Being: Finding Belongingness Through the Women Veterans Network.

Loss of belongingness may be particularly pronounced for women veterans, representing a threat to long-term well-being. Improvements in social support through engagement in a structured peer support program may mitigate the negative effects of loss of belongingness on well-being. We assessed the impact of participation in a peer-led, structured, social support group-based network on outcomes related to well-being [i.e., belongingness, social support, quality of life, posttraumatic stress disorder (PTSD), depression]. Subgroup analyses examined relative impact among those who completed the intervention and those reporting clinical levels of PTSD and depression symptoms. We analyzed survey data consisting of reliable and valid measures collected at baseline, postgroup and 3-month follow-up among 393 participants in the Woven Veterans Network's (WoVeN) group program. We observed improvements in posttraumatic stress disorder (PTSD) symptoms over time. We observed additional benefits among those who received an adequate dose of the intervention (significant improvements on PTSD, belongingness) and those with clinical levels of mental health symptoms (significant improvements on PTSD, depression, belongingness, quality of life). Impacts on social support may have been masked due to ceiling effects given wide dispersion baseline social support in this sample. This social support network had particularly profound impacts on well-being for those veterans who suffered from conditions for which isolation and loneliness are particularly salient.

Patient Positional Uncertainty and Margin Reduction in Lung Stereotactic Ablative Radiation Therapy Using Pneumatic Abdominal Compression.

Motion management presents a significant challenge in thoracic stereotactic ablative radiation therapy (SABR). Currently, a 5.0-mm standard planning target volume (PTV) margin is widely used to ensure adequate dose to the tumor. Considering recent advancements in tumor localization and motion management, there is merit to reassessing the necessary PTV margins for modern techniques. This work presents a large-scale analysis of intrafraction repositioning for lung SABR under forced shallow breathing to determine the margin requirements for modern delivery techniques. Treatment data for 124 lung SABR patients treated in 607 fractions on a linear accelerator were retrospectively collected for analysis. All patients were treated using pneumatic abdominal compression and intrafraction 4-dimensional (4D) cone beam computed tomography (4D CBCT)-guided repositioning halfway through treatment. Executed repositioning shifts were collected and used to calculate margin requirements using the 2-SD method and an analytical model which accounts for systematic and random errors in treatment. A total of 85.7% of treated fractions had 3-dimensional repositioning shifts under 5.0 mm. Fifty-three fractions (8.7%) had shifts ≥ 5.0 mm in at least 1 direction. Margins in the right-left, inferior-superior, and posterior-anterior directions were 3.62 mm, 4.34 mm, and 3.50 mm, respectively, calculated using the 2-SD method. The analytical approach estimated that 4.01 mm, 4.37 mm, and 3.95 mm margins were appropriate for our workflow. Executing intrafraction repositioning reduced margin requirements by 0.73 ± 0.07 mm. Clinical data suggest that the uniform 5.0-mm margin is conservative for our workflow. Using modern techniques such as 4D CT, 4D CBCT, and effective motion management can significantly reduce required margins, and therefore necessary healthy tissue dose. However, the limitations of margin calculation models must be considered, and margin reduction must be approached with caution. Users should conduct a formal risk assessment prior to adopting new standard PTV margins.