6-week Course Research Articles

Repetitive transcranial magnetic stimulation can improve negative symptoms and/or neurocognitive impairments in the first psychosis episode: A randomized controlled trial

ObjectiveNegative symptoms and neurocognitive impairments in psychosis correlate with their severity. Currently, there is no satisfactory treatment. We aimed to evaluate and compare the effects of repetitive transcranial magnetic stimulation(rTMS) on negative symptoms and neurocognitive impairments in patients in first-episode of psychosis(FEP) in a randomized controlled trial(RCT). MethodThis is a single-site RCT of 85 patients with FEP. Patients were randomized to receive a 4-week course of active(n = 45) or sham rTMS(n = 40). Factor analysis was applied to a cross-sectional dataset of 744 FEP patients who completed negative symptom evaluation and neurocognitive battery tests. Two independent dimensions were generated and used for the K-means cluster analysis to produce sub-clusters. rTMS of 1-Hz was delivered to the right orbitofrontal(OFC) cortex. ResultsTwo distinct dimensional factors of neurocognitive functions(factor-1) and negative symptoms(factor-2), and three clusters with distinctive features were generated. Significant improvements in factor-1 and factor-2 were observed after 4-weeks of rTMS treatment in both the active and sham rTMS groups. The repeated-measures analysis of variance revealed a significant effect of time×group(F = 5.594, p = 0.021, η2 = 0.073) on factor-2, but no effect of time×group on factor-1. Only improvements in negative symptoms were significantly different between the active and sham rTMS groups(p = 0.028). Patients in cluster-3 characterized by extensive negative symptoms, showed greater improvement in the active rTMS group than in the sham rTMS group. ConclusionsThe 1-Hz right OFC cortex rTMS is more effective in reducing negative symptoms than neurocognitive impairments. It is especially effective in patients with dominantly negative symptoms in FEP.

The effectiveness of a short course to improve coaches’ knowledge on considerations for female athletes

ABSTRACT This study aimed to assess the effectiveness of an online short course in improving the knowledge and confidence of coaching and support staff when working with female athletes. A mixed-methods survey design was used, where participants completed surveys pre-, post-, and 6 months following an 8-week online course. Qualitative responses were analysed inductively using thematic analysis based on two pre-identified themes. Of the 92 participants who completed both pre- and post-course surveys, 72% (n = 66) were female and 67% (n = 62) were from team sports. Perceived knowledge and confidence improved following the course (p < 0.001) and were above pre-course values 6-months post (p < 0.001). A-priori theme Course Expectations generated two sub-themes: ’Empowering [me] to empower and support [them]’, and “Sharing knowledge and experiences”. A-priori theme Changes in Practice had subthemes of “Relaxing into it” and “Embedding support structures”. Participants indicated that they enjoyed learning from a variety of content experts as well as other participants in an online format. Future courses aimed at coaching/support staff should design and deliver accessible programs aligned with the learning preferences of these individuals. When delivering specific education regarding supporting female athletes, targeting and encouraging men to participate may be beneficial.

Feasibility, Acceptability, and Potential Efficacy of a Mobile Health Application for Community-Dwelling Older Adults with Frailty and Pre-Frailty: A Pilot Study.

Smartphone applications aimed at enhancing physical, cognitive, and social activities through mobile health (mHealth) technology are of increasing interest. Their feasibility and acceptability, alongside impacts on frailty phenotype scores and step counts among older adults with frailty, remain to be fully validated. This study presents a 13-week preliminary intervention trial assessing an mHealth app's feasibility in a cohort of 34 eligible older adults, including 5 frail and 29 pre-frail participants. The intervention entailed a 6-week course on app usage, followed by 7 weeks of observation, with four participants withdrawing early. Feasibility was determined by login and active use rates, with a target login rate of 60% or higher. Post-intervention, 100% session attendance and a median login rate of 88.4% were observed. Acceptability was high, with 73% affirming the app's health benefits. Notably, frailty scores and step counts improved post-intervention, underscoring the app's potential for supporting older adults with frailty.

LSD increases sleep duration the night after microdosing

Microdosing psychedelic drugs at a level below the threshold to induce hallucinations is an increasingly common lifestyle practice. However, the effects of microdosing on sleep have not been previously reported. Here, we report results from a Phase 1 randomized controlled trial in which 80 healthy adult male volunteers received a 6-week course of either LSD (10 µg) or placebo with doses self-administered every third day. Participants used a commercially available sleep/activity tracker for the duration of the trial. Data from 3231 nights of sleep showed that on the night after microdosing, participants in the LSD group slept an extra 24.3 min per night (95% Confidence Interval 10.3–38.3 min) compared to placebo—with no reductions of sleep observed on the dosing day itself. There were no changes in the proportion of time spent in various sleep stages or in participant physical activity. These results show a clear modification of the physiological sleep requirements in healthy male volunteers who microdose LSD. The clear, clinically significant changes in objective measurements of sleep observed are difficult to explain as a placebo effect. Trial registration: Australian New Zealand Clinical Trials Registry: A randomized, double-blind, placebo-controlled trial of repeated microdoses of lysergic acid diethylamide (LSD) in healthy volunteers; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381476; ACTRN12621000436875.

Sequential endoluminal gemcitabine and docetaxel vs. Bacillus Calmette–Guérin for the treatment of upper tract carcinoma in situ

IntroductionNephroureterectomy is commonly performed for high-grade (HG) upper tract (UT) urothelial carcinoma (UC). However, some patients may benefit from a de-escalation of surgical management, particularly for noninvasive disease and carcinoma in situ (CIS). Bacillus Calmette–Guerin (BCG) is currently the only guideline-recommended endoluminal treatment option. Gemcitabine/Docetaxel (Gem/Doce) has shown promising efficacy as a treatment for noninvasive HG UTUC, though a comparison to BCG is lacking. We report the outcomes of patients treated with endoluminal Gem/Doce vs. BCG for UT-CIS. MethodsA single-institutional retrospective review of patients treated with Gem/Doce vs. BCG for UT-CIS was performed. Treatment was instilled via nephrostomy or retrograde ureteral catheter. In both treatment groups, induction consisted of 6 weekly instillations. Maintenance was initiated if disease-free and consisted of 6 monthly instillations in the Gem/Doce group and a reduced dose (one-tenth) 3-week course at 3 months in the BCG group. Recurrence was defined as biopsy-proven disease or HG cytology. ResultsThe final cohort included 53 patients with 65 upper tract units; 31 received BCG and 34 received Gem/Doce. Median follow-up was 88 and 29 months in the BCG and Gem/Doce groups, respectively. Presenting pathology included biopsy-proven CIS and HG cytology in 9.7% and 90% of the BCG group, and 8.8% and 91% of the Gem/Doce group, respectively. The 2-year estimates for recurrence-free and nephroureterectomy-free survival were 61% and 89% for the BCG group and 54% and 100% for the Gem/Doce group, respectively. Upon multivariable analysis, instillation via percutaneous nephrostomy tube was associated with an increased risk of recurrence (HR 3.89, 95% CI 1.59–9.53). The development of any symptom was not statistically different between treatment groups (P = 0.12). There were 2 treatment-related deaths that occurred, 1 within each treatment group. ConclusionEndoluminal Gem/Doce and BCG have similar oncological outcomes and major adverse event rates in the treatment of UT-CIS. Further prospective evaluation is warranted.

Impact of a Special Operations Forces Basic Training on Body Composition and Energy Expenditure.

The Belgian Special Operations Regiment undergoes an 8-week basic training course (SOF Basic Course) following the Military Initiation Phase. The aims of the present study were to estimate energy expenditure and changes in body composition during SOF Basic Course. A multi frequency body composition analyser assessed baseline and endpoint body composition. For the purpose of estimating energy expenditure, 41 participants were fitted with triaxial accelerometers. T-tests were performed on paired and unpaired samples in order to estimate statistical significance. Effect size was estimated with Cohen's d. SOF Basic Course was completed by 88 out of 126 participants. The participants' mean (SD) age was 25.0 (4.1) years, weight was 77.6 (8.6) kg, and body fat percentage was 15.3% (3.3). Body weight of completers decreased from 78.3 (8.8) kg to 76.4 (8.0) kg (P = 0.01). Also, body fat decreased by 3.1 (1.8) kg (P = 0.01), and muscle mass increased by 1.2 (1.7) kg (P = 0.01). There was a decrease in body fat percentage from 15.3% (3.3) to 11.6% (3.4) (P = 0.01), with a Cohen's effect size of 1.86.The loss of 3.1 kg of body fat corresponds to a loss of 21,700.0 kcal (90.3 MJ) or 362.0 kcal.d-1 (1.5 MJ.d-1). The mean (SD) energy expenditure by physical activity was 1,943.0 (653.8) kcal.d-1 (14.6 [2.7] MJ.d-1). The average (SD) total energy expenditure was 4,088.0 (710.0) kcal.d-1 (36.8 [3.8] MJ.d-1). Tactical athletes must perform in hypo-energetic environment. Research in the future should investigate the impact of increased energy intake on body composition.

A Rare Case of Tuberculous Constrictive Pericarditis Due to Disseminated Tuberculosis with Response to Anti-tuberculosis Chemotherapy and Steroids in a Developed City State

A 27-year-old man presented with a 1-week history of atypical chest pain and sinus tachycardia. His physical examination was unremarkable. His resting ECG showed sinus tachycardia with widespread T-wave inversion. His initial blood tests show mildly raised troponin T and inflammatory markers and marked raised D-dimer. A CT pulmonary angiogram was performed to exclude pulmonary embolism but incidentally revealed an anterior mediastinal mass. A transthoracic echocardiogram and cardiac MRI showed features of constrictive pericarditis. A video-assisted thoracoscopic surgical biopsy of the anterior mediastinal mass showed thymic tissue with necrotising granulomatous inflammation and an acid-fast bacilli culture was positive to tuberculosis infection. The patient was started on anti-tuberculosis chemotherapy and a 6-week tapering course of oral steroids. A repeat cardiac MRI performed after 6 weeks of treatment showed a significant response to treatment with resolution of constrictive physiology.

Early Experience With Biologically Effective Dose-Comparable Short-Course Whole Brain Radiation Therapy for Metastatic Intracranial Disease.

For inpatients with metastatic intracranial disease burden exceeding established guidelines for stereotactic radiosurgery (SRS), the standard of care involves whole brain radiation therapy (WBRT), typically administered as a 2-week course of treatment with biologically effective dose (BED) of 60Gy. However, shorter course WBRT provides theoretical advantages in quality of life and decreasing systemic therapy delay. This retrospective study evaluates our early experience with BED-comparable short-course WBRT (23Gy in 5 fractions; BED=58.3Gy) for metastatic intracranial disease. Over a recent 2-month timeframe, 3 inpatients with intracranial disease burden exceeding SRS guidelines were administered BED-comparable short-course WBRT. Due to the high intracranial disease burden, 23Gy was chosen over 20Gy for 5-fraction WBRT due to the desire to optimally mimic the durability of the classic 30Gy in 10 fraction treatment regimen. The mean age at treatment was 65.7 years, the mean Karnofsky Performance Status (KPS) was 60, and the mean number of intracranial metastases was 20.3. The mean duration between inpatient Radiation Oncology consultation and the start of WBRT (following CT radiation therapy simulation) was 6.7 days. All patients completed WBRT no later than 2 weeks from the initial inpatient consultation. For inpatients with intracranial metastatic disease burden exceeding established SRS guidelines, BED-comparable short-course WBRT administered to 23Gy in 5 fractions (4.6Gy/fraction) is safe and efficacious. Given previous literature indicating that nearly half of the patients prescribed traditional 2-week WBRT die without completing treatment, BED-comparable WBRT represents an attractive and promising WBRT alternative in this patient population.

Emphasizing the Importance of Naproxen Prophylaxis May Decrease the Rate of Heterotopic Ossification After Hip Arthroscopy

To investigate the incidence of heterotopic ossification (HO) in patients prescribed prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs), both before and after the introduction of a standardized education protocol. A retrospective review was conducted using a database of hip arthroscopy patients treated by a single surgeon at an academic hospital from 2015 to 2023. The inclusion criteria were (1) primary hip arthroscopy for the treatment of femoroacetabular impingement, (2) completion of a 2-week course of prophylactic postoperative NSAIDs (500 mg of naproxen twice daily), and (3) availability of follow-up radiographs at the 6-month postoperative visit. The control cohort was merely prescribed the postoperative prophylactic NSAIDs, whereas the intervention cohort also received dedicated in-person education, emphasizing the importance of NSAID adherence. The presence of HO was determined through review of follow-up radiographs. Standard descriptive statistics were used to describe the findings. Both the control and intervention groups consisted of 200 continuous hip arthroscopy patients, with the control group treated from 2015 to 2017 and the intervention group treated from 2020 to 2023. Within the control group, 10 cases of HO (5%) were detected. Within the intervention group, 2 cases of HO (1%) were found. The Pearson χ2 test with Yates continuity correction produced a value of 4.21, with a P value of .04. In this study, we found a significantly lower incidence rate of HO in patients who received standardized education on the importance of NSAID compliance versus those who did not. This finding suggests that patient education may play a contributory role in reducing the incidence of HO after hip arthroscopy. Level III, comparative cohort study.

The significance of subjective mechanical symptoms in rotator cuff pathology

BackgroundThe presence of subjective mechanical symptoms, such as clicking or popping, is common in patients presenting for shoulder pain and dysfunction, with unclear clinical significance. The primary objective of this study was to assess whether subjective mechanical symptoms in the affected shoulder were associated with full-thickness rotator cuff tearing in a consecutive, prospective cohort of patients undergoing shoulder magnetic resonance imaging (MRI) for suspected rotator cuff pathology. MethodsA prospective cohort study was performed of 100 consecutive patients with suspected rotator cuff tendinopathy and/or tearing who underwent shoulder MRI. The presence of subjective shoulder mechanical symptoms, including clicking or popping, was documented prior to MRI. Indications for MRI included weakness on isolated testing of rotator cuff muscle(s) or symptoms refractory to conservative treatment including at least a 6-week course of physical therapy. The primary outcome variable was the presence of full-thickness rotator cuff tearing; secondary outcome variables included any (full-thickness or partial-thickness) rotator cuff tearing and biceps long head subluxation. Radiographic parameters, including critical shoulder angle, Goutallier grade, tear retraction, and tear size were quantified. One patient was lost to follow-up, and 99 patients completed MRI imaging. ResultsIn our cohort, 60% of patients reported subjective mechanical symptoms in the affected shoulder. Full-thickness rotator cuff tearing was identified in 42% of patients, any rotator cuff tearing in 69% of patients, and biceps long head subluxation in 14% of patients. Subjective mechanical symptoms were not associated with full-thickness rotator cuff tearing, any rotator cuff tearing, biceps long head subluxation, critical shoulder angle, Goutallier grade, tear size, or tear retraction. Older age was associated with full-thickness and any rotator cuff tearing. As a diagnostic test for full-thickness rotator cuff tearing, subjective shoulder mechanical symptoms has a sensitivity of 64%, a specificity of 44%, and Youden’s index of 0.08, consistent with poor diagnostic accuracy. ConclusionsSubjective mechanical symptoms in the affected shoulder are a common complaint in patients with suspected rotator cuff pathology. Patients may be reassured that a sensation of clicking or popping alone does not necessarily entail structural shoulder derangement.

A Case of Deep Cutaneous Mycosis Caused by Purpureocillium lilacinum

Purpureocillium lilacinum, previously known as Paecilomyces lilacinus, is a saprophytic fungus typically found in soil and decaying vegetation. Although it is infrequently pathogenic to humans, recent reports of P. lilacinum infections, primarily affecting the skin and eyes, have shown an increase. This report details a cutaneous infection caused by P. lilacinum in an 89-year-old woman. She presented with a 3-month history of an erythematous patch and nodule on her right forearm. A skin biopsy revealed inflammation, granuloma, and fungal organisms in the dermis. Periodic acid-Schiff (PAS) staining confirmed the presence of fungal elements. The fungal culture of the medium produced colonies with a velvety pink and brown hue. PCR testing on these cultured samples identified P. lilacinum. The patient received a 2-week course of oral itraconazole (200 mg/day), which improved her symptoms. However, ongoing antifungal treatment was necessary. Additionally, due to a recent myocardiac infarction, the patient required a statin. A MIC test was conducted to identify an antifungal drug compatible with statin therapy.

The First Case of Phaeohyphomycosis Caused by Exophiala xenobiotica in an Immunocompetent Patient in Korea

Phaeohyphomycosis is a rare fungal infection caused by dematiaceous fungi commonly associated with immunocompromised patients. Exophiala (E.) species are linked to phaeohyphomycosis, and in Korea, E. dermatitidis, E. jeanselmei, and E. salmonis were previously isolated from affected patients. Here, we describe a unique instance of phaeohyphomycosis in an immunocompetent patient attributed to E. xenobiotica. A 75-year-old female presented with an asymptomatic erythematous crusted subcutaneous nodule on the dorsum of her left-hand. Her past medical history was negative for immunosuppression or trauma to the affected area. Histopathological examination revealed suppurative granulomatous infiltration, with septate hyphae and spores detected by periodic acid-Schiff staining in the dermis. A fungal culture made from a tissue sample revealed E. xenobiotica, with subsequent confirmation through phylogenetic analyses of the internal transcribed spacer (ITS) and large subunit regions (LSU) of ribosomal ribonucleic acid (rRNA). The patient was diagnosed with phaeohyphomycosis and underwent a 3-week course of terbinafine, followed by 7 weeks of fluconazole. These treatments significantly improved the lesion. To our knowledge, this is the first reported case of phaeohyphomycosis caused by E. xenobiotica in Korea.

Predictors of Tumor Dynamics Over a 6-Week Course of Concurrent Chemoradiotherapy for Glioblastoma and the Effect on Survival

We present the final analyses of tumor dynamics and their prognostic significance during a 6-week course of concurrent chemoradiotherapy for glioblastoma in the Glioblastoma Longitudinal Imaging Observational study. This is a prospective serial magnetic resonance imaging study in 129 patients with glioblastoma who had magnetic resonance imaging obtained at radiation therapy (RT) planning (F0), fraction 10 (F10), fraction 20 (F20), and 1-month post-RT. Tumor dynamics assessed included gross tumor volume relative to F0 (Vrel) and tumor migration distance (dmigration). Covariables evaluated included: corpus callosum involvement, extent of surgery, O6-methylguanine-DNA-methyltransferase methylation, and isocitrate dehydrogenase mutation status. The median Vrel were 0.85 (range, 0.25-2.29) at F10, 0.79 (range, 0.09-2.22) at F20, and 0.78 (range, 0.13-4.27) at 1 month after completion of RT. The median dmigration were 4.7 mm (range, 1.1-20.4 mm) at F10, 4.7 mm (range, 0.8-20.7 mm) at F20, and 6.1 mm (range, 0.0-45.5 mm) at 1 month after completion of RT. Compared with patients who had corpus callosum involvement (n = 26), those without corpus callosum involvement (n = 103) had significant Vrel reduction at F20 (P = .03) and smaller dmigration at F20 (P = .007). Compared with patients who had biopsy alone (n = 19) and subtotal resection (n = 71), those who had gross total resection (n = 38) had significant Vrel reduction at F10 (P = .001) and F20 (P = .001) and a smaller dmigration at F10 (P = .03) and F20 (P = .002). O6-Methylguanine-DNA-methyltransferase methylation and isocitrate dehydrogenase mutation status were not significantly associated with tumor dynamics. The median progression-free survival and overall survival (OS) were 8.5 months (95% CI, 6.9-9.9) and 20.4 months (95% CI, 17.6-25.2). In multivariable analyses, patients with Vrel ≥ 1.33 at F10 had worse OS (hazard ratio [HR], 4.6; 95% CI, 1.8-11.4; P = .001), and patients with dmigration ≥ 5 mm at 1-month post-RT had worse progression-free survival (HR, 1.76; 95% CI, 1.08-2.87) and OS (HR, 2.2; 95% CI, 1.2-4.0; P = .007). Corpus callosum involvement and extent of surgery are independent predictors of tumor dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumor enlargement at F10 and tumor migration 1-month post-RT were associated with poorer OS.

Cumulative Blast Impulse Is Predictive for Changes in Chronic Neurobehavioral Symptoms Following Low Level Blast Exposure during Military Training.

Cumulative low-level blast exposure during military training may be a significant occupational hazard, increasing the risk of poor long-term outcomes in brain function. US Public Law 116-92 section717 mandates that US Department of Defense agencies document the blast exposure of each Service member to help inform later disability and health care decisions. However, which empirical measures of training blast exposure, such as the number of incidents, peak overpressure, or impulse, best inform changes in the neurobehavioral symptoms reflecting brain health have not been established. This study was approved by the US Army Special Operations Command, the University of North Carolina at Chapel Hill, and the VA Puget Sound Health Care System. Using methods easily deployable across different organizational structures, this study sought to identify and measure candidate risk factors related to career occupational blast exposure predictive of changes in neurobehavioral symptom burden. Blast dosimetry-symptom relationships were first evaluated in mice and then tested in a military training environment. In mice, the righting time neurobehavioral response was measured after exposure to a repetitive low-level blast paradigm modeled after Special Operations training. In the military training environment, 23 trainees enrolled in a 6-week explosive breaching training course, 13 instructors, and 10 Service member controls without blast exposure participated in the study (46 total). All participants provided weekly Neurobehavioral Symptom Inventory (NSI) surveys. Peak blast overpressure, impulse, total number of blasts, Time in Low-Level Blast Occupation, and Time in Service were analyzed by Bayesian analysis of regression modeling to determine their probability of influence on the post-training symptoms reported by participants. We tested the hypothesis that cumulative measures of low-level blast exposure were predictive of changes in neurobehavioral symptoms. In mice, repetitive blast resulted in reduced righting times correlated with cumulative blast impulse. In Service members, peak blast overpressure, impulse, total number of blasts, Time in Low-Level Blast Occupation, and Time in Service all showed strong evidence of influence on NSI scores after blast exposure. However, only models including baseline NSI scores and cumulative blast impulse provided significant predictive value following validation. These results indicate that measures of cumulative blast impulse may have utility in predicting changes in NSI scores. Such paired dosimetry-symptom measures are expected to be an important tool in safely guiding Service members' occupational exposure and optimizing force readiness and lethality.

A combination nutritional supplement reduces DNA methylation age only in older adults with a raised epigenetic age

An increase in systemic inflammation (inflammaging) is one of the hallmarks of aging. Epigenetic (DNA methylation) clocks can quantify the degree of biological aging and this can be reversed by lifestyle and pharmacological intervention. We aimed to investigate whether a multi-component nutritional supplement could reduce systemic inflammation and epigenetic age in healthy older adults.We recruited 80 healthy older participants (mean age ± SD: 71.85 ± 6.23; males = 31, females = 49). Blood and saliva were obtained pre and post a 12-week course of a multi-component supplement, containing: Vitamin B3, Vitamin C, Vitamin D, Omega 3 fish oils, Resveratrol, Olive fruit phenols and Astaxanthin. Plasma GDF-15 and C-reactive protein (CRP) concentrations were quantified as markers of biological aging and inflammation respectively. DNA methylation was assessed in whole blood and saliva and used to derive epigenetic age using various clock algorithms.No difference between the epigenetic and chronological ages of participants was observed pre- and post-treatment by the blood-based Horvath or Hannum clocks, or the saliva-based InflammAge clock. However, in those with epigenetic age acceleration of ≥ 2 years at baseline, a significant reduction in epigenetic age (p = 0.015) and epigenetic age acceleration (p = 0.0058) was observed post-treatment using the saliva-based InflammAge clock. No differences were observed pre- and post-treatment in plasma GDF-15 and CRP, though participants with CRP indicative of an elevated cardiovascular disease risk (hsCRP ≥ 3µg/ml), had a reduction in CRP post-supplementation (p = 0.0195).Our data suggest a possible benefit of combined nutritional supplementation in individuals with an accelerated epigenetic age and inflammaging.

Language Learning for People Living with Dementia and Their Caregivers: Feasibility and the Quality of Experience.

A body of research from around the world has reported positive effects of bilingualism on cognitive ageing and dementia. However, little is known about whether foreign language learning could be applied as an intervention for people already living with dementia. Yet, before it is possible to determine the efficacy of language courses as an intervention for people living with dementia (PLWD), it is necessary to establish whether such an intervention is feasible. Our study explored this possibility. We conducted an exploratory study to examine the feasibility and tolerability of 2-week Italian beginner courses for PLWD in early stages and their family carers in two Scottish Dementia Resource Centres (DRCs). The courses were delivered by trained tutors from Lingo Flamingo, a social enterprise specialising in language teaching for older learners and learners with dementia. Twelve PLWD and seven carers participated in the study. Focus groups preceded and followed the courses. Additional post-course open interviews with the DRC managers were conducted, with a follow-up via telephone approximately one year later. Qualitative content analysis resulted in 12 themes, 5 reflected in the interview schedule and 7 arising from the focus groups and interviews. Overall, the courses were perceived positively by PLWD, carers, and DRC managers, although a few logistically and linguistically challenging aspects were also mentioned. The courses were found to positively impact both the individual by increasing self-esteem and producing a sense of accomplishment as well as the group by creating a sense of community. Notably, no adverse effects (in particular no confusion or frustration) were reported. The positive outcomes of our study open a novel avenue for future research to explore foreign language training in dementia as an intervention and its implications.

Appropriate Duration of Antimicrobial Treatment for Prosthetic Joint Infections: A Narrative Review.

Prosthetic joint infections are considered difficult to treat they needing aggressive surgery and long antimicrobial treatments. However, the exact duration of these therapies has been established empirically. In the last years, several studies have explored the possibility of reducing the length of treatment in this setting, with conflicting results. In this narrative review, we critically appraise the published evidence, considering the different surgical approaches (implant retention [DAIR] and one-step and two-step exchange procedures) separately. In patients managed with DAIR, usually treated for at least 12 weeks, a large, randomized trial failed to show that 6 weeks were non-inferior. However, another randomized clinical trial supports the use of 8 weeks, as long as the surgical conditions are favorable and antibiotics with good antibiofilm activity can be administered. In patients managed with a two-step exchange procedure, usually treated during 6 weeks, a randomized clinical trial showed the efficacy of a 4-week course of antimicrobials. Also, the use of local antibiotics may allow the use of even shorter treatments. Finally, in the case of one-step exchange procedures, there is a trend towards reducing the length of therapy, and the largest randomized clinical trial supports the use of 6 weeks of therapy.

Local delivery of linezolid in the treatment of complex orthopedic bone and joint infections in patients with vancomycin allergy: a case series.

Introduction: Osteomyelitis is a challenging bone infection associated with ischemia, trauma, or various surgical procedures (e.g., joint reconstruction). Treatment involves eradicating infected bone and soft tissue, local antibiotic delivery, and a 6-week course of antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) infections are common, and vancomycin is the standard treatment, but alternatives like linezolid are needed in vancomycin-resistant and vancomycin-allergic patients. Methods: A retrospective chart review was conducted on patients treated by the senior author between 2013 and 2021. The study included patients who received local delivery of linezolid for bone and/or joint infection with documented evidence of vancomycin allergy. Patient demographics, surgical details, linezolid delivery method, and outcomes were recorded. Clinical outcomes and subsequent procedures leading to infection eradication were documented. Results: A total of 13 patients were treated with linezolid-antibiotic-laden spacers with polymethyl methacrylate (PMMA) carrier. Nine patients were successfully treated using limb-salvage techniques and were still infection-free after a mean follow-up of 55.5 months. Conclusions: Linezolid-loaded bone cement is an option for managing chronic bone and joint infections, particularly MRSA, in patients with vancomycin allergy.

Abstract 3294: The GSPT1 molecular glue degrader MRT-2359 is active against prostate cancer

Abstract We have previously described our GSPT1 molecular glue degrader MRT-2359, which was optimized to achieve preferential antiproliferative activity in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) expressing high N-MYC or L-MYC mRNA. A clinical trial with this new drug candidate is ongoing (NCT05546268). Here, we present pre-clinical profiling of MRT-2359 across hundreds of cancer cell lines representing multiple cancer types, aiming at identifying other cancers where preferential sensitivity is associated with high expression of a MYC family member. These studies showed that prostate cancer cell lines clearly segregate into groups that are either sensitive or insensitive. Sensitive prostate cancer cell lines could be further divided into two subgroups: (1) androgen receptor positive cell lines displaying higher c-MYC mRNA expression levels than the other prostate cancer cell lines, (2) neuroendocrine prostate cancer cell lines with or without high N-MYC. The latter is in line with our previous observation that the neuroendocrine phenotype is generally associated with heightened sensitivity to MRT-2359 independently of MYC status. The insensitive cell lines were androgen receptor and neuroendocrine negative and displayed lower c-MYC mRNA levels. GSPT1 degradation in androgen receptor-positive cell lines led to rapid and deep loss of c-MYC protein as well as reduction of androgen receptor, including the splice variant AR-V7 that is associated with resistance to agents targeting androgen signaling. In androgen receptor-negative cell lines, the levels of c-MYC protein decreased only modestly upon GSPT1 degradation. Finally, in immunocompromised mice, xenografts of the AR-V7-positive cell line 22RV1 and the neuroendocrine prostate cell line NCI-H660, both of which are sensitive to MRT-2359 in vitro, were treated with several MRT-2359 dose regimens including continuous as well as intermittent (5 days on/9 days off) dosing. Most regimens led to marked tumor regression. Tumors of both models fully regressed after a 4-week course of 10 mg/kg MRT-2359 once daily, and no tumor regrowth could be detected after cessation of treatment. No significant in vivo response was observed for xenografts of the insensitive cell line PC-3. These data support the clinical investigation of MRT-2359 in prostate cancer. Citation Format: Ralph Tiedt, Martin Schillo, Arnaud Osmont, Débora Bonenfant, Rajiv Narayan, Owen Wallace, Markus Warmuth. The GSPT1 molecular glue degrader MRT-2359 is active against prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3294.

Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression.

There is growing evidence for the therapeutic effects of the psychedelic drug psilocybin for major depression. However, due to the lack of safety data on combining psilocybin with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and concerns that there may be a negative interaction on efficacy, participants enrolling in psychedelic trials are usually required to discontinue SNRI/SNRIs prior to enrolling. Using data from a recent clinical trial examining the comparative efficacy the psychedelic drug psilocybin (P) combined with approximately 20 h of psychological support to a 6-week (daily) course of the SSRI escitalopram plus matched psychological support for major depressive disorder, we explored the effects of discontinuing SSRI/SNRIs prior to study enrolment on study outcomes. Exploratory post hoc analyses using linear mixed effects model were performed to investigate the discontinuation effect on various validated depression symptom severity scales and well-being. The impact of SSRI/SNRIs discontinuation on the acute psychedelic experience was also explored. In the psilocybin group, there was a reduced treatment effect on all outcome measures for SSRI/SNRIs discontinuers compared with unmedicated patients at trial entry. However, no effects of discontinuation on measures of the acute psychedelic experience were found. Discontinuation of SSRI/SNRIs before psilocybin might diminish response to treatment; however, as we did not test SSRI/SNRI continuation in our trial, we cannot infer such causation. Moreover, the exploratory nature of the analyses makes them hypothesis generating, and not confirmatory. A controlled trial of SSRI/SNRI discontinuation versus continuation prior to psilocybin is urgently required.