Ischemic Heart Disease with In-Stent Re-Stenosis with Complete Heart Block and Isolated Persistent Left Superior Vena Cava - Rare Case Report with Challenges and Clinical Implications.

ABSTRACT: Isolated persistent left superior vena cava (PLSVC) is a very rare congenital thoracic venous system anomaly and is commonly an incidental finding, usually detected during central venous access, cardiac catheterization, or cardiothoracic surgeries. This is a rare case report wherein the patient is a known case of ischemic heart disease with s/p percutaneous transluminal coronary angioplasty (PTCA) with a stent to left anterior descending (LAD) artery with in-stent re-stenosis presented with complete heart block and had an unanticipated discovery of isolated PLSVC on facing difficulty during the transvenous approach of permanent pacemaker implantation (PPI). In this case report, we inspect the challenges associated with and various clinical implications of isolated PLSVC.

Programmable chitosan-based double layer seed coating for biotic and abiotic-stress tolerance in groundnut.

In the face of agricultural challenges posed by both abiotic and biotic stressors, phytopathogens emerge as formidable threats to crop productivity. Conventional methods, involving the use of pesticides and microbes, often lead to unintended consequences. In addressing this issue, ICAR -Indian Institute of Oilseeds Research (ICAR-IIOR) has developed a chitosan-based double-layer seed coating. Emphasizing crop input compatibility, entrapment, and characterization, the study has yielded promising results. The double-layer coating on groundnut seeds enhanced germination and seedling vigor. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) confirmed the structural changes and entrapment of crop inputs. The persistence of T. harzianum (Th4d) and Bradyrhizobium sp. in chitosan blended film in studied soils revealed that viable propogules of Th4d were recorded in double layer treatment combination with 3.54 and 3.50 Log CFUs/g of soil (colony forming units) and Bradyrhizobium sp. with 5.34 and 5.27 Log CFUs/g of soil at 90 days after application (DAA). Root colonization efficacy studies of Th4d and Bradyrhizobium sp. in groundnut crop in studied soils revealed that, maximum viable colonies were observed at 45 days after sowing (DAS). This comprehensive study highlights the potential of chitosan-based double-layer seed coating providing a promising and sustainable strategy for stress management in agriculture.

Adverse effects of methylphenidate for apathy in patients with Alzheimer's disease (ADMET2 trial).

OBJECTIVES: To examine clinically important adverse events (AEs) associated with methylphenidate (MPH) treatment of apathy in Alzheimer's Disease (AD) versus placebo, including weight loss, vital signs, falls, and insomnia. METHODS: The Apathy in Dementia Methylphenidate Trial 2 (ADMET2) trial was a multicenter randomized, placebo-controlled trial of MPH to treat apathy in individuals with apathy and AD. Participants in ADMET2 had vital signs and weight measured at monthly visits through 6 months. AEs, including insomnia, falls, and cardiovascular events, were reported at every visit by participants and families using a symptom checklist. RESULTS: The study included 98 participants in the MPH group and 101 in the placebo group. Participants in the MPH group experienced greater weight loss on average than the placebo through the 6-month follow-up, with a difference in change between MPH and placebo of 2.8 lb (95% confidence interval, CI: 0.7, 4.9 lb). No treatment group differences in change during the trial were found in systolic and diastolic blood pressure. More participants in the MPH group reported falls during the follow-up, 10 versus 6 in MPH and placebo groups, respectively. No differences in post-baseline insomnia were observed between the treatment groups. No participants reported instances of myocardial infarction, congestive heart failure, arrhythmia, stroke, or cardiomyopathy throughout the study period. CONCLUSIONS: MPH use in AD patients for treating apathy is relatively safe, particularly notable given the many medical comorbidities in this population. There was a statistically significant but modest weight loss associated with MPH use, and clinicians are thus advised to monitor weight during MPH treatment.

The Clinical Efficacy of Accelerated Deep Repetitive Transcranial Magnetic Stimulation in Depression and Obsessive-Compulsive Disorder: Multi-centric Real-World Observational Data.

Background Of late, the interest in accelerated treatment protocols in repetitive transcranial magnetic stimulation (TMS) for the treatment of depression and obsessive-compulsive disorder (OCD) has been gaining momentum. Studies have already found that the patterned theta burst stimulation is non-inferior to the standard high-frequency stimulation in treating depression. The objective of the present study was to evaluate the clinical efficacy of a customized accelerated combination TMS naturalistic setting. Methods Retrospective analysis of pre and post-deep repetitive TMS responses in depression and OCD patients was performed. About 391 Depression and 239 OCD patients' data was analyzed. Customized treatment protocols consisted of twice daily high-frequency stimulations intervened by one theta burst stimulation. The outcome measures were a day six score in depression and a day 10 score in OCD, compared to day one baseline scores. Results The overall response rate in depression was 60.86%, estimated as a >50% reduction in the Hamilton Depression Rating Scale (HAM-D) 21 items score, and 62.76% in OCD, estimated as a >35% reduction in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score. The mean reduction of YBOCS and HAM-D was statistically significant at p<0.0001 (Mann-Whitney U test statistic=9442.5, z=12.66 for YBOCS and 16673.5, z=18.92 for HAM-D). Corresponding effect size estimations revealed Cohen's d value of 1.40 and 1.59, respectively. Conclusions The response rates achieved at day six and day 10 in depression and OCD, respectively, were comparable to previous studies employing standard treatment protocols. The accelerated protocol produced satisfactory short-term clinical outcomes that were effective in the early management of the illness without any serious adverse effects.

Preoperative Prostate Magnetic Resonance Imaging-based Anatomical Predictors of Early Urinary Continence Following Single-port Transvesical Robot-assisted Radical Prostatectomy.

BACKGROUND AND OBJECTIVE: The introduction of the single-port (SP) robotic system has led to new approaches in robot-assisted radical prostatectomy (RARP), such as the transvesical (TV) approach, offering high rates of early urinary continence. While previous studies of SP TV RARP have identified perioperative factors influencing continence outcomes, the impact of anatomical factors remains unexplored. This study aims to assess magnetic resonance imaging (MRI)-based anatomical predictors of urinary continence after SP TV RARP. METHODS: A retrospective analysis of consecutive SP TV RARP cases (November 2020 to June 2023) with preoperative prostate MRI was performed. Two urogenital radiologists independently evaluated ten anatomical parameters to distinguish patients achieving urinary continence within 1 wk and 3 mo. Nonparametric methods estimated receiver operating characteristic curves (area under the curve [AUC]) and inter-reader agreement. KEY FINDINGS AND LIMITATIONS: In 120 cases, 40% achieved continence within 1 wk, rising to 71.7% by 3 mo. Membranous urethra length (MUL) alone was significantly associated with continence at 3 mo (AUC: 0.67, p = 0.003). At 1 wk, several parameters, including anteroposterior diameter of the prostate, coronal membranous urethra length, prostate volume, and transverse diameter of the prostate, showed promise in predicting continence. CONCLUSIONS AND CLINICAL IMPLICATIONS: A longer preoperative MUL was significantly associated with better odds of an early return to urinary continence after SP TV RARP. Each 1-mm increase in coronal MUL was associated with a 27% increase in the odds of continence at 3 mo. This information can aid in patient counseling and expectations preoperatively. PATIENT SUMMARY: Urinary incontinence is a common outcome after prostate cancer surgery, particularly in the early months. Recently, the single-port (SP) robotic system has emerged, localizing surgery to the diseased area. With the SP robot, accessing the prostate via the bladder leads to high rates of early continence. Our study reveals that the longer the urethral portion beneath the prostate, the higher the likelihood of regaining continence within 3 mo after surgery.

Small Molecule Functional Converter of B-Cell Lymphoma-2 (Bcl-2) Suppresses Breast Cancer Lung Metastasis.

The B-cell lymphoma-2 (Bcl-2) family of proteins plays a vital role in tumorigenesis. Cancer cells utilize the expression of Bcl-2 to evade therapy and develop resistance. Bcl-2 overexpression also causes cancer cells to be more invasive and metastatic. About 80% of cancer deaths are due to metastases, and yet targeted therapies for metastatic cancers are scarce. We discovered a small molecule, BFC1103, which changes the conformation of Bcl-2 to convert the antiapoptotic protein to a proapoptotic protein. BFC1103-induced apoptosis is dependent on the expression levels of Bcl-2, with higher levels causing more apoptosis. BFC1103 suppressed the growth of breast cancer lung metastasis. BFC1103 has the potential for further optimization and development for clinical testing in metastatic cancers that express Bcl-2. This study demonstrates a new approach to target Bcl-2 using a small molecule, BFC1103, to suppress metastatic disease.

Accelerated microbial identification "directly" from positive blood cultures using MALDI-TOF MS: Local clinical laboratory challenges.

Rapid identification of microbial pathogens "directly" from positive blood cultures (PBCs) is critical for prompt initiation of empirical antibiotic therapy and clinical outcomes. Towards higher microbial identification rates, we modified a published initial serum separator tubes-based MALDI-TOF-MS protocol, for blood culture specimens received at a non-hospital based standalone diagnostic laboratory, Bangalore, India: (a) "Initial" protocol #1: From 28 PBCs, identification= 39% (Gram-negative= 43%: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa; Gram-positive: 36%: Enterococcus faecalis, Staphylococcus aureus, Staphylococcus haemolyticus); mis-identification= 14%; non-identification= 47%. (b) "Modified" protocol #2: Quality controls (ATCC colonies spiked in negative blood cultures) From 7 analysis, identification= 100% (Escherichia coli, Klebsiella pneumonia, Klebsiella oxytoca, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus); From 7 PBCs, identification= 57%; mis-identification= 14%; non-identification= 29%. Microbial preparations of highest quality and quantity for proteomic analysis and separate spectra matching reference databases for colonies and PBCs are needed for best clinical utility.

Regioselective synthesis of 4-arylamino-1,2-naphthoquinones in eutectogel as a confined reaction medium using LED light.

Predicting selectivity and conversion in a confined reaction medium under photochemical conditions is highly challenging as compared to the corresponding conventional synthesis. Herein, we report the use of a simple carbohydrate-derived eutectogel to facilitate LED-light-induced regioselective synthesis of 4-arylamino-1,2-naphthoquinones in good yield. This methodology, by including a reusable reaction medium, proved to have the potential of affording the regioselective formation of various desired products in good yields.

Psychiatrists' Illustration of Awe in Empathic Listening Assessments: A Pilot Study.

Background "Awe" is typically an inspiring emotional response to perceptually vast stimuli signifying the transcendence beyond all cognitive frames of reference when we encounter the unexpected. Physicians' experience of awe in clinical care interactions has not been studied in an empirical, evidence-based way. We aim to present a focused study of awe in a psychiatrist's empathic listening (EL) assessments and propose an evidence-based framework to study it. Methodology This is an exploratory case series of a psychiatrist's EL interactions (mean duration/x̄ of 46.17 minutes) with six patients (two males and four females) aged 32-72 years (x̄ =54.67, σ = 16.64). Using the method of autoethnography, the verbal and nonverbal aspects of the EL assessments were analyzed and open-coded to generate qualitative data. Results The study revealed that the data in all the case studies could be classed into two thematic groups, namely, mindfulness and transpersonal mindfulness. The emotions of "awe" and "non-agency" were ubiquitous in all six case studies both for the psychiatrist and patients. Conclusions Recognizing the awe and non-agency in EL interaction is essential in conceptualizing the "mindfulness-to-transcendence" framework and the first step toward the evidence-based study of transcendence/metaphysics in phenomenological psychiatry.

Direct Quantification of Gadolinium Retention in Young Patients by ICP-MS Analysis of Extracted Teeth.

In this 10-patient prospective pilot study, we show the feasibility of pragmatic direct ex vivo measurement of gadolinium retention from group II gadolinium-based contrasts agents (GBCAs) in young patients after routine tooth extraction. This noninvasive method may support future research attempting to understand the link between GBCA exposure and clinical outcomes.

Postoperative discal pseudocyst: Report of A case with an unusual complication after microlumbar discectomy and successful treatment by transforaminal endoscopic lumbar decompression.

Background: Lumbar discal pseudocysts are uncommon complications that can arise following lumbar spine surgery. It manifests as a fluid-filled sac near the intervertebral disc, causing pain and discomfort. Understanding its causes, symptoms, and management is crucial for patients and healthcare professionals involved in postoperative spinal care. Case Description A: 35-year-old female developed a discal pseudocyst after undergoing laminectomy and discectomy for lumbar disc herniation. The patient presented with recurrent lower back pain, radiculopathy, and neurological deficit two months post-surgery. Imaging revealed a discal pseudo cyst causing compression of the traversing right L5 nerve root. Given the refractory nature of her symptoms, an endoscopic procedure was offered. Using the transforaminal endoscopic technique, the pseudo cyst was identified and removed, leading to immediate symptomatic relief. Conclusion: This article reports the rare occurrence of discal pseudocyst and highlights the use of endoscopic techniques in its surgical management. Surgeons should be aware of the minimally invasive techniques, as they can offer less morbidity, shorter recovery times, and reduced healthcare costs compared to traditional open surgery.

Radiologists predict differential resource utilization but not clinical outcome in emergency department patients imaged with ultrasound for right upper quadrant pain.

PURPOSE: Radiologists with diverse training, specialization, and habits interpret imaging in the Emergency Department. It is necessary to understand if their variation predicts differential value. The purpose of this study was to determine whether attending radiologist variation predicts major clinical outcomes in adult Emergency Department patients imaged with ultrasound for right upper quadrant pain. METHODS: Consecutive ED patients imaged with ultrasound for RUQ pain from 10/8/2016 to 8/10/2022 were included (N = 7097). The primary outcome was prediction of hospital admission by signing attending radiologist. Secondary outcomes included: ED and hospital length of stay (LOS), 30-day mortality, 30-day re-presentation rate, subspecialty consultation, advanced imaging follow up (HIDA, MRI, CT), and intervention (ERCP, drainage or surgery). Sample size was determined a priori (detectable effect size: w = 0.06). Data were adjusted for demographic data, Elixhauser comorbidities, number of ED visits in prior year, clinical data, and system factors (38 covariates). P-values were corrected for multiple comparisons (false discovery rate-adjusted p-values). RESULTS: The included ultrasounds were read by 35 radiologists (median exams/radiologist: 145 [74.5-241.5]). Signing radiologist did not predict hospitalization (p = 0.85), abdominopelvic surgery or intervention within 30 days, re-presentation to the Emergency Department within 30 days, or subspecialty consultation. Radiologist did predict difference in Emergency Department length of stay (p < 0.001) although this difference was small and imprecise. HIDA was mentioned variably by radiologists (range 0-19%, p < 0.001), and mention of HIDA in the ultrasound report increased 10-fold the odds of HIDA being performed in the next 72 h (odds ratio 10.4 [8.0-13.4], p < 0.001). CONCLUSION: Radiologist variability did not predict meaningful outcome differences for patients with right upper quadrant pain undergoing ultrasound in the Emergency Department, but when radiologists mention HIDA in their reports, it predicts a 10-fold increase in the odds a HIDA is performed. Radiologists are relied on for interpretation that shapes subsequent patient care, and it is important to consider how radiologist variability can influence both outcome and resource utilization.

Retroperitoneal Sarcomatoid Yolk Sac Tumor in a Chemotherapy-Naive Patient With Testicular Postpubertal Type Teratoma: A Rare Case Report With Emphasis on Molecular Features.

Sarcomatoid yolk sac tumor is a very rare histologic type of testicular germ cell tumor and is mainly reported in testicular germ cell tumor patients who receive chemotherapy. Herein, we report an extremely rare concurrent retroperitoneal sarcomatoid yolk sac tumor in a man with a testicular postpuberal teratoma before he received chemotherapy. A 37-year-old man initially presented with a persistent abdominal pain. Subsequent imaging studies revealed a 9.6-cm retroperitoneal mass, and 2 testicular masses (3.1 cm and 0.9 cm in greatest dimension, respectively). His serum tumor markers were within normal ranges. His radical orchiectomy demonstrated a postpubertal type teratoma with an adjacent scarring nodule. Later, his retroperitoneal tumor showed spindle tumor cells embedded in predominantly myxoid and focally fibrous stroma with diffuse and strong immunoreactivity for keratin AE1/AE3, SALL4 and glypican 3. No tumor necrosis or brisk mitotic figures were observed. A diagnosis of sarcomatoid yolk sac tumor was rendered. Fluorescence in situ hybridization analysis of his retroperitoneal sarcomatoid yolk sac tumor revealed polysomy 12 and MYC amplification, whereas no evidence of isochromosome 12p [i(12p)], and DNA sequencing showed 6 mutations per megabase (muts/Mb), and the somatic alterations included ARAF amplification and ATR I774Yfs*5. Considering its rarity, sarcomatoid yolk sac tumor may pose diagnostic challenges. Therefore, relevant clinicoradiologic information and ancillary work up, including immunohistochemistry and molecular studies, may be helpful for the accurate classification. Our tumor further raises awareness of this rare event, expands the spectrum of its clinical presentation, and explores the molecular features.

Identification and Characterization of a Small Molecule Bcl-2 Functional Converter.

Cancer cells exploit the expression of anti-apoptotic protein Bcl-2 to evade apoptosis and develop resistance to therapeutics. High levels of Bcl-2 leads to sequestration of pro-apoptotic proteins causing the apoptotic machinery to halt. In this study, we report discovery of a small molecule, BFC1108 (5-chloro-N-(2-ethoxyphenyl)-2-[(4-methoxybenzyol)amino]benzamide), which targets Bcl-2 and converts it into a pro-apoptotic protein. The apoptotic effect of BFC1108 is not inhibited, but rather potentiated, by Bcl-2 overexpression. BFC1108 induces a conformational change in Bcl-2, resulting in the exposure of its BH3 domain both in vitro and in vivo. BFC1108 suppresses the growth of triple-negative breast cancer xenografts with high Bcl-2 expression and inhibits breast cancer lung metastasis. This study demonstrates a novel approach to targeting Bcl-2 using BFC1108, a small molecule Bcl-2 functional converter that effectively induces apoptosis in Bcl-2-expressing cancers. SIGNIFICANCE: We report the identification of a small molecule that exposes the Bcl-2 killer conformation and induces death in Bcl-2-expressing cancer cells. Selective targeting of Bcl-2 and elimination of cancer cells expressing Bcl-2 opens up new therapeutic avenues.

Epigenome-wide association study of DNA methylation in maternal blood leukocytes with BMI in pregnancy and gestational weight gain.

OBJECTIVES: We aimed to discover CpG sites with differential DNA methylation in peripheral blood leukocytes associated with body mass index (BMI) in pregnancy and gestational weight gain (GWG) in women of European and South Asian ancestry. Furthermore, we aimed to investigate how the identified sites were associated with methylation quantitative trait loci, gene ontology, and cardiometabolic parameters. METHODS: In the Epigenetics in pregnancy (EPIPREG) sample we quantified maternal DNA methylation in peripheral blood leukocytes in gestational week 28 with Illumina's MethylationEPIC BeadChip. In women with European (n = 303) and South Asian (n = 164) ancestry, we performed an epigenome-wide association study of BMI in gestational week 28 and GWG between gestational weeks 15 and 28 using a meta-analysis approach. Replication was performed in the Norwegian Mother, Father, and Child Cohort Study, the Study of Assisted Reproductive Technologies (MoBa-START) (n = 877, mainly European/Norwegian). RESULTS: We identified one CpG site significantly associated with GWG (p 5.8 × 10-8) and five CpG sites associated with BMI at gestational week 28 (p from 4.0 × 10-8 to 2.1 × 10-10). Of these, we were able to replicate three in MoBa-START; cg02786370, cg19758958 and cg10472537. Two sites are located in genes previously associated with blood pressure and BMI. DNA methylation at the three replicated CpG sites were associated with levels of blood pressure, lipids and glucose in EPIPREG (p from 1.2 × 10-8 to 0.04). CONCLUSIONS: We identified five CpG sites associated with BMI at gestational week 28, and one with GWG. Three of the sites were replicated in an independent cohort. Several genetic variants were associated with DNA methylation at cg02786379 and cg16733643 suggesting a genetic component influencing differential methylation. The identified CpG sites were associated with cardiometabolic traits. GOV REGISTRATION NO: Not applicable.

Continuity of Radiologists Between Diagnostic Breast Imaging and Image-Guided Breast Biopsy: Impact on Patient-Reported Biopsy Morbidity Experiences.

OBJECTIVE: To determine whether continuity of care between diagnostic breast imaging and subsequent image-guided breast biopsy could reduce patient-reported biopsy-related morbidity. METHODS: This was a prospective, pragmatically randomized, 2-arm health utilities analysis of 200 women undergoing diagnostic breast imaging followed by US- or stereotactic-guided breast biopsy at a single quaternary care center from September 3, 2019, to April 10, 2023. Breast biopsy-naive women with a BI-RADS 4 or 5 finding at diagnostic imaging were randomly scheduled for the typically first available biopsy appointment. One day after biopsy, enrolled patients were administered the Testing Morbidities Index (TMI). The primary outcome was the difference in TMI summary utility scores in patients who did vs did not have the same radiologist perform diagnostic imaging and biopsy. RESULTS: Response rates were 63% (100/159) for the different radiologist cohort and 71% (100/140) for the same radiologist cohort; all respondents answered all questions in both arms. Mean time to biopsy was 7 ± 6 days and 10 ± 9 days, and the number of participating radiologists was 11 and 18, respectively. There was no difference in individual measured domains (pain, fear, or anxiety before procedure; pain, embarrassment, fear, or anxiety during procedure; mental or physical impact after procedure; all P >.00625) or in overall patient morbidity (0.83 [95% CI, 0.81-0.85] vs 0.82 [95% CI: 0.80-0.84], P = .66). CONCLUSION: Continuity of care between diagnostic breast imaging and image-guided breast biopsy did not affect morbidity associated with breast biopsy, suggesting that patients should be scheduled for the soonest available biopsy appointment rather than waiting for the same radiologist.

Comparison of the effects of caffeine, aminophylline, and saline on the recovery from total intravenous anesthesia in laparoscopic surgeries: A randomized controlled trial.

Background and Aims: The return of consciousness (ROC) after general anesthesia (GA) is by stopping the administration of anesthetic agents. At present, no drug is given to reverse the loss of consciousness produced by general anesthetic agents. This study is conducted to find whether caffeine and aminophylline hasten the ROC. Material and Methods: This study was conducted on 75 American Society of Anesthesiologists (ASA) I and II female patients undergoing laparoscopic hysterectomy, aged between 18 and 60 years. The patients were divided into three equal groups (Group C: caffeine citrate, Group A: aminophylline, and Group S: saline) of 25 each by a computer-generated random number table. GA was induced with propofol, fentanyl, and maintained with propofol infusion. On completion of the surgery, the neuromuscular blocking agent was reversed and then the infusion of propofol was stopped. The study drug was administered intravenously when the BIS 60 was achieved. Time to achieve BIS 90, return of first gag reflex, eye-opening on verbal command, and extubation after study drug administration were noted. Hemodynamic parameters and SpO2 were also monitored. Results: The time for BIS 60 to 90 was 10 (4.25) min in the caffeine group, 13 (4.25) min in the aminophylline group, and 26 (9.0) min in the saline group. The time to return of gag reflex and time to extubation were shorter in the caffeine and aminophylline group compared to the saline group. The time to eye-opening on verbal command was shorter in the aminophylline group compared to the saline group. Hemodynamic parameters after infusion of the study drug were comparable in all three groups. Conclusion: Caffeine hastens the recovery from total intravenous anesthesia with propofol and fentanyl in laparoscopic hysterectomy as effectively as aminophylline.

Topiramate Monotherapy for Civilian Posttraumatic Stress Disorder: A Controlled Pilot Study.

Objective: To assess the efficacy, safety, and tolerability of topiramate for the treatment of posttraumatic stress disorder (PTSD) in civilians.Methods: This 12-week double-blind, randomized, placebo-controlled study enrolled 72 outpatients (aged 19-64 years) with a DSM-IV-TR diagnosis of non-combat-related PTSD and a score ≥ 50 on the Clinician-Administered PTSD Scale (CAPS). The primary efficacy endpoint, percent change in total CAPS score, and secondary efficacy measures were assessed by analysis of covariance. Safety assessments included monitoring of vital signs, physical examinations, clinical laboratory parameters, electrocardiograms, and adverse events (AEs). The study was conducted from October 2001 to March 2004.Results: The intent-to-treat (ITT) population (N = 68; mean age = 35 years; 87% women; 74% White) showed greater percent reduction in total CAPS scores with topiramate versus placebo (39.5% vs 29.5%), but the difference was not statistically significant (P = .31). Similarly, higher reductions with topiramate versus placebo were seen in the CAPS subscale scores for symptoms of reexperiencing (43.6% vs 34.8%), avoidance/numbing (38.3% vs 30.6%), and hyperarousal (36.6% vs 21.4%). However, these differences were not statistically significant. Six patients in the topiramate arm had a final CAPS score < 20, whereas only 2 in the placebo arm achieved the result (P = .075). The median final topiramate daily dose was 100 mg/d (range, 25-400 mg/d), and mean ± SD treatment duration was 55 ± 32 days, showing the tolerability of the medication. In topiramate-treated patients, treatment-emergent AEs included paresthesia, headache, fatigue, and insomnia; treatment-limiting AEs included influenza-like symptoms, agitation, cognitive problems not otherwise specified, and somnolence. However, a higher rate of AE-related discontinuation was seen in the placebo group than in the treatment group (26% vs 18%).Conclusions: In this 12-week civilian PTSD study, topiramate improved the primary and secondary outcome measures at a higher rate than did placebo, but the difference did not reach statistical significance. Further adequately powered studies may be warranted.Trial Registration: Clinical Trials.gov identifier: NCT00208130.Prim Care Companion CNS Disord 2023;25(5):23m03555. Author affiliations are listed at the end of this article.

Effects of methylphenidate on neuropsychiatric symptoms in Alzheimer's disease: Evidence from the ADMET 2 study.

INTRODUCTION: Methylphenidate has been shown to improve apathy in patients with Alzheimer's disease (AD). The authors evaluated the impact of methylphenidate on neuropsychiatric symptoms (NPS) of AD, excluding apathy, using data from the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) study. METHODS: A secondary analysis was conducted on data from the ADMET 2 study to determine the effect of methylphenidate on Neuropsychiatric Inventory (NPI) scores outside of apathy. Caregiver scores were compared from baseline to month 6 in 199 participants receiving methylphenidate (20 mg/day) or placebo regarding the presence or absence of individual neuropsychiatric symptoms, emergence of new symptoms, and individual domain scores. RESULTS: No clinically meaningful improvement was observed in any NPI domain, excluding apathy, in participants treated with methylphenidate compared to placebo after 6 months. A statistical difference between groups was appreciated in the domains of elation/euphoria (P = 0.044) and appetite/eating disorders (P = 0.014); however, these findings were not considered significant. DISCUSSION: Methylphenidate is a selective agent for symptoms of apathy in patients with AD with no meaningful impact on other NPS. Findings from this secondary analysis are considered exploratory and multiple limitations should be considered when interpreting these results, including small sample size and use of a single questionnaire.HIGHLIGHTS: Methylphenidate was not associated with significant improvement on the Neuropsychiatric Inventory in domains outside of apathy.Methylphenidate did not show a statistically significant emergence of new neuropsychiatric symptoms (NPS) throughout the 6-month treatment period compared to placebo.Methylphenidate appears to be a highly selective agent for apathy in Alzheimer's disease, potentially supporting catecholaminergic dysfunction as the driving force behind this presentation of symptoms.