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1.
Eur Urol Focus ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38866663

RESUMO

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.

3.
Cureus ; 16(5): e60895, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38836152

RESUMO

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.

4.
Int J Geriatr Psychiatry ; 39(6): e6108, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38858522

RESUMO

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.


Assuntos
Acidentes por Quedas , Doença de Alzheimer , Apatia , Estimulantes do Sistema Nervoso Central , Metilfenidato , Redução de Peso , Humanos , Doença de Alzheimer/tratamento farmacológico , Metilfenidato/uso terapêutico , Metilfenidato/efeitos adversos , Feminino , Masculino , Apatia/efeitos dos fármacos , Idoso , Estimulantes do Sistema Nervoso Central/uso terapêutico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Idoso de 80 Anos ou mais , Redução de Peso/efeitos dos fármacos , Acidentes por Quedas/estatística & dados numéricos , Método Duplo-Cego , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico
5.
ACS Pharmacol Transl Sci ; 7(5): 1302-1309, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38751629

RESUMO

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.

6.
Diagn Microbiol Infect Dis ; 109(3): 116306, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38735146

RESUMO

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.


Assuntos
Hemocultura , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Humanos , Hemocultura/métodos , Índia , Bactérias/isolamento & purificação , Bactérias/classificação , Bacteriemia/diagnóstico , Bacteriemia/microbiologia
7.
Cureus ; 16(3): e55684, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586691

RESUMO

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.

8.
Org Biomol Chem ; 22(19): 3876-3881, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38651749

RESUMO

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.

10.
Surg Neurol Int ; 15: 56, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38468674

RESUMO

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.

11.
Abdom Radiol (NY) ; 49(6): 2145-2154, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38400982

RESUMO

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.


Assuntos
Dor Abdominal , Serviço Hospitalar de Emergência , Radiologistas , Ultrassonografia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Ultrassonografia/métodos , Radiologistas/estatística & dados numéricos , Dor Abdominal/diagnóstico por imagem , Estudos Retrospectivos , Adulto , Tempo de Internação/estatística & dados numéricos , Idoso
12.
Int J Surg Pathol ; : 10668969241231973, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377960

RESUMO

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.

13.
Cancer Res Commun ; 4(3): 634-644, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38329389

RESUMO

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.


Assuntos
Proteínas Reguladoras de Apoptose , Apoptose , Humanos , Proteínas Reguladoras de Apoptose/metabolismo , Ligação Proteica
14.
Int J Obes (Lond) ; 48(4): 584-593, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38219005

RESUMO

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.


Assuntos
Doenças Cardiovasculares , Ganho de Peso na Gestação , Feminino , Humanos , Gravidez , Índice de Massa Corporal , Doenças Cardiovasculares/genética , Estudos de Coortes , Metilação de DNA/genética , Epigênese Genética/genética , Epigenoma , População Europeia , Estudo de Associação Genômica Ampla , Ganho de Peso na Gestação/genética , Leucócitos , População do Sul da Ásia , Metanálise como Assunto
15.
J Breast Imaging ; 6(2): 141-148, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38170567

RESUMO

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.


Assuntos
Biópsia Guiada por Imagem , Radiologistas , Feminino , Humanos , Diagnóstico por Imagem , Morbidade , Dor , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos
16.
J Anaesthesiol Clin Pharmacol ; 39(3): 404-410, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38025567

RESUMO

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.

17.
Artigo em Inglês | MEDLINE | ID: mdl-37857291

RESUMO

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.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Humanos , Feminino , Adulto , Masculino , Topiramato/efeitos adversos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Projetos Piloto , Frutose/efeitos adversos , Resultado do Tratamento , Método Duplo-Cego
18.
Alzheimers Dement (N Y) ; 9(3): e12403, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37538343

RESUMO

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.

19.
Indian J Ophthalmol ; 71(8): 2978-2983, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37530268

RESUMO

Purpose: To compare the slit-lamp method and wavefront aberrometry method based on outcomes of toric realignment surgeries. Settings: Tertiary care ophthalmic hospital. Design: Retrospective study. Methods: This study included all eyes undergoing toric intraocular lens (TIOL) realignment surgery between January 2019 and December 2021 for which TIOL axis assessment by slit-lamp method and wavefront aberrometry method was available. Data were retrieved from electronic medical records, and we documented demographics, uncorrected visual acuity (UCVA), subjective refraction, and TIOL axis by slit-lamp and wavefront aberrometry methods on postoperative day 1 and day 14. In patients with misalignment, TIOL was realigned to the original position in group 1 (27 patients) and to an axis based on calculations provided by wavefront aberrometer in group 2 (25 patients). Post-realignment surgery, UCVA, subjective refraction, and TIOL axis by slit-lamp and wavefront aberrometry methods were assessed and analyzed. Results: We analyzed 52 eyes and found that the mean preoperative misalignment with the slit-lamp method (44.9° ±20.0°) and wavefront aberrometry (47.1° ±19.5°) was similar. The corresponding degrees of misalignment post-TIOL repositioning surgeries were 5.2° ±5.2° (slit-lamp method) and 4.7° ±5.1° (wavefront aberrometry) (P = 0.615). Both groups showed significant improvement in median log of minimum angle of resolution (logMAR) UCVA and reduction in median refractive cylinder. Conclusions: Slit-lamp method is as good as wavefront aberrometer method to assess TIOL axis. Toric realignment surgery is found to be safe, and realigning TIOL based on either slit-lamp method or wavefront aberrometer method equally improved UCVA and decreased residual refractive cylinder.


Assuntos
Astigmatismo , Aberrações de Frente de Onda da Córnea , Lentes Intraoculares , Facoemulsificação , Humanos , Implante de Lente Intraocular/métodos , Aberrometria , Estudos Retrospectivos , Facoemulsificação/métodos , Astigmatismo/diagnóstico , Astigmatismo/cirurgia , Estudos Prospectivos , Refração Ocular , Córnea
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