Tag: pubmed

Neurology. 2024 Dec 24;103(12):e210088. doi: 10.1212/WNL.0000000000210088. Epub 2024 Nov 26.

ABSTRACT

BACKGROUND AND OBJECTIVES: Spinal and bulbar muscular atrophy (SBMA) is a rare, slowly progressive, and debilitating disease without effective treatments available. Lack of reliable biomarkers and sensitive outcome measures makes clinical research conduct challenging. The primary objective of this study was to identify clinically meaningful and statistically sensitive outcome measures enabling the evaluation of therapeutic interventions in late-stage clinical trials.

METHODS: This study was a meta-analysis of SBMA patient-level data from 6 observational studies conducted in Italy, South Korea, Denmark, United Kingdom, Japan, and United States. Patients with confirmed SBMA genetic diagnosis and differing severity were enrolled following individual site protocols. Routine assessments were performed longitudinally for approximately 3 years, including one or more clinical outcomes, such as SBMA functional rating scale (SBMAFRS), 6-minute walk test (6MWT), quantitative muscle testing (QMT), and Adult Myopathy Assessment Tool (AMAT). A modified scale, m-SBMAFRS, was derived by including only lower limb and trunk subscales having lower variability and larger effect size compared with the others. Changes from baseline at follow-up time points were calculated for all measures, and percent changes using random slope models were calculated to compare clinical measure performances. A survey conducted on 196 patients by the Coordination of Rare Diseases at Sanford (CoRDS), elucidating the impact of specific disease aspects on patients’ lives, was also evaluated to corroborate these research outcomes.

RESULTS: This global SBMA dataset analyzed data from 278 men (mean age = 59.7 ± 10.8 years, mean disease duration = 17.7 ± 11.9 years). Patients progressed on SBMAFRS (-4.7 ± 6.2 points after 38 months with 1-year standard response mean [SRM] = 0.6) and 6MWT (distance walked decreased by -53.2 ± 87.0 meters after 26 months with 1-year SRM = 0.5). These measures showed lower variability and larger effect size than AMAT and QMT (1-year SRM = 0.1 and -0.2, respectively) and confirmed SBMA linear progression across a range of disease stages. The m-SBMAFRS also showed a significant yearly decline of 0.9 ± 1.5 points (SRM = 0.6) and more consistent performance with less variability across clinical sites. The CoRDS survey confirmed the relevance of lower limb strength and mobility, which correlated with higher quality-of-life metrics and were reported by patients as predominant disease issues.

DISCUSSION: We generated a comprehensive global SBMA dataset, enabling the identification of sensitive functional end points for clinical trials. Possible limitations relate to data collection nuances across sites that a single study protocol could override.

PMID:39591556 | DOI:10.1212/WNL.0000000000210088

J Clin Oncol. 2024 Nov 26:JCO2401326. doi: 10.1200/JCO-24-01326. Online ahead of print.

ABSTRACT

PURPOSE: Lenvatinib plus pembrolizumab (len + pembro) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in previously treated advanced or recurrent endometrial cancer (aEC) in the phase III Study 309/KEYNOTE-775. We report results from the phase III, randomized, open-label European Network of Gynaecological Oncological Trial-en9/LEAP-001 study (ClinicalTrials.gov identifier: NCT03884101) that evaluated len + pembro versus chemotherapy in first-line aEC.

METHODS: Patients with stage III to IV or recurrent, radiographically apparent EC and no previous chemotherapy or disease progression ≥6 months after neo/adjuvant platinum-based chemotherapy were randomly assigned 1:1 to lenvatinib 20 mg once daily plus pembrolizumab 200 mg once every 3 weeks or paclitaxel 175 mg/m² plus carboplatin AUC 6 mg/mL/min once every 3 weeks. Primary end points were PFS and OS, evaluated in the mismatch repair-proficient (pMMR) and all-comers populations. Noninferiority was assessed for OS at final analysis (FA) for len + pembro versus chemotherapy (multiplicity-adjusted, one-sided nominal alpha, .0159; null hypothesis-tested hazard ratio [HR], 1.1).

RESULTS: Eight hundred forty-two patients were randomly assigned (len + pembro, n = 420 [pMMR population, n = 320]; chemotherapy, n = 422 [pMMR population, n = 322]). At FA (data cutoff, October 2, 2023), median PFS (95% CI) in the pMMR population was 9.6 (8.2 to 11.9) versus 10.2 (8.4 to 10.5) months with len + pembro versus chemotherapy (hazard ratio [HR], 0.99 [95% CI, 0.82 to 1.21]) and among all-comers was 12.5 (10.3 to 15.1) versus 10.2 (8.4 to 10.4) months (HR, 0.91 [95% CI, 0.76 to 1.09]; descriptive analyses). Median OS (95% CI) in the pMMR population was 30.9 (25.4 to 37.7) versus 29.4 (26.2 to 35.4) months with len + pembro versus chemotherapy (HR, 1.02 [95% CI, 0.83 to 1.26]; noninferiority P = .246, not statistically significant per multiplicity control strategy) and among all-comers was 37.7 (32.2 to 43.6) versus 32.1 (27.2 to 35.7) months (HR, 0.93 [95% CI, 0.77 to 1.12]). Grade ≥3 treatment-related adverse events occurred in 331/420 (79%) versus 274/411 (67%) treated patients.

CONCLUSION: First-line len + pembro did not meet prespecified statistical criteria for PFS or OS versus chemotherapy in pMMR aEC.

PMID:39591551 | DOI:10.1200/JCO-24-01326

Schizophr Bull. 2024 Nov 26:sbae187. doi: 10.1093/schbul/sbae187. Online ahead of print.

ABSTRACT

BACKGROUND AND HYPOTHESIS: Schizophrenia is a complex disorder thought to have neurodevelopmental and neurodegenerative aspects. Optical coherence tomography (OCT) measurements of schizophrenia patients revealed that the retinal layers of these patients were thinner than those of healthy controls. This study aimed to examine retinal changes in first-episode psychosis patients treated with electroconvulsive therapy (ECT) via OCT.

STUDY DESIGN: Thirty first-episode psychosis patients (13 men, 17 women) aged 18 to 65 years who had no comorbidities and no smoking, alcohol, or substance use disorders and who were treated with ECT were included in the study. The patients were evaluated using OCT before treatment and after an average of 7.4 sessions of ECT in remission, and the results were compared.

STUDY RESULTS: Statistically significant increases were observed in retinal layer thickness, inner plexiform layer, outer plexiform layer, and total retinal thickness within the 1 mm ring (P = .015, P = .045, and P = .025, respectively). The inner nuclear layer thickness significantly increased within the 6 mm ring (P = .037).

CONCLUSIONS: In conclusion, ECT noticeably affected retinal structures, particularly according to similar measurements, indicating potential improvements in and the ability to reverse neuronal degeneration after one month of treatment. This study highlights the potential impact of ECT on retinal structures in individuals experiencing first-episode psychosis, as it can enhance specific retinal layers and reverse neuronal degeneration.

PMID:39591543 | DOI:10.1093/schbul/sbae187

J Proteome Res. 2024 Nov 26. doi: 10.1021/acs.jproteome.4c00173. Online ahead of print.

ABSTRACT

Psoriasis, an immune-mediated chronic inflammatory skin disease, is primarily diagnosed through clinical assessment. Currently, specific markers for the accurate diagnosis and prediction of psoriatic disease are lacking. Here, we employed a three-step designed study to perform untargeted metabolomics, with the aim of identifying candidate biomarkers for psoriasis. Through comprehensive multivariate and univariate statistical analyses, we screened eight potential biomarkers specific to psoriasis, with five structurally identified. Two dipeptide biomarkers, γ-GluSer and ThrGly, along with a lysine glycation metabolite, Nα-fructosyl-lysine (Fruc-Lys), were found to be psoriasis biomarkers for the first time. Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) values of these eight metabolites/features ranged from 0.68 to 0.94. A biomarker panel comprising ThrGly and feature m/z 120.0656 (C₄H₉NO₃) demonstrated high diagnostic accuracy (AUC = 0.97) in distinguishing psoriasis patients from healthy controls. Overall, our study identified and validated a panel of plasma metabolites/features that could serve as potential biomarkers for the diagnosis of psoriasis, providing new insights into the diagnosis and pathogenesis of this disease.

PMID:39591524 | DOI:10.1021/acs.jproteome.4c00173

Clin Neuropharmacol. 2024 Nov 25. doi: 10.1097/WNF.0000000000000618. Online ahead of print.

ABSTRACT

OBJECTIVES: Traditional antidepressant therapy is associated with an inadequate response and a low remission rate. Our aim was to synthesize published randomized controlled trials on the potential effects of minocycline in patients with depression.

METHODS: PubMed, Web of Science, Embase, and Cochrane Library databases were searched for studies published. Randomized controlled trials published in English that evaluated the efficacy of minocycline in patients with depression were selected for inclusion. Changes from baseline in the Hamilton Depression Rating Scale (HDRS) or Montgomery-Åsberg Depression Rating Scale (MADRS) were pooled to determine the antidepressant effect of minocycline compared with placebo. The quality of the included studies was assessed using the Cochrane risk-of-bias tool.

RESULTS: Eight trials with 567 participants were eligible and included in the analysis. The meta-analysis did not reveal a statistically significant effect of minocycline on depression based on HDRS or MADRS scores.

CONCLUSIONS: According to the HDRS and MADRS scores, minocycline did not demonstrate effectiveness in reducing depressive symptoms.

PMID:39591510 | DOI:10.1097/WNF.0000000000000618

J Stud Alcohol Drugs. 2024 Nov 26. doi: 10.15288/jsad.24-00104. Online ahead of print.

ABSTRACT

OBJECTIVE: An inability to correctly perceive chemosensory stimuli can lead to a poor quality of life. Such defects can be concomitant with excess alcohol consumption, but a large-scale cohort study linking these effects is lacking. This study aimed to investigate the impact of chronic alcohol consumption on chemosensory function by analyzing data from the NHANES 2013-2014, involving 395 participants categorized by alcohol intake behavior: 219 no-intake, 136 light-intake, and 40 risky-intake groups.

METHODS: Chemosensory function was assessed using a self-reported Chemosensory Questionnaire along with objective tests for taste (quinine solution) and smell (appetitive and hazardous odors). Adjusted regression analyses were conducted, controlling for age, gender, smoking status, and multiple pairwise comparisons. Weighted regression analyses were also performed.

RESULTS: Risky drinkers had significantly lower odds of identifying quinine (bitter taste) compared to light drinkers (OR = 0.37, p-adjusted = 0.04). Risky drinkers also had higher odds of identifying appetitive odors like strawberry (OR = 5.44, p-adjusted = 0.03) but lower odds for detecting hazardous odors like natural gas (OR = 0.11, p-adjusted = 0.001) compared to light drinkers. Additionally, light drinkers identified the leather scent more effectively than no drinkers (OR = 2.54, p = 0.02).

CONCLUSIONS: Chronic alcohol consumption, particularly at risky levels, is associated with altered chemosensory function. These findings emphasize the importance of assessing chemosensory symptoms in individuals with alcohol-related behaviors.

PMID:39589797 | DOI:10.15288/jsad.24-00104

J Stud Alcohol Drugs. 2024 Nov 26. doi: 10.15288/jsad.24-00003. Online ahead of print.

ABSTRACT

OBJECTIVE: Personalized normative feedback interventions show efficacy in reducing health risk behaviors (e.g., alcohol use, sexual aggression). However, complex personalized normative feedback interventions may require manual methods of inputting participant data into graphics, which introduces error, and automated approaches require substantial technical costs and funding and may limit the types of feedback that can be provided.

METHOD: To make personalized normative feedback more accessible, we outline a method of using easily accessible software programs including IBM Statistical Package for the Social Sciences (SPSS), Microsoft Excel, and Microsoft PowerPoint, to create and display complex personalized normative feedback graphics. We also describe methods through which personalized normative feedback graphics can be created within a larger preventive intervention for alcohol and sexual assault in college men.

RESULTS: We first provide step-by-step instructions for collecting data and then creating semi-automated syntax files within SPSS and Excel to merge participant data into complex personalized normative feedback graphics in Excel. To do so, we append annotated syntax in text and in supplemental material. Next, we outline the process of creating risk feedback graphics, whereby individual items or exact wording of items are displayed back to the participant. Finally, we provide guidance regarding the process of translating graphics from Excel for viewing via PowerPoint without having to manually update PowerPoint slides for each presentation.

CONCLUSIONS: Via the described syntax and graphic generation, researchers are then able to create semi-automated personalized normative feedback and risk feedback graphics. This tutorial may help in increasing the dissemination of complex personalized normative feedback interventions.

PMID:39589790 | DOI:10.15288/jsad.24-00003

Am J Hypertens. 2024 Nov 26:hpae147. doi: 10.1093/ajh/hpae147. Online ahead of print.

ABSTRACT

BACKGROUND: Lercanidipine, a newer-generation calcium channel blocker, is recognized for its effective antihypertensive properties and reduced side effects. This study aims to compare the effectiveness of lercanidipine and amlodipine in preventing major adverse cardiovascular events (MACE) in hypertensive patients.

METHODS: A multicenter, retrospective observational study was conducted using the electronic medical records database from three tertiary hospitals in South Korea between 2017 and 2021. Hypertensive patients treated with either amlodipine or lercanidipine were analyzed. Propensity score matching (PSM) was utilized to minimize confounders, matching patients in a 3:1 ratio. The primary endpoint was the incidence of MACE, a composite of cardiovascular death, myocardial infarction, stroke, heart failure hospitalizations, and coronary revascularization over a 3-year follow-up period.

RESULTS: A total of 47640 patients were evaluated, and 6029 patients were matched. Before PSM, the lercanidipine group had a higher cardiovascular risk (SCORE-2/SCORE-2OP value: 11.6% ± 9.2 vs 10.9% ± 8.8, p<0.01) and a higher incidence of MACE compared to the amlodipine group (4.1% vs 3.4%, p<0.01). After PSM, the incidence of MACE was numerically lower in the lercanidipine group compared to the amlodipine group (2.8% vs 4.1%, p=0.11), though this difference was not statistically significant. Blood pressure control remained comparable between the two groups over the 3-year follow-up period.

CONCLUSIONS: Lercanidipine demonstrated comparable effectiveness to amlodipine in preventing MACE among hypertensive patients. Given its comparable antihypertensive efficacy and potential for fewer side effects based on prior studies, lercanidipine may be considered a preferable option for hypertension management.

PMID:39589752 | DOI:10.1093/ajh/hpae147

JAMA Netw Open. 2024 Nov 4;7(11):e2447335. doi: 10.1001/jamanetworkopen.2024.47335.

ABSTRACT

IMPORTANCE: The kidney transplant (KT) evaluation process is particularly time consuming and burdensome for Black patients, who report more discrimination, racism, and mistrust in health care than White patients. Whether alleviating patient burden in the KT evaluation process may improve perceptions of health care and enhance patients’ experiences is important to understand.

OBJECTIVE: To investigate whether Black and White participants would experience improvements in perceptions of health care after undergoing a streamlined, concierge-based approach to KT evaluation.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study from a single urban transplant center included Black and White English-speaking adults who were referred for KT and deemed eligible to proceed with the KT evaluation process. The patients responded to baseline and follow-up questionnaires. The study was conducted from May 2015 to June 2018. Questionnaires were collected before KT evaluation initiation (baseline) and after KT evaluation completion (follow-up). Data were analyzed from October 2022 to January 2024.

EXPOSURE: Data were stratified by race (Black compared with White) and time (baseline compared with follow-up).

MAIN OUTCOMES AND MEASURES: The main outcomes were experiences of discrimination in health care, perceived racism in health care, medical mistrust of health care systems, and trust in physician. Repeated-measures regression was used to assess race, time, and the race-by-time interaction as factors associated with each outcome.

RESULTS: The study included 820 participants (mean [SD] age, 56.50 [12.93] years; 514 [63%] male), of whom 205 (25%) were Black and 615 (75%) were White. At baseline and follow-up, Black participants reported higher discrimination (119 [58%]; χ21 = 121.89; P < .001 and 77 [38%]; χ21 = 96.09; P < .001, respectively), racism (mean [SD], 2.73 [0.91]; t290.46 = 7.77; P < .001 and mean [SD], 2.63 [0.85]; t296.90 = 7.52; P < .001, respectively), and mistrust (mean [SD], 3.32 [0.68]; t816.00 = 7.29; P < .001 and mean [SD], 3.18 [0.71]; t805.00 = 6.43; P < .001, respectively) scores but lower trust in physician scores (mean [SD], 3.93 [0.65]; t818.00 = -2.01; P = .04 and mean [SD], 3.78 [0.65]; t811.00 = -5.42; P < .001, respectively) compared with White participants. All participants experienced statistically significant reductions in discrimination (Black participants: odds ratio, 0.27 [95% CI, 0.16-0.45]; P < .001; White participants: odds ratio, 0.37 [95% CI, 0.25-0.55]; P < .001) and medical mistrust in health care (Black participants: β [SE], -0.16 [0.05]; P < .001; White participants: β [SE], -0.09 [0.03]; P < .001), and Black participants reported lower perceived racism at follow-up (β [SE], -0.11 [0.05]; P = .04). There was a statistically significant race-by-time interaction outcome in which Black participants’ trust in physicians was significantly lower at follow-up, but White participants reported no change.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study of patients who underwent a streamlined, concierge-based KT evaluation process suggest that a streamlined approach to clinic-level procedures may improve patients’ perceptions of the health care system but may not improve their trust in physicians. Future research should determine whether these factors are associated with KT outcome, type of KT received, and time to KT.

PMID:39589742 | DOI:10.1001/jamanetworkopen.2024.47335

JAMA Netw Open. 2024 Nov 4;7(11):e2447352. doi: 10.1001/jamanetworkopen.2024.47352.

ABSTRACT

IMPORTANCE: Recent evolutions in clinical care and remote monitoring suggest that some acute illnesses no longer require intravenous therapy and inpatient hospitalization.

OBJECTIVE: To describe outcomes of patients receiving care in a new, outpatient, virtual, home-based acute care model called Safer@Home.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort analysis, conducted from September 1, 2022, through August 31, 2023, included 2466 patients treated at a safety net hospital in Los Angeles County for 10 core illnesses and 24 other acute illnesses for which patients are commonly hospitalized.

EXPOSURE: Outpatient, home-based, acute care with virtual monitoring and clinic visits in lieu of inpatient or in-home care.

MAIN OUTCOMES AND MEASURES: The primary measure was hospital length of stay. Secondary measures included all-cause mortality, 30-day readmission, return urgent care visit rates, and return emergency department (ED) visit rates.

RESULTS: Safer@Home provided care to 876 patients (mean [SD] age, 54.0 [14.5] years; 541 men [61.8%]) during the study period, compared with a cohort of 1590 patients (mean [SD] age, 52.3 [19.6] years; 901 men [56.7%]) with matching diagnoses who received standard, hospital-based care. Safer@Home patients had significantly shorter mean (SD) lengths of inpatient stay than the comparison cohort (1.3 [2.0] vs 5.3 [10.4] days; P < .001), totaling 3505 bed-days avoided (mean [SD], 4.0 [10.6] bed-days saved per patient), with no significant difference in all-cause mortality at last follow-up (2.6% [23 of 876] vs 4.0% [64 of 1590]; P = .07). Safer@Home patients and control patients also had no significant difference in the proportion experiencing 30-day hospital readmission (19.9% [174 of 876] vs 16.7% [266 of 1590]; P = .06). As intended, more Safer@Home than control patients had at least one 30-day return urgent care visit (37.3% [327 of 876] vs 5.2% [82 of 1590]; P < .001). In contrast, the Safer@Home and control cohorts did not significantly differ in experiencing at least one 30-day return ED visit (15.2% [133 of 876] vs 12.5% [199 of 1590]; P = .06). Safer@Home patients had significantly fewer mean (SD) total 30-day return ED visits per patient than control patients (0.19 [0.50] vs 0.21 [0.85]; P < .001).

CONCLUSIONS AND RELEVANCE: In this cohort study, patients receiving acute, virtual, home care with remote monitoring and as-needed return urgent care visits had markedly shorter hospital stays than patients receiving standard inpatient hospital care, with no significant increase in mortality, ED revisits, or return hospitalizations. This new care model is promising for systems that cannot staff Medicare-compliant hospital-at-home visits.

PMID:39589741 | DOI:10.1001/jamanetworkopen.2024.47352