Relationships of change in Clinical Dementia Rating (CDR) on patient outcomes and probability of progression: observational analysis.

BACKGROUND: Understanding the relationship among changes in Clinical Dementia Rating (CDR), patient outcomes, and probability of progression is crucial for evaluating the long-term benefits of disease-modifying treatments. We examined associations among changes in Alzheimer's disease (AD) stages and outcomes that are important to patients and their care partners including activities of daily living (ADLs), geriatric depression, neuropsychiatric features, cognitive impairment, and the probabilities of being transitioned to a long-term care facility (i.e., institutionalization). We also estimated the total time spent at each stage and annual transition probabilities in AD. METHODS: The study included participants with unimpaired cognition, mild cognitive impairment (MCI) due to AD, and mild, moderate, and severe AD dementia in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) database. The associations among change in AD stages and change in relevant outcomes were estimated using linear mixed models with random intercepts. The probability of transitioning to long-term care facilities was modeled using generalized estimating equations. The total length of time spent at AD stages and annual transition probabilities were estimated with multistate Markov models. RESULTS: The estimated average time spent in each stage was 3.2 years in MCI due to AD and 2.2, 2.0, and 2.8 years for mild, moderate, and severe AD dementia, respectively. The annual probabilities of progressing from MCI to mild, moderate, and severe AD dementia were 20, 4, and 0.7%, respectively. The incremental change to the next stage of participants with unimpaired cognition, MCI, and mild, moderate, and severe AD dementia (to death) was 3.2, 20, 26.6, 31, and 25.3%, respectively. Changes in ADLs, neuropsychiatric features, and cognitive measures were greatest among participants who transitioned from MCI and mild AD dementia to more advanced stages. Participants with MCI and mild and moderate AD dementia had increasing odds of being transitioned to long-term care facilities over time during the follow-up period. CONCLUSIONS: The findings demonstrated that participants with early stages AD (MCI or mild dementia) were associated with the largest changes in clinical scale scores. Early detection, diagnosis, and intervention by disease-modifying therapies are required for delaying AD progression. Additionally, estimates of transition probabilities can inform future studies and health economic modeling.

Semaglutide 2.4 mg clinical outcomes in patients with obesity or overweight in a real-world setting: A 6-month retrospective study in the United States (SCOPE).

Background: Management guidelines for obesity suggest maintaining a minimum of 5% body weight reduction to help prevent or lower the risk of developing conditions such as hypertension and type 2 diabetes. However, achieving long-term weight control is difficult with lifestyle modification alone, making it essential to combine pharmacotherapy with diet and exercise in individual cases. Semaglutide 2.4 mg has demonstrated significant reductions in body weight and cardiometabolic risk factors in clinical trials, but information on outcomes in a real-world setting is limited. Objective: To assess changes in body weight and other clinical outcomes at 6-month follow-up among adults on semaglutide 2.4 mg in a real-world setting in the United States (US). Methods: Observational and retrospective cohort study of patients initiating treatment between 15 June 2021, and 31 March 2022, using a large US claims-linked electronic health record database. Results: Mean (±SD) body mass index (BMI) of the 343 patients included in the analysis was 37.9 ± 5.5 kg/m2. After 6 months, mean body weight change was -10.5 ± 6.8 kg (95% CI: -11.2; -9.8, p < 0.001) and mean percentage body weight change was -10.0% ± 6.6% (95% CI: -10.7; -9.3, p < 0.001). Most (79.0%) patients had ≥5% body weight reduction, 48.1% had ≥10% body weight reduction, and 19.0% had ≥15% body weight reduction. Among patients with available data, the mean change in HbA1c (n = 30) was -0.6% ± 1.2% (95% CI: -1.0; -0.1, p = 0.016) and nearly two-thirds of patients with prediabetes or diabetes at baseline reverted to normoglycemia. Mean reductions of -4.4 ± 12.3 mmHg (95% CI: -5.7; -3.0, p < 0.001) and -1.7 ± 8.4 mmHg (95% CI: -2.6; -0.7, p < 0.001) were observed in systolic and diastolic blood pressure, respectively (n = 307). Statistically significant reductions in mean total cholesterol (-12.2 ± 38.8 mg/dl [95% CI: -24.3 to -0.06, p < 0.049]) and triglycerides (-18.3 ± 43.6 mg/dl [95% CI: -4.7; -31.9, p < 0.009]) were also observed (n = 42). Conclusions: This study demonstrated the effectiveness of semaglutide 2.4 mg in reducing body weight and improving cardiometabolic parameters in adults with overweight or obesity in a real-world clinical practice setting, showing a significant mean body weight reduction and improvements in biomarkers like blood pressure and HbA1c over a 6-month period. These findings, aligning with previous clinical trials at comparable time points, highlight the clinical relevance of semaglutide as an effective therapeutic option for obesity.

Rescreening on RBANS Delayed Memory Index? Forget About It!

OBJECTIVE: To assess the value of rescreening patients with Alzheimer's disease who do not meet the inclusion criteria for the Repeatable Battery for the Assessment of Neuropsychological Status Delayed Memory Index (RBANS DMI) at the initial assessment. PATIENTS AND METHODS: Participants (aged 50-85 years, without dementia, Mini-Mental State Examination score ≥22, valid Clinical Dementia Rating [CDR] global score, and amyloid status at baseline) were identified in the European Prevention of Alzheimer's Dementia database. Changes from baseline in RBANS DMI were estimated using a mixed model for repeated measurements. Logistic regressions were used to estimate the probability of participants with baseline RBANS DMI 86-95 having RBANS DMI ≤85, CDR global score ≥0.5, and amyloid positivity at 6 and 12 months. RESULTS: There was significant variability in the change in RBANS DMI scores over time (median change at 6 months: 2.0). An estimated 15% of participants with RBANS DMI 86-95 at baseline progressed to ≤85 at 6 months; 8% also achieved CDR global score ≥0.5 and 5% were also amyloid positive. CONCLUSIONS: The results from our analysis indicate that there is limited value in rescreening patients based on their initial RBANS DMI score.

Association between clinical dementia rating and clinical outcomes in Alzheimer's disease.

INTRODUCTION: We examined associations between the Clinical Dementia Rating Scale (CDR) and function (Functional Assessment Scale [FAS]), neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire [NPI-Q]), and cognitive impairment in Alzheimer's disease (AD). METHODS: We used data from the National Alzheimer's Coordinating Center Uniform Data Set and defined cognitively unimpaired and AD stages using CDR-global. RESULTS: Functional and neuropsychiatric symptoms occur as early as the mild cognitive impairment (MCI) phase. The adjusted lest square mean FAS (95% confidence interval [CI]) was lowest in cognitively unimpaired (3.88 [3.66, 4.11] to 5.01 [4.76, 5.26]) and higher with more advanced AD (MCI: 8.17 [6.92, 9.43] to 20.87 [19.53, 22.20]; mild: 18.54 [17.57, 19.50] to 28.13 [27.14, 29.12]; moderate: 26.01 [25.31, 26.70] to 29.42 [28.73, 30.10]). FAS and NPI-Q scores increased steeply with MCI (NPI-Q: 5.55 [4.89, 6.20] to 7.11 [6.43, 7.78]) and mild AD dementia (NPI-Q: 6.66 [5.72, 7.60] to 8.32 [7.32, 9.33]). DISCUSSION: CDR-global staged AD by capturing differences in relevant outcomes along AD progression. Highlights: There were strong associations among CDR and the various outcomes relevant to healthcare providers, patients, and their care givers, such as activities of daily living.Overall, activities of daily living, neuropsychiatric symptoms, and cognitive function outcomes deteriorated over time and can be observed in early stages of AD (MCI or mild dementia).Our findings directly inform the current understanding of AD progression and can aid in care planning and benefit assessments of early AD interventions to delay the progression of AD to more advanced stages.

High-Intensity Focused-Ultrasound Focal Therapy Versus Laparoscopic Radical Prostatectomy: A Comparison of Oncological and Functional Outcomes in Low- and Intermediate-Risk Prostate Cancer Patients.

To compare oncological and functional outcomes of high-intensity focused-ultrasound (HIFU) focal therapy (FT) versus laparoscopic radical prostatectomy (LRP) in patients treated for low- or intermediate-risk prostate cancer (PCa), we retrospectively analyzed data of consecutive patients comprising 30 men, who underwent HIFU-FT, and 96 men who underwent LRP, in an academic center. Oncological outcomes were assessed based on the follow-up prostate-specific antigen values. We used the International Index of Erectile Function short form score to assess erectile function (EF). Urinary continence status was defined based on the number of pads used per day. Median follow-up was 12.5 and 19.1 months in the LRP and HIFU-FT groups, respectively. The effects were computed after propensity score matching and expressed as average treatment effect (ATE). Compared to LRP, HIFU-FT was associated with increased risk of treatment failure (ATE 0.103-0.164, depending on definition, p < 0.01) and lower risk of urinary incontinence (ATE -0.808 at 12 months, p < 0.01). Risk of erectile dysfunction was higher in the LRP group (ATE 5.092, p < 0.01). Our results demonstrate that HIFU-FT may be a reasonable treatment option in selected PCa patients, willing to preserve their EF and urinary continence yet accepting a higher risk of treatment failure.

ComplexBrowser: A Tool for Identification and Quantification of Protein Complexes in Large-scale Proteomics Datasets.

We have developed ComplexBrowser, an open source, online platform for supervised analysis of quantitative proteomic data (label free and isobaric mass tag based) that focuses on protein complexes. The software uses manually curated information from CORUM and Complex Portal databases to identify protein complex components. For the first time, we provide a Complex Fold Change (CFC) factor that identifies up- and downregulated complexes based on the level of complex subunits coregulation. The software provides interactive visualization of protein complexes' composition and expression for exploratory analysis and incorporates a quality control step that includes normalization and statistical analysis based on the limma package. ComplexBrowser was tested on two published studies identifying changes in protein expression within either human adenocarcinoma tissue or activated mouse T-cells. The analysis revealed 1519 and 332 protein complexes, of which 233 and 41 were found coordinately regulated in the respective studies. The adopted approach provided evidence for a shift to glucose-based metabolism and high proliferation in adenocarcinoma tissues, and the identification of chromatin remodeling complexes involved in mouse T-cell activation. The results correlate with the original interpretation of the experiments and provide novel biological details about the protein complexes affected. ComplexBrowser is, to our knowledge, the first tool to automate quantitative protein complex analysis for high-throughput studies, providing insights into protein complex regulation within minutes of analysis.

Clinical utility of MRI in the decision-making process before radical prostatectomy: Systematic review and meta-analysis.

CONTEXT: Magnetic resonance imaging (MRI) is currently the most accurate imaging modality to assess local prostate cancer stage. Despite a growing body of evidence, incorporation of MRI images into decision-making process concerning surgical template of radical prostatectomy, is complex and still poorly understood. OBJECTIVE: We sought to determine the value of MRI in preoperative planning before radical prostatectomy. MATERIALS AND METHODS: Systematic search through electronic PubMed, EMBASE, and Cochrane databases from 2000 up to April 2018 was performed. Only studies that used preoperative MRI in decision-making process regarding extension of resection in patients with prostate cancer, in whom radical prostatectomy was an initial form of treatment were included into analysis. Their quality was scored by Risk Of Bias In Non-Randomized Studies of Interventions system. Meta-analysis was performed to calculate the weighted summary proportion under the fixed or random effects model as appropriate and pooled effects were depicted on forest plots. RESULTS: The results showed that the preoperative MRI led to the modification of initial surgical template in one third of cases (35%). This occurred increasingly with the rising prostate cancer-risk category: 28%, 33%, 52% in low-, intermediate- and high-risk group, respectively. Modification of neurovascular bundle-sparing surgery based on MRI appeared to have no impact on the positive surgical margin rate. The decision based on MRI was correct on average in 77% of cases and differed across prostate cancer-risk categories: 63%, 75% and 91% in low-, intermediate- and high-risk group, accordingly. CONCLUSIONS: In summary, MRI has a considerable impact on the decision-making process regarding the extent of resection during radical prostatectomy. Adaptation of MRI images by operating surgeons has at worst no significant impact on surgical margin status, however its ability to decrease the positive surgical margin rates remains unconfirmed.

3.0-T multiparametric magnetic resonance imaging modifies the template of endoscopic, conventional radical prostatectomy in all cancer risk categories.

INTRODUCTION: We aimed to evaluate the diagnostic performance of 3.0-T multiparametric magnetic resonance imaging (mpMRI) in preoperative staging of prostate cancer (PCa) and its influence on the extent of resection during endoscopic radical prostatectomy (ERP) among cancer risk groups. MATERIAL AND METHODS: The data of 154 patients with PCa in whom mpMRI was performed prior to ERP between 2011 and 2015 were included. The initial decision whether to perform neurovascular bundle (NVB) sparing surgery was based on EAU guidelines. mpMRI images were reevaluated prior to prostatectomy to modify the surgical template. Imaging was compared with pathological reports to investigate the diagnostic performance of mpMRI. RESULTS: The surgical template was modified in 69 (44.8%) patients after reevaluation of mpMRI. More preserving NVB sparing was attempted in 17 (11.0%) men, in whom NVB would have been resected if mpMRI had not been available. More aggressive NVB resection was performed in 52 (33.8%) men, in whom innervation would have been spared if basing solely based on guidelines. Among all PCa risk groups mpMRI had an impact on the surgical template with more aggressive surgery in 63.0% and 33.3% of men in the low- and intermediate-risk group, respectively, and more preserving in 21.4% of the high-risk patients. The change in extent of resection was not correlated with a higher risk of positive surgical margins (p = 0.196). CONCLUSIONS: Preoperative mpMRI exerts a significant impact on decision making concerning the extent of resection during ERP irrespective of the PCa risk group.