Interplay Between Statins, Cav1 (Caveolin-1), and Aldosterone

Statin use is associated with lower aldosterone levels. We hypothesized that caveolin-1 may be important for the uptake of statins into the adrenal gland and would affect statin’s aldosterone-lowering effects. The aim of this study was to test whether the caveolin-1 risk allele (rs926198) would affect aldosterone levels associated with statin use. The Hypertensive Pathotype database includes healthy and hypertensive individuals who have undergone assessment of adrenal hormones. Individuals were studied off antihypertensive medications but were maintained on statins if prescribed by their personal physician. Adrenal hormones were measured at baseline and after 1 hour of angiotensin II stimulation on both high- and low-sodium diets. A mixed-model repeated-measures analysis was employed with a priori selected covariates of age, sex, body mass index, and protocol (low versus high sodium, baseline versus angiotensin II stimulated aldosterone). A total of 250 individuals were included in the study; 31 individuals were taking statins (12.4%) and 219 were not. Among statin users, carrying a caveolin-1 risk allele resulted in a 25% (95% CI, 1–43.2) lower aldosterone level ( P =0.04). However, among nonstatin users, carrying a caveolin-1 risk allele resulted in no significant effect on aldosterone levels ( P =0.38). Additionally, the interaction between caveolin-1 risk allele and statin use on aldosterone levels was significant ( P =0.03). These findings suggest caveolin-1 risk allele carrying individuals are likely to receive the most benefit from statin’s aldosterone-lowering properties; however, due to the observational nature of this study, these findings need further investigation.

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Treatment with Angiotensin II Inhibitors and Residual Renal Function in Peritoneal Dialysis Patients

Peritoneal Dialysis International ◽

10.3747/pdi.2009.00088 ◽

2011 ◽

Vol 31 (1) ◽

pp. 53-59 ◽

Cited By ~ 26

Author(s):

Inna Kolesnyk ◽

Marlies Noordzij ◽

Friedo W. Dekker ◽

Elisabeth W. Boeschoten ◽

Raymond T. Krediet

Keyword(s):

Peritoneal Dialysis ◽

Angiotensin Ii ◽

Repeated Measures ◽

Time Course ◽

Mixed Model ◽

Linear Mixed Model ◽

Cox Regression ◽

Antihypertensive Medications ◽

Converting Enzyme Inhibitors

BackgroundMany studies have shown the renoprotective effect of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) in patients with chronic kidney disease stages I–IV. Two randomized controlled trials (RCTs) showed a positive effect of AII inhibitors on residual glomerular filtration rate (rGFR) in peritoneal dialysis (PD) patients. However, these studies were small and were performed in a highly selected group of PD patients. Our aim was to confirm the above findings in a larger number of prospectively followed PD patients.MethodsFirst we analyzed the time course of decline of rGFR in 452 incident PD patients that were not anuric at the start of dialysis and that had structured follow-up data, with measurements at 3, 6, 12, 18, 24, 30, and 36 months after the start of dialysis. Changes in rGFR over time were analyzed with a linear mixed model for repeated measures. In addition, Cox regression models were used to estimate the risk of developing anuria. In a second approach, we aimed to repeat the above analyses in a selected group of patients that theoretically could have been randomized and therefore resembled the population studied in the 2 mentioned RCTs. In this group the follow-up was restricted to 1 year.Results201 patients were treated with ACEi/ARBs and 251 did not take these drugs at the start of PD. More patients from the treated group had diabetes and used more antihypertensive medications. The time course of decline of rGFR was not different between the 2 groups over the 3 years of PD treatment ( p = 0.52). Less than 25% of patients from each group became anuric and there was no difference in time to development of complete anuria between the treated and untreated groups. In the second approach, 130 patients were included: 37 were treated with ACEi/ARBs and 93 were not. Again, no difference was found between the 2 groups with respect to the rate of decline of rGFR and time of anuria development.ConclusionOur findings are not in line with the results of previous RCTs. The biggest limitation of observational studies is the inability to avoid confounding by indication. However, a RCT in such a setting also does not give a reliable answer. Given all the benefits of ACEi/ARBs, the medications should not be withheld from PD patients. However, their renoprotective effects may often be overruled by other factors influencing the time course of rGFR.

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Detecting variable responses in time-series using repeated measures ANOVA: Application to physiologic challenges

F1000Research ◽

10.12688/f1000research.8252.2 ◽

2016 ◽

Vol 5 ◽

pp. 563

Author(s):

Paul M. Macey ◽

Philip J. Schluter ◽

Katherine E. Macey ◽

Ronald M. Harper

Keyword(s):

Repeated Measures ◽

Mixed Model ◽

A Priori ◽

Brain Regions ◽

Single Step ◽

Response Patterns ◽

Whole Brain ◽

Average Signal Intensity ◽

Respiratory Challenge ◽

Time Point

We present an approach to analyzing physiologic timetrends recorded during a stimulus by comparing means at each time point using repeated measures analysis of variance (RMANOVA). The approach allows temporal patterns to be examined without an a priori model of expected timing or pattern of response. The approach was originally applied to signals recorded from functional magnetic resonance imaging (fMRI) volumes-of-interest (VOI) during a physiologic challenge, but we have used the same technique to analyze continuous recordings of other physiological signals such as heart rate, breathing rate, and pulse oximetry. For fMRI, the method serves as a complement to whole-brain voxel-based analyses, and is useful for detecting complex responses within pre-determined brain regions, or as a post-hoc analysis of regions of interest identified by whole-brain assessments. We illustrate an implementation of the technique in the statistical software packages R and SAS. VOI timetrends are extracted from conventionally preprocessed fMRI images. A timetrend of average signal intensity across the VOI during the scanning period is calculated for each subject. The values are scaled relative to baseline periods, and time points are binned. In SAS, the procedure PROC MIXED implements the RMANOVA in a single step. In R, we present one option for implementing RMANOVA with the mixed model function “lme”. Model diagnostics, and predicted means and differences are best performed with additional libraries and commands in R; we present one example. The ensuing results allow determination of significant overall effects, and time-point specific within- and between-group responses relative to baseline. We illustrate the technique using fMRI data from two groups of subjects who underwent a respiratory challenge. RMANOVA allows insight into the timing of responses and response differences between groups, and so is suited to physiologic testing paradigms eliciting complex response patterns.

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Effects of Aging on the Subcortical Encoding of Stop Consonants

American Journal of Audiology ◽

10.1044/2020_aja-19-00044 ◽

2020 ◽

Vol 29 (3) ◽

pp. 391-403

Author(s):

Dania Rishiq ◽

Ashley Harkrider ◽

Cary Springer ◽

Mark Hedrick

Keyword(s):

Older Adults ◽

Repeated Measures ◽

Mixed Model ◽

Auditory Brainstem ◽

Auditory Brainstem Responses ◽

Aging Effects ◽

Formant Frequency ◽

Place Of Articulation ◽

Second Formant ◽

Effects Of Aging

Purpose The main purpose of this study was to evaluate aging effects on the predominantly subcortical (brainstem) encoding of the second-formant frequency transition, an essential acoustic cue for perceiving place of articulation. Method Synthetic consonant–vowel syllables varying in second-formant onset frequency (i.e., /ba/, /da/, and /ga/ stimuli) were used to elicit speech-evoked auditory brainstem responses (speech-ABRs) in 16 young adults ( M age = 21 years) and 11 older adults ( M age = 59 years). Repeated-measures mixed-model analyses of variance were performed on the latencies and amplitudes of the speech-ABR peaks. Fixed factors were phoneme (repeated measures on three levels: /b/ vs. /d/ vs. /g/) and age (two levels: young vs. older). Results Speech-ABR differences were observed between the two groups (young vs. older adults). Specifically, older listeners showed generalized amplitude reductions for onset and major peaks. Significant Phoneme × Group interactions were not observed. Conclusions Results showed aging effects in speech-ABR amplitudes that may reflect diminished subcortical encoding of consonants in older listeners. These aging effects were not phoneme dependent as observed using the statistical methods of this study.

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Power of Modified Brown-Forsythe and Mixed-Model Approaches in Split-Plot Designs

Methodology ◽

10.1027/1614-2241/a000124 ◽

2017 ◽

Vol 13 (1) ◽

pp. 9-22 ◽

Cited By ~ 1

Author(s):

Pablo Livacic-Rojas ◽

Guillermo Vallejo ◽

Paula Fernández ◽

Ellián Tuero-Herrero

Keyword(s):

Repeated Measures ◽

Statistical Power ◽

Mixed Model ◽

Covariance Structure ◽

Simulation Method ◽

Future Research ◽

Repeated Measures Design ◽

Fixed And Random Effects ◽

Split Plot ◽

High Level

Abstract. Low precision of the inferences of data analyzed with univariate or multivariate models of the Analysis of Variance (ANOVA) in repeated-measures design is associated to the absence of normality distribution of data, nonspherical covariance structures and free variation of the variance and covariance, the lack of knowledge of the error structure underlying the data, and the wrong choice of covariance structure from different selectors. In this study, levels of statistical power presented the Modified Brown Forsythe (MBF) and two procedures with the Mixed-Model Approaches (the Akaike’s Criterion, the Correctly Identified Model [CIM]) are compared. The data were analyzed using Monte Carlo simulation method with the statistical package SAS 9.2, a split-plot design, and considering six manipulated variables. The results show that the procedures exhibit high statistical power levels for within and interactional effects, and moderate and low levels for the between-groups effects under the different conditions analyzed. For the latter, only the Modified Brown Forsythe shows high level of power mainly for groups with 30 cases and Unstructured (UN) and Autoregressive Heterogeneity (ARH) matrices. For this reason, we recommend using this procedure since it exhibits higher levels of power for all effects and does not require a matrix type that underlies the structure of the data. Future research needs to be done in order to compare the power with corrected selectors using single-level and multilevel designs for fixed and random effects.

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Long-term seizure outcomes after pediatric temporal lobectomy: does brain MRI lesion matter?

Journal of Neurosurgery Pediatrics ◽

10.3171/2019.4.peds18677 ◽

2019 ◽

Vol 24 (2) ◽

pp. 200-208

Author(s):

Ravindra Arya ◽

Francesco T. Mangano ◽

Paul S. Horn ◽

Sabrina K. Kaul ◽

Serena K. Kaul ◽

...

Keyword(s):

Repeated Measures ◽

Mixed Model ◽

Linear Mixed Model ◽

Hippocampal Sclerosis ◽

Brain Mri ◽

Temporal Lobectomy ◽

Seizure Freedom ◽

Seizure Onset

OBJECTIVEThere is emerging data that adults with temporal lobe epilepsy (TLE) without a discrete lesion on brain MRI have surgical outcomes comparable to those with hippocampal sclerosis (HS). However, pediatric TLE is different from its adult counterpart. In this study, the authors investigated if the presence of a potentially epileptogenic lesion on presurgical brain MRI influences the long-term seizure outcomes after pediatric temporal lobectomy.METHODSChildren who underwent temporal lobectomy between 2007 and 2015 and had at least 1 year of seizure outcomes data were identified. These were classified into lesional and MRI-negative groups based on whether an epilepsy-protocol brain MRI showed a lesion sufficiently specific to guide surgical decisions. These patients were also categorized into pure TLE and temporal plus epilepsies based on the neurophysiological localization of the seizure-onset zone. Seizure outcomes at each follow-up visit were incorporated into a repeated-measures generalized linear mixed model (GLMM) with MRI status as a grouping variable. Clinical variables were incorporated into GLMM as covariates.RESULTSOne hundred nine patients (44 females) were included, aged 5 to 21 years, and were classified as lesional (73%), MRI negative (27%), pure TLE (56%), and temporal plus (44%). After a mean follow-up of 3.2 years (range 1.2–8.8 years), 66% of the patients were seizure free for ≥ 1 year at last follow-up. GLMM analysis revealed that lesional patients were more likely to be seizure free over the long term compared to MRI-negative patients for the overall cohort (OR 2.58, p < 0.0001) and for temporal plus epilepsies (OR 1.85, p = 0.0052). The effect of MRI lesion was not significant for pure TLE (OR 2.64, p = 0.0635). Concordance of ictal electroencephalography (OR 3.46, p < 0.0001), magnetoencephalography (OR 4.26, p < 0.0001), and later age of seizure onset (OR 1.05, p = 0.0091) were associated with a higher likelihood of seizure freedom. The most common histological findings included cortical dysplasia types 1B and 2A, HS (40% with dual pathology), and tuberous sclerosis.CONCLUSIONSA lesion on presurgical brain MRI is an important determinant of long-term seizure freedom after pediatric temporal lobectomy. Pediatric TLE is heterogeneous regarding etiologies and organization of seizure-onset zones with many patients qualifying for temporal plus nosology. The presence of an MRI lesion determined seizure outcomes in patients with temporal plus epilepsies. However, pure TLE had comparable surgical seizure outcomes for lesional and MRI-negative groups.

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Efficacy of galcanezumab in patients with migraine who did not benefit from commonly prescribed preventive treatments

BMC Neurology ◽

10.1186/s12883-021-02196-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dulanji K. Kuruppu ◽

Joshua Tobin ◽

Yan Dong ◽

Sheena K. Aurora ◽

Laura Yunes-Medina ◽

...

Keyword(s):

Repeated Measures ◽

Migraine Headache ◽

Mixed Model ◽

Preventive Treatment ◽

Response Rates ◽

Toxin A ◽

Double Blind ◽

Preventive Medication ◽

Onabotulinum Toxin A ◽

Post Hoc

Abstract Background Galcanezumab is a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) indicated for the preventive treatment of migraine. While galcanezumab has demonstrated efficacy in patients who did not respond to prior preventive medications in general, its efficacy in patients who did not benefit from individual, commonly prescribed preventive treatments due to inadequate efficacy or safety/tolerability remains unknown. Methods CONQUER was a 3-month, randomized, double-blind, placebo-controlled, phase 3b study that enrolled patients with episodic or chronic migraine who had 2 to 4 migraine preventive medication category failures in the past 10 years. Patients were randomly assigned 1:1 to receive placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose; N = 232). Post hoc analyses were conducted to determine the efficacy of galcanezumab in patients who had not benefited from six of the most commonly prescribed migraine preventive medications. The mean change from baseline in monthly migraine headache days and ≥ 50 % response rates were assessed over months 1–3. Improvement in Migraine-Specific Questionnaire Role Function-Restrictive (MSQ-RFR) scores were assessed at month 3. The endpoints were estimated via mixed model with repeated measures. Results The most common treatment failures due to inadequate efficacy or safety/tolerability, which at least 20 % of patients reported trying without benefit, included topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and metoprolol. Patients who had not previously benefited from these treatments had a greater mean reduction in monthly migraine headache days across months 1–3 in the galcanezumab group compared to placebo (all p < 0.01). More patients treated with galcanezumab experienced a ≥ 50 % reduction from baseline in monthly migraine headache days across months 1–3 compared to placebo (all p < 0.05). Galcanezumab-treated patients had a greater improvement in mean MSQ-RFR scores at month 3 compared to placebo (all p < 0.01). Conclusions In this population, galcanezumab was effective in reducing monthly migraine headache days, improving response rates, and enhancing quality of life in patients who had not previously benefited from topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and/or metoprolol due to inadequate efficacy or safety/tolerability. Trial registration ClinicalTrials.gov NCT03559257 (CONQUER).

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The Effect of Different Turn Speeds on Whole-Body Coordination in Younger and Older Healthy Adults

Sensors ◽

10.3390/s21082827 ◽

2021 ◽

Vol 21 (8) ◽

pp. 2827

Author(s):

Fuengfa Khobkhun ◽

Mark Hollands ◽

Jim Richards

Keyword(s):

Older Adults ◽

Repeated Measures ◽

Mixed Model ◽

Healthy Adults ◽

Whole Body ◽

Onset Latency ◽

Step Frequency ◽

Step Size ◽

Younger Adults ◽

Mixed Model Analysis

Difficulty in turning is prevalent in older adults and results in postural instability and risk of falling. Despite this, the mechanisms of turning problems have yet to be fully determined, and it is unclear if different speeds directly result in altered posture and turning characteristics. The aim of this study was to identify the effects of turning speeds on whole-body coordination and to explore if these can be used to help inform fall prevention programs in older adults. Forty-two participants (21 healthy older adults and 21 younger adults) completed standing turns on level ground. Inertial Measurement Units (XSENS) were used to measure turning kinematics and stepping characteristics. Participants were randomly tasked to turn 180° at one of three speeds; fast, moderate, or slow to the left and right. Two factors mixed model analysis of variance (MM ANOVA) with post hoc pairwise comparisons were performed to assess the two groups and three turning speeds. Significant interaction effects (p < 0.05) were seen in; reorientation onset latency of head, pelvis, and feet, peak segmental angular separation, and stepping characteristics (step frequency and step size), which all changed with increasing turn speed. Repeated measures ANOVA revealed the main effects of speeds within the older adults group on those variables as well as the younger adults group. Our results suggest that turning speeds result in altered whole-body coordination and stepping behavior in older adults, which use the same temporospatial sequence as younger adults. However, some characteristics differ significantly, e.g., onset latency of segments, peak head velocity, step frequency, and step size. Therefore, the assessment of turning speeds elucidates the exact temporospatial differences between older and younger healthy adults and may help to determine some of the issues that the older population face during turning, and ultimately the altered whole-body coordination, which lead to falls.

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Firm characteristics and excellence in integrated reporting

South African Journal of Economic and Management Sciences ◽

10.4102/sajems.v20i1.1307 ◽

2017 ◽

Vol 20 (1) ◽

Cited By ~ 9

Author(s):

Natasha Buitendag ◽

Gail S. Fortuin ◽

Amber De Laan

Keyword(s):

Repeated Measures ◽

Mixed Model ◽

Stock Exchange ◽

Categorical Variables ◽

Firm Characteristics ◽

Integrated Reporting ◽

Johannesburg Stock Exchange ◽

Annual Survey ◽

The Board Of Directors

Background: Integrated reporting has attracted much attention in the past few years, and South Africa has taken the lead in its development worldwide. An annual survey is published by Ernst & Young regarding the quality of the integrated reports of the top 100 entities listed on the Johannesburg Stock Exchange (JSE).Aim: The study on which this article is based was aimed at determining whether the assessment of an entity’s characteristics can predetermine the quality of the integrated report generated by that entity. Setting: This article focuses on an analysis of the integrated reporting of the top 100 entities listed on JSE for the financial years ending in 2013, 2014 and 2015.Methods: Comparison of categorical variables, mixed-model repeated measures ANOVA and generalised estimating equations were applied to identify the best classificators to distinguish between excellent integrated reporting and those reports where progress could still be made. Results: The results show that the type of industry the entity finds itself in, the size and profitability of the entity, as well as the composition of the members of the board, have an effect on the quality of the integrated report.Conclusion: Our results indicated that the type of industry, size of an entity, the profitability and composition of the board of directors, all have an effect on the quality of the integrated reporting. Our evidence will assist current and prospective stakeholders in evaluating the expected quality of an entity’s integrated report, through the evaluation of certain firm characteristics.

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The Efficacy of Lurasidone on PANSS Subscales in Adolescent Patients with Schizophrenia: Results from a 6-week, Double-blind, Placebo-controlled, Multicenter Study

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.284 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S90-S91 ◽

Cited By ~ 1

Author(s):

C. Correll ◽

R. Goldman ◽

J. Cucchiaro ◽

L. Deng ◽

A. Loebel

Keyword(s):

Repeated Measures ◽

Mixed Model ◽

Wide Spectrum ◽

Dose Range ◽

Data Safety Monitoring Board ◽

Double Blind ◽

Meaningful Improvement ◽

General Psychopathology ◽

Adolescent Patients ◽

Adjusted Least Squares

IntroductionLurasidone is an atypical antipsychotic that demonstrated efficacy in the treatment of adults with schizophrenia in the dose range of 37–148 mg/day.Objective/AimsThe objective of this analysis was to evaluate the efficacy of lurasidone in adolescent patients with schizophrenia.MethodsAdolescents (13–17 years old) diagnosed with schizophrenia were randomly assigned to six weeks of double-blind treatment with lurasidone 37 mg/day, 74 mg/day or placebo. Changes from baseline to week 6 in PANSS total and subscale (positive, negative, general psychopathology, excitability) scores were evaluated using mixed-model repeated-measures analysis.ResultsA total of 326 patients (mean age, 15.4 years) were randomized and received lurasidone 37 mg/day (n = 108), 74 mg/day (n = 106), or placebo (n = 112). The PANSS total score at week 6 demonstrated a placebo-adjusted, least-squares (LS) mean improvement of –8.0 (P < 0.001; effect size [ES], 0.51) for the 37 mg/day group and –7.7 (P < 0.001; ES = 0.48) for the 74 mg/day group. Placebo-adjusted LS mean change for lurasidone 37 mg/day and 74 mg/day, respectively, was –3.2 (P < 0.001; ES = 0.62) and –3.2 (P < 0.001; ES = 0.60) on the PANSS positive subscale, –1.7 (P = 0.011; ES = 0.41) and –1.6 (P = 0.022; ES = 0.35) on the PANSS negative subscale, –2.8 (P = 0.012; ES = 0.38) and –2.8 (P = 0.011; ES = 0.37) on the PANSS general psychopathology subscale, and –1.1 (P = 0.016; ES = 0.36) and –1.8 (P < 0.001; ES = 0.53) on the PANSS excitability subscale.ConclusionsIn adolescent patients with schizophrenia, lurasidone (37 mg/day and 74 mg/day) demonstrated statistically significant efficacy and clinically meaningful improvement across a wide spectrum of symptoms associated with schizophrenia. Sponsored by Sunovion Pharmaceuticals Inc. ClinicalTrials.gov identifier: NCT01911429.Disclosure of interestDr Correll reports being a consultant and/or advisor for Alkermes, Forum Pharmaceuticals Inc., Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, Lundbeck, Medavante, Medscape, Otsuka, Pfizer Inc, ProPhase, Sunovion Pharmaceuticals Inc., Supernus, Takeda, and Teva providing expert testimony for Bristol-Myers Squibb Company, Janssen, and Otsuka serving on a Data Safety Monitoring Board for Lundbeck and Pfizer Inc and receiving grant support from Takeda. Drs Goldman, Cucchiaro, Deng and Loebel are employees of Sunovion Pharmaceuticals Inc.

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Mood and Global Symptom Changes among Psychotherapy Clients with Depressive Personality

Depression Research and Treatment ◽

10.1155/2012/208435 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12

Author(s):

Rachel E. Maddux ◽

Lars-Gunnar Lundh

Keyword(s):

Repeated Measures ◽

Mixed Model ◽

Psychological Symptoms ◽

Self Report ◽

Treatment Results ◽

Repeated Measures Analysis ◽

Depressive Personality ◽

Symptom Changes ◽

Psychotherapy Clients ◽

Over Time

The present study assessed the rate of depressive personality (DP), as measured by the self-report instrument depressive personality disorder inventory (DPDI), among 159 clients entering psychotherapy at an outpatient university clinic. The presenting clinical profile was evaluated for those with and without DP, including levels of depressed mood, other psychological symptoms, and global severity of psychopathology. Clients were followed naturalistically over the course of therapy, up to 40 weeks, and reassessed on these variables again after treatment. Results indicated that 44 percent of the sample qualified for DP prior to treatment, and these individuals had a comparatively more severe and complex presenting disposition than those without DP. Mixed-model repeated-measures analysis of variance was used to examine between-groups changes on mood and global severity over time, with those with DP demonstrating larger reductions on both outcome variables, although still showing more symptoms after treatment, than those without DP. Only eleven percent of the sample continued to endorse DP following treatment. These findings suggest that in routine clinical situations, psychotherapy may benefit individuals with DP.

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