Mixed-effect Analysis Of Variance Research Articles

Descended Social Anxiety Disorder and Craving in Women Heroin Dependence Through Exercise Alerts Plasma Oxytocin Levels.

Purpose: This study explored the association between peripheral blood oxytocin (OT) and social anxiety disorder (SAD) and cue-induced cravings in female heroin addicts. The effect of exercise on alleviation of SAD and OT levels was also explored.Methods: A total of 72 females with heroin dependence were assigned to three groups based on SAD severity. The three groups were Non-SAD control, SAD control, and SAD exercise groups. Subjects in the SAD exercise group underwent aerobic exercise and resistance training for 8 weeks (60 min/day, 5 days/week). Enzyme-linked immunosorbent assay analysis and Liebowitz Social Anxiety Scale (LSAS) scores were used to determine plasma OT concentration and SAD, respectively. Cue-induced craving was assessed using Visual Analog Scale (VAS) and Desires for Drug Questionnaire (DDQ). Mixed-effect analysis of variance and Pearson correlation analysis were used to explore the effect and correlation between different parameters.Results: OT levels in the SAD exercise group were significantly high after exercise (p < 0.01). LSAS, VAS, and DDQ (“Desire and Intention” and “Negative reinforcement”) scores in the SAD exercise group were significantly lower after exercise (p < 0.01). Plasma OT level was negatively correlated with LSAS score (r = −0.534, p < 0.001), VAS score (r = −0.609, p < 0.001), “Desire and Intention” score (r = −0.555, p < 0.001), and “Negative reinforcement” score (r = −0.332, p < 0.01) and positively correlated with the “control” score (r = 0.258, p < 0.05). LSAS was positively correlated with VAS score (r = 0.588, p < 0.001) and “Desire and Intention” score (r = 0.282, p < 0.05).Conclusions: The findings of the present study indicate that plasma OT is a potential peripheral biomarker for prediction of the severity of social anxiety in female heroin withdrawal patients. Aerobic exercise combined with resistance training plus incremental load for 8 weeks can increase plasma OT levels and significantly reduce severity of SAD and cue-induced cravings in female heroin addicts.

Consistent differences in lumbar spine alignment between low back pain subgroups and genders during clinical and functional activity sitting tests

BackgroundSubgroups of people with low back pain display differences in their lumbar alignment during tests from a clinical examination. However, it is unknown if subgroups display the same patterns during a functional activity test and if gender influences subgroup-related differences. ObjectivesTest if differences in lumbar alignment between two LBP subgroups are 1) present during a functional activity test of preferred sitting and 2) independent of gender. DesignCross-sectional. Method154 participants with chronic low back pain were classified based on the Movement System Impairment Classification System by a physical therapist. Participants performed a functional activity test of preferred sitting and clinical tests of maximum flexed and extended sitting. 3D marker co-ordinate data were collected. Sagittal plane lumbar alignment, indexed by lumbar curvature angle, was calculated. A three-way mixed effect analysis of variance was used to examine effects of test, subgroup, gender, subgroup × test, gender × test and subgroup × gender. Results/findingsThe lumbar rotation with extension subgroup [LCA = −8.0° (−9.5,-6.5)] displayed a more extended lumbar alignment than lumbar rotation [LCA = −5.9° (−7.4,-4.4)]. Women [LCA = −10.7° (−12.3,-9.2)] displayed a more extended lumbar alignment than men [LCA = −3.2° (−4.7,-1.7)]. There was a significant gender × test interaction (p = 0.01). The subgroup × test (p = 0.99) and subgroup × gender (p = 0.76) interactions were not significant. ConclusionsLBP subgroup differences in lumbar alignment are present during preferred sitting. Gender-related differences in lumbar alignment are not driving subgroup differences. These findings highlight the need to use patient-specific clinical characteristics to guide treatment of a functional activity of preferred sitting limited due to low back pain.

Effect of Meperidine on Equine Blood Histamine, Tryptase, and Immunoglobulin-E Concentrations.

Objectives: To evaluate changes in immunological parameters following subcutaneous (SC) and intramuscular (IM) administration of meperidine in horses through quantitative analysis of plasma tryptase, histamine, and IgE levels.Methods: Six adult horses were enrolled in a prospective randomized crossover design. Horses were administered one treatment per day, with a seven day washout period: (a) meperidine 1 mg/kg IM, saline 6 mL SC; (b) saline 6 mL IM, meperidine 1 mg/kg SC; (c) saline 6 mL SC, saline 6 mL IM. Blood samples were obtained for plasmatic histamine (baseline, 5, 10, 15, 30, and 60 min) via LC-MS/MS and plasmatic tryptase (baseline, 15, 30, 60, 120, and 240 min) quantification with enzyme-linked immunoabsorbent assays. Serum immunoglobulin E (IgE) concentrations prior to any meperidine treatment and 7–14 days following the first meperidine treatment were evaluated with enzyme-linked immunoabsorbent assays. Histamine and tryptase concentrations were evaluated with a mixed-effect analysis of variance. The levels of IgE at baseline (before the administration of the first dose of meperidine) were compared with the IgE values at 60 min following the second meperidine administration with the Paired t test. Biopsies of localized injection site reactions from subcutaneous meperidine administration were collected from two horses.Results: No statistically significant elevations from baseline in histamine (p = 0.595), tryptase (p = 0.836), or IgE (p = 0.844) were found in any of the horses in this study. There were no differences between treatment groups. Administration of SC meperidine caused a localized vasculitis and thrombosis with regional edema and hemorrhage.Conclusion: No evidence of anaphylactoid or anaphylactic type reactions occurred following IM or SC meperidine administration.

The Use of Communication Technology to Affect Patient Outcomes in the Intensive Care Unit.

Effective two-way patient-provider communication is challenging and is even more difficult when patients are communication vulnerable. The results of being unheard and unacknowledged can contribute to negative feelings and may manifest as symptoms of anxiety and depression. Researchers explored symptoms of anxiety and depression when using a team-developed, patient-centered, and nurse-led intervention called Speak for Myself-Voice (formerly published as Speak for Myself) in five intensive care units at a Magnet status, university-affiliated medical center in East Tennessee. This was an equivalent control group design. The data were analyzed with a mixed-effect analysis of variance (between and within groups) with repeated measures to see if the treatment group changed differently than the control group across time (48 hours). This study report adds information about anxiety and depression in patients who are communication vulnerable and using communication technology.

Consistency and effect of body position change on measurement of upper and lower esophageal sphincter geometry using impedance planimetry in a canine model.

The EndoFLIP (Endolumenal Functional Lumen Imaging Probe, Crospon Inc, Galway, Ireland) device uses the technique of impedance planimetry to evaluate dimensions and distensibility of the upper and lower esophageal sphincter. The null hypotheses for this study were that EndoFLIP variables would be stable between anesthestic episodes and would not be affected by body position when evaluating the upper and lower esophageal sphincters in healthy dogs. During each of three consecutive general anesthesia episodes administered to eight healthy adult research colony dogs with a standardized protocol, the EndoFLIP catheter was positioned to measure cross-sectional area, intrabag pressure, upper and lower esophageal sphincter length at two different balloon fill volumes (30 and 40 mL) and two body positions (lateral and dorsal recumbency). From these measured variables, a distensibility index was also calculated. Mixed effect analysis of variance was used to evaluate the fixed marginal and interaction effects of anesthesia episode, body position, and balloon volume on measured and calculated variables. For the upper esophageal sphincter significant interactions were present between anesthetic episode and body position for all variables except intrabag pressure; adjusting for body position significant differences were present between anesthetic episodes for all variables except distensibility index; adjusting for anesthetic episode cross-sectional area, intrabag pressure, upper esophageal sphincter length and distensibility index were all affected by body position. For the lower esophageal sphincter distensibility index was the only variable where a significant interaction between anesthesia episode and body position occurred; cross-sectional area, intrabag pressure, and lower esophageal length were not significantly affected by anesthesia episode when adjusting for body position; distensibility index was the only variable significantly affected by body position. Measurements of the geometry of the lower esophageal sphincter as measured by the EndoFLIP device were consistent under conditions of general anesthesia. Similar measurements taken at the upper esophageal sphincter displayed greater variability between anesthetic episodes and were affected to a greater extent by body position. Body position should be standardized in studies using the EndoFLIP to assess geometric and functional characteristics of the upper and lower esophageal sphincters.

The burden and spatial distribution of bovine African trypanosomes in small holder crop-livestock production systems in Tororo District, south-eastern Uganda.

BackgroundAfrican animal trypanosomiasis (AAT) is considered to be one of the greatest constraints to livestock production and livestock-crop integration in most African countries. South-eastern Uganda has suffered for more than two decades from outbreaks of zoonotic Human African Trypanosomiasis (HAT), adding to the burden faced by communities from AAT. There is insufficient AAT and HAT data available (in the animal reservoir) to guide and prioritize AAT control programs that has been generated using contemporary, sensitive and specific molecular techniques. This study was undertaken to evaluate the burden that AAT presents to the small-scale cattle production systems in south-eastern Uganda.MethodsRandomised cluster sampling was used to select 14% (57/401) of all cattle containing villages across Tororo District. Blood samples were taken from all cattle in the selected villages between September-December 2011; preserved on FTA cards and analysed for different trypanosomes using a suite of molecular techniques. Generalized estimating equation and Rogen-Gladen estimator models were used to calculate apparent and true prevalences of different trypanosomes while intra cluster correlations were estimated using a 1-way mixed effect analysis of variance (ANOVA) in R statistical software version 3.0.2.ResultsThe prevalence of all trypanosome species in cattle was 15.3% (95% CI; 12.2-19.1) while herd level trypanosome species prevalence varied greatly between 0-43%. Trypanosoma vivax (17.4%, 95% CI; 10.6-16.8) and Trypanosoma brucei rhodesiense (0.03%) were respectively, the most, and least prevalent trypanosome species identified.ConclusionsThe prevalence of bovine trypanosomes in this study indicates that AAT remains a significant constraint to livestock health and livestock production. There is need to implement tsetse and trypanosomiasis control efforts across Tororo District by employing effective, cheap and sustainable tsetse and trypanosomiasis control methods that could be integrated in the control of other endemic vector borne diseases like tick-borne diseases.

Effect of levetiracetam on cardiac repolarization in healthy subjects: A single-dose, randomized, placebo- and active-controlled, four-way crossover study

Background: Nonantiarrhythmic drugs may have the potential to prolong the QT interval, leading to potentially fatal ventricular tachycardias, including torsades de pointes.Objective: This study evaluated the potential of the newer-generation, multiple-action antiepileptic drug levetiracetam, which binds to the synaptic vesicle protein SV2A, to affect cardiac repolarization, as detected by prolongation of the QT/corrected QT (QTc) interval.Methods: This was a single-dose, randomized, placebo- and active-controlled, 4-way crossover study in healthy subjects. Subjects were randomly allocated to 1 of 4 different administration sequences. Each sequence included 3 double-blind treatments (levetirace-tam 1000 mg, levetiracetam 5000 mg, and placebo) and 1 open-label treatment (moxifloxacin 400 mg). Triplicate electrocardiograms (ECGs) were obtained at baseline and at various time points over 24 hours after each treatment using continuous Holter monitoring. ECGs were read centrally in a blinded manner. Blood samples for the determination of plasma concentrations of levetiracetam and moxifloxacin were collected before dosing and at 0.5, 1, 1.5, 2, 4, 6, 12, and 24 hours after dosing, within 5 minutes after the ECG recordings. The QT interval was corrected for heart rate using a sex- and study-specific correction (QTcss) as the primary outcome measure and Fridericia's correction (QTcF)as a secondary outcome measure. The primary analysis was performed on the time-matched, baseline-subtracted QTcss (ΔQTcss). The maximum ΔQTcss difference between each active treatment and placebo (ΔΔTcss) was derived from a mixed-effect analysis of variance. Clinical laboratory tests, standard 12-lead ECGs, and vital signs were monitored at regular intervals. Spontaneously reported adverse events were recorded throughout the study.Results: Fifty-two healthy, nonsmoking subjects (26 men, 26 women; 37 white, 9 black, 3 Hispanic, and 3 Asian/Pacific Islander) with a mean (SD) age of 28.4 (7.5) years (range, 18-45 years) and a mean weight of 71.5 (12.6) kg (range, 49-103 kg) participated in the study. Levetiracetam did not significantly prolong the QTcss. The upper bound of the 1-sided 95% CI for the maximum ΔΔTcss was 8.0 milliseconds for levetiracetam 1000 mg and 8.1 milliseconds for levetiracetam 5000 mg, with mean estimates of 4.0 and 4.1 milliseconds, respectively; similar results were obtained for the maximum ΔΔQTcF. Moxifloxacin significantly prolonged the QTcss, with a lower bound of the 1-sided 95% CI for the maximum ΔΔQTcss of 3.7 milliseconds and a mean estimate of 7.7 milliseconds. There was no statistically significant relationship between measured ΔQTcss and the levetiracetam plasma concentration, whereas a significant linear relationship was observed between measured ΔQTcss and the moxifloxacin plasma concentration (slope estimate: 4.4 milliseconds/[μg/mL]); 95% CI, 3.2-5.7; P < 0.001). No unexpected safety concerns arose based on reported adverse events, clinical laboratory evaluations, physical examinations, vital signs, or ECG monitoring during the course of the study.Conclusion: This randomized, placebo- and active-controlled study in healthy adult subjects found no clinically relevant changes in the QTc interval after a single levetiracetam dose of 1000 or 5000 mg.

Pharmacokinetic profile of a 24-hour controlled-release OROS formulation of hydromorphone in the presence of alcohol

ABSTRACTObjective: The purpose of this study was to investigate the pharmacokinetic properties of a novel, once-daily, controlled-release formulation of hydromorphone (OROS hydromorphone) in the presence of alcohol.* OROS is a registered trade name of ALZA Corporation, Mountain View, CA, USAResearch design and methods: In a single-centre, open-label, four-treatment, four-period, four-sequence, crossover study, two groups of 24 healthy subjects (fasted or fed) were randomised to receive four single doses of OROS hydromorphone 16 mg with solutions of either 0%, 4%, 20% or 40% alcohol, and with a naltrexone block.Main outcome measures: Plasma samples taken predose and at regular intervals up to 48 h after dosing were assayed for hydromorphone concentrations; a mixed-effect analysis of variance was done on log-transformed data. Bioequivalence was concluded if 90% confidence intervals of treatment mean ratios were between 80% and 125%.Results: Plasma hydromorphone concentrations were slightly higher after dosing with all alcohol treatments in both the fasted and fed subject groups. Median Tmax values were between 12 and 16 h and ranges were similar for all treatments. Cmax values increased after alcohol compared with no alcohol, with the increase slightly lower in the fed state. The greatest mean increase in Cmax observed was 1.3-fold in the fasted state and 1.1-fold in the fed state. Confidence intervals were within 80–125% for AUC but were slightly higher for Cmax.Conclusions: The pharmacokinetics of once-daily OROS hydromorphone were only minimally affected by alcohol, with no dose dumping of hydromorphone. The results indicate that the controlled-release properties of this formulation are maintained in the presence of alcohol.

Levocetirizine does not prolong the QT/QTc interval in healthy subjects: results from a thorough QT study

To conduct a thorough QT study of levocetirizine, a non-sedating antihistamine, in accordance with International Conference on Harmonisation (ICH) E14 guidance. The study was designed as a single-dose, placebo and positive-controlled, four-way crossover, randomised trial in which 52 healthy male and female subjects participated. Levocetirizine (5 and 30 mg) and placebo were administered double-blind, and the positive control, moxifloxacin (400 mg), was open-label. Electrocardiograms (ECGs) were obtained by continuous Holter monitoring at various time points (three per time point) during a 24-h period at baseline and after each treatment. The ECGs were read centrally in a blinded manner. QT intervals were corrected for heart rate using a gender- and study-specific correction (QTcSS) and Fridericia's correction (QTcF). The largest QTc time-matched and baseline-subtracted difference between each active drug and the placebo (largest delta delta QTcSS) was derived from a mixed-effect analysis of variance. The one-sided 95% upper limits of the largest delta delta QTcSS for levocetirizine were 5.7 ms (5 mg) and 3.9 ms (30 mg), with mean estimates of 2.9 and 1.1 ms, respectively. Similar results were obtained for the delta delta QTcF data. Statistically, moxifloxacin significantly lengthened the QTcSS, with a one-sided 95% lower limit of the largest delta delta QTcSS of 10.5 ms and a mean estimate of 13.4 ms. There was no relationship between the measured delta QTcSS and the plasma concentration of levocetirizine, whereas a statistically significant linear relationship was observed with the plasma concentration of moxifloxacin [slope estimate 0.004 ms/(ng/mL); 95% confidence interval: 0.003-0.005]. Overall, the results of this thorough QT study indicate that the methodology of the trial was valid and sensitive enough to demonstrate the absence of effect of levocetirizine at both therapeutic (5 mg) and supra-therapeutic (30 mg) doses on cardiac repolarisation.

Optic nerve head neuroretinal rim blood flow differences in monkeys with laser‐induced glaucoma

The blood flow of the neuroretinal rim (NRR) of the optic nerve head (ONH) of the rhesus monkey with laser-induced glaucoma was examined. Argon laser photocoagulation of the trabecular meshwork to induce elevated intraocular pressure (IOP) was performed in one eye of nine normal male rhesus monkeys. The nasal and temporal NRR of the monkey ONH were examined by the Heidelberg retina tomograph/flowmeter (HRT/HRF) under neuromuscular blockade. A mixed effect analysis of variance was used to determine significant differences between eyes and between locations in the eyes. The average IOP in the hypertensive glaucoma and normal eyes was 34.8 +/- 7.2 and 16.0 +/- 1.9 mmHg, respectively. The HRT determined average overall cup to disc (C/D) area ratio in the glaucoma and normal eyes, which was 0.49 +/- 0.28 and 0.22 +/- 0.16, respectively. The mean temporal NRR HRF flow in the hypertensive eyes was significantly greater than in the normotensive eyes (P < 0.0001), than in the nasal NRR of the hypertensive eyes (P < 0.0001) and than in the nasal NRR of the normotensive eyes (P < 0.01). The mean nasal NRR HRF flow in the hypertensive eyes was significantly less than in the nasal NRR of the normotensive eyes (P < 0.01). There was no statistical difference between the mean HRF flow of the temporal and nasal NRR of the normotensive eyes. The elevated IOP positively influenced the flow values in the hypertensive eye (r = 0.724). The capillary microcirculation of the temporal NRR of the rhesus monkey ONH with laser-induced glaucoma has significantly increased blood flow, and the nasal NRR significantly reduced blood flow compared to blood flow in the NRR of normal normotensive monkey eyes.

Estimating Treatment Means in a Mixed-Effect ANOVA Model for Bioequivalence Studies

In order to establish bioequivalence between two formulations in a crossover trial, it is common to assume a mixed-effect analysis of variance (ANOVA) model and perform two one-sided tests. When the analysis is done on the untransformed data, the numerators of the test statistics are not, in general, treatment contrasts. Consequently, the standard errors of the numerators are difficult to compute. The usual practice is to approximate these with the standard errors of treatment contrasts (the "usual approximation"). This paper examines the goodness of this approximation. We present a few technical issues involved in analyzing the untransformed data with a mixed-effect ANOVA model, and state a parametric definition for the terminology "treatment means." The best linear unbiased estimator (BLUE) for the treatment means is derived, as well as its covariance matrix. Due to the presence of the intersubject variability, the variances and covariances of the BLUE of the treatment means are much larger than is commonly believed. A simulation study shows that these larger-than-expected variances/covariances may widen the usual approximate 90% confidence interval by as much as 10%.