Nonparametric Analysis Of Covariance Research Articles

Okra (Abelmoschus esculentus) Intake Improves Lipid Profile and Liver Transaminases in Pre-diabetic Adults: A Randomized Double-blinded Trial

Background: Okra (Abelmoschus esculentus) has garnered scientific attention for its beneficial effects on various chronic disorders, including type 2 diabetes mellitus. Objectives: The current study was designed and conducted to assess the influence of whole okra fruit powder on the serum levels of specific biochemical parameters in individuals with pre-diabetes. Methods: Seventy pre-diabetic patients, aged 30 - 55 years, were divided into two groups: The okra group (n = 35, fasting plasma glucose: 116.26 ± 6.02) and the placebo group (n = 35, fasting plasma glucose: 112.26 ± 5.8). The okra group received 3000 mg of okra capsules daily for eight weeks, while the placebo group received placebo capsules. Liver function, renal markers, and lipid profiles were assessed at both the baseline and the end of the experiment using a spectrophotometer. The impact of the okra intervention on biochemical parameters was determined using parametric or non-parametric analysis of covariance (ANCOVA). Results: The serum levels of total cholesterol, low-density lipoprotein cholesterol, liver transaminases, and uric acid were significantly lower in the okra group compared to the placebo group. Conversely, the high-density lipoprotein cholesterol levels were significantly higher in the okra group than in the placebo group. However, there were no statistically significant differences between the two groups regarding triglycerides, creatinine, blood urea nitrogen, and alkaline phosphatase levels. Conclusions: The consumption of okra effectively improved the lipid profile and certain serum parameters (alanine transaminase, aspartate transaminase, and uric acid) related to liver and kidney health in pre-diabetic participants.

Relation entre l’état musculosquelettique et les mobilités passives (mesures des résultats exprimés par les patients) dans le cadre des douleurs atraumatiques de l’épaule

IntroductionPatient-reported outcome measures (PROMs) are commonly utilized to assess patient-derived orthopaedic health status and function. The prevalence of limited musculoskeletal health literacy (MHL) has been demonstrated to be high within the orthopaedic literature. The purpose of this study was to evaluate the association between MHL and upper extremity-specific PROMs and to determine which patient- and symptom-related factors affect baseline PROMs in patients with atraumatic shoulder pain. HypothesisPatients with limited MHL would demonstrate lower median scores on baseline PROMs compared with those with adequate MHL. Materials and methodsNew patients with atraumatic shoulder pain presenting to an academic practice were administered the Literacy in Musculoskeletal Problems (LiMP), in addition to the American Shoulder and Elbow Surgeons (ASES), Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), and Single Assessment Numeric Evaluation (SANE) questionnaires. A detailed physical exam and history was performed by a fellowship-trained shoulder surgeon. Demographic patient data, in addition to prior imaging and orthopaedic treatment, was tabulated. The association between demographics, pain-related variables, and MHL with the ASES, SANE, and QuickDASH scores were examined using Spearman correlation coefficients for continuous variables and Wilcoxon rank-sum tests for categorical variables. Non-parametric analysis of covariance (ANCOVA) was used to examine the independent association of predictor variables with PROMs. ResultsA total of 439 patients met the inclusion criteria and were enrolled. The mean age was 58,8±12.6 years (range, 24–93) with 162 (37 %) being men. Overall, 172 patients (39.2 %) attained a college degree or higher and 183 (41.7 %) were currently employed. MHL was significantly associated with ASES (p=0.03), but not with the QuickDASH (p=0.75) or SANE score (p=0.16). Similarly, age, having been in the medical profession or having previously visited an orthopaedist, was not associated with PROMs, while employment status correlated to the SANE score (p=0.002). Visual Analogue Scale (VAS) pain level demonstrated varying strengths of association with each of the scores (ASES (r=−0.729, p<0.001), QuickDASH (r=0.557, p<0.001), and SANE (r=−0.430, p<0.001)). MHL demonstrated no association with initial patient-derived treatment selection. DiscussionThe SANE and QuickDASH may be administered to patients presenting for atraumatic shoulder pain in the outpatient setting regardless of MHL. Further research should be focused on the utility of the ASES instrument amongst patients with lower educational levels and/or limited MHL. Level of evidenceII; diagnostic.

A Comparison of Operative Time and Intraoperative Blood Volume Loss Between Stemless and Short-stem Anatomic Total Shoulder Arthroplasty: A Single Institution's Experience.

Introduction:There has been increasing interest in the use of stemless humeral implants for total shoulder arthroplasty when compared with both short-stem (SS) and standard-length implants. Although evidence for decreased surgical time and blood loss exists for stemless versus standard-length stems, far less literature exists comparing these clinical parameters for stemless versus SS implants.Methods:A retrospective review of consecutive anatomic total shoulder arthroplasty (aTSA) cases conducted by a single, fellowship-trained shoulder surgeon was undertaken from January 2016 through January 2022 with the exception of March 2020 through January 2021 secondary to the COVID-19 pandemic. Demographic patient and surgical data, including age, sex, body mass index, American Society of Anesthesiologists score, age-adjusted Charlson Comorbidity Index, prior ipsilateral shoulder arthroscopy, surgical time, use of a Hemovac drain and/or tranexamic acid, hospital length of stay (LOS), and both postoperative day #1 (POD 1) and discharge visual analog scores. The use of a stemless or SS implant was recorded. Intraoperative total blood volume loss (TBVL) was calculated, in addition to the need for either intraoperative or postoperative transfusions. Nonparametric analysis of covariance was used to examine effects of stemless versus SS aTSA on surgical time and intraoperative TBVL adjusted for demographic, clinical, and surgical variables.Results:There were 47 SS and 83 stemless anatomic implants included, of which 74 patients (57%) overall were women. The median surgical time for the stemless cohort was 111 minutes (IQR 96-130) versus 137 minutes (IQR 113-169) for the SS cohort (P < 0.00001). The median intraoperative TBVL for the stemless cohort was 298.3 mL (IQR 212.6-402.8) versus 359.7 mL (IQR 253.9-415.0) for the SS cohort (P = 0.05). After multivariable regression analysis, use of stemless humeral implants was independently associated with both decreased surgical time and intraoperative blood loss (P < 0.001 and P = 0.005, respectively). There was a shorter median hospital LOS in the stemless group (2 days [IQR 1-2] versus 2 days [IQR 2-3], P = 0.03). The visual analog score pain score at discharge was lower among the stemless cohort (0 [IQR 0-3] versus 4 [IQR 2-6], P < 0.00001). Increased surgical time was associated with intraoperative TBVL (r = 0.340, P < 0.0001).Discussion:Stemless aTSA is associated with a markedly decreased surgical time and intraoperative TBVL when compared with a SS aTSA. Furthermore, the use of a stemless implant results in a shorter hospital LOS and lower discharge pain scores.

Effects of low-dose oral micronised progesterone on sleep, psychological distress, and breast development in transgender individuals undergoing feminising hormone therapy: a prospective controlled study.

ObjectiveThe role of micronised progesterone in hormone regimens for transgender individuals undergoing feminising hormone therapy remains uncertain. We aimed to determine the effect of oral micronised progesterone on sleep quality, psychological distress, and breast development in transgender individuals undergoing feminising hormone therapy.DesignProspective case–control study. Twenty-three transgender individuals on stable oestradiol treatment newly commencing 100 mg oral progesterone (n = 23) and controls continuing standard care (n = 19) were assessed over 3 months.MethodsPittsburgh Sleep Quality Index (PSQI), Kessler psychological distress scale (K10), and Tanner stage to assess breast development were assessed at 0 and 3 months. Non-parametric analysis of covariance was used to compare differences between groups.ResultsCompared with controls over 3 months, there was no difference in PSQI (P = 0.35), K10 (P = 0.64), or Tanner stage (P = 0.42). There was no significant difference in the proportion of individuals with clinically significant improvement in PSQI (25% vs 22%, P = 0.84). One individual had a significant deterioration in psychological distress that improved following the cessation of progesterone.ConclusionsLow-dose progesterone was not associated with changes in sleep quality, psychological distress, or breast development over 3 months follow-up, though there was significant inter-individual variability. Larger, placebo-controlled trials are required to further evaluate different doses of progesterone in feminising hormone therapy regimens.

Distress among Korean Cancer Survivors: A Latent Profile Analysis.

This study aimed to classify cancer survivors’ latent profile analysis (LPA) according to the problem list and identify the differences in distress between subgroups. Furthermore, this study identified differences between subgroups based on their demographic and clinical characteristics. A self-reported cross-sectional survey was administered to 446 adult cancer survivors in Korea. A distress thermometer and problem list were used, and four domains of the problem list were used to perform LPA and create subgroups. Quade’s non-parametric analysis of covariance was used to determine the difference in distress between the profiles. The three identified subgroups of the problem list were: “low problem group” (36.7%), “high problem group” (49.1%), and “family only low problem group” (14.2%). The analysis showed that there was a difference in the distress level according to the sub-profile of the problem list (F = 43.69, p < 0.001). In interventions for distress, integrative interventions that are not limited to one area are necessary, and cultural characteristics as well as the problem list relevant to cancer survivors should be considered.

Twelve Weeks of Additional Fish Intake Improves the Cognition of Cognitively Intact, Resource-Limited Elderly People: A Randomized Control Trial.

Dietary omega 3 polyunsaturated fatty acids (PUFA) may reduce the risk of dementia. Many studies have investigated PUFA supplementation in high-income countries, yet food-based randomized control trials using omega 3 PUFA rich fish in lower to middle income countries, are lacking. To determine the effect on cognition of adding either fish or non-fish foods for twelve weeks to an enhanced diet of cognitively intact, independently living, resource-limited elderly people. Randomized control trial (National Health Trial register: DOH-27-061-6026). Retirement center in urban South Africa. Fifty-seven (74% female, mean age: 72±7 years) elderly participants with cognitive function exceeding 22 on the Mini Mental State Examination were randomized into an intervention (n=31) and control (n=26) group. The usual diets of both groups were enhanced with context-appropriate foods to mimic elements of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. The intervention group additionally received canned pilchards and fish spread every week amounting to an additional (theoretical) intake of 2.2g omega 3 PUFA daily. The control group received canned meatballs and texturized soya every week. Cognition was measured twice before and once after the intervention phase using the Cognitive Abilities Screening Instrument (CASI). Adherence was assessed by a study-specific food frequency questionnaire and red blood cell (RBC) PUFA biomarkers. Data were analyzed using a non-parametric analysis of covariance (ANCOVA) with, and without, bootstrap imputation. Participants in the intervention group had a significantly higher post intervention (P=0.036) CASI score than the control group, when the model was fitted with imputation and controlled for baseline scores. Participants in the intervention group also had a significantly higher intake of calculated dietary omega 3 PUFA and higher levels of RBC eicosapentaenoic acid and docosapentaenoic acid content than the control group (P < 0.05). Twelve weeks of fish intake in the context of a modified MIND diet may improve the cognition of cognitively intact, resource-limited elderly people.

The relationship between musculoskeletal health literacy and upper extremity patient-reported outcome measures (PROMs) in the setting of atraumatic shoulder pain

IntroductionPatient-reported outcome measures (PROMs) are commonly utilized to assess patient-derived orthopaedic health status and function. The prevalence of limited musculoskeletal health literacy (MHL) has been demonstrated to be high within the orthopaedic literature. The purpose of this study was to evaluate the association between MHL and upper extremity-specific PROMs and to determine which patient- and symptom-related factors affect baseline PROMs in patients with atraumatic shoulder pain. HypothesisPatients with limited MHL would demonstrate lower median scores on baseline PROMs compared with those with adequate MHL. Materials and methodsNew patients with atraumatic shoulder pain presenting to an academic practice were administered the Literacy in Musculoskeletal Problems (LiMP), in addition to the American Shoulder and Elbow Surgeons (ASES), Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), and Single Assessment Numeric Evaluation (SANE) questionnaires. A detailed physical exam and history was performed by a fellowship-trained shoulder surgeon. Demographic patient data, in addition to prior imaging and orthopaedic treatment, was tabulated. The association between demographics, pain-related variables, and MHL with the ASES, SANE, and QuickDASH scores were examined using Spearman correlation coefficients for continuous variables and Wilcoxon rank-sum tests for categorical variables. Non-parametric analysis of covariance (ANCOVA) was used to examine the independent association of predictor variables with PROMs. ResultsA total of 439 patients met the inclusion criteria and were enrolled. The mean age was 58.8±12.6years (range: 24–93) with 162 (37%) being men. Overall, 172 patients (39.2%) attained a college degree or higher and 183 (41.7%) were currently employed. MHL was significantly associated with ASES (p=0.03), but not with the QuickDASH (p=0.75) or SANE score (p=0.16). Similarly, age, having been in the medical profession or having previously visited an orthopaedist were not associated with PROMs, while employment status correlated to the SANE score (p=0.002). Visual Analogue Scale (VAS) pain level demonstrated varying strengths of association with each of the scores [ASES (r=−0.729, p<0.001), QuickDASH (r=0.557, p<0.001), and SANE (r=−0.430, p<0.001)]. MHL demonstrated no association with initial patient-derived treatment selection. DiscussionThe SANE and QuickDASH may be administered to patients presenting for atraumatic shoulder pain in the outpatient setting regardless of MHL. Further research should be focused on the utility of the ASES instrument amongst patients with lower educational levels and/or limited MHL. Level of evidenceII; diagnostic.

Spatial distribution of cerebral microbleeds reveals heterogeneous pathogenesis in CADASIL

ObjectivesRadiological diagnosis of subtypes of cerebral small vessel diseases remains challenging. This study aimed to explore the spatial distribution of cerebral microbleeds (CMBs) in cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) in contrast to cerebral amyloid angiopathy (CAA) in the lobar regions.MethodsThirty-two patients with CADASIL and 33 patients with probable CAA were prospectively and consecutively included. On 3-Tesla susceptibility-weighted magnetic resonance images, CMBs were analyzed for incidence and volume within atlas-based regions of interest, followed by voxel-wise analysis using risk mapping. The distribution of CMBs was correlated with the status of hypertension. Correlation and group differences with a p-value less than 0.05 were considered to be significant.ResultsAs compared with the CAA group, the CADASIL group presents a larger CMB volume in hippocampus/amygdala and white matter (nonparametric analysis of covariance, p = 0.014 and 0.037, respectively), a smaller CMB volume in parietal lobe (p = 0.038), and a higher incidence in hippocampus/amygdala, white matter, and insula (logistic regression, p = 0.019, 0.024, and 0.30, respectively). As part of the exclusion criteria of probable CAA, thalamus, basal ganglia, and pons exhibit greater CMB volume/incidence in the CADASIL group. In CADASIL patients, hot spots of CMBs are identified in the putamen and posteromedial thalamus; hypertension is associated with larger CMB volumes in insula, basal ganglia, and pons.ConclusionsThe spatial distribution of CMBs is differentiable between CADASIL and CAA in lobar regions. In CADASIL patients, hypertension has a region-dependent mediating effect on the CMB volume.Key Points• The topological distribution of lobar CMBs is differentiable between CADASIL and CAA.• In CADASIL patients, hypertension mediates CMB volume and the mediation is region dependent.• CMB risk mapping allows for voxel-wise exploration of CMB distribution and reveals hot spots in the putamen and posteromedial thalamus in CADASIL.

Van Hiele Theory-Based Instruction and Grade 11 Students’ Geometric Proof Competencies

South African matric results on the National Senior Certificate indicate low success in geometry, as do other African countries such as Nigeria. This poor performance affects potential career choices for students and limits the number of students who enter the highly-needed engineering fields on the African continent. Hence, this paper reports findings from a quasi-experiment involving 186 Grade 11 students from four conveniently selected township secondary schools in the Limpopo province of South Africa. The study tested the effect of Van Hiele theory-based instruction on the students’ geometric proof competencies. Data were collected using a geometry proof test and analysed using nonparametric analysis of covariance. Results showed that there was a statistically significant difference in students’ performance between the treatment and control groups (𝑇=595.9,𝑝=.005,𝜂𝑝2 =.684). Analysis of nonparametric regression curves fitted for the treatment and control groups showed that the treatment group had higher post-test scores than the control group. It was therefore concluded that Van Hiele theory-based instruction is more effective in teaching non-routine geometric proofs than conventional instruction. The study recommends that geometry teachers in upper secondary school should consider implementing Van Hiele theory-based instruction to enhance students’ geometric proof competence.

The potential of serum fetal DNA for early diagnosis of gestational trophoblastic disease.

Objective:To study cell-free DNA (cfDNA) levels in patients with gestational trophoblastic disease (GTD) in order to test the hypothesis that cfDNA circulating in maternal plasma could provide early detection of GTD.Materials and Methods:This study included 32 patients with GTD (complete mole and partial mole) and 30 non-GTD patients in the first trimester of pregnancy with no other medical problems. cfDNA levels in maternal serum were measured using polymerase chain reaction analysis on Y-chromosome–specific sequences.Results:cfDNA was found as 327±367 pg on average in the control group and 600±535 pg in the GTD group. Within the GTD group, the partial mole group had an cfDNA average of 636±549 pg, and the complete mole group had an cfDNA average of 563±536 pg. Although there was a statistically significant difference between the GTD group and the control group in terms of cfDNA (p=0.02), there was no statistically significant difference between the complete mole group and the partial mole group (p=0.76).Conclusion:Non-parametric analysis of covariance in terms of cfDNA in GTD was performed, thereby increasing its power and revealing a significant difference compared with the control group. This indicates that maternal peripheral bloodstream cfDNA monitoring might be significant in the early diagnosis of GTD.

Regional impairment of cortical and deep gray matter perfusion in preterm neonates with low-grade germinal matrix-intraventricular hemorrhage: an ASL study.

The long-term impact of low-grade germinal matrix-intraventricular hemorrhage (GMH-IVH) on brain perfusion has not been fully investigated. We aimed to compare cortical and deep gray matter (GM) cerebral blood flow (CBF) obtained with pseudo-continuous arterial spin labeling (pCASL), among preterm neonates with and without low-grade GMH-IVH and full-term controls. 3T-pCASL examinations of 9 healthy full-term neonates (mean gestational age 38.5weeks, range 38-39) and 28 preterm neonates studied at term-equivalent age were analyzed. Eighteen preterm neonates presented normal brain MRI (mean gestational age 30.50weeks, range 29-31) and 10 low-grade GMH-IVH according to Volpe's grading system (mean gestational age 32weeks, range 28-34). A ROI-based mean CBF quantification was performed in 5 cortical (frontal, parietal, temporal, insula, occipital), and 4 subcortical GM regions (caudate, putamen, pallidum, thalamus) for each cerebral hemisphere. CBF differences were explored using a nonparametric analysis of covariance. Low-grade GMH-IVH hemispheres showed consistently lower CBF in all GM regions when compared with healthy preterm neonates, after controlling the confounding effect of gestational age, postmenstrual age, and birth weight P < .001, η2 = .394. No significant differences were observed between neonates with low-grade GMH and full-term controls. Healthy preterm neonates showed significantly higher CBF than full-term controls in parietal (P = .032), temporal (P = .016), and occipital cortex (P = .024), and at level of thalamus (P = .023) and caudate nucleus (P = .014). Low-grade GMH-IVH is associated with lower CBF in posterior cortical and subcortical gray matter regions in preterm neonates, suggesting regional vulnerability of these developing brain structures.

PF790 RELATIONSHIP BETWEEN LIVER IRON CONCENTRATION MEASURED BY MRI T2∗ AND SERUM FERRITIN IN HEMOGLOBIN H DISEASE

Background:Patients with non‐transfusion dependent thalassemia (NTDT) are at risk of developing liver iron overload. T2∗‐weighted magnetic resonance imaging (MRI T2∗) is an accurate and reproducible method to determine liver iron concentration (LIC) but it is not always readily available especially in resources limited setting. Serum ferritin (SF) level remains important in the quantification of body iron. Past studies demonstrated (1) a positive correlation between LIC and SF in β‐thalassemia intermedia (TI) and transfusion dependent thalassemia (TDT), and (2) lower SF values in TI patients than in TDT patients with comparable LICs because of preferential iron accumulation in the liver in TI.Aims:The relationship between LIC measured by MRI T2∗ and SF in hemoglobin H (HbH) disease, the most common type of NTDT in Southern China, was determined in this study.Methods:Data was obtained from 82 patients with HbH disease (male 34%, mean age 51 ± 15 years) identified in a cross‐sectional single‐center study performed during Jan 2017 to Jun 2018 to evaluate the complication profile of Southern Chinese adults with NTDT. Data collection included review of medical charts, blood samples tested for steady‐state SF, and MRI T2∗ (SIEMENS 1.5T Aera) to determine LIC. SF and LIC data from 27 TDT patients (male 52%, mean age 32 ± 8 years) managed in the center during the same period were collected for comparison. Nonparametric analysis of covariance (ANCOVA) was used to evaluate for any difference in the LIC‐SF relationship in patients with HbH disease and TDT. The LIC‐SF relationship was subsequently studied by regression analysis. Transformation of variables was adopted to handle nonlinearity of residuals. Robust regression with robust sandwich variance estimator was used to address the problem of outliers, influential observations and heteroscedasticity.Results:Among patients with HbH disease, 63 (77%) and 19 (23%) were of deletional vs. non‐deletional type respectively, 45 (55%) received blood transfusion before, 10 (12%) had history of iron chelation therapy, 8 (10%) were splenectomized, 3 (4%) and 2 (2%) were hepatitis B and C virus carriers respectively. All TDT patients received blood transfusions every 3–4 weeks and iron chelation. Median SF was 394 (range 19–2,159) μg/L and median LIC was 3.14 (range 0.23–14.24) mg Fe/g dry weight (dw) in HbH disease patients. Median SF was 1,325 (range 79–5,409) μg/L and median LIC was 3.94 (range 1.12–9.27) mg Fe/g dw in TDT patients. ANCOVA showed that the relationship between LIC and SF was different in HbH disease and TDT (p &lt; 0.001) and thus regression analysis was performed separately in the two groups of patients. The models best predicted LIC when SF was raised to the power of 0.5 and 0.3 in HbH disease and TDT respectively. LIC was positively correlated with SF0.5 in HbH disease (p &lt; 0.001) and SF0.3 in TDT (p &lt; 0.001). The estimated regression equation for HbH disease was LIC = 0.21 × SF0.5 – 0.81 (R2 = 0.52; 95% CI for the slope: 0.17–0.25), and for TDT was LIC = 0.97 × SF0.3 – 3.81 (R2 = 0.57; 95% CI for the slope: 0.73–1.20) (Figure 1).Summary/Conclusion:The study demonstrated a positive correlation between LIC and SF. Patients with HbH disease had lower SF values than in TDT patients when their LICs were comparable. SF had moderate predictive ability of LIC in both HbH disease and TDT, suggesting that it is an acceptable marker to estimate liver iron deposition. However, result has to be interpreted cautiously because the relationship between LIC and SF alters with the type of thalassemia syndrome and SF could also be affected by other factors.image

Testing in nonparametric ANCOVA model based on ridit reliability functional

In the spirit of Bross (Biometrics 14:18–38, 1958), this paper considers ridit reliability functionals to develop test procedures for the equality of $$K(>2)$$ treatment effects in nonparametric analysis of covariance (ANCOVA) model with d covariates based on two different methods. The procedures are asymptotically distribution free and are not based on the assumption that the distribution functions (d.f.’s) of the response variable and the associated covariates are continuous. By means of simulation study, the proposed methods are compared with the methods provided by Tsangari and Akritas (J Multivar Anal 88:298–319, 2004) and Bathke and Brunner (Recent advances and trends in nonparametric statistics, Elsevier, Amsterdam, 2003) under ANCOVA in terms of type I error rate and power.

A somatization comorbidity phenotype impacts response to therapy in rheumatoid arthritis: post-hoc results from the certolizumab pegol phase 4 PREDICT trial

BackgroundComorbidities may contribute to disease activity and treatment response in rheumatoid arthritis (RA) patients. We defined a somatization comorbidity phenotype (SCP) and examined its influence on response to certolizumab pegol (CZP) using data from the PREDICT trial.MethodsPatients in PREDICT were randomized to the patient-reported Routine Assessment of Patient Index Data 3 (RAPID3) or physician-based Clinical Disease Activity Index (CDAI) for treatment response assessment. Post-hoc analyses identified patients with the SCP, which included diagnosis of depression, fibromyalgia/myalgias, and/or use of medications indicated for treatment of depression, anxiety, or neuropathic pain. The effect of the SCP on RAPID3 or CDAI response at week 12 and low disease activity (LDA; Disease Activity Score in 28 joints based on erythrocyte sedimentation rate ≤ 3.2) at week 52, in week-12 responders, was analyzed using non-parametric analysis of covariance (ANCOVA).ResultsAt baseline, 43% (313/733) of patients met the SCP classification. Patients with the SCP were 9% more likely to withdraw from the trial. American College of Rheumatology 20% (ACR20), ACR50, and ACR70 responses were 5–14% lower among those with the SCP, and 11% more patients reported adverse events (AEs). Patients without SCP in the CDAI arm were twice as likely to achieve LDA at week 52 compared with those with SCP (32% versus 16%). No differentiation by SCP was observed in the RAPID3 arm (pooled result 21.5%).ConclusionsWe operationalized a potentially important somatization comorbidity phenotype in a trial setting that was associated with a substantially lower likelihood of treatment response and a higher frequency of AEs. Including large numbers of patients with this phenotype in RA trials may reduce the measured clinical effectiveness of a new molecule.Trial registrationClinicalTrials.gov, NCT01255761. Registered on 6 December 2010.

A 10-year follow-up of the European multicenter trial of interferon β-1b in secondary-progressive multiple sclerosis

Objectives: To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b). Methods: We assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied. Results: Median EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R2: 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited (R2: 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained < 5% of the variability. Conclusions: The results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed.

Sensitivity analysis for missing outcomes in time-to-event data with covariate adjustment

ABSTRACTCovariate-adjusted sensitivity analyses is proposed for missing time-to-event outcomes. The method invokes multiple imputation (MI) for the missing failure times under a variety of specifications regarding the post-withdrawal tendency for having the event of interest. With a clinical trial example, we compared methods of covariance analyses for time-to-event data, i.e., the multivariable Cox proportional hazards (PH) model and nonparametric analysis of covariance, and then illustrated how to incorporate these methods into the proposed sensitivity analysis for covariate adjustment. The MI methods considered are Kaplan–Meier multiple imputation and covariate-adjusted and unadjusted PH multiple imputation. The assumptions, statistical issues, and features for these methods are discussed.

Comparison of Statistical Methods for Pretest–Posttest Designs in Terms of Type I Error Probability and Statistical Power

The pretest–posttest design is widely used to investigate the effect of an experimental treatment in biomedical research. The treatment effect may be assessed using analysis of variance (ANOVA) or analysis of covariance (ANCOVA). The normality assumption for parametric ANOVA and ANCOVA may be violated due to outliers and skewness of data. Nonparametric methods, robust statistics, and data transformation may be used to address the nonnormality issue. However, there is no simultaneous comparison for the four statistical approaches in terms of empirical type I error probability and statistical power. We studied 13 ANOVA and ANCOVA models based on parametric approach, rank and normal score-based nonparametric approach, Huber M-estimation, and Box–Cox transformation using normal data with and without outliers and lognormal data. We found that ANCOVA models preserve the nominal significance level better and are more powerful than their ANOVA counterparts when the dependent variable and covariate are correlated. Huber M-estimation is the most liberal method. Nonparametric ANCOVA, especially ANCOVA based on normal score transformation, preserves the nominal significance level, has good statistical power, and is robust for data distribution.

Oral Chloral Hydrate Compare with Rectal Thiopental in Pediatric Procedural Sedation and Analgesia; a Randomized Clinical Trial.

The increasing use of diagnostic imaging in pediatric medicine has resulted in growing need for procedural sedation and analgesia (PSA) to minimize motion artifacts during procedures. The drug of choice in pediatric PSA was not introduced until now. The aim of the present study was comparison of oral chloral hydrate (OCH) and rectal sodium thiopental (RST) in pediatric PSA. In the present randomized clinical trial, 2-6 years old pediatrics who referred for performing brain computed tomography scan was enrolled and were randomly divided in to two groups. OCH (50mg/kg) and RST (25mg/kg) were prescribed and a trained nurse recorded the time from drug prescription to receiving the conscious sedation (onset of action), the total period which the patient has the Ramsay score≥4 (duration of action), and adverse effect of agents. Mann-Whitney U test and chi-squared test, and Non-parametric analysis of covariance (ANCOVA) were used for comparisons. One hundred and forty children were entered to two groups of OCH and RST, randomly. The patients of two groups had similar age, sex, weight, and baseline vital signs except for diastolic blood pressure (p<0.001). The onset of action in OCH and RST groups were 24.5±6.1and 28.7±5.2 minutes, respectively (p<0.001). Duration of action in OCH and RST groups were 12.9±2.8 minutes and 13.7±2.6 minutes, respectively (p=0.085). Non-parametric ANCOVA revealed that only diastolic blood pressure was affected by drug prescription (p=0.001). In 11(15.7%) patients in RST group, diarrhea was observed during 24 hours (p=0.001). Oxygen desaturation was observed only in two patients, both in OCH group. Each of the sedative has advantages and disadvantages that should be considered when selecting one for inducing short-term sedation. It seems that rectal sodium thiopental and oral chloral hydrate are equally effective in pediatric PSA and based on patient's condition we can administrate one of these agents.

OP0145 Induction therapy with adalimumab plus methotrexate versus methotrexate monotherapy in recent onset rheumatoid arthritis (RA) – an investigator initiated randomized controlled trial

BackgroundTo study the prolonged effect on disease activity by an early induction therapy with adalimumab (ADA) plus methotrexate (MTX) versus MTX alone in DMARD naïve patients (pts) with early RA...

Estimating Covariate-Adjusted Log Hazard Ratios in Randomized Clinical Trials Using Cox Proportional Hazards Models and Nonparametric Randomization Based Analysis of Covariance

In the context of randomized clinical trials with time-to-event outcomes, estimates of covariate-adjusted log hazard ratios for comparing two treatments are obtained via nonparametric analysis of covariance by forcing the difference in means for covariables to zero. The method avoids the assumption of proportional hazards for each of the covariates, and it provides an adjusted analysis for the same population average treatment effect that the unadjusted analysis addresses. It is primarily useful in regulatory clinical trials that require analyses to be specified a priori. To illustrate, the method is applied to a study of lung disease with multivariate time-to-event outcomes.