scholarly journals Predictors of a placebo response in patients with hand osteoarthritis: post-hoc analysis of two randomized controlled trials

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jin Kyun Park ◽  
Se Han Ahn ◽  
Kichul Shin ◽  
Yun Jong Lee ◽  
Yeong Wook Song ◽  
...  
Keyword(s):  
Pain Score ◽  
Multivariable Analysis ◽  
Placebo Response ◽  
Hand Osteoarthritis ◽  
Double Blind ◽  
Meaningful Improvement ◽  
Post Hoc Analysis ◽  
Factors Associated ◽  
Pain Scores ◽  
Post Hoc

Abstract Background Placebo can have a significant therapeutic effect in patients with hand osteoarthritis (OA). This aim of the study is to identify factors associated with a clinically meaningful placebo response in patients with hand OA. Methods This post-hoc analysis of two double-blind, placebo-controlled, randomized trials (RCTs) investigating the efficacy of GCSB-5 or diacerein as treatments for hand OA analyzed the efficacy of a placebo. Clinical and laboratory factors associated with a clinically meaningful response, defined as an improvement in the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain score > 10 at 4 weeks relative to baseline, were identified. Results The mean improvement in the AUSCAN pain score was − 6.0 ± 20.3, with marked variation between 143 hand OA patients (range: − 76.4 to 33.2). A clinically meaningful improvement was observed in 54 (37.8%) patients. Placebo responders had worse AUSCAN pain scores (55.7 ± 19.7 vs. 43.6 ± 21.6, p = 0.001) and a worse AUSCAN stiffness (68.2 ± 20.5 vs. 57.5 ± 24.5, p = 0.008) at baseline than non-responders. Improvements in pain correlated with the baseline pain level (Pearson r = − 427, p < 0.001). Structural joint changes such as tender, swollen, enlarged, or deformed joint counts did not differ between placebo responders and non-responders. In a multivariable analysis, only baseline AUSCAN pain was associated with a clinically meaningful placebo response (OR: 1.054, 95% CI [1.019–1.089], p = 0.002). Conclusions High levels of pain at baseline are predictive of a clinically meaningful placebo response in patients with hand OA. Further studies are needed to optimize and utilize the benefit of placebo responses in patients with hand OA.

scholarly journals The influence of brain metastases on the central nervous system effects of methylnaltrexone: a post hoc analysis of 3 randomized, double-blind studies

2021 ◽  
Author(s):  
Darren M. Brenner ◽  
Neal E. Slatkin ◽  
Nancy Stambler ◽  
Robert J. Israel ◽  
Paul H. Coluzzi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Opioid Withdrawal ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Pain Scores ◽  
Opioid Receptor Antagonists ◽  
Post Hoc

Abstract Purpose Peripherally acting μ-opioid receptor antagonists such as methylnaltrexone (MNTX, Relistor®) are indicated for the treatment of opioid-induced constipation (OIC). The structural properties unique to MNTX restrict it from traversing the blood-brain barrier (BBB); however, the BBB may become more permeable in patients with brain metastases. We investigated whether the presence of brain metastases in cancer patients compromises the central effects of opioids among patients receiving MNTX for OIC. Methods This post hoc analysis of pooled data from 3 randomized, placebo-controlled trials included cancer patients with OIC who received MNTX or placebo. Endpoints included changes from baseline in pain scores, rescue-free laxation (RFL) within 4 or 24 h of the first dose, and treatment-emergent adverse events (TEAEs), including those potentially related to opioid withdrawal symptoms. Results Among 356 cancer patients in the pooled population, 47 (MNTX n = 27; placebo n = 20) had brain metastases and 309 (MNTX n = 172; placebo n = 137) did not have brain metastases. No significant differences in current pain, worst pain, or change in pain scores from baseline were observed between patients treated with MNTX or placebo. Among patients with brain metastases, a significantly greater proportion of patients who received MNTX versus placebo achieved an RFL within 4 h after the first dose (70.4% vs 15.0%, respectively, p = 0.0002). TEAEs were similar between treatment groups and were generally gastrointestinal in nature and not related to opioid withdrawal. Conclusion Focal disruptions of the BBB caused by brain metastases did not appear to alter central nervous system penetrance of MNTX.

scholarly journals Factors Associated with Inadequate Intravenous Colistin Dosages: Post Hoc Analysis of a Multicenter, Cross-Sectional Study

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1554
Author(s):  
Daniele Roberto Giacobbe ◽  
Michele Mirabella ◽  
Matteo Rinaldi ◽  
Angela Raffaella Losito ◽  
Francesca Raffaelli ◽  
...  
Keyword(s):  
Random Effect ◽  
Multivariable Analysis ◽  
Cross Sectional Study ◽  
Primary Objective ◽  
Sectional Study ◽  
Cross Sectional ◽  
Post Hoc Analysis ◽  
Factors Associated ◽  
Increased Risk ◽  
Post Hoc

Colistin is a last-resort agent for the treatment of infections due to Gram-negative bacteria with difficult-to-treat resistance. The primary objective of this post hoc analysis of a cross-sectional study conducted in 22 Italian hospitals was to assess factors associated with inadequate intravenous colistin dosage. Overall, 187 patients receiving intravenous colistin were included in the analyses. Inadequate colistin dosages were administered in 27% of cases (50/187). In multivariable analysis, AKI (dummy variable with KDIGO stage 0 as a reference, odds ratio (OR) 3.98 with 95% confidence interval (CI) 1.48–10.74 for stage 1, OR 4.44 with 95% CI 1.17–16.93 for stage 2, OR 9.41 with 95% CI 1.59–55.70 for stage 3; overall p = 0.001) retained an independent association with inadequate colistin dosage, whereas the presence of a central venous catheter was associated with adequate colistin dosage (OR: 0.34 for inadequate dosage, 95% CI: 0.16–0.72, p = 0.004). These results were confirmed in an additional multivariable model with the center as a random effect. The association between AKI and inadequate dosage may reflect the perception of an increased risk of nephrotoxicity in patients with impaired renal function, which nonetheless should not be accompanied by dosage reductions beyond those recommended and could represent the target of dedicated antimicrobial stewardship efforts.

scholarly journals Effect of the Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, on Nocturnal Hypertension: A Post Hoc Analysis of the ESAX-HTN Study

2020 ◽  
Author(s):  
Kazuomi Kario ◽  
Sadayoshi Ito ◽  
Hiroshi Itoh ◽  
Hiromi Rakugi ◽  
Yasuyuki Okuda ◽  
...  
Keyword(s):  
Older Patients ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Effective Treatment Option ◽  
Double Blind ◽  
Nocturnal Hypertension ◽  
Post Hoc Analysis ◽  
Nocturnal Dipping ◽  
Parallel Group ◽  
Post Hoc

Abstract BACKGROUND Nocturnal hypertension is an important phenotype of abnormal diurnal blood pressure (BP) variability and a known risk marker for target organ damage and cardiovascular events. This study aimed to assess the differential BP-lowering effects of esaxerenone vs. eplerenone on nocturnal BP in hypertensive patients with different nocturnal dipping patterns. METHODS This was a post hoc analysis of the “Esaxerenone (CS-3150) Compared to Eplerenone in Patients with Essential Hypertension” study (NCT02890173), which was a phase 3, multicenter, randomized, controlled, double-blind, parallel-group clinical study conducted in Japan. Ambulatory BP monitoring data were collected. RESULTS Patients (n = 1,001) were randomized to esaxerenone 2.5 mg/day (n = 331) or 5 mg/day (n = 338), or eplerenone 50 mg/day (n = 332). Reductions in nighttime systolic BP (95% confidence interval) were significantly greater with 2.5 and 5 mg/day esaxerenone vs. eplerenone (−2.6 [−5.0, −0.2] and −6.4 mm Hg [−8.8, −4.0], respectively). Esaxerenone significantly reduced nighttime BP from baseline compared with eplerenone in non-dippers with previously uncontrolled BP. In addition, esaxerenone did not markedly alter nighttime BP in extreme dipper patients. In the esaxerenone 5 mg/day group, esaxerenone-induced decreases in nighttime BP were greater than eplerenone-induced decreases in older patients. CONCLUSIONS Esaxerenone may be an effective treatment option for nocturnal hypertension, especially in older patients and those with a non-dipper pattern of nocturnal BP.

scholarly journals 935. Effect of Tesamorelin in People with HIV with and without Dorsocervical Fat: Post Hoc Analysis of Phase III Double Blind Placebo Control Trial

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S500-S501
Author(s):  
Farah Rahman ◽  
Marilyn de Chantal ◽  
Pedro Mesquita ◽  
Judith A Aberg
Keyword(s):  
Growth Hormone ◽  
Abdominal Fat ◽  
Fat Deposition ◽  
Phase Iii ◽  
Placebo Control ◽  
People Living With Hiv ◽  
Anthropometric Parameters ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Background Lipohypertrophy is defined as excess fat deposition in abdominal defined as visceral adipose tissue (VAT) as well as in the dorsocervical region, breasts, trunk, and along with possible fat deposition in liver, muscle, myocardium and epicardium. Multiple factors have been described as contributing to lipohypertrophy in people living with HIV (PLWH), including patient characteristics, antiretroviral therapy (ART) and also impaired growth hormone (GH) secretion. Tesamorelin, a synthetic form of growth-hormone-releasing hormone (GHRH), is indicated for reduction of excess abdominal fat in PLWH with lipodystrophy Methods Post-hoc analysis was done on phase 3 randomized, double-blind, multicenter trials. Patients were eligible if between 18 and 65 years of age, had confirmed HIV infection, had evidence of excess abdominal fat accumulation and on stable ART regimen for 8 weeks or more. Participants were randomized to receive tesamorelin 2 mg daily or placebo daily for 26 weeks. Only tesamorelin responders, defined as patients with at least 8% decrease in VAT and who were adherent to the medication, were used for this analysis. Results are reported for patients with and without dorsocervical (DC) fat deposition. Results Demographic characteristics of responders at week 26 are shown according to presence or absence of DC fat (Table 1). At week 26, on average, the patients with DC fat deposition had higher BMI and waist circumference (WC) than the group without DC fat. Most patients in both groups had lipoatrophy. Metabolic and anthropometric parameters were measured at week 26 in patients with and without DC fat (Table 2). There was a decrease in VAT and also an improvement in their WC at week 26 in both groups. Table 1: Baseline Characteristics of Tesamorelin Responder Subjects at Week 26, by Dorsocervical Status Table 2: Change in Abdominal Adiposity, Insulin-Like Growth Factor-1 Levels, and Metabolic Parameters Between Baseline and Week 26 Among Tesamorelin Responders Conclusion This data demonstrates that tesamorelin is effective at reducing VAT in both patients with and without DC fat. The medication was well tolerated without significant changes to metabolic based measurements. Treatment of excessive VAT with tesamorelin has seemingly positive results in fat reduction in patients with or without DC fat deposition and our study contributes to the growing literature. Disclosures Marilyn de Chantal, PhD, Theratechnologies Inc (Employee) Pedro Mesquita, PhD, Theratechnologies, Inc. (Employee) Judith A. Aberg, MD, Theratechnology (Consultant)

scholarly journals Therapeutic potential of targeting Tfr/Tfh cell balance by low-dose-IL-2 in active SLE: a post hoc analysis from a double-blind RCT study

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Miao Miao ◽  
Xian Xiao ◽  
Jiayi Tian ◽  
Yunzhi Zhufeng ◽  
Ruiling Feng ◽  
...  
Keyword(s):  
Low Dose ◽  
Activity Index ◽  
Cell Subset ◽  
Immunoglobulin M ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Immune Balance ◽  
Cell Balance ◽  
Post Hoc

Abstract Objective To investigate the regulation of T follicular regulatory (Tfr) and T follicular (Tfh) cell subtypes by low-dose IL-2 in systemic lupus erythematosus (SLE) in a randomized, double-blind, placebo-controlled clinical trial. Methods A post hoc analysis was performed in a randomized cohort of SLE patients (n=60) receiving low-dose IL-2 therapy (n=30) or placebo (n=30), along with the standard of care treatment. The primary endpoint was the attainment of SLE responder index-4 (SRI-4) at week 12 in the trial. Twenty-three healthy controls were enrolled for T cell subset detection at the same time as the trial. The t-stochastic neighbor embedding (tSNE) analysis of CD4 T subsets based on immune cells flow cytometry markers was performed to distinguish Tfh, Tfh1, Tfh2, Tfh17, and Tfr cell subsets. Results Compared with HC, the frequency of Tfr (CXCR5+PD-1low Treg and CXCR5+PD-1high Treg) cells was significantly reduced, while the pro-inflammatory Tfh cells were increased in patients with SLE. The imbalanced Tfh cell was associated with several pathogenic factors (anti-dsDNA antibodies (r=0.309, P=0.027) and serum IL-17 (r=0.328, P=0.021)) and SLE Disease Activity Index (SLEDAI) score (r=0.273, P=0.052). Decreased CXCR5+PD-1low Treg/Tfh and CXCR5+PD-1low Treg/Tfh17 were both associated with increased immunoglobulin M (IgM) (r=−0.448, P=0.002 and r=−0.336, P=0.024, respectively). Efficacy of low-dose IL-2 therapy was associated with a restored Tfr/Tfh cell balance. Conclusion These data support the hypothesis that promotion of Tfr is associated with decreased disease activities and that low-dose IL-2 therapy can recover Tfr/Tfh immune balance. Trial registration number ClinicalTrials.gov Registries (NCT02465580).

scholarly journals Validation of the pediatric refractory septic shock definition: post hoc analysis of a controlled trial

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luc Morin ◽  
Karthik Narayanan Ramaswamy ◽  
Muralidharan Jayashree ◽  
Arun Bansal ◽  
Karthi Nallasamy ◽  
...  
Keyword(s):  
Septic Shock ◽  
Intensive Care ◽  
Neonatal Intensive Care ◽  
Controlled Trial ◽  
Receiver Operating Curve ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Prognostic Accuracy ◽  
Refractory Septic Shock ◽  
Post Hoc

Abstract Background The European Society of Pediatric and Neonatal Intensive Care (ESPNIC) developed and validated a definition of pediatric refractory septic shock (RSS), based on two septic shock scores (SSS). Both bedside SSS (bSSS) and computed SSS (cSSS) were found to be strongly associated with mortality. We aimed at assessing the accuracy of the RSS definition on a prospective cohort from India. Methods Post hoc analysis of a cohort issued from a double-blind randomized trial that compared first-line vasoactive drugs in children with septic shock. Sequential bSSS and cSSS from 60 children (single-center study, 53% mortality) were analyzed. The prognostic value of the ESPNIC RSS definition was tested for 28-day all-cause mortality. Results In this septic shock cohort, RSS was diagnosed in 35 patients (58.3%) during the first 24 h. Death occurred in 30 RSS patients (85.7% mortality) and in 2 non-RSS patients (8% mortality), OR = 60.9 [95% CI: 10.5–676.2], p < 0.001 with a median delay from sepsis onset of 3 days [1.0–6.7]. Among patients diagnosed with RSS, the mortality was not significantly different according to vasopressors randomization. Diagnosis of RSS with bSSS and cSSS had a high discrimination for death with an area under the receiver operating curve of 0.916 [95% CI: 0.843–0.990] and 0.925 [95% CI: 0.845–1.000], respectively. High prognostic accuracy of the bSSS was found in the first hours following intensive care admission. The best interval of prognostication occurs after the 12th hour following treatment initiation (AUC 0.973 [95% CI: 0.925–1.000]). Conclusions The ESPNIC refractory septic shock definition accurately identifies, within the first 6 h of septic shock management, children with lethal outcome.

Sign in / Sign up

Export Citation Format

Share Document