scholarly journals Renal Impairment, C. difficile Recurrence, and the Differential Effect of Bezlotoxumab: A Post Hoc Analysis of Pooled Data From 2 Randomized Clinical Trials

2020 ◽  
Vol 7 (7) ◽  
Author(s):  
Yoav Golan ◽  
Herbert L DuPont ◽  
Fernando Aldomiro ◽  
Erin H Jensen ◽  
Mary E Hanson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Trials ◽  
Risk Factor ◽  
Renal Impairment ◽  
Randomized Clinical Trials ◽  
Adjunctive Treatment ◽  
Antibacterial Drug ◽  
Post Hoc Analysis ◽  
Pooled Data ◽  
Post Hoc

Abstract Background Renal impairment is not a consistently cited risk factor for recurrent Clostridioides difficile infection (rCDI). We examined the association between renal impairment and rCDI and the effect of bezlotoxumab, an anti–toxin B monoclonal antibody, in reducing rCDI in participants with renal impairment. Methods We pooled data from 2 randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trials conducted in participants receiving bezlotoxumab or placebo infusion during oral antibacterial drug treatment for CDI. We assessed the association between renal impairment and rCDI in placebo-treated participants and evaluated the effect of bezlotoxumab vs placebo in reducing rCDI among participants with renal impairment, defined as an estimated glomerular filtration rate <90 mL/min. Results The proportion of placebo-treated participants experiencing rCDI within 12 weeks was higher in those with renal impairment (n = 919) vs those without renal impairment (n = 612; 36.6% and 27.7%, respectively; difference, 8.9%; 95% CI, 1.3% to 16.3%). Renal impairment was significantly associated with a higher rate of recurrence in placebo-treated participants lacking commonly recognized risk factors for rCDI (renal impairment as only risk factor, 28.8%; vs normal renal function and no risk factors, 12.5%; difference, 16.3%; 95% CI, 3.4% to 28.8%). Among all participants with renal impairment, the rate of rCDI was 19.5% among bezlotoxumab-treated vs 36.6% among placebo-treated participants (difference, –17.1%; 95% CI, –23.4% to –10.6%). Conclusions This post hoc analysis adds to the literature suggesting an association of renal impairment as an independent risk factor for rCDI and provides preliminary evidence that patients with renal impairment who suffer with CDI may benefit from adjunctive treatment with bezlotoxumab.

scholarly journals High-quality colon cleansing and multiple neoplasia detection with 1L NER1006 versus mid-volume options: Post hoc analysis of phase 3 clinical trials

2020 ◽  
Vol 08 (05) ◽  
pp. E628-E635
Author(s):  
Michael S. Epstein ◽  
Robert Benamouzig ◽  
Juha Halonen ◽  
Raf Bisschops
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Combined Treatment ◽  
Sulfate Solution ◽  
Lesion Detection ◽  
High Quality ◽  
Post Hoc Analysis ◽  
Colon Cleansing ◽  
Adenoma Detection ◽  
Post Hoc

Abstract Background and study aims Multiple neoplasia increase the risk of colorectal cancer. High-quality cleansing may improve adenoma detection. We assessed whether a new bowel preparation can improve colon cleansing and multiple lesion detection. Patients and methods This post hoc analysis of two randomized clinical trials in Europe and the US assessed the per study and combined cleansing efficacy of overnight split dosing with (preparation + clear fluids) 1 + 1 L polyethylene glycol (PEG) NER1006 versus 2 + 1 L PEG + ascorbate (2LPEG) or 1 + 2 L oral sulfate solution (OSS) combined. Treatment-blinded central readers assessed cleansing quality using the Harefield Cleansing Scale (HCS). Patients with full segmental scoring were included. HCS segmental scores 0–4 (high-quality = HCS 3–4) were analyzed for NER1006 versus 2LPEG/OSS. Mean number of polyps or adenomas per patient (MPP/MAP) was calculated for treatments in patients with at least one polyp or adenoma. Results In 1037 patients, NER1006 attained a greater rate of HCS 3 scores (29 % vs. 20 %; P < 0.001) and HCS 4 scores (20 % vs. 17 %; P = 0.007) versus 2LPEG/OSS. More polyps (678 versus 585) and adenomas (397 versus 331) were detected with NER1006 (N = 517) versus 2LPEG/OSS (N = 520). In all neoplasia-positive patients, with increasing minimal per-patient neoplasia multiplicity from 1 to 10, NER1006 numerically improved MPP (difference ± SE: 0.48 ± 0.24 to 3.89 ± 3.37) and MAP (0.47 ± 0.26 to 7.50 ± 9.00) versus 2LPEG/OSS. Conclusions Low-volume NER1006 enhances high-quality cleansing versus medium-volume 2LPEG or OSS, individually and when combined. NER1006 may consequently facilitate the detection of multiple neoplasia in patients.

scholarly journals Is migraine a risk factor for pediatric stroke?

Cephalalgia ◽  
2015 ◽  
Vol 35 (14) ◽  
pp. 1252-1260 ◽  
Author(s):  
Amy A Gelfand ◽  
Heather J Fullerton ◽  
Alice Jacobson ◽  
Stephen Sidney ◽  
Peter J Goadsby ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cohort Study ◽  
Ischemic Stroke ◽  
Incidence Rate ◽  
Stroke Risk ◽  
Stroke Incidence ◽  
Post Hoc Analysis ◽  
Ischemic Stroke Risk ◽  
Post Hoc

Importance Our understanding of risk factors for childhood stroke is incomplete. In adults, migraine with aura is associated with a two-fold increase in ischemic stroke risk. Objective In this cohort study we examine the association between migraine and stroke among children in Kaiser Permanente Northern California (KPNC). Design, setting, and participants Children ages 2–17 years who were members of KPNC for ≥6 months between 1997 and 2007 were included. Migraine cohort members had one or more of: an ICD-9 code for migraine, migraine listed as a significant health problem, or a prescription for a migraine-specific medication. The comparison group was children with no evidence of headache. Main outcome measures Main outcome measures included stroke incidence rates and incidence rate ratios (IR). Results Among the 1,566,952 children within KPNC during the study period, 88,164 had migraine, and 1,323,142 had no evidence of headache. Eight migraineurs had a stroke (three (38%) hemorrhagic; five (63%) ischemic). Eighty strokes occurred in children without headache (53 (66%) hemorrhagic; 27 (34%) ischemic). The ischemic stroke incidence rate was 0.9/100,000 person-years in migraineurs vs. 0.4/100,000 person-years in those without headache; IR 2.0 (95% CI 0.8–5.2). A post-hoc analysis of adolescents (12–17 years) showed an increased risk of ischemic stroke among those with migraine; IR 3.4 (95% CI 1.2–9.5). The hemorrhagic stroke incidence rate was 0.5/100,000 person-years in migraineurs and 0.9/100,000 person-years in those without headache; IR 0.6 (95% CI 0.2–2.0). Conclusions There was no statistically significant increase in hemorrhagic or ischemic stroke risk in pediatric migraineurs in this cohort study. A post-hoc analysis found that ischemic stroke risk was significantly elevated in adolescents with migraine. Future studies should focus on identifying risk factors for ischemic stroke among adolescent migraineurs. Based on adult data, we recommend that migraine aura status should be studied as a possible risk factor for ischemic stroke among adolescent migraineurs.

Combination of statin/vitamin D and metastatic castration-resistant prostate cancer (mCRPC): A post-hoc analysis of two randomized clinical trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6617-6617
Author(s):  
Guillermo de Velasco ◽  
David Lora ◽  
Alberto Carretero-Gonzalez ◽  
Maria Cruz Martin Soberón ◽  
Juan Manuel Manuel Sepulveda Sanchez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Data Access ◽  
Phase Iii ◽  
Cox Regression Analysis ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
The Impact

6617 Background: Retrospective database studies have suggested that statins and vitamin D have a positive impact on prostate cancer survival and specifically in mCRPC patients (pt). Methods: We conducted a post-hoc analysis of individual pt data of mCRPC pts treated with abiraterone (AA) and/or Prednisone (P) on two randomized phase III clinical trials COU -AA-301 and COU-AA-302 to analyze the impact of statins and vitamin D in overall survival (OS). Statistical analyses were performed using the Kaplan Meier method and Independent predictors were investigated using Cox regression analysis. This study, carried out under YODA Project #2016-1136, used data obtained from the Yale University Open Data Access Project. Results: These two studies included 2280 patients (1340 treated with AA/P and 640 with P). Use of Statin + vitamin D was associated with a 38% reduction in mortality in the postdocetaxel setting and 32% in the predocetaxel setting in patients treated with abiraterone (Table 1 and 2). No significant reduction in the rate of skeletal-related events was seen in patients treated with vitamin D or statins. Conclusions: To our knowledge this is the first report suggesting the impact of vitamin D+statin in mCPRC treated with abiraterone. The potential benefits of vitamin D do not seem to be secondary to concomitant statin use in this population. Further studies are needed to confirm these results. [Table: see text][Table: see text]

scholarly journals OARSI/OMERACT Initiative to Define States of Severity and Indication for Joint Replacement in Hip and Knee Osteoarthritis. An OMERACT 10 Special Interest Group

2011 ◽  
Vol 38 (8) ◽  
pp. 1765-1769 ◽  
Author(s):  
LAURE GOSSEC ◽  
SIMON PATERNOTTE ◽  
CLIFTON O. BINGHAM ◽  
DANIEL O. CLEGG ◽  
PHILIPPE COSTE ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Physical Function ◽  
Joint Replacement ◽  
Randomized Clinical Trials ◽  
Cross Sectional ◽  
Specific Level ◽  
Disease Modifying Drugs ◽  
Post Hoc Analysis ◽  
Joint Replacement Surgery ◽  
Post Hoc

Objective.To define pain and physical function cutpoints that would, coupled with structural severity, define a surrogate measure of “need for joint replacement surgery,” for use as an outcome measure for potential structure-modifying interventions for osteoarthritis (OA).Methods.New scores were developed for pain and physical function in knee and hip OA. A cross-sectional international study in 1909 patients was conducted to define data-driven cutpoints corresponding to the orthopedic surgeons’ indication for joint replacement. A post hoc analysis of 8 randomized clinical trials (1379 patients) evaluated the prevalence and validity of cutpoints, among patients with symptomatic hip/knee OA.Results.In the international cross-sectional study, there was substantial overlap in symptom levels between patients with and patients without indication for joint replacement; indeed, it was not possible to determine cutpoints for pain and function defining this indication. The post hoc analysis of trial data showed that the prevalence of cases that combined radiological progression, high level of pain, and high degree of function impairment was low (2%–12%). The most discriminatory cutpoint to define an indication for joint replacement was found to be [pain (0–100) + physical function (0–100) > 80].Conclusion.These results do not support a specific level of pain or function that defines an indication for joint replacement. However, a tentative cutpoint for pain and physical function levels is proposed for further evaluation. Potentially, this symptom level, coupled with radiographic progression, could be used to define “nonresponders” to disease-modifying drugs in OA clinical trials.

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