scholarly journals 762. Real-World Utilization of C. difficile Drug Treatments and Associated Clinical Outcomes in a US Hospital System

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S478-S479
Author(s):  
Lauren McDaniel ◽  
Nathan Everson ◽  
Melissa White ◽  
Engels N Obi ◽  
Yiyun Chen ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Clinical Cure ◽  
Treatment Options ◽  
Sustained Response ◽  
Oral Vancomycin ◽  
Research Support ◽  
Recurrence Rates ◽  
Hospital System ◽  
Drug Treatments ◽  
Order Set

Abstract Background IDSA recommends use of fidaxomicin or oral vancomycin for treatment of initial episode or first recurrence of Clostridioides difficile infection (CDI). This study aimed to evaluate impact of a clinical decision support order set driving appropriate use of fidaxomicin on utilization of CDI drug treatments and associated clinical outcomes. Methods This was a retrospective, quasi-experimental study evaluating CDI therapies pre- (8/2016-11/2017) and post- (5/2018-1/2020) CDI order set implementation at a level-one trauma center located in Virginia. Admitted adult patients were included if CDI testing was positive for a 1st or 2nd episode and received active CDI treatment. Exclusions included fulminant CDI and CDI diagnosis by PCR with < 3 bowel movements or laxative use within 24 hours. The primary outcome was CDI recurrence within 30 days of completing therapy in patients who achieved clinical cure. Secondary outcomes were evaluated at 30 and 90 days and included sustained response and CDI-related readmissions. Results After screening, 186 patients in the pre-group and 187 in the post-group were included. Median age was 68 [59-77], most patients had an initial CDI episode (88.2%) and were diagnosed with severe CDI (50.7%). Baseline characteristics were similar between each group on Charlson comorbidity index, ICU admission, CDI risk factors, and concomitant antibiotic use. Primary treatment options in the pre-group were most commonly metronidazole 47.9% and oral vancomycin 50.5%, and in the post-group were fidaxomicin 56.7% and oral vancomycin 41.7% (Figure 1). CDI recurrence rates at 30 days post-index medication (17.2% vs. 6.3%, p=0.004) were lower in the post-group (Table 1). Clinical cure (84.4% vs. 94.1%, p=0.002) and sustained response at 90 days (55.9% vs. 73.3%, p< 0.001) were higher in the post-group. CDI recurrence rates at 90 days and CDI-related readmissions at 30 and 90 days were also lower in the post group. Figure 1. CDI Treatment Utilization Table 1. Clinical Outcomes Conclusion Implementation of the CDI order set increased fidaxomicin use and was associated with a decrease in CDI recurrences and CDI-related readmissions and increase in clinical cure and sustained response. Findings suggest increased first-line use of fidaxomicin results in better clinical outcomes. Disclosures Lauren McDaniel, Pharm.D., BCIDP, Merck Sharp & Dohme Corp (Grant/Research Support) Nathan Everson, Pharm.D., BCIDP, AAHIVE, Merck & Co. (Grant/Research Support) Melissa White, PharmD, Merck Sharpe & Co (Grant/Research Support) Engels N. Obi, PhD, Merck & Co. (Employee, Shareholder) Yiyun Chen, PhD, Merck & Co., Inc (Employee) Rose Kohinke, PharmD, Merck Sharpe & Co (Research Grant or Support)

scholarly journals 15. Real-World Changes in Clostridioides difficile infection (CDI) Treatment Utilization and Clinical Outcomes Associated with Updated 2017 IDSA Guidelines among Medicare Beneficiaries in the U.S

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S11-S11
Author(s):  
Erik R Dubberke ◽  
Justin T Puckett ◽  
Engels N Obi ◽  
Sachin Kamal-Bahl ◽  
Kaushal Desai ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Panel Member ◽  
Sustained Response ◽  
Medicare Beneficiaries ◽  
First Line ◽  
Research Support ◽  
Recurrence Rates ◽  
Review Panel ◽  
Improved Outcomes ◽  
Post Period

Abstract Background The 2017 IDSA CDI guideline update phased out metronidazole (MTZ) and recommended vancomycin (VAN) or fidaxomicin (FDX) for first-line use. This study examined changes in CDI antibiotic use and clinical outcomes among Medicare beneficiaries with CDI pre- vs. post- the guideline update. Methods This retrospective claims analysis used 2016-2018 national Medicare claims data. The two study samples included continuously eligible fee-for-service Medicare beneficiaries aged ≥66 years with a new CDI diagnosis followed by an antibiotic fill in the pre-period (04/01/2017-09/30/2017) and post-period (04/01/2018-09/30/2018), respectively. Outcomes included type of CDI antibiotic received; sustained response and CDI recurrence. Multivariable regressions compared pre- vs. post-period outcomes while controlling for sociodemographic and clinical factors. Results The pre-period (N=7,389) and post-period (N=7,746) samples had similar characteristics (59% > 75 years, 32% male). Post-guideline update, absolute rates of MTZ use declined 27.7% (relative change [RC] -34.1%, p< 0.001) and VAN use increased 26.9% (RC +150.2%, p< 0.001) (Figure 1). While FDX use increased 0.8% (RC +87.8%, p< 0.001), overall use remained low (1.63%). Surprisingly, clinical outcomes did not improve between the pre- and post-period (Table 1). Even after adjustment, overall sustained response rates decreased (Odds Ratio [OR]: 0.93, p=0.0197) and overall CDI recurrence rates increased (OR: 1.13, p=0.0018) slightly in the post- vs. pre-period. Additional analyses by type of antibiotic showed that VAN (55.0% and 35.1%) was similar in outcomes to MTZ (54.2% and 33.0%), whereas FDX (71.4% and 20.9%) had higher sustained response and lower CDI recurrence rates, respectively (Figure 2). Figure 1. First-line use of CDI treatments, pre- vs. post- the guideline update, among Medicare beneficiaries with CDI Table 1. Clinical outcomes, pre- vs. post- the guideline update, among Medicare beneficiaries with CDI Figure 2. Clinical outcomes* by type of index CDI treatment among Medicare beneficiaries with CDI Note Pooled rates among patients on each index CDI treatment across the pre- and post-index periods. Conclusion The 2017 IDSA guideline update was associated with a substantial increase in VAN use and decrease in MTZ use. FDX use rates remained low (< 2%). Overall CDI outcomes did not improve post guideline update despite the shift to guideline-indicated VAN. This may be because VAN was not associated with meaningfully improved outcomes relative to MTZ. However, improved outcomes seen with FDX relative to VAN and MTZ suggest potential benefits from its greater use in Medicare patients. Disclosures Erik R. Dubberke, MD, MSPH, Ferring (Grant/Research Support)Merck (Consultant)Pfizer (Consultant, Grant/Research Support)Seres (Consultant)Summit (Consultant) Justin T. Puckett, BA, COVIA Health Solutions (Employee) Engels N. Obi, PhD, Merck & Co. (Employee, Shareholder) Sachin Kamal-Bahl, PhD, AbbVie (Consultant)Arena Pharmaceuticals, Inc. (Consultant)COVIA Health Solutions (Employee)Janssen, Inc. (Consultant)Merck (Consultant, Shareholder)Novartis (Consultant)Pfizer, Inc. (Consultant, Shareholder)PhRMA (Consultant) Kaushal Desai, PhD, AstraZeneca Pharmaceuticals (Shareholder)Merck & Co. Inc. (Employee) Bruce Stuart, PhD, COVIA Health Solutions (Consultant) Jalpa A. Doshi, PhD, Acadia (Consultant, Advisor or Review Panel member)Allergan (Advisor or Review Panel member)Biogen (Grant/Research Support)Boehringer Ingelheim (Other Financial or Material Support, Scientific lecture)Catabasis (Consultant)Humana (Grant/Research Support)Janssen, Inc. (Consultant, Grant/Research Support)MeiraGTX (Consultant)Merck (Grant/Research Support, Advisor or Review Panel member)Novartis (Grant/Research Support)Otsuka (Advisor or Review Panel member)Regeneron (Grant/Research Support)SAGE Therapeutics (Consultant)Sanofi (Grant/Research Support)Shire (Advisor or Review Panel member)The Medicines Company (Advisor or Review Panel member)

scholarly journals 784. A Novel Method to Assess Virulence of Clostridioides difficile: Focus on C. difficile Ribotype 106

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S436-S437
Author(s):  
Masaad Almutairi ◽  
Kevin W Garey ◽  
Faris S Alnezary ◽  
Saad Fallatah ◽  
Anne J Gonzales-Luna ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Disease Severity ◽  
Clinical Cure ◽  
Analysis Method ◽  
Research Support ◽  
Recurrence Rates ◽  
Clostridioides Difficile ◽  
The Usa ◽  
Novel Method ◽  
Cure Rates

Abstract Background Clostridioides difficile ribotype (RT) 106 has emerged as one of the most commonly isolated strains in the USA and worldwide. However, studies investigating clinical outcomes associated with this strain are lacking. The purpose of this study was to compare disease severity, clinical cure, and recurrence rates associated with CDI caused by RT106 vs two other comparator strains. Methods This multicenter study (20 hospitals) assessed hospitalized patients infected with C. difficile RT106 compared to patients infected with a known hypervirulent strain (RT027) and a strain associated with less virulence (RT014-020). Electronic medical records were reviewed by investigators blinded to RT. Disease severity was calculated using the 2017 IDSA/SHEA guidelines, initial clinical cure was defined as resolution of symptoms by day 6 of treatment, and recurrence assessed 90-days after the initial positive toxin test. All isolates were ribotyped using PCR fluorescent ribotyping. Results A total of 380 patients with CDI aged 66 ± 17 years (Female: 59.5%; White: 70.5%) infected with RT 106 (115/380; 30.3%), RT027 (116/380; 30.5%), and RT014-020 (149/380; 39.2%) were included. Approximately half of the patients had severe CDI (47.6%). Disease severity was highest for RT027 (59.3%) followed by RT014-020 (45%), and RT106 (41.2%). Clinical cure rates were lowest for RT027 (74.8%) followed by RT106 (77.8%), and RT014-020 (85.5%). 90-day recurrence rates were highest for RT027 (20.7%) followed by RT106 (13.3%), and RT014-020 (8.7%). Compared to RT014-020, virulence increased with RT106 (OR:1.10; 95% CI: 0.67-1.8) and RT027 (OR: 2.0: 95% CI: 1.2-3.5) was noted. Conclusion Our novel analysis method established RT106 as a moderately virulent C. difficile strain vs. comparator ribotypes. This study presents a novel method for comparing clinical outcomes for emerging ribotypes. Disclosures Kevin W. Garey, PharmD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator)

scholarly journals 2437. First-line Fidaxomicin Use in High-risk Inpatients Reduces Recurrence Rates

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S842-S842
Author(s):  
Rose Kohinke ◽  
Lauren McDaniel ◽  
Angela Perhac ◽  
Nathan Everson
Keyword(s):  
High Risk ◽  
Clinical Decision ◽  
First Episode ◽  
First Line ◽  
Oral Vancomycin ◽  
Recurrence Rates ◽  
Clostridioides Difficile ◽  
Quasi Experimental ◽  
The Impact ◽  
Order Set

Abstract Background Fidaxomicin is recommended by the 2018 Infectious Diseases Society of America (IDSA) guidelines as a first-line treatment in adult patients with uncomplicated Clostridioides difficile infection (CDI). Carilion Roanoke Memorial Hospital (CRMH) implemented a clinical decision order set directing providers to initiate fidaxomicin for CDI in patients at high risk of recurrence. The purpose of this study was to assess the impact of fidaxomicin on patient outcomes. Methods This quasi-experimental study included adults with a first episode or first recurrence of CDI before and after order set implementation. Patients receiving laxatives within 24 hours of testing and those with fulminant CDI were excluded. Pre-implementation was defined as May 2017 to November 2017 and post-implementation as May 2018 to November 2018. The primary endpoint was recurrence (diarrhea and a positive GDH with toxin or PCR within 30 days post-treatment). Secondary endpoints were clinical cure (resolution of symptoms within 2 days of completing therapy), global cure (cure with no recurrence at 3 months), mortality, and readmissions. Partial courses of fidaxomicin (i.e., patients discharged on another agent) were also evaluated. Results A total of 282 patients were included. In the pre-group, 59.1% received metronidazole, 39.6% oral vancomycin, and 1.3% fidaxomicin. In the post-group, fidaxomicin use increased to 52.3% and oral vancomycin was 44.5%. There was a significant improvement in recurrence (30.2% vs 17.1%, P = 0.019). Global cure and CDI upon readmission also improved in the post-group (Table 1). In patients receiving partial courses of fidaxomicin, recurrence (9.3% vs 25%, P = 0.19), global cure (86% vs 75%, P = 0.44), and infection on readmission (28.6% vs 37.5%, P = 0.67) were similar. Conclusion Fidaxomicin as a first-line agent in high-risk CDI patients decreased recurrence and increased global cure. Disclosures All authors: No reported disclosures.

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals 1186. Cefazolin inoculum effect predicts reduced susceptibility to other antibiotics and patient outcomes in MSSA endovascular infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S617-S617
Author(s):  
Dan Smelter ◽  
Sue McCrone ◽  
Warren Rose
Keyword(s):  
Infective Endocarditis ◽  
Mortality Rate ◽  
Patient Outcomes ◽  
Treatment Options ◽  
Fold Increase ◽  
Specific Mechanism ◽  
Research Support ◽  
High Burden ◽  
Low Toxicity ◽  
Inoculum Effect

Abstract Background MSSA Infective endocarditis (IE) is inherently a high-burden infection with up to a 30% mortality rate. Cefazolin is an appealing treatment option for IE with low toxicity and a favorable dosing scheme. However, cefazolin has been associated with treatment failure in IE, attributed to an inoculum effect. The specific mechanism underlying the cefazolin inoculum effect (CIE) remains undetermined, but CIE has been linked to both blaZ expression and agr dysfunction. This study aims to determine whether CIE is linked to reduced susceptibility to other antibiotics and worse outcomes regardless of therapy in MSSA endovascular infections. Methods Sixty-four MSSA strains were collected from patients with endovascular infections not treated with cefazolin. To determine CIE phenotype, strains were cultured and MICs assayed for cefazolin, nafcillin, and vancomycin at 107 CFU/mL for high-inocula (HI) and 105 CFU/mL for standard-inocula (SI). This study defined CIE as a ≥ 4-fold increase in MIC at HI compared to SI, with at least an MIC of 4 mg/L at HI. Nitrocefin disks identified blaZ expression, and beta lysin disks were used to determine hemolysin type and agr function. Patient outcomes of mortality and bacteremia duration were assessed across cohorts. Results Twenty-four strains exhibit a CIE (38%), with 10 strains having an MIC of ≥ 32mg/L at HI. Nafcillin and vancomycin also had an inoculum effect, uncoupled from the CIE and occurring at a lower frequency and amplitude at HI. Presence of CIE had a greater association with blaZ expression (71% vs 25%) than agr dysfunction (38% vs 20%). 50% (9/18) of CIE infections were cleared within 48 hours while 77% (20/26) of CIE-negative infections were cleared within 48 hours (P=0.106). However, presence of CIE was not associated with increased mortality (25% CIE-positive vs 35%; P=0.578) Conclusion Previous studies for CIE failed to enrich for isolates from endovascular sources, where inocula are known to be high. This study presents one of the largest endovascular source cohorts for CIE evaluation. It identifies that CIE prevalence (38%) is higher than reports from diverse infection sources (10-36%). CIE appears to predict bacteremia duration with other MSSA treatment options, suggesting mechanisms independent of blaZ and agr function for this phenomenon. Disclosures Warren Rose, PharmD, MPH, Merck (Grant/Research Support)Paratek (Grant/Research Support)

scholarly journals AB0436 OUTCOMES OF DOSE-REDUCTION OR DISCONTINUATION OF TOCILIZUMAB IN PATIENTS WITH EARLY DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1246.3-1247
Author(s):  
Y. Isomura ◽  
Y. Yamasaki ◽  
Y. Shirai ◽  
M. Kuwana
Keyword(s):  
Systemic Sclerosis ◽  
Dose Reduction ◽  
Clinical Outcomes ◽  
Inflammatory Markers ◽  
Topoisomerase I ◽  
Phase Iii ◽  
Optimal Timing ◽  
Skin Thickness ◽  
Research Support ◽  
Diffuse Cutaneous Systemic Sclerosis

Background:Potential efficacy and favorable safety profiles of tocilizumab (TCZ) have been demonstrated in patients with diffuse cutaneous systemic sclerosis (dcSSc) [1, 2]. However, clinical outcomes after dose-reduction or discontinuation of TCZ due to an improvement of skin thickness remain unclear.Objectives:To investigate the clinical outcomes after dose-reduction or discontinuation of TCZ in patients with dcSSc in a real-world setting.Methods:This is a single-center, retrospective, observational study using a database of consecutive SSc patients who visited our center between April 2014 and October 2020. For this study, we selected eligible patients from the database based on the following criteria: patients who (i) fulfilled the ACR/EULAR classification criteria, (ii) were classified as having dcSSc, (iii) had been treated with TCZ for at least 6 months, and (iv) were follow-up >6 months after TCZ introduction. Clinical information including demographic and clinical characteristics at TCZ introduction; dosing, administration route, and adherence of TCZ; and serial clinical parameters (modified Rondan total skin thickness score [mRSS], and percent predicted forced vital capacity [%FVC]), safety profiles, and outcomes after TCZ introduction regardless of TCZ continuation were extracted from the database.Results:Of 404 patients enrolled in the database, 13 dcSSc patients were eligible for this study. Baseline characteristics included a mean age of 51 ± 9 years, 85% female, disease duration of 27 ± 24 months, and mRSS of 19.5 ± 10.6. Seven patients (54%) had HRCT-confirmed ILD at baseline, and 9 (69%) were positive for anti-topoisomerase I antibody. Two (14%) and 11 (85%) were on mycophenolate mofetil and low-dose prednisolone (7.2 ± 6.0 mg/day), respectively. Seven patients (54%) each had active skin disease and elevated inflammatory markers defined in the phase III clinical trial [2], while only 4 (31%) fulfilled the inclusion criteria. TCZ was initially administered intravenously (8 mg/kg every 4 weeks) in 8 patients and subcutaneously in 5 (162 mg every 2 weeks in 4 and every week in one). At one year, mRSS was improved from 20.9 ± 11.4 to 10.7 ± 8.9 in 11 patients (p = 0.007), and %FVC was stable in 7 patients with ILD (76.8 ± 15.0 to 78.6 ± 16.1). During the observation period of 60.4 ± 26.7 months, 4 patients were treated with a stable dose of TCZ, while TCZ dose was reduced and/or discontinued in 9. Four of them discontinued TCZ due to adverse events (n = 2; acute lung injury and phlegmon) or prominent improvement of skin thickening (n = 2). Of 9 patients with dose reduction/discontinuation of TCZ, 4 patients who discontinued TCZ (n = 3) or received dose reduction of TCZ (n = 1) experienced a recurrence of progressive skin thickening together with inflammatory complications, including edematous induration of the skin, progression of ILD, polyarthritis, and/or pericarditis with increased inflammatory markers. The interval between dose-reduction/discontinuation of TCZ and clinical worsening ranged from 2 to 11 months. These manifestations were promptly improved by dose-escalation or resumption of TCZ in all patients except one who experienced progressive ILD and died of respiratory failure 27 months later.Conclusion:In dcSSc patients who experienced improvement of skin thickness during treatment with TCZ, dose-reduction or discontinuation of TCZ may result in a recurrence of the disease. Randomized comparative studies are necessary to examine optimal timing for dose-reduction or discontinuation of TCZ in dcSSc patients after improvement of skin thickness.References:[1]Khanna, D., et al., Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate). Ann Rheum Dis, 2018. 77(2):212-220.[2]Khanna, D., et al., Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med, 2020; 8(10): 963-974.Disclosure of Interests:Yohei Isomura: None declared, Yoshioki Yamasaki Speakers bureau: Boehringer-Ingelheim, Nippon Shinyaku, Bristol Myers, Yuichiro Shirai Speakers bureau: Janssen, Grant/research support from: Janssen, Masataka Kuwana Speakers bureau: Abbie, Astellas, Asahi Kasei Parma, Boehringer-Ingelheim, Chugai, Eisai, Janssen, MBL, Mochida, Nippon Shinyaku, Ono Pharmaceuticals, Pfizer, Tanabe-Mitsubishi, Consultant of: Boehringer-Ingelheim, Chugai, Corbus, MBL, Mochida, Grant/research support from: Boehringer-Ingelheim, Chugai, Eisai, MBL, Ono Pharmaceuticals, Tanabe-Mitsubishi

scholarly journals RADT-37. THE IMPACT OF POSTOPERATIVE RADIATION THERAPY (PORT) AND EXTENT OF SURGERY ON CLINICAL OUTCOMES OF ATYPICAL MENINGIOMA (AM): A META-ANALYSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii189-ii189
Author(s):  
Philip Haddad ◽  
Furqan Akhtar ◽  
Kevin Gallagher
Keyword(s):  
Clinical Outcomes ◽  
Comparative Studies ◽  
English Language ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Subtotal Resection ◽  
Recurrence Rates ◽  
Postoperative Radiation Therapy ◽  
Extent Of Surgery ◽  
The Impact

Abstract BACKGROUND Although meningiomas are among the most prevalent types of brain tumors, AMs account for around 4% of all meningiomas. AMs tend to be more aggressive with relatively higher rates of recurrence and mortality. Gross total resection (GTR) has been the standard of care when possible. However, GTR itself is not always enough to prevent the recurrence of AMs. The role of PORT remains controversial in AM as the comparative studies to support its use have provided conflicting RESULTS: The purpose of this meta-analysis is to evaluate the impact of PORT on clinical outcomes according to the extent of resection in AMs. METHODS A review of the medical literature was conducted using online databases. Inclusion criteria consisted of AM diagnosis, English language, Simpson graded resections, and comparative studies reporting recurrence rates (RcR), Progression-Free Survival (PFS), and Overall Survival (OS) with hazard ratios (HR) or Kaplan-Meier curves. A meta-analysis was conducted using an inverse variance method with a random-effects model. RESULTS Twenty-two comparative studies with a total of 5,129 patients were included and analyzed. When GTR was attained, PORT was associated with improved RcR (HR =0.72, 95%CI:0.59-0.86) and PFS (HR=0.77, 95%CI:0.65-0.90), but not OS (HR=0.93, 95%CI:0.83-1.04). When subtotal resection (STR) was attained, PORT was associated with improved PFS (HR=0.35, 95%CI:0.26-0.48) as well as OS (HR=0.70, 95%CI:0.54-0.89). The extent of surgery also impacted AM outcomes as GTR demonstrated superior PFS (HR=0.45, 95%CI:0.31-0.65) and OS (HR=0.30, 95%CI:0.13-0.72). CONCLUSIONS This is the first meta-analysis to show that PORT is associated with PFS benefit in AMs with GTR and STR. Moreover, PORT significantly improved OS of AMs that underwent STR but had no impact on OS when GTR was achieved. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the use of PORT in this patient population.

scholarly journals 168. Efficacy of the Novel gwt1 Inhibitor APX2039 in a Rabbit Model of cryptococcus Meningitis

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S213-S213
Author(s):  
Karen J Shaw ◽  
Charles D Giamberardino ◽  
Quinlyn A Soltow ◽  
Jennifer Tenor ◽  
Dena Toffaletti ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Oral Treatment ◽  
Treatment Options ◽  
Rabbit Model ◽  
Experimental Period ◽  
Control Group ◽  
Log10 Reduction ◽  
Research Support ◽  
Rapid Reduction ◽  
Geographical Regions

Abstract Background Cryptococcal meningitis (CM), caused primarily by Cryptococcus neoformans, is uniformly fatal if not treated. Treatment options are limited especially in resource-poor geographical regions, and mortality rates remain high despite current therapies. New oral treatment options are needed that demonstrate rapid reductions in CFU in CSF and brain tissue. APX2039 is a novel inhibitor of the fungal Gwt1 enzyme, which catalyzes an early step in glycosylphosphatidyl inositol (GPI) anchor biosynthesis. It is highly active against both C. neoformans and C. gattii and has previously demonstrated significant efficacy in a mouse delayed-treatment model of CM. CSF Fungal Burden in Rabbits Methods Male New Zealand White rabbits were inoculated with C. neoformans H99 (1.4 ×106 CFU) directly into the cisterna magna. Rabbits were immunosuppressed with cortisone acetate at 7.5 mg/kg (i.m.), starting on Day -1 relative to inoculation and then administered drug daily throughout the 14-day experimental period. Treatment was initiated on Day 2 postinfection and continued through Day 14 consisting of: 50 mg/kg APX2039 PO (BID), 80 mg/kg fluconazole (FLU) PO (QD), c) 1 mg/kg amphotericin B deoxycholate (AMB) IV (QD); and vehicle control. CSF was removed via an intracisternal tap on Days 2, 7, 10 and 14 post-infection and CFU/ml was assessed. Animals were sacrificed on Day 14 and CFU/g brain tissue was assessed. Results APX2039 demonstrated rapid reduction in CFU in both CSF and brain tissue. The range in CFU values in rabbit CSF is shown (Figure). Reductions in CFU were statistically different from the control group for all treatment groups. APX2039 was also different from both FLU and AMB and resulted in sterilization in CSF by Day 10. Brain harvested on Day 14 demonstrated a reduction in CFU/g tissue vs control of 1.8 log10 and 3.4 log10 for FLU and AMB, respectively, while a > 6 log10 reduction (tissue sterilization) was observed for APX2039. Conclusion APX2039 demonstrated potent efficacy in a rabbit model of CM. The more rapid clearance in CSF than either AMB or FLU, as well as > 6 log10 reduction in brain CFU highlights the unique properties of this drug, warranting further investigation of this molecule for the treatment of CM. Disclosures Karen J. Shaw, PhD, Amplyx (Consultant)Forge Therapeutics (Consultant) Charles D. Giamberardino, Jr., MR, Box (Shareholder) John R. Perfect, MD, amplyx (Grant/Research Support)astellas (Grant/Research Support)astellas (Grant/Research Support)

scholarly journals Perspectives and experiences of patients and healthcare professionals with geriatric assessment in chronic kidney disease: a qualitative study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Carlijn G. N. Voorend ◽  
Noeleen C. Berkhout-Byrne ◽  
Yvette Meuleman ◽  
Simon P. Mooijaart ◽  
Willem Jan W. Bos ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Qualitative Study ◽  
Clinical Outcomes ◽  
Geriatric Assessment ◽  
Clinical Care ◽  
Treatment Options ◽  
Routine Care ◽  
Treatment Team ◽  
Dutch Hospital ◽  
Additional Support

Abstract Background Older patients with end-stage kidney disease (ESKD) often live with unidentified frailty and multimorbidity. Despite guideline recommendations, geriatric assessment is not part of standard clinical care, resulting in a missed opportunity to enhance (clinical) outcomes including quality of life in these patients. To develop routine geriatric assessment programs for patients approaching ESKD, it is crucial to understand patients’ and professionals’ experiences with and perspectives about the benefits, facilitators and barriers for geriatric assessment. Methods In this qualitative study, semi-structured focus group discussions were conducted with ESKD patients, caregivers and professionals. Participants were purposively sampled from three Dutch hospital-based study- and routine care initiatives involving geriatric assessment for (pre-)ESKD care. Transcripts were analysed inductively using thematic analysis. Results In six focus-groups, participants (n = 47) demonstrated four major themes: (1) Perceived characteristics of the older (pre)ESKD patient group. Patients and professionals recognized increased vulnerability and (cognitive) comorbidity, which is often unrelated to calendar age. Both believed that often patients are in need of additional support in various geriatric domains. (2) Experiences with geriatric assessment. Patients regarded the content and the time spent on the geriatric assessment predominantly positive. Professionals emphasized that assessment creates awareness among the whole treatment team for cognitive and social problems, shifting the focus from mainly somatic to multidimensional problems. Outcomes of geriatric assessment were observed to enhance a dialogue on suitability of treatment options, (re)adjust treatment and provide/seek additional (social) support. (3) Barriers and facilitators for implementation of geriatric assessment in routine care. Discussed barriers included lack of communication about goals and interpretation of geriatric assessment, burden for patients, illiteracy, and organizational aspects. Major facilitators are good multidisciplinary cooperation, involvement of geriatrics and multidisciplinary team meetings. (4) Desired characteristics of a suitable geriatric assessment concerned the scope and use of tests and timing of assessment. Conclusions Patients and professionals were positive about using geriatric assessment in routine nephrology care. Implementation seems achievable, once barriers are overcome and facilitators are endorsed. Geriatric assessment in routine care appears promising to improve (clinical) outcomes in patients approaching ESKD.

scholarly journals THU0652-HPR ONLINE EDUCATION YIELDS SIGNIFICANT GAINS IN RHEUMATOLOGISTS’ KNOWLEDGE OF BIOLOGICS AND BIOSIMILARS BUT A SUBSTANTIAL GAP REMAINS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 570.2-571
Author(s):  
A. Stan ◽  
E. Bell ◽  
P. Schoonheim ◽  
E. Mysler
Keyword(s):  
Online Education ◽  
Statistical Significance ◽  
Treatment Options ◽  
Educational Activity ◽  
Round Table Discussion ◽  
Knowledge Gain ◽  
Regulatory Requirements ◽  
Research Support ◽  
Significance Level ◽  
Post Assessment

Background:Biologics are complex proteins which have revolutionized the treatment of many serious diseases. Due to their complexity and manufacturing which involves living organisms, it is not possible to create identical versions of reference biologics, but it is possible to create biosimilar drugs. Biosimilars have the potential to yield high cost savings and expand treatment options to meet the growing demand for biological therapies.Objectives:This study assessed whether the online CME-accredited round-table-discussion titled “Understanding Biologics: from protein to clinical practice” improved physicians’ understanding of the inherent variability of biologics and what similarity means in the context of biologics as well as the analytical assessment of quality that applies to both biologics and biosimilars.Methods:Rheumatologists participated in an online CME activity (www.medscape.org/viewarticle/900121) consisting of a 30-minute video discussion between 4 experts with accompanying slides. Educational effect was assessed using a 4-question repeated pairs, pre-/post-assessment. A chi-square test was used to determine if a statistically significant improvement (P<.05 significance level) existed in the number of pre-/post-test correct responses. Cramer’s V was used to estimate the level of impact of the education. The CME activity launched on 22 Aug 2018, and the data were collected through 9 Oct 2018.Results:A total of 622 rheumatologists participated in the educational activity, and 87 completed the pre- and postassessment. Overall the activity had a signficiant impact (P<.001) on rheumatologists’ understanding of the inherent variability of biologics and the regulatory requirements for approval of a biosimilar. The Cramer’s V value of 0.186 indicates a considerable effect of the education. The average perecentage of correct responses rose from 33% pre-activity to 51% post-activity. A linked learning assessment (individual responses matched pre- and post-education) showed that 25% of learners improved their knowledge and 26% reinforced their knowledge. The change in percentage of correct responses from pre- to post-assessment achieved statistical significance (P<.05) in 2 of the 3 questions presented: (i) understanding the type of studies needed to demonstrate comparability of a biosimilar to an originator (11% at baseline; 45% post activity), (ii) understanding the type of variability considered acceptable for a biologic (46% at baseline; 63% post activity). However, no knowledge gain was observed regarding basic analytic attributes evaluated to ensure batch to batch consistency (37% at baseline; 38% post activity). Almost 45% of rheumatologists gained confidence in their ability to describe the regulatory requirements for approval of a biosimilar.Conclusion:This online CME activity significantly improved rheumatologists’ understanding of the inherent variability of complex biologic medicines and the role of analytical studies in the regulatory approval of biosimilars. However, there is room for further improving physicians’ knowledge, especially of basic analytics of biologics and biosimilars.Acknowledgments:This CME-certified activity was supported by independent funding from Sandoz.Disclosure of Interests:Adriana Stan Grant/research support from: The CME-certified activity was supported by anindependent educational grant from Sandoz., Elaine Bell: None declared, Peter Schoonheim Grant/research support from: This CME-certified activity was supported by independent funding from Sandoz., Eduardo Mysler Grant/research support from: AbbVie, Lilly, Pfizer, Roche, BMS, Sandoz, Amgen, and Janssen., Consultant of: AbbVie, Lilly, Pfizer, Roche, BMS, Sandoz, Amgen, and Janssen.

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