Resolution of Clostridium difficile–Associated Diarrhea in Patients With Cancer Treated With Fidaxomicin or Vancomycin

2013 ◽  
Vol 31 (19) ◽  
pp. 2493-2499 ◽  
Author(s):  
Oliver A. Cornely ◽  
Mark A. Miller ◽  
Bruno Fantin ◽  
Kathleen Mullane ◽  
Yin Kean ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Cancer Recurrence ◽  
Patient Characteristics ◽  
Sustained Response ◽  
Recurrence Rates ◽  
Double Blind ◽  
Patients With Cancer ◽  
Increased Risk ◽  
Intent To Treat ◽  
Clostridium Difficile Associated Diarrhea

Purpose Patients with cancer are at increased risk for Clostridium difficile–associated diarrhea (CDAD). Little is known about treatment response. Patients and Methods Two double-blind trials randomly allocated 1,105 patients with CDAD to fidaxomicin or vancomycin treatment (modified intent-to-treat [mITT]), and 183 of these had cancer. Univariate and multivariate post hoc analyses compared effects of treatment and patient characteristics on cure, recurrence, and sustained response after 4 weeks. Time to resolution of diarrhea (TTROD) was also evaluated. Results Patients with cancer had a lower cure rate and longer TTROD than patients without cancer. Recurrence rates were similar. Cure was more likely with fidaxomicin than vancomycin (odds ratio [OR] 2.0; P = .065), recurrence was less likely (OR = 0.37; P = .018), and sustained response more frequent (OR = 2.56; P = .003). Under vancomycin, median TTROD was longer in patients with cancer than in those without (123 v 58 hours; log-rank P < .001). With fidaxomicin, median TTROD was not significantly affected by presence of cancer (74 v 54 hours; log-rank P = .145). In the full mITT population, age, hypoalbuminemia, and cancer were inversely associated with clinical cure by multivariate analysis. Study treatment with vancomycin was a significant predictor of recurrence (P < .001). Within the cancer population, low albumin was negatively and fidaxomicin was positively associated with improved cure. Conclusion For patients with cancer, fidaxomicin treatment was superior to vancomycin, resulting in higher cure and sustained response rates, shorter TTROD, and fewer recurrences.

scholarly journals Incidence, characteristics, determinants and prognostic impact of recurrent syncope

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Zimmermann ◽  
J Du Fay De Lavallaz ◽  
T Nestelberger ◽  
D Gualandro ◽  
P Badertscher ◽  
...  
Keyword(s):  
Patient Characteristics ◽  
Coronary Intervention ◽  
Final Diagnosis ◽  
Major Adverse Cardiovascular Events ◽  
Unknown Etiology ◽  
Funding Source ◽  
Prognostic Impact ◽  
Lasso Regression ◽  
Recurrence Rates ◽  
Increased Risk

Abstract Background The incidence, characteristics, determinants, and prognostic impact of recurrent syncope are largely unknown, causing uncertainty for both patients and physicians. Methods We characterized recurrent syncope including sex-specific aspects and its impact on death and major adverse cardiovascular events (MACE) in a large prospective international multicenter study enrolling patients ≥40 years presenting with syncope to the emergency department (ED). Syncope etiology was centrally adjudicated by two independent and blinded cardiologists using all information becoming available during syncope work-up and 12-month follow-up. MACE were defined as a composite of all-cause death, acute myocardial infarction, surgical or percutaneous coronary intervention, life-threatening arrhythmia including cardiac arrest, pacemaker or implantable cardioverter defibrillator implantation, valve intervention, heart-failure, gastrointestinal bleeding or other bleeding requiring transfusion, intracranial hemorrhage, ischemic stroke or transient ischemic attack, sepsis and pulmonary embolism. Results Incidence of recurrent syncope among 1790 patients was 20% (95%-confidence interval (CI) 18% to 22%) within 24 months. Patients with an adjudicated final diagnosis of cardiac syncope (hazard ratio (HR) 1.50, 95%-CI 1.11 to 2.01) or syncope of unknown etiology even after central adjudication (HR 2.11, 95%-CI 1.54 to 2.89) had an increased risk for syncope recurrence (Figure). LASSO regression fit on all patient information available early in the ED identified more than three previous episodes of syncope as the only independent predictor for recurrent syncope (HR 2.13, 95%-CI 1.64 to 2.75). Recurrent syncope within the first 12 months after the index event carried an increased risk for all-cause death (HR 1.59, 95%-CI 1.06 to 2.38) and MACE (HR 2.24, 95%-CI 1.67 to 3.01), whereas recurrences after 12 months did not have a significant impact on outcome measures. Conclusion Recurrence rates of syncope are substantial and vary depending on syncope etiology. There seem to be no reliable patient characteristics available early on the ED that allow for the prediction of recurrent syncope with only a history of more than three previous syncope being associated with a higher risk for future recurrences. Importantly, recurrent syncope within the first 12 months carries an increased risk for death and MACE. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation, Swiss Heart Foundation

scholarly journals LB2. TORC1 Inhibition with RTB101 as a Potential Pan-Antiviral Immunotherapy to Decrease the Incidence of Respiratory Tract Infections Due to Multiple Respiratory Viruses in Older Adults

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S993-S994 ◽  
Author(s):  
Joan Mannick ◽  
Amelia Tomlinson ◽  
Sarb Shergill ◽  
Grace Teo ◽  
Lloyd Klickstein
Keyword(s):  
Gene Expression ◽  
Older Adults ◽  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Controlled Study ◽  
Double Blind ◽  
Increased Risk ◽  
Intent To Treat ◽  
Tract Infections ◽  
Antiviral Gene

Abstract Background Respiratory tract infections (RTIs) are a leading cause of hospitalization and death in people age ≥65 years. RTIs are caused by multiple viruses, most of which lack effective treatments. An immunotherapy that enhances pan-antiviral innate immunity may reduce RTI incidence in older adults. Inhibition of targets downstream of target of rapamycin complex 1 (TORC1) was reported to upregulate pan-antiviral gene expression and protect mice from a viral RTI (York AG et al. Cell 2015). We evaluated whether TORC1 inhibition increased antiviral gene expression and decreased RTI incidence in older adults. Methods A randomized, double-blind, placebo, controlled study was conducted to determine whether the TORC1 inhibitor RTB101 alone or in combination with the TORC1 inhibitor everolimus reduced the incidence of laboratory-confirmed RTIs. The study enrolled 652 older adults at increased risk of RTI-related morbidity and mortality (defined as age ≥85 years, or age ≥65 years with asthma, COPD, type 2 diabetes mellitus, or current smokers). Subjects were treated for 16 weeks during winter cold and flu season with oral RTB101 5 mg or 10 mg once daily (QD), RTB101 10 mg twice daily, RTB101 10 mg + everolimus 0.1 mg QD, or matched placebo. The primary endpoint was the percentage of subjects with ≥1 laboratory-confirmed RTI through Week 16. Results RTB101 was well tolerated. In the intent-to-treat analysis, RTB101 10 mg QD was observed to: reduce the percentage of subjects with laboratory-confirmed RTIs by 30.6% compared with placebo (P = 0.025); reduce the incidence of RTIs caused by multiple different viruses; and upregulate interferon-stimulated pan-antiviral gene expression in whole blood (P = 0.00001 vs. placebo, Figure 1). Furthermore, RTB101 10 mg QD was observed to reduce the time to alleviation of moderate to severe RTI symptoms by 5 days, and to reduce the rate of all-cause hospitalization (rate ratio 0.439, 90% CI 0.196–0.983, P = 0.047). Conclusion RTB101 10 mg QD was associated with a significant reduction in laboratory-confirmed RTIs due to multiple viral pathogens that lack effective medicines for treatment or prevention. RTB101 was observed to upregulate interferon-stimulated pan-antiviral gene expression, which may underlie the reduction in RTI incidence. Disclosures Joan Mannick, MD, resTORbio (Employee, Shareholder), Amelia Tomlinson, PhD, resTORbio (Employee), Sarb Shergill, PhD, resTORbio (Employee), Grace Teo, PhD, resTORbio (Employee), Lloyd Klickstein, MD, PhD, resTORbio (Employee).

scholarly journals Clostridium Difficile-Associated Diarrhea in 200 Canadian Children

2005 ◽  
Vol 19 (8) ◽  
pp. 497-501 ◽  
Author(s):  
Véronique Morinville ◽  
Jane McDonald
Keyword(s):  
Clostridium Difficile ◽  
Pediatric Patients ◽  
Single Agent ◽  
Hirschsprung Disease ◽  
Pediatric Hospital ◽  
Recurrence Rates ◽  
Treatment Data ◽  
Prior Literature ◽  
Clostridium Difficile Associated Diarrhea ◽  
Bloody Stools

OBJECTIVE: Clostridium difficile-associated diarrhea is a major problem in adults. The present study was conducted to assess risk factors and outcomes in children with C difficile-associated diarrhea.METHODS: Laboratory records at a university-affiliated pediatric hospital were reviewed for all C difficile toxin-positive stools (cell culture cytotoxin assay) between 2000 and 2003. Charts on identified patients were reviewed.RESULTS: Two hundred patients with a diagnosis of C difficile-associated diarrhea were identified between February 2000 and November 2003. There were 107 males and 93 females (mean age 5.4 years; median age 2.6 years). Underlying factors were identified in 19% (12 patients underwent chemotherapy; seven patients had Crohn's disease; six were transplantation recipients; seven an immunodeficiency; four with Hirschsprung disease; two diagnoses of 'other'). Of the 200 identified patients, 149 (74.5%) had documentation of antibiotics in the previous two months (32 penicillins; 38 cephalosporins; three clindamycin, nine other single-agent, 59 multiple; eight not specified), and 111 (55.5%) had been hospitalized in the previous month. The symptoms of C difficile-associated diarrhea included bloody stools in 12.5% and frequent watery stools in 79%. Hospitalization was required in 27 of 116 outpatients; stay was prolonged in seven of the 84 patients already hospitalized. Fifty-five per cent received metronidazole, 34% were not treated, and treatment data were not available for the remainder. Recurrence occurred in 31% of those treated and retreatment consisted of vancomycin (15%), probiotics (15%) and cholestyramine (6%). No colectomies were required but two deaths occurred.CONCLUSIONS: The majority of pediatric patients developing symptomatic C difficile-associated diarrhea had antibiotic exposure or hospitalization within the previous one to two months. This is higher than previously reported. One-third had spontaneous symptom resolution. For those treated, recurrence rates were high. Mortality was significantly lower than described in adults, in agreement with prior literature.

scholarly journals Detailed methodological recommendations for the treatment of Clostridium difficile-associated diarrhea with faecal transplantation

2013 ◽  
Vol 154 (1) ◽  
pp. 10-19 ◽  
Author(s):  
Gergely György Nagy ◽  
Csaba Várvölgyi ◽  
Zoltán Balogh ◽  
Piroska Orosi ◽  
György Paragh
Keyword(s):  
Clostridium Difficile ◽  
Therapeutic Strategies ◽  
Routine Clinical Practice ◽  
Cure Rate ◽  
Recurrence Rates ◽  
Professional Societies ◽  
Significant Interest ◽  
Clostridium Difficile Associated Diarrhea ◽  
Methodological Guidelines ◽  
High Treatment

The incidence of Clostridium difficile associated enteral disease shows dramatic increase worldwide, with appallingly high treatment costs, mortality figures, recurrence rates and treatment refractoriness. It is not surprising, that there is significant interest in the development and introduction of alternative therapeutic strategies. Among these only stool transplantation (or faecal bacteriotherapy) is gaining international acceptance due to its excellent cure rate (≈92%), low recurrence rate (≈6%), safety and cost-effectiveness. Unfortunately faecal transplantation is not available for most patients, although based on promising international results, its introduction into the routine clinical practice is well justified and widely expected. The authors would like to facilitate this process, by presenting a detailed faecal transplantation protocol prepared in their Institution based on the available literature and clinical rationality. Officially accepted national methodological guidelines will need to be issued in the future, founded on the expert opinion of relevant professional societies and upcoming advances in this field. Orv. Hetil., 2013, 154, 10–19.

scholarly journals Managing the competing risks of thrombosis, bleeding, and anticoagulation in patients with malignancy

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Hanny Al-Samkari ◽  
Jean M. Connors
Keyword(s):  
Cancer Patients ◽  
Competing Risks ◽  
Bleeding Risk ◽  
Patient Specific ◽  
Severe Thrombocytopenia ◽  
Recurrence Rates ◽  
Patients With Cancer ◽  
Clinical Scenarios ◽  
Increased Risk ◽  
Recurrent Vte

Abstract The association between malignancy and thrombosis has been recognized for over a century and a half. Patients with cancer have an elevated risk of both initial and recurrent venous thromboembolism (VTE) compared with patients without cancer owing to cancer- and patient-specific factors. Recurrent VTE is common despite anticoagulation, presenting additional management challenges. Patients with cancer also have an increased risk of bleeding when on anticoagulants compared with patients without cancer. This bleeding risk is heightened by the thrombocytopenia common in patients with hematologic malignancies and those treated with intensive myelosuppressive chemotherapy regimens. Despite the advancements in cancer-directed therapy made over the past 15 years, numerous large studies have confirmed that bleeding and VTE recurrence rates remain high in cancer patients. Balancing the increased and competing risks of clotting and bleeding in these patients can be difficult, because management of cancer-associated thrombosis requires anticoagulation despite known increased risks for bleeding. In the context of challenging illustrative cases, this review will describe management approaches to clinical scenarios in which data are sparse: cancer patients with recurrent VTE despite anticoagulation and cancer patients with a new VTE in the setting of severe thrombocytopenia.

scholarly journals Hospice Admissions for Cancer in the Final Days of Life: Independent Predictors and Implications for Quality Measures

2014 ◽  
Vol 32 (28) ◽  
pp. 3184-3189 ◽  
Author(s):  
Nina R. O'Connor ◽  
Rong Hu ◽  
Pamela S. Harris ◽  
Kevin Ache ◽  
David J. Casarett
Keyword(s):  
Hematologic Malignancy ◽  
Multivariable Analysis ◽  
Patient Characteristics ◽  
Quality Measures ◽  
Hematologic Malignancies ◽  
Patients With Cancer ◽  
Lengths Of Stay ◽  
Younger Age ◽  
Increased Risk ◽  
Patient Mix

Purpose To define patient characteristics associated with hospice enrollment in the last 3 days of life, and to describe adjusted proportions of patients with late referrals among patient subgroups that could be considered patient-mix adjustment variables for this quality measure. Methods Electronic health record–based retrospective cohort study of patients with cancer admitted to 12 hospices in the Coalition of Hospices Organized to Investigate Comparative Effectiveness network. Results Of 64,264 patients admitted to hospice with cancer, 10,460 (16.3%) had a length of stay ≤ 3 days. There was significant variation among hospices (range, 11.4% to 24.5%). In multivariable analysis, among patients referred to hospice, patients who were admitted in the last 3 days of life were more likely to have a hematologic malignancy, were more likely to be male and married, and were younger (age < 65 years). Patients with Medicaid or self-insurance were less likely to be admitted to hospice within 3 days of death. Conclusion Quality measures of hospice lengths of stay should include patient-mix adjustments for type of cancer and site of care. Patients with hematologic malignancies are at especially increased risk for late admission to hospice.

scholarly journals Fidaxomicin Compared With Oral Vancomycin for the Treatment of Severe Clostridium difficile–Associated Diarrhea: A Retrospective Review

2019 ◽  
Vol 55 (4) ◽  
pp. 268-272
Author(s):  
Bryant B. Summers ◽  
Mary Yates ◽  
Kerry O. Cleveland ◽  
Michael S. Gelfand ◽  
Justin Usery
Keyword(s):  
Clostridium Difficile ◽  
Length Of Stay ◽  
Medical Center ◽  
Academic Medical Center ◽  
Recurrence Time ◽  
Financial Benefit ◽  
Oral Vancomycin ◽  
Recurrence Rates ◽  
Time To Recurrence ◽  
Clostridium Difficile Associated Diarrhea

Purpose: The most recent published guidelines on Clostridium difficile–associated diarrhea (CDAD) developed by the Infectious Diseases Society of America (IDSA) were released in 2017 and outline its treatment based on severity of the disease and recurrence; however, a clear first-line agent has not been recommended specifically for severe CDAD. Methods: This retrospective chart review was approved by the institutional review board and consisted of three community hospitals and one academic medical center. To be included, patients need to meet criteria for severe CDAD and receive at least 72 hours of therapy. Patients received either oral vancomycin or fidaxomicin, in addition to other therapies for CDAD, and differences in outcomes such as cost obtained from a common charge center, rates of recurrence, time to recurrence as measured at time of positive to negative polymerase chain reaction (PCR) test, and mortality were assessed. Results: Of the 147 patients, 74 patients received fidaxomicin and 73 patients received oral vancomycin. The average hospitalization cost for patients receiving fidaxomicin was $129,338.69 and for patients receiving vancomycin was $153,563.81 ( P = .26). Recurrence rates were lower with fidaxomicin compared with vancomycin (6.8% vs 17.6%; P = .047), and time to recurrence was longer with fidaxomicin versus vancomycin, but not statistically significant (96.8 ± 45.9 days vs 63.2 ± 66.9 days; P = .321). Mortality, length of stay in the intensive care unit, and overall length of stay were similar between the two therapies. Conclusions: In the treatment of severe CDAD, recurrence rates were lower and time to recurrence was higher with fidaxomicin compared with oral vancomycin. A clear financial benefit has yet to translate from these known findings.

scholarly journals Venous thromboembolism and bleeding in a community setting

2009 ◽  
Vol 101 (05) ◽  
pp. 878-885 ◽  
Author(s):  
Joel Gore ◽  
George Reed ◽  
Darleen Lessard ◽  
Luigi Pacifico ◽  
Cathy Emery ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Total Mortality ◽  
Community Setting ◽  
Patient Characteristics ◽  
Recurrence Rates ◽  
Increased Risk ◽  
History Of ◽  
Recurrent Vte ◽  
The Impact

SummaryBleeding is the most frequent complication of antithrombotic therapy for venous thromboembolism (VTE). However, little attention has been paid to the impact of bleeding after VTE in the community setting. The purpose of this investigation was to describe the incidence rate of bleeding after VTE, to characterize patients most at risk for bleeding, and to assess the impact of bleeding on rates of recurrent VTE and all-cause mortality. The medical records of residents of the Worcester (MA, USA) metropolitan area diagnosed with ICD-9 codes consistent with potential VTE during 1999, 2001, and 2003 were individually validated and reviewed by trained data abstracters. Clinical characteristics, acute treatment, and outcomes (including VTE recurrence rates, bleeding rates, and mortality) over follow-up (up to 3 years maximum) were evaluated. Bleeding occurred in 228 (12%) of 1,897 patients with VTE during our follow-up. Of these, 115 (58.8%) had evidence of early bleeding occurring within 30 days of VTE diagnosis. Patient characteristics associated with bleeding included impaired renal function and recent trauma. Other than a history of prior VTE, the occurrence of bleeding was the strongest predictor of recurrent VTE (hazard ratio [HR] 2.18; 95% confidence interval [CI] 1.54–3.09) and was also a predictor of total mortality (HR 1.97; 95%CI 1.57–2.47). The occur-rence of bleeding following VTE is associated with an increased risk of recurrent VTE and mortality. Future study of antithrombotic strategies for VTE should be informed by this finding. Advances that result in decreased bleeding rates may paradoxically decrease the risk of VTE recurrence.

Is there value to routine oncologic surveillance after radical cystectomy? Comparative outcomes of symptomatic versus asymptomatic recurrence.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 421-421
Author(s):  
Abhinav Khanna ◽  
Andrew Zganjar ◽  
Paras Shah ◽  
Matthew K. Tollefson ◽  
Vidit Sharma ◽  
...  
Keyword(s):  
Radical Cystectomy ◽  
Gastrointestinal Symptoms ◽  
Cancer Recurrence ◽  
Patients With Cancer ◽  
Presenting Symptoms ◽  
Voiding Symptoms ◽  
Routine Surveillance ◽  
Increased Risk ◽  
Risk Of Cancer

421 Background: Reported rates of adherence to post-radical cystectomy (RC) surveillance guidelines in real-world practice have been as low as 9%, in part reflecting a nihilistic view held by many of the value of routine follow-up. Indeed, conflicting data exist regarding the outcomes of patients with cancer recurrence detected by scheduled surveillance versus symptom-directed evaluation. Herein, we assessed comparative outcomes of patients with symptomatic recurrence (SR) versus asymptomatic recurrence (AR) after RC. Methods: We reviewed our Institutional Registry of RC patients to identify patients with cancer recurrence following RC. Presenting symptoms in the SR cohort included pain, constitutional symptoms, gastrointestinal symptoms, and hematuria/voiding symptoms, whereas AR was defined as recurrence detected on routine surveillance in the absence of symptoms. Baseline demographic and clinical characteristics were compared between study groups using chi-square and t-test. Kaplan-Meier and Cox survival analyses were performed to compare cancer-specific survival (CSS) and overall survival (OS) between AR and SR groups. Results: Of 3822 patients who underwent RC from 1980-2018 (with a median follow-up after RC of 2.4 years (IQR 1.1,5.5), a total of 1100 were subsequently diagnosed with recurrence, including 311 (28.3%) with AR and 789 (71.7%) with SR. Median time from RC to recurrence was longer in the AR group (13.2 months) than in the SR group (10.8 months; p = 0.01). Presenting symptoms included pain (70.2%), constitutional symptoms (50.7%), gastrointestinal symptoms (23.3%), and urinary symptoms (23.3%). Median follow-up after recurrence was 2.4 years (IQR 1.1-5.5), during which time 997 patients died, including 840 who died of bladder cancer. Compared to patients with SR, patients with AR had a longer median CSS (54.5 months vs 27.3 months, p < 0.001) and OS (43.0 months vs 25.8 months, p < 0.001). On multivariable Cox proportional hazards models adjusting for demographic and clinical factors, SR was associated with a significantly increased risk of cancer-specific (hazard ratio [HR] 1.66 [95% confidence interval 1.41-1.96], p < 0.0001) and all-cause mortality (HR 1.48 [1.23-1.71], p < 0.0001). Conclusions: SR after RC is associated with worse oncologic outcomes than post-RC recurrence detected by routine surveillance. As such, continued surveillance is warranted, while further study is needed to determine the optimal follow-up regimen balancing patient and disease risks.

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