The evolution of Clostridium difficile infection in cancer patients: epidemiology, pathophysiology, and guidelines for prevention and management.

Clostridium difficile infection (CDI) has emerged as a significant challenge to the healthcare system. The availability of anti-cancer chemotherapeutic regimens has contemporaneously resulted in a larger population of patients who are susceptible to CDI. The outbreak of a novel, hypervirulent, resistant strain, NAP-1/027 as well as resistance to antibiotic therapy have further contributed to an increase in prevalence as well as in disease severity. Recent data show high fatality rates in cancer patients with CDI. In this review, we have discussed the incidence, epidemiology, pathophysiology, clinical signs and symptoms and therapeutic guidelines for patients who are on chemotherapy and present with CDI and highlighted clinical reports documenting severe CDI associated with chemotherapeutic agents such as methotrexate, 5FU, cisplatin, carboplatin, paclitaxel, vinorelbine and cyclophosphamide. The review article also has the discussion of patents pertaining to infections caused by Clostridium difficile in cancer patients. We underscore the urgent need for early recognition and diagnosis of CDI in cancer patients and for the design and implementation of randomized clinical trials of new treatment modalities in the management of chemotherapy- associated CDI.

Warfarin: implementing its safe use in hospitalized patients from nursing homes and community through a performance improvement initiative.

INTRODUCTION: Warfarin is increasingly used to prevent thromboembolism but adverse drug events (ADEs) are common. The National Safety Goals (3E) 2008 recommend that institutions develop processes to monitor the safe use of warfarin. Despite these guidelines, adverse events (bleeding) are common. This initiative, in an academic hospital, tracked warfarin use before and after using a PI process aimed at improving safe use of warfarin in hospitalized adults. METHODS: Retrospective (PRE-initiative, September-December 2007) and prospective (POST-initiative, January-December 2008) data were collected on in-hospital and prior warfarin use, demographics, medical history, initial and in-hospital warfarin maintenance dosing, hematocrit, International Normalized Ratio (INR), hepatic and renal function and adverse events related to warfarin use. Education on the appropriate use of warfarin was provided through formal and informal sessions and during daily hand-off sessions. RESULTS: A total of 308 patients receiving oral warfarin were examined (mean age 70 ± 17(SD) years, 47% males, 36% from nursing homes). Age, sex ratios, and place of residence were similar PRE- versus POST-initiative. Overall initial and maintenance warfarin doses were significantly lower POST-initiative (P = .0129 and P = .0319, respectively) and these decreases occurred exclusively in patients with supratherapeutic INR levels (>3.0). During the POST-period, the prevalence of high INR levels and bleeding events during hospitalization also decreased significantly (P = .015 and P < .0005, respectively). Finally, concomitant use of anticoagulant and/or antiplatelet drugs was significantly decreased POST-initiative (P = .028). CONCLUSIONS: Most hospitalized patients (PRE- and POST-) presented with INRs in the sub- or supratherapeutic ranges (<2 and >3, respectively), requiring warfarin dose adjustments. Education through this initiative resulted in significantly lower average maintenance doses of warfarin, less use of concomitant anticoagulant or antiplatelet drugs, fewer supratherapeutic range INRs, and fewer adverse events during warfarin therapy. Education through a PI initiative is a simple and effective means to implement safer use of warfarin in the in-hospital setting.

Emerging therapies in the treatment of locally advanced squamous cell cancers of head and neck.

Head and neck squamous cell cancers (HNSCCs) represent 4 to 5% of all solid malignancies. Despite improvements in diagnostic techniques, 60% of patients will present with locally advanced HNSCCs with a median survival of about 12 months and 5-year overall survival of approximately 10-40%. Recent clinical trials have altered the treatment landscape by refining existing forms of radiation, incorporation of IMRT, choice of chemotherapeutic agents, introduction of biological and targeted therapy, immunotherapy and gene therapy. Cetuximab, a monoclonal antibody directed against the human epidermal growth factor receptor (EGFR), has recently been approved in combination with RT in patients with locally advanced HNSCCs. Antiangiogenic therapies and tyrosine kinase inhibitors (gefitinib and erlotinib) have also shown promise in the clinical trials. Vandetanib, an antagonist of both vascular endothelial growth factor receptor (VEGFR) and the EGFR is currently being tested in phase II trial. New patents on hypoxia-inducible factor 1 alpha, mesenchymal-epithelial transition factor, insulin-like growth factor or the PI3K/AKT/mTOR pathway, farnesyl transferase inhibitors have shown promise in the management of HNSCCs. Nevertheless, identification of predictive biomarkers of resistance or sensitivity to these therapies remains a fundamental challenge in the optimal selection of patients most likely to benefit from them. However, increase in efficacy comes at the cost of increased toxicity. The current review focuses on insight into recent patents and updates on the clinical trials using new investigational agents in the management for HNSCCs.

Clostridium difficile infection following chemotherapy.

Clostridium difficile infection (CDI) is a major concern for health care system and clinicians. Interest in C. difficile infection has increased recently due to an ongoing C. difficile epidemic with a hypervirulent strain and mortality. Disease due to C. difficile is responsible for substantial strain on the hospital system by increasing patients' length of stayand increasing costs. Present studies have demonstrated chemotherapeutic agents as an independent risk factor for CDI potentially leading towards serious morbidity and mortality. However, the current strategies lack randomized trials on management in chemotherapy-associated CDI. The changing face of the disease, emergence of more resistant strains, and the rising cancer incidence have heightened the need for identification of risk factors, rapid diagnosis including prompt identification of toxins, and management algorithms. This review focuses on recent insights on the epidemiology, diagnosis, current management, recent patents, and advances on treating strategies of CDI with reference to current studies.