A systematic review of clostridium difficile infection in patients with iatrogenic immunesuppression

Background: Incidence of C. difficile infection (CDI) has increased dramatically in the past decade and is the most frequent cause of nosocomial infectious diarrhea. The outcome of infection may range from mild diarrhea to life-threatening pseudomembranous colitis depending on the immunological response of the host, which is highly compromised in this special population that includes bone marrow transplant (BMT), solid organ transplant (SOT) and cancer patients on cytotoxic chemotherapy. ^ Objectives: We conducted a meta-analysis to assess the incidence rates of CDI and the time to onset of infection in patients with iatrogenic immune suppression. ^ Methods: Original studies were identified through an extensive search of electronic databases including PubMed, Ovid Medline (R), RefWorks and Biological Abstracts and their references. The overall incidence rate of CDI in the immune suppressed population was calculated using random effects model and their 95% confidence interval was derived. Differences in the incidence of CDI and time to onset of infection were calculated between the groups and within the groups. Publication bias was assessed using a funnel plot. Results: Twenty nine published articles involving 7,424 patients met the eligibility requirements. The overall incidence of CDI in the immune suppressed population is 11.1% (95% Confidence Interval (CI): 9.2–13.4%). The incidence of CDI was higher in SOT patients (14.2%, 95% CI: 6.8–21.5%); (p-value-0.022) and in cancer patients on cytotoxic chemotherapy (11.4%, 95% CI: 8.4–15.4%); (p = 0.042) than in BMT patients (10.5%, 95% CI: 7.9–13.1%). In a subgroup analysis of BMT population, the incidence of CDI is significantly higher in patients who received allogeneic BMT (15.1%, 95% CI: 11.2–20.0%; p value <0.0001). Similarly, in the SOT population, the incidence of CDI was higher in patients who underwent liver transplantation (11.0%, 95% CI: 5.6–20.3%); (p= 0.0672). The median time to onset of infection was shorter in BMT patients (p=0.0025). ^ Conclusions: It is evident from the combined analysis of these 29 published studies that the incidence of CDI in the immune suppressed population is higher. However, early diagnosis and treatment of CDI will help reduce the morbidity and mortality due to CDI in this special population.^

A systematic review of personalized therapy in patients with advanced cancer

Background: An increased understanding of the pathogenesis of cancer at the molecular level has led to the development of personalized cancer therapy based on the mutation status of the tumor. Tailoring treatments to genetic signatures has improved treatment outcomes in patients with advanced cancer. We conducted a meta-analysis to provide a quantitative summary of the response to treatment on a phase I clinical trial matched to molecular aberration in patients with advanced solid tumors. ^ Methods: Original studies that reported the results of phase I clinical trials in patients with advanced cancer treated with matched anti-cancer therapies between January 2006 and November 2011 were identified through an extensive search of Medline, Embase, Web of Science and Cochrane Library databases. Odds Ratio (OR) with 95% confidence interval (CI) was estimated for each study to assess the strength of an association between objective response rate (ORR) and mutation status. Random effects model was used to estimate the pooled OR and their 95% CI was derived. Funnel plot was used to assess publication bias. ^ Results: Thirteen studies published between January 2006 and November 2011that reported on responses to matched phase I clinical trials in patients with advanced cancer were included in the meta-analysis. Nine studies reported on the responses seen in 538 of the 835 patients with driver mutations responsive to therapy and seven studies on the responses observed in 234 of the 306 patients with mutation predictive for negative response. Random effects model was used to estimate pooled OR, which was 7.767(95% CI = 4.199 − 14.366; p-value=0.000) in patients with activating mutations that were responsive to therapy and 0.287 (95% CI = 0.119 − 0.694; p-value=0.009) in patients with mutation predictive of negative response. ^ Conclusion: It is evident from the meta-analysis that somatic mutations present in tumor tissue of patients are predictive of responses to therapy in patients with advanced cancer in phase I setting. Plethora of research and growing evidence base indicate that selection of patients based on mutation analysis of the tumor and personalizing therapy is a step forward in the war against cancer.^