Abstract. Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.

Previous work has suggested that central-line-associated bloodstream infection (CLABSI) is associated with increased costs and risk of mortality; however, no studies have looked at both total and variable costs, and information on outcomes outside of the intensive-care unit (ICU) is sparse. The aim of this study was to determine the excess in-hospital mortality and costs attributable to CLABSI in ICU and non-ICU patients. We conducted a retrospective cohort and cost-of-illness study from the hospital perspective of 398 patients at a tertiary-care academic medical centre from 1 January 2008 to 31 December 2010. All CLABSI patients and a simple random sample drawn from a list of all central lines inserted during the study period were included. Generalized linear models with log link and gamma distribution were used to model costs as a function of CLABSI and important covariates. Costs were adjusted to 2010 US dollars by use of the personal consumption expenditures for medical care index. We used multivariable logistic regression to identify independent predictors of in-hospital mortality. Among both ICU and non-ICU patients, adjusted variable costs for patients with CLABSI were c. $32 000 (2010 US dollars) higher on average than for patients without CLABSI. After we controlled for severity of illness and other healthcare-associated infections, CLABSI was associated with a 2.27-fold (95% CI 1.15-4.46) increased risk of mortality. Other healthcare-associated infections were also significantly associated with greater costs and mortality. Overall, CLABSI was associated with significantly higher adjusted in-hospital mortality and total and variable costs than those for patients without CLABSI.

This investigation compared the validities of three widely used self-report depression measures: the Beck Depression Inventory, the MMPI Depression scale, and the Zung Self-Rating Depression Scale. Each inventory was administered to 101 inpatient psychiatric ward patients and to 99 chemical dependency ward patients. The three scales were correlated with clinicians' global ratings of depression, with scores on five Diagnostic and Statistical Manual of Mental Disorders (DSM-III; American Psychiatric Association, 1980)-based, factor-analytic depression scales, and with an overall depression score based on the DSM-III criteria. In general, the Zung produced better validity coefficients than the Beck, which in turn yielded higher correlations with our criteria than did the MMPI Depression scale.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of complicated bacteremia (CB) and infective endocarditis (IE).The gold standard treatment for these infections is vancomycin. A vancomycin area under the concentration-time curve from 0 to 24 h (AUC 24 )/MIC ratio of >400 has been suggested as a target to achieve clinical effectiveness, and yet to date no study has quantitatively investigated the AUC 24 /MIC ratio and its association with attributable mortality (AM). We performed a review of patients treated for MRSA CB and IE from 1 July 2006 to 30 June 2008. AM was defined as deaths where CB or IE was documented as the main cause or was mentioned as the main diagnosis. Classification and regression tree analysis (CART) was used to identify the AUC 24 /MIC ratio associated with AM. Mann-Whitney and Fisher exact tests were used for univariate analysis, and logistic regression was used for multivariate modeling. The MICs were determined by Etest, and the AUC 24 was determined using a maximum a posteriori probability-Bayesian estimator. A total of 32 CB and 18 IE patients were enrolled. The overall crude mortality and AM were 24 and 16%, respectively. The CART-derived partition for the AUC 24 /MIC ratio and AM was <211. Patients with an AUC 24 /MIC ratio of <211 had a >4-fold increase in AM than patients who received vancomycin doses that achieved an AUC 24 /MIC ratio of >211 (38 and 8%, respectively; P ‫؍‬ 0.02). In bivariate analysis the APACHE-II score and an AUC 24 /MIC ratio of <211 were significantly associated with AM. In the multivariate model, the APACHE-II score (odds ratio, 1.24; P ‫؍‬ 0.04) and a vancomycin AUC/MIC ratio of <211 (odds ratio, 10.4; P ‫؍‬ 0.01) were independent predictors of AM. In our analysis, independent predictors of AM were the APACHE-II score and an AUC 24 /MIC ratio of <211. We believe further investigations are warranted.

Aerosolized delivery of antimicrobial agents is an attractive option for management of pulmonary infections, as this is an ideal method of providing high local drug concentrations while minimizing systemic exposure. With the paucity of consensus regarding the safety, efficacy, and means with which to use aerosolized antimicrobials, a task force was created by the Society of Infectious Diseases Pharmacists to critically review and evaluate the literature on the use of aerosolized antiinfective agents. This article summarizes key findings and statements for preventing or treating a variety of infectious diseases, including cystic fibrosis, bronchiecstasis, hospital-acquired pneumonia, fungal infections, nontuberculosis mycobacterial infection, and Pneumocystis jiroveci pneumonia. Our intention was to provide guidance for clinicians on the use of aerosolized antibiotics through evidence-based pharmacotherapy. Further research with well-designed clinical trials is necessary to elucidate the optimal dosage and duration of therapy and, of equal importance, to appreciate the true risks associated with the use of aerosolized delivery systems.

Rapid PCR testing for MRSA appears to have the potential to reduce mortality rates while being less costly than empiric therapy in the EU and US, across a wide range of MRSA prevalence rates and PCR test costs.

Zygomycosis appears to be on the rise in the United States. The standard treatment is a combination of amphotericin B therapy, surgical debridement, and reversal of the underlying disease or immunosuppression.

Medicare stopped reimbursing United States hospitals for several complications or comorbidities developed during hospitalizations effective 1 October 2008. The Centers for Medicare and Medicaid Services selected high-cost or high-frequency events from the National Quality Forum's list of "never events" for inclusion in this reimbursement change. Several of these complications and/or comorbidities are nosocomial infections, a significant proportion of which are not likely to be preventable. Attempts to eliminate these events may have unwanted clinical and economic outcomes, and compliance with coding and billing requirements will have a significant effect on research conducted using administrative databases. Although this reimbursement change is a step toward reducing the rate of preventable adverse events, its current form does not provide guidance with regard to how hospitals may hope to reduce the rate of these infections, and it uses individual case-based rather than process-based or population-based outcome measures, which makes benchmarking and goalsetting difficult.