Karen Doucette

Bio: Karen Doucette is an academic researcher from University of Alberta. The author has contributed to research in topics: Medicine & Transplantation. The author has an hindex of 26, co-authored 77 publications receiving 2451 citations. Previous affiliations of Karen Doucette include University of Calgary & Harvard University.

Efficacy of Antiretroviral Therapy Programs in Resource-Poor Settings: A Meta-analysis of the Published Literature

Abstract: Despite the advent of effective combination antiretroviral drug therapy (ART) for the treatment of human immunodeficiency virus (HIV) infection many doubt the feasibility of ART treatment programs in resource-poor settings. We performed a meta-analysis of the efficacy of ART programs in the developing world. We searched the Medline database with the index terms “HIV” “antiretroviral therapy” “CD4 count” “viral load” “experience” and “outcomes.” A total of 201 abstracts were reviewed and 25 articles were selected for detailed review. Ten observational studies with details on patient outcomes were ultimately included in the analysis. Three readers independently extracted data from the articles. The details recorded included patient demographic characteristics baseline CD4 cell counts baseline HIV RNA viral loads ART histories outcomes and timing of the outcome measure. The proportion of subjects with an undetectable HIV viral load provided the measure of treatment efficacy. A random-effects model weighted the proportion of patients with undetectable viral load at various time points during ART. The proportion was 0.697 (95% CI 0.582–0.812) at month 6 and 0.573 (95% CI 0.432– 0.715) at month 12 of ART. The provision of medications free of charge to the patient was associated with a 29%– 31% higher probability of having an undetectable viral load at months 6 and 12 than was the requirement that patients pay part or all of the cost of therapy. ART treatment programs in resource-poor settings have efficacy rates similar to those reported for developed countries. The provision of medications free of charge to the patient is associated with a significantly increased probability of virologic suppression at months 6 and 12 of ART. (authors)

Nontuberculous Mycobacterial Infection in Hematopoietic Stem Cell and Solid Organ Transplant Recipients

Abstract: Nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms. In immunocompetent hosts, they are a rare cause of disease. In immunocompromised hosts, disease due to NTM is well documented. Reports of NTM disease have increased in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. This increase may reflect increased numbers of transplants, intensification of immune suppressive regimens, prolonged survival of transplant recipients, and/or improved diagnostic techniques. The difficulty of diagnosis and the impact associated with infections due to NTM in HSCT and SOT recipients necessitates that, to ensure prompt diagnosis and early initiation of therapy, a high level of suspicion for NTM disease be maintained. The most common manifestations of NTM infection in SOT recipients include cutaneous and pleuropulmonary disease, and, in HSCT recipients, catheter-related infection. Skin and pulmonary lesions should be biopsied for histologic examination, special staining, and microbiologic cultures, including cultures for bacteria, Nocardia species, fungi, and mycobacteria. Mycobacterial infections associated with catheters may be documented by tunnel or blood (isolator) cultures. Susceptibility testing of mycobacterial isolates is an essential component of optimal care. The frequent isolation of NTM other than Mycobacterium avium complex (MAC) from transplant recipients limits the extrapolation of therapeutic data from human immunodeficiency virus-infected individuals to the population of transplant recipients. Issues involved in the management of NTM disease in transplant recipients are characterized by a case of disseminated infection due to Mycobacterium avium complex in a lung transplant recipient, with a review of the relevant literature.

A prospective molecular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung transplant recipients.

Abstract: Background Community-acquired respiratory viral infections (RVIs) are common in lung transplant patients and may be associated with acute rejection and bronchiolitis obliterans syndrome (BOS). The use of sensitive molecular methods that can simultaneously detect a large panel of respiratory viruses may help better define their effects. Methods Lung transplant recipients undergoing serial surveillance and diagnostic bronchoalveolar lavages (BALs) during a period of 3 years were enrolled. BAL samples underwent multiplex testing for a panel of 19 respiratory viral types/subtypes using the Luminex xTAG respiratory virus panel assay. Results Demographics, symptoms, and forced expiratory volume in 1 sec were prospectively collected for 93 lung transplant recipients enrolled. Mean number of BAL samples was 6.2+/-3.1 per patient. A respiratory virus was isolated in 48 of 93 (51.6%) patients on at least one BAL sample. Of 81 positive samples, the viruses isolated included rhinovirus (n=46), parainfluenza 1 to 4 (n=17), coronavirus (n=11), influenza (n=4), metapneumovirus (n=4), and respiratory syncytial virus (n=2). Biopsy-proven acute rejection (> or =grade 2) or decline in forced expiratory volume in 1 sec > or =20% occurred in 16 of 48 (33.3%) patients within 3 months of RVI when compared with 3 of 45 (6.7%) RVI-negative patients within a comparable time frame (P=0.001). No significant difference was seen in incidence of acute rejection between symptomatic and asymptomatic patients. Biopsy-proven obliterative bronchiolitis or BOS was diagnosed in 10 of 16 (62.5%) patients within 1 year of infection. Conclusion Community-acquired RVIs are frequently detected in BAL samples from lung transplant patients. In a significant percentage of patients, symptomatic or asymptomatic viral infection is a trigger for acute rejection and obliterative bronchiolitis/BOS.

Management of chronic hepatitis C: Consensus guidelines

Abstract: Since the last consensus conference on the management of chronic viral hepatitis, a number of studies looking at modifications of the standard course of treatment have been published. These changes have been sufficiently substantive to warrant review to determine whether any changes in the recommended treatment algorithms are needed. A consensus development conference was held in January 2007, and the present document highlights the results of the presentations and discussion about these issues. It reviews the epidemiology of hepatitis C in Canada, treatment of acute hepatitis C and new algorithms in chronic hepatitis C, including retreatment of previous treatment failures. In addition, sections on management of hepatitis C in special populations have been updated. There is also a section on the use of hematopoietic growth factors to help manage patients on therapy. The document should be read in conjunction with the previous document to identify changes. Some recommendations made in the previous document remain and are not discussed here.

Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America

Abstract: A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.

Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update.

Abstract: Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.

Prodrugs: design and clinical applications

Abstract: Prodrugs are bioreversible derivatives of drug molecules that undergo an enzymatic and/or chemical transformation in vivo to release the active parent drug, which can then exert the desired pharmacological effect. In both drug discovery and development, prodrugs have become an established tool for improving physicochemical, biopharmaceutical or pharmacokinetic properties of pharmacologically active agents. About 5-7% of drugs approved worldwide can be classified as prodrugs, and the implementation of a prodrug approach in the early stages of drug discovery is a growing trend. To illustrate the applicability of the prodrug strategy, this article describes the most common functional groups that are amenable to prodrug design, and highlights examples of prodrugs that are either launched or are undergoing human trials.