Rabia Ahmed

Serum drug concentrations of INH and RMP predict 2-month sputum culture results in tuberculosis patients.

BACKGROUND In Alberta provincial tuberculosis (TB) clinics, serum drug concentrations (SDCs) are measured in patients with human immunodeficiency virus, diabetes mellitus or at extremes of weight, or showing slow clinical response to treatment, to guide treatment. DESIGN A retrospective review was performed of TB cases in Northern Alberta with SDCs measured from 1998 to 2013. Adequacy of SDC was based on the maximum concentration (Cmax) achieved in serum, with rifampicin (RMP) values <8 μg/ml and isoniazid (INH) values <3 μg/ml for daily dosing and <9 μg/ml for intermittent dosing considered inadequate. Clinical variables and microbiological outcomes were then compared between the adequate and inadequate groups. RESULTS Of 134 pulmonary TB cases with SDCs for INH and/or RMP, we found a significant increase in 2-month sputum culture positivity in the cohort with inadequate concentrations of INH compared to those with adequate INH concentrations (42.5% vs. 18.3%, P = 0.0084). A similar trend was seen in the cohort with inadequate concentrations of RMP (39% vs. 21%, P = 0.0725). CONCLUSIONS Among our study population, low SDCs of INH and, to a lesser extent, RMP, appear to be associated with reduced sputum culture conversion after 2 months of treatment.

A 10-Year Population Based Study of ‘Opt-Out’ HIV Testing of Tuberculosis Patients in Alberta, Canada: National Implications

Introduction Compliance with the recommendation that all tuberculosis (TB) patients be tested for human immunodeficiency virus (HIV) has not yet been achieved in Canada or globally. Methods The experience of “opt-out” HIV testing of TB patients in the Province of Alberta, Canada is described over a 10-year period, 2003–2012. Testing rates are reported before and after the introduction of the “opt-out” approach. Risk factors for HIV seropositivity are described and demographic, clinical and laboratory characteristics of TB patients who were newly diagnosed versus previously diagnosed with HIV are compared. Genotypic clusters, defined as groups of two or more cases whose isolates of Mycobacterium tuberculosis had identical DNA fingerprints over the 10-year period or within 2 years of one another, were analyzed for their ability to predict HIV co-infection. Results HIV testing rates were 26% before and 90% after the introduction of “opt-out” testing. During the “opt-out” testing years those <15 or >64 years of age at diagnosis were less likely to have been tested. In those tested the prevalence of HIV was 5.6%. In the age group 15–64 years, risk factors for HIV were: age (35–64 years), Canadian-born Aboriginal or foreign-born sub-Saharan African origin, and combined respiratory and non-respiratory disease. Compared to TB patients previously known to be HIV positive, TB patients newly discovered to be HIV positive had more advanced HIV disease (lower CD4 counts; higher viral loads) at diagnosis. Large cluster size was associated with Aboriginal ancestry. Cluster size predicted HIV co-infection in Aboriginal peoples when clusters included all cases reported over 10 years but not when clusters included cases reported within 2 years of one another. Conclusion “Opt-out” HIV testing of TB patients is effective and well received. Universal HIV testing of TB patients (>80% of patients tested) has immediate (patients) and longer-term (TB/HIV program planning) benefits.

Factors Associated with Reduced Antituberculous Serum Drug Concentrations in Patients with HIV-TB Coinfection

We describe correlates of reduced antituberculous serum drug concentrations (SDCs) in HIV-infected patients receiving treatment for active tuberculosis (TB). Cross-sectional analysis of individuals diagnosed with HIV and active TB in Northern Alberta, Canada, was performed. Of the 30 HIV-TB cases, 27 underwent measurement of SDCs. Rates of low SDCs were 9 of 26 (34%) for isoniazid (INH) and 16 of 25 (64%) for rifamycins. Increased weight and elevated body mass index (BMI) correlated with low SDCs for rifampin (P < .05) and increased weight also correlated with reduced SDCs for INH (P < .05). This suggests that conventional antituberculous dosing may be too low and consideration should be given to increase the maximum initial weight-based doses in HIV-infected patients.

Building capacity for education research among clinical educators in the health professions: A BEME (Best Evidence Medical Education) Systematic Review of the outcomes of interventions: BEME Guide No. 34.

Abstract Background/purpose: There is a growing desire for health professions educators to generate high-quality education research; yet, few of them encounter the training to do so. In response, health professions faculties have increasingly been devoting resources to provide members with the skills necessary for education research. The form and impact of these efforts have not been reviewed, though such a synthesis could be useful for practice. The objectives of this systematic review were to (1) identify interventions aimed at building capacity for education research among health professions clinical educators and (2) review the outcomes of these interventions. Methodology: We developed a systematic review protocol based on our pilot scoping search. This protocol underwent peer review and was prospectively registered with the Best Evidence Medical Education Collaboration. Based on this protocol, we conducted a comprehensive search of health professions’ databases and related grey literature. Systematic methods were applied: two independent reviewers completed title screening and full text review for inclusion, data extraction, and methodological quality assessment. Studies were included if they reported outcomes for interventions designed to increase capacity for health professions clinical educators to conduct education research. We conducted a qualitative synthesis of the evidence which included detailed reporting of intervention characteristics and outcomes. Results: Our search returned 14, 149 results, 241 of which were retained after title and abstract screening, and 30 of which met inclusion criteria after full text review. Seven groups of interventions were identified, the most frequent being teaching scholars programs (n = 10), health professions education fellowships (n = 3) or master’s programs (n = 4). The most commonly measured outcome was change related to enhanced scholarly outputs (grants, papers, abstracts, and presentations) post-intervention. Unfortunately, most of the included studies lacked detailed description of the intervention and were of low to moderate quality with post-test only design. Discussion/conclusions: This review demonstrates that various interventions can have a positive impact on the ability of health professions clinical educators to conduct education research. We note several key elements of the interventions including: (1) protected time, (2) mentorship and/or collaboration, (3) departmental and institutional commitment and leadership, and (4) financial support. Through our analysis we describe the complexities around evaluating clinical educators’ health professions research activities and the interventions used to promote education research. While improved study quality would allow more detailed understanding and evaluation of these key features, we are able to provide recommendations for potential strategies for improving participation in and quality of health professions education research based on this analysis.

The Impact of Homelessness and Incarceration on Women's Health.

Female inmates have multiple challenges during incarceration and as they transition into the community including: barriers to accessing health care within correctional facilities, poor transitional preparation preceding release, and inadequate continuity of health care after release. This qualitative study explored the health-seeking experiences and the health and housing needs of female inmates. Four focus groups were conducted in a remand facility in Canada. Women described poor health at entry to the correctional system and viewed incarceration as a means to access health care services. Transition back into the community represented a crossroad that was dependent on the stability of housing status. These findings support gender-sensitive health and housing programs to reduce addictions, recidivism, and poor health among this vulnerable population.

Is Early Tuberculosis Death Associated with Increased Tuberculosis Transmission

Introduction Tuberculosis (TB) is now a relatively uncommon disease in high income countries. As such, its diagnosis may be missed or delayed resulting in death before or shortly after the introduction of treatment. Whether early TB death is associated with increased TB transmission is unknown. To determine the transmission risk attributable to early TB death we undertook a case-control study. Methods All adults who were: (1) diagnosed with culture-positive pulmonary TB in the Province of Alberta, Canada between 1996 and 2012, and (2) died a TB-related death before or within the first 60 days of treatment, were identified. For each of these “cases” two sets of “controls” were randomly selected from among culture-positive pulmonary TB cases that survived beyond 60 days of treatment. “Controls” were matched by age, sex, population group, +/- smear status. Secondary cases of “cases” and “controls” were identified using conventional and molecular epidemiologic tools and compared. In addition, new infections were identified and compared in contacts of “cases” that died before treatment and contacts of their smear-matched “controls”. Conditional logistic regression was used to find associations in both univariate and multivariate analysis. Results “Cases” were as, but not more, likely than “controls” to transmit. This was so whether transmission was measured in terms of the number of “cases” and smear-unmatched or -matched “controls” that had a secondary case, the number of secondary cases that they had or the number of new infections found in contacts of “cases” that died before treatment and their smear-matched “controls”. Conclusion In a low TB incidence/low HIV prevalence country, pulmonary TB patients that die a TB-related death before or in the initial phase of treatment and pulmonary TB patients that survive beyond the initial phase of treatment are equally likely to transmit.

A population-based study of tuberculosis case fatality in Canada: do Aboriginal peoples fare less well?

SETTING The Province of Alberta, Canada. OBJECTIVES To explore trends in tuberculosis (TB) case fatality, compare TB case-fatality rates by population group and determine prognostic factors associated with TB-related death in Alberta from 1996 to 2012. DESIGN Retrospective cohort analysis. RESULTS During the study years, all-cause TB case fatality fell from 10.7% to 6.3%; the fall was attributable to a change in population structure, as there were more foreign-born and fewer older cases with time. A stable 2% of TB cases died without treatment. Compared to other population groups, Canadian-born Aboriginal case patients were more likely to die without treatment and to die younger. Of TB deaths that were TB-related, 68.9% occurred before or during the initial phase of treatment; of these, TB was a contributory cause of death in 77.5%, i.e., another medical condition was the primary cause of death. In multivariate analysis, age >64 years, aboriginality and miliary/disseminated or central nervous system disease were independent predictors for TB-related death. CONCLUSION Preventive therapy for those with latent tuberculous infection and a high-risk medical condition, early diagnosis of disease, and special support of older, Aboriginal or comorbid cases, once diagnosed, are necessary to further minimise TB case fatality in Alberta, Canada.

Factors Associated with Noncompletion of Latent Tuberculosis Infection Treatment in an Inner-City Population in Edmonton, Alberta

One of the most useful strategies to control the spread of tuberculosis is treating latent tuberculosis infections. Certain populations at higher risk for tuberculosis infection, such as homeless individuals, are also at increased risk for treatment nonadherence. This article describes the treatment completion rate for latent tuberculosis infections at a health clinic in Edmonton, Alberta, including an assessment of the correlates of noncompletion as well as potential means to improve treatment adherence.

Assessment of linezolid efficacy, safety and tolerability in the treatment of tuberculosis: A retrospective case review.

Linezolid is a potentially effective drug for the treatment of patients with drug-resistant tuberculosis. Among 13 patients treated for tuberculosis with linezolid in the present study, nine had treatment success and four remain on treatment. Adverse effects occurred in 11 (85%) patients, of whom three discontinued treatment because of adverse effects. The present study adds to the growing evidence supporting the efficacy of linezolid for tuberculosis, although treatment remains complicated by adverse effects.

Probable interaction between levothyroxine and ritonavir: Case report and literature review

PURPOSE A case of probable interaction of levothyroxine and ritonavir is presented along with a review of the relevant literature and recommendations on clinical management. SUMMARY A 37-year-old woman with human immunodeficiency virus infection who had recently undergone thyroidectomy for a benign multinodular goiter presented to a clinic with hypothyroidism (she was also found to be pregnant), and treatment with levothyroxine 75 μg daily was initiated. While receiving antiretroviral therapy (abacavir-lamivudine and lopinavir-ritonavir) during pregnancy, the patient had persistently elevated serum thyroid-stimulating hormone (TSH) concentrations (up to 125.89 μIU/mL) despite gradual escalation of the levothyroxine dosage to 175 μg daily. An interaction between ritonavir and levothyroxine was suspected, and dolutegravir was substituted for lopinavir-ritonavir. Within 4 months, the TSH concentration had normalized. The daily levothyroxine dose was tapered over a 5-month period and stabilized at 125 μg, and TSH concentrations remained within the normal range over an 18-month follow-up period. Scoring of the case using the Drug Interaction Probability Scale yielded a score of 6 out of 11, indicating a probable interaction between levothyroxine and ritonavir. A literature search identified 4 reported cases of interactions involving levothyroxine and ritonavir. CONCLUSION A potentially serious and underrecognized drug interaction between ritonavir and levothyroxine was observed in a pregnant woman with postthyroidectomy-related hypothyroidism. This case and a review of other cases reported in the literature indicate that higher-than-usual doses of levothyroxine may be required in patients who are taking ritonavir concurrently.