Stephen Symes

Pharmacokinetic Evaluation of Rifabutin in Combination with Lopinavir-Ritonavir in Patients with HIV Infection and Active Tuberculosis

BACKGROUND Human immunodeficiency virus (HIV)-associated tuberculosis is difficult to treat, given the propensity for drug interactions between the rifamycins and the antiretroviral drugs. We examined the pharmacokinetics of rifabutin before and after the addition of lopinavir-ritonavir. METHODS We analyzed 10 patients with HIV infection and active tuberculosis in a state tuberculosis hospital. Plasma was collected for measurement of rifabutin, the microbiologically active 25-desacetyl-rifabutin, and lopinavir by validated high-performance liquid chromatography assays. Samples were collected 2-4 weeks after starting rifabutin at 300 mg thrice weekly without lopinavir-ritonavir, 2 weeks after the addition of lopinavir-ritonavir at 400 and 100 mg, respectively, twice daily to rifabutin at 150 mg thrice weekly, and (if rifabutin plasma concentrations were below the normal range) 2 weeks after an increase in rifabutin to 300 mg thrice weekly with lopinavir-ritonavir. Noncompartmental and population pharmacokinetic analyses (2-compartment open model) were performed. RESULTS Rifabutin at 300 mg without lopinavir-ritonavir produced a low maximum plasma concentration (C(max)) in 5 of 10 patients. After the addition of lopinavir-ritonavir to rifabutin at 150 mg, 9 of 10 had low C(max) values. Eight patients had dose increases to 300 mg of rifabutin with lopinavir-ritonavir. Most free rifabutin (unbound to plasma protein) C(max) values were below the tuberculosis minimal inhibitory concentration. For most patients, values for the area under the plasma concentration-time curve were as low or lower than those associated with treatment failure or relapse and with acquired rifamycin resistance in Tuberculosis Trials Consortium/US Public Health Service Study 23. One of the 10 patients experienced relapse with acquired rifamycin resistance. CONCLUSION The recommended rifabutin doses for use with lopinavir-ritonavir may be inadequate in many patients. Monitoring of plasma concentrations is recommended.

Can community health workers improve adherence to highly active antiretroviral therapy in the USA? A review of the literature.

Highly active antiretroviral therapy (HAART) has transformed HIV infection into a manageable chronic illness, yet AIDS mortality among ethnic minorities persists in the USA. HAART nonadherence is associated with increased HIV viral load, low CD4 cell count and racial disparities in HIV outcomes. While there is no universal consensus on how to improve medical adherence in HIV‐positive populations, the community health worker (CHW) model is emerging as an effective strategy to overcome barriers to HAART adherence. Although utilized in international settings, there is little evidence regarding the effects of CHWs on HIV outcomes in the USA.

The Script Concordance Test as a Measure of Clinical Reasoning Skills in Geriatric Urinary Incontinence

OBJECTIVES: To validate the use of a script concordance test (SCT), a tool to assess clinical reasoning in contexts of uncertainty, which are common in clinical geriatrics practice, on geriatric urinary incontinence (UI) to discriminate levels of expertise in this content area.

Localized Mycobacterium avium complex infection of vertebral and paravertebral structures in an HIV patient on highly active antiretroviral therapy.

Before the introduction of highly active antiretroviral therapy (HAART) Mycobacterium avium complex (MAC) disease was the most common bacterial infection in patients with acquired immune deficiency syndrome (AIDS) in developed countries. Effective antiviral therapy against HIV has allowed for control of viral replication, improvement in immune function, and a significant decrease in opportunistic infections (OIs). However, atypical presentations of these infections have been increasingly described in patients a few weeks after the initiation of HAART. This clinical worsening despite decrease in HIV viral load and increase in CD4 lymphocyte cell count is called immune reconstitution syndrome (IRS). We report a case of localized vertebral and paravertebral MAC infection in an HIVinfected patient with high CD4 lymphocyte counts, more than one year after starting antiretroviral therapy.

Predictors of Scholarly Success among Internal Medicine Residents

AAIM is the largest academically focused specialty organization representing departments of internal medicine at medical schools and teaching hospitals in the United States and Canada. As a consortium of five organizations, AAIM represents department chairs and chiefs; clerkship, residency, and fellowship program directors; division chiefs; and academic and business administrators as well as other faculty and staff in departments of internal medicine and their divisions. s

Determinants of Default from Tuberculosis Treatment among Patients with Drug-Susceptible Tuberculosis in Karachi, Pakistan: A Mixed Methods Study

Purpose Non-adherence to tuberculosis therapy can lead to drug resistance, prolonged infectiousness, and death; therefore, understanding what causes treatment default is important. Pakistan has one of the highest burdens of tuberculosis in the world, yet there have been no qualitative studies in Pakistan that have specifically examined why default occurs. We conducted a mixed methods study at a tuberculosis clinic in Karachi to understand why patients with drug-susceptible tuberculosis default from treatment, and to identify factors associated with default. Patients attending this clinic pick up medications weekly and undergo family-supported directly observed therapy. Methods In-depth interviews were administered to 21 patients who had defaulted. We also compared patients who defaulted with those who were cured, had completed, or had failed treatment in 2013. Results Qualitative analyses showed the most common reasons for default were the financial burden of treatment, and medication side effects and beliefs. The influence of finances on other causes of default was also prominent, as was concern about the effect of treatment on family members. In quantitative analysis, of 2120 patients, 301 (14.2%) defaulted. Univariate analysis found that male gender (OR: 1.34, 95% CI: 1.04–1.71), being 35–59 years of age (OR: 1.54, 95% CI: 1.14–2.08), or being 60 years of age or older (OR: 1.84, 95% CI: 1.17–2.88) were associated with default. After adjusting for gender, disease site, and patient category, being 35–59 years of age (aOR: 1.49, 95% CI: 1.10–2.03) or 60 years of age or older (aOR: 1.76, 95% CI: 1.12–2.77) were associated with default. Conclusions In multivariate analysis age was the only variable associated with default. This lack of identifiable risk factors and our qualitative findings imply that default is complex and often due to extrinsic and medication-related factors. More tolerable medications, improved side effect management, and innovative cost-reduction measures are needed to reduce default from tuberculosis treatment.

Education Research: Can my electronic health record teach me something? A multi-institutional pilot study

On average, 4 clinical questions arise per patient encounter1 and about half the time, information needs are left unresolved.2 There is significant interest in capturing, sharing, and using knowledge within the daily work of health professionals in order to improve health outcomes. The 2009 Health Information Technology for Economic and Clinical Health (HITECH) Act offers up to

Pulmonary embolism in patients with acquired immunodeficiency syndrome presenting with clinical picture of Pneumocystis jiroveci pneumonia: Report of two cases

27 billion over 10 years to providers demonstrating “meaningful use” of electronic health records (EHRs).3 “Meaningful use” implies more than just recording information; use of the EHR should improve patient care.

A case illustration about the importance of integrating women's anal health in an HIV primary care clinic.

cerebral malignancies. We therefore feel convinced that this patient had ADEM, supported by the clinical response to corticosteroid therapy. At the time of presentation the patient had already fully seroconverted and there is no negative HIV test available within the previous 6 months. Therefore, the patient does not strictly fulfil the definition of primary HIV infection, namely detectable HIV-RNA or p24-antigen concomitant with negative or inconclusive HIV serology, or alternatively, evidence of seroconversion within the last 6 months [10]. However the clinical history with sexual exposure followed within 4 to 5 weeks by a febrile illness and subsequently after 1 month a positive HIV test with very high viral loads in both plasma and CSF as well as high CD4 count is fully compatible with and highly suggestive of primary HIV infection and very recent seroconversion. We therefore believe that this patient did have ADEM triggered by primary HIV infection, although it cannot be excluded that the patient had chronic HIV infection and ADEM caused by another infectious agent. In conclusion, we suggest that ADEM might be a possible, although rare, manifestation of primary HIV infection, and that ADEM should be considered among the multiple differential diagnoses in an HIV-infected patient presenting with neurological symptoms. References

Transforming invasive bedside procedural instruction

A 49-year-old African American woman (S.A.) has been receiving HIV specialty and primary care in an urban hospital-based adult HIVoutpatient clinic since 2001. She has also been followed by colorectal surgery and HIV gynecology clinics. Her social history includes a 45-pack/year tobacco habit and crack cocaine use since 1982, but she has denied alcohol use. S.A. presented to the emergency room in March 1997 with shortness of breath, and the hospital admitted her with presumptive Pneumocystis jiroveci pneumonia. She tested positive for HIVinfection, and her CD41 T cell count was 7 cells/mm 3 . Her surgical history was significant for a Bartholin cyst incision and drainage 15 years prior. Her discharge medications included sulfamethoxazole/trimethoprim and azithromycin with a follow-up appointment in the adult HIV clinic scheduled for 2 weeks later; she was not started or discharged on antiretroviral therapy (ART). She failed to follow up in the adult HIVoutpatient clinic but was subsequently admitted in 1998 for orbital cellulitis and cytomegalovirus retinitis with blindness, and in 1999 for seizures, at which time she was diagnosed with cryptococcol meningitis. The last admission note indicated that the patient had not taken her ART in 5 months; however, the names of the medications that she was previously on were not specified. S.A. was lost to follow-up until July 2001 when she was brought to the emergency room from