Anchoring Bias, Lyme Disease, and the Diagnosis Conundrum.

Lyme disease remains the most common vector-borne disease in North America. This academic teaching case highlights a full diagnostic workup fueled by anchoring bias, resulting in a presumptive diagnosis of early disseminated Lyme meningitis. Patient report of direct tick exposure, neurocranial defects, and equivocal serologies, despite geographic region of low pretest probability, confounded the clinical picture. Infectious workup confirmed the true diagnosis to be aseptic meningitis due to enterovirus. This clinical vignette acknowledges the habitual anchoring biases in the daily decision-making among internists and trainees contributing to misdiagnoses and subsequently, overtreatment.

Influence of immune activation on the risk of allograft rejection in human immunodeficiency virus-infected kidney transplant recipients.

BACKGROUND: HIV infection is associated with high rates of acute rejection following kidney transplantation. The underlying mechanisms for such predisposition are incompletely understood. Pathological immune activation is a hallmark of chronic HIV infection that persists despite effective antiretroviral therapy. We hypothesized that the baseline levels of T cell activation in HIV(+) candidates would correlate with their risk of acute rejection following kidney transplantation. METHODS: Single-center retrospective cohort analysis of HIV(+) adult kidney transplants performed between October 2006 and September 2013. The frequency of CD3(+)HLA-DR(+) cells measured by flow cytometry served as a surrogate marker of immune activation. Patients were categorized into tertiles of activation, and the rates of biopsy-proven acute rejection were compared across groups. RESULTS: (1) Compared to matched HIV(-) controls, the baseline number of CD3(+)HLA-DR(+) cells was higher in HIV(+) kidney transplant candidates. (2) Abnormally high levels of activation did not decrease with transplant-associated immunosuppression. (3) Patients categorized within the lower and middle CD3(+)HLA-DR(+) tertiles had higher probability of rejection during the first 3years post-transplant compared to those in the higher activation tertile (36.9% vs. 0%; log-rank P=0.04). CONCLUSIONS: Pathological immune activation in HIV(+) transplant candidates does not explain their increased susceptibility to allograft rejection. Paradoxically, those with the highest levels of immune activation seem to be less prone to rejection.

Impact of antiretroviral therapy on clinical outcomes in HIV + kidney transplant recipients: Review of 58 cases.

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients.  We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV + kidney transplant recipients.  Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV - to HIV + adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation.  The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant.  Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% ( p=0.06) and 82% vs. 100% ( p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02).  Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01).  Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV + kidney transplant recipients.

Adverse Drug Reactions to Antiretroviral Therapy in HIV-Infected Patients at the Largest Public Hospital in Nicaragua.

OBJECTIVE: Adverse drug reactions (ADRs) to antiretroviral therapy (ART) are an important cause of hospitalization, treatment discontinuation, and regimen changes in both developed and developing countries. This study is the first to examine and understand ADRs in HIV-infected patients in Nicaragua. METHODS: A retrospective descriptive study was conducted from May 2010 to March 2011, in a cohort of HIV-infected patients receiving ART at the largest public hospital in Managua, Nicaragua. Patients were identified based on ADRs reporting on a standardized antiretroviral pharmacotherapy form. Subsequently, chart reviews of these patients were performed in order to document the specific ADRs. RESULTS: Six hundred ninety-two patients on ART were included. The incidence of ADRs was 6.4% (95% confidence interval [CI] 4.5-8.2). Females demonstrated a higher incidence, that is, 10.2% (95% CI 5.3-15.1, P = .020). Patients treated with combinations of zidovudine (ZDV)/lamivudine (3TC) and emtricitabine (FTC)/tenofovir (TDF) had fewer ADRs (P < .01) than those using other combinations. Five patients were hospitalized or had a prolonged hospitalization secondary to ADRs, with no mortality attributed to ADR. The most common manifestations of ADRs were central nervous system (20 of 44), gastrointestinal (12 of 44), and dermatologic (8 of 44) reactions. Adverse drug reactions were classified as "likely ADRs" (25 of 44) and "possible ADRs" (19 of 44). No ADRs were preventable. CONCLUSION: Adverse drug reactions most frequently affected the central nervous system. No ADR was life threatening. The frequency of ADRs in this Nicaraguan patient population was less than that reported from other studies in resource-limited settings.