Cody A. Chastain

Predicting outcomes of traumatic brain injury by imaging modality and injury distribution.

Early prediction of outcomes after traumatic brain injury (TBI) is often difficult. To improve prognostic accuracy soon after trauma, we compared different radiological modalities and anatomical injury distribution in a group of adult TBI patients. The four methods studied were computed tomography (CT), magnetic resonance imaging (MRI) with T2-weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR) imaging, and susceptibility weighted imaging (SWI). The objective of this study was to identify which modality and anatomic model best predict outcome. The patient population consisted of 38 adults admitted between February 2001 and May 2003. Early CT, T2WI, FLAIR, and SWI were obtained for each patient as well as a Glasgow Outcome Score (GOS) between 0.1 and 22 months (mean 9.2 months) after injury. Using a semi-automated computer method, intraparenchymal lesions were traced, measured, and converted to lesion volumes based on slice thickness and pixel size. Lesions were assigned to zones and regions. Outcomes were dichotomized into good (GOS 4-5) and poor (GOS 1-3) outcome groups. Brain injury detected by imaging was analyzed by median total lesion volume, median volume per lesion, and median number of lesions per outcome group. T2WI and FLAIR imaging most consistently discriminated between good and poor outcomes by median total lesion volume, median volume per lesion, and median number of lesions. In addition, T2WI and FLAIR imaging most consistently discriminated between good and poor outcomes by zonal distribution. While SWI rarely discriminated by outcome, it was very sensitive to intraparenchymal injury and its optimal use in evaluating TBI is unclear. SWI and other new imaging modalities should be further studied to fully evaluate their prognostic utility in TBI evaluation.

Comparison and temporal trends of three groups with cryptococcosis: HIV-infected, solid organ transplant, and HIV-negative/non-transplant.

Background The Infectious Disease Society of America (IDSA) 2010 Clinical Practice Guidelines for the management of cryptococcosis outlined three key populations at risk of disease: (1) HIV-infected, (2) transplant recipient, and (3) HIV-negative/non-transplant. However, direct comparisons of management, severity and outcomes of these groups have not been conducted. Methodology/Principal Findings Annual changes in frequency of cryptococcosis diagnoses, cryptococcosis-attributable mortality and mortality were captured. Differences examined between severe and non-severe disease within the context of the three groups included: demographics, symptoms, microbiology, clinical management and treatment. An average of nearly 15 patients per year presented at Duke University Medical Center (DUMC) with cryptococcosis. Out of 207 study patients, 86 (42%) were HIV-positive, 42 (20%) were transplant recipients, and 79 (38%) were HIV-negative/non-transplant. HIV-infected individuals had profound CD4 lymphocytopenia and a majority had elevated intracranial pressure. Transplant recipients commonly (38%) had renal dysfunction. Nearly one-quarter (24%) had their immunosuppressive regimens stopped or changed. The HIV-negative/non-transplant population reported longer duration of symptoms than HIV-positive or transplant recipients and 28% (22/79) had liver insufficiency or underlying hematological malignancies. HIV-positive and HIV-negative/non-transplant patients accounted for 89% of severe disease cryptococcosis-attributable deaths and 86% of all-cause mortality. Conclusions/Significance In this single-center study, the frequency of cryptococcosis did not change in the last two decades, although the underlying case mix shifted (fewer HIV-positive cases, stable transplant cases, more cases with neither). Cryptococcosis had a relatively uniform and informed treatment strategy, but disease-attributable mortality was still common.

Transforaminal Lumbar Interbody Fusion: A Retrospective Study of Long-term Pain Relief and Fusion Outcomes

No long-term studies exist on the effectiveness of transforaminal lumbar interbody fusion. This study sought to determine postoperative pain, disability, and fusion status of transforaminal lumbar interbody fusion patients after > or = 4 years to establish long-term outcomes. A retrospective analysis of 42 patients with minimum 4-year follow-up was conducted. Patients completed visual analog pain scale (VAS) and Oswestry functional capacity evaluation pre- and postoperatively. Statistically significant improvement was noted in VAS and Oswestry functional capacity evaluation scores. Transforaminal lumbar interbody fusion is effective in alleviating intractable back pain over an extended time period. Solid radiographic fusion is unnecessary for clinically successful outcomes.

Approaches to Antifungal Therapies and Their Effectiveness among Patients with Cryptococcosis

ABSTRACT The goal of this study was to determine the degree to which the persistence of cryptococcosis, overall 1-year mortality, and 1-year mortality due to cryptococcosis were influenced by initial antifungal treatment regimen in a cohort of adults with cryptococcosis treated at a tertiary care medical center. Risk factors, underlying conditions, treatment, and mortality information were obtained for 204 adults with cryptococcosis from Duke University Medical Center (DUMC) from 1996 to 2009. Adjusted risk ratios (RR) for persistence and hazard ratios (HR) for mortality were estimated for each exposure. The all-cause mortality rate among patients with nonsevere disease (20%) was similar to that in the group with disease (26%). However, the rate of cryptococcosis-attributable mortality with nonsevere disease (5%) was much lower than with severe disease (20%). Flucytosine exposure was associated with a lower overall mortality rate (HR, 0.4; 95% confidence interval [CI], 0.2 to 0.9) and attributable mortality rate (HR, 0.5; 95% CI, 0.2 to 1.2). Receiving a nonrecommended antifungal regimen was associated with a higher relative risk of persistent infection at 4 weeks (RR, 1.9; 95% CI, 0.9 to 4.3), and the rate of attributable mortality among those not receiving the recommended dose of initial therapy was higher than that of those receiving recommended dosing (HR, 2.3; 95% CI, 1.0 to 5.0). Thus, the 2010 Infectious Diseases Society of America (IDSA) guidelines are supported by this retrospective review as a best-practice protocol for cryptococcal management. Future investigations should consider highlighting the distinction between all-cause mortality and attributable mortality so as not to overestimate the true effect of cryptococcosis on patient death.

Treatment of genotype 1 HCV infection in the HIV coinfected patient in 2014.

Hepatitis C (HCV) coinfection is the leading cause of liver-related morbidity and is a leading cause of mortality in human immunodeficiency virus (HIV)-infected individuals in the antiretroviral therapy era. Direct-acting antiviral (DAA) therapies are transforming how HCV is treated with significant improvements in efficacy and tolerability. In this article, DAA agents expected to be available in 2014 are reviewed, including telaprevir, boceprevir, sofosbuvir, simeprevir, faldaprevir, and daclatasvir. Available data regarding clinical efficacy, adverse effects, and drug interactions in HIV-HCV coinfection are discussed. The management of adverse effects of HCV therapy and treatment considerations in patients with cirrhosis are also reviewed.

Community-Acquired Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infections: Management and Prevention

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was a rare phenomenon until the past decade; now CA-MRSA is endemic in many communities and is the most common cause of skin and soft tissue infections presenting to emergency rooms. CA-MRSA is distinct from its hospital-acquired counterpart, and has caused devastating infections in many healthy individuals. The epidemiology of CA-MRSA continues to evolve, and the challenge is to use the most appropriate and effective therapeutic and preventative strategies against this pathogen. This article reviews the current epidemiology of CA-MRSA, its definitions, and common clinical manifestations in the community. The article also summarizes current therapeutic options for CA-MRSA as well as strategies to reduce the transmission and the impact of CA-MRSA in both community and health care settings.

Iatrogenic Cushing Syndrome Secondary to a Probable Interaction Between Voriconazole and Budesonide

Oral budesonide is commonly used for the management of Crohns disease given its high affinity for glucocorticoid receptors and low systemic activity due to extensive first‐pass metabolism through hepatic cytochrome P450 (CYP) 3A4. Voriconazole, a second‐generation triazole antifungal agent, is both a substrate and potent inhibitor of CYP isoenzymes, specifically CYP2C19, CYP2C9, and CYP3A4; thus, the potential for drug‐drug interactions with voriconazole is high. To our knowledge, drug‐drug interactions between voriconazole and corticosteroids have not been specifically reported in the literature. We describe a 48‐year‐old woman who was receiving oral budesonide 9 mg/day for the management of Crohns disease and was diagnosed with fluconazole‐resistant Candida albicans esophagitis; oral voriconazole 200 mg every 12 hours for 3 weeks was prescribed for treatment. Because the patient experienced recurrent symptoms of dysphagia, a second 3‐week course of voriconazole therapy was taken. Seven weeks after originally being prescribed voriconazole, she came to her primary care clinic with elevated blood pressure, lower extremity edema, and weight gain; she was prescribed a diuretic and evaluated for renal dysfunction. At a follow‐up visit 6 weeks later with her specialty clinic, the patients blood pressure was elevated, and her physical examination was notable for moon facies, posterior cervical fat pad prominence, and lower extremity pitting edema. Iatrogenic Cushing syndrome due to a drug‐drug interaction between voriconazole and budesonide was suspected, and voriconazole was discontinued. Budesonide was continued as previously prescribed for her Crohns disease. On reevaluation 2 months later, the patients Cushingoid features had markedly regressed. To our knowledge, this is the first published case report of iatrogenic Cushing syndrome due to a probable interaction between voriconazole and oral budesonide. In patients presenting with Cushingoid features who have received these drugs concomitantly, clinicians should consider the potential drug interaction between these agents, and the risks and benefits of continued therapy must be considered.

Hepatitis C Management and the Infectious Diseases Physician: A Survey of Current and Anticipated Practice Patterns

This query of North American infectious diseases physicians reviews current and anticipated practice patterns related to hepatitis C virus (HCV) care. Less than 20% of survey respondents evaluated and/or treated >10 HCV-infected individuals in the past year. We review HCV practice patterns, barriers to management, and education among infectious diseases physicians.

Increasing success and evolving barriers in the hepatitis C cascade of care during the direct acting antiviral era

Barriers remain in the hepatitis C virus (HCV) cascade of care (CoC), limiting the overall impact of direct acting antivirals. This study examines movement between the stages of the HCV CoC and identifies reasons why patients and specific patient populations fail to advance through care in a real world population. We performed a single-center, ambispective cohort study of patients receiving care in an outpatient infectious diseases clinic between October 2015 and September 2016. Patients were followed from treatment referral through sustained virologic response. Univariate and multivariate analyses were performed to identify factors related to completion of each step of the CoC. Of 187 patients meeting inclusion criteria, 120 (64%) completed an evaluation for HCV treatment, 119 (64%) were prescribed treatment, 114 (61%) were approved for treatment, 113 (60%) initiated treatment, 107 (57%) completed treatment, and 100 (53%) achieved a sustained virologic response. In univariate and multivariate analyses, patients with Medicaid insurance were less likely to complete an evaluation and were less likely to be approved for treatment. Treatment completion and SVR rates are much improved from historical CoC reports. However, linkage to care following referral continues to be a formidable challenge for the HCV CoC in the DAA era. Ongoing efforts should focus on linkage to care to capitalize on DAA treatment advances and improving access for patients with Medicaid insurance.

Retreatment Options Following HCV Direct-Acting Antiviral Failure

Opinion StatementDespite the excellent efficacy of direct-acting antivirals (DAA) for hepatitis C virus (HCV), treatment failures do occur. Until recently, retreatment decisions after DAA failure were influenced by the number of available agents, concerns about HCV drug resistance, and lack of data regarding retreatment. Recommended treatment approaches previously depended on limited clinical trials and expert opinion. In this article, we review the current state of the evidence for HCV retreatment after DAA failure. Based on recent clinical trial data, most patients who fail HCV treatment with DAA agents now have excellent retreatment options. While some patients may benefit from resistance testing after DAA therapy failure to select the optimal treatment and duration, newly approved salvage therapies are not significantly impacted by common mutations and have been approved by the Food and Drug Administration for HCV retreatment without regard for the presence of resistance-associated substitutions. While prior retreatment efforts were limited to longer courses of therapy, the addition of ribavirin, or novel combinations of approved therapies based on expert guidance, current DAA options make HCV retreatment in the DAA era more streamlined and evidence-based.