Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients With Heart Failure.

BACKGROUND: Mesenchymal precursor cells (MPCs) are allogeneic, immunoselected cells with anti-inflammatory properties that could improve outcomes in heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: This study assessed the efficacy and safety of MPCs in patients with high-risk HFrEF. METHODS: This randomized, double-blind, multicenter study evaluated a single transendocardial administration procedure of MPCs or sham-control in 565 intention-to-treat patients with HFrEF on guideline-directed therapies. The primary endpoint was time-to-recurrent events caused by decompensated HFrEF or successfully resuscitated symptomatic ventricular arrhythmias. Hierarchical secondary endpoints included components of the primary endpoint, time-to-first terminal cardiac events, and all-cause death. Separate and composite major adverse cardiovascular events analyses were performed for myocardial infarction or stroke or cardiovascular death. Baseline and 12-month echocardiography was performed. Baseline plasma high-sensitivity C-reactive protein levels were evaluated for disease severity. RESULTS: The primary endpoint was similar between treatment groups (HR: 1.17; 95% CI: 0.81-1.69; P = 0.41) as were terminal cardiac events and secondary endpoints. Compared with control subjects, MPCs increased left ventricular ejection fraction from baseline to 12 months, especially in patients with inflammation. MPCs decreased the risk of myocardial infarction or stroke by 58% (HR: 0.42; 95% CI: 0.23-0.76) and the risk of 3-point major adverse cardiovascular events by 28% (HR: 0.72; 95% CI: 0.51-1.03) in the analysis population (n = 537), and by 75% (HR: 0.25; 95% CI: 0.09-0.66) and 38% (HR: 0.62; 95% CI: 0.39-1.00), respectively, in patients with inflammation (baseline high-sensitivity C-reactive protein ≥2 mg/L). CONCLUSIONS: The primary and secondary endpoints of the trial were negative. Positive signals in prespecified, and post hoc exploratory analyses suggest MPCs may improve outcomes, especially in patients with inflammation.

Low-level viremia associated with the use of TaqMan assay.

Poor correlation has been reported between the Roche Cobas AmpliPrep/Cobas (TaqMan) HIV-1 TaqMan assay and the Roche Cobas Amplicor HIV-1 Monitor version 1.5 Amplicor assay. We report 8 patients who experienced unexplained detectable viremia, despite exemplary medication adherence, following a change in viral quantification assay from Amplicor to TaqMan in January 2008. All patients were found to have undetectable HIV RNA by branched DNA (bDNA) assay.

Prevalence of antiretroviral drug resistance in antiretroviral-naive individuals.

Transmitted antiretroviral drug resistance has been an ongoing consideration even in patients who are treatment naive. The authors retrospectively selected all eligible patients from a US-based urban HIV clinic who had a genotypic resistance assay performed prior to the initiation of antiretroviral therapy. Clinically significant resistance was detected in 8% of assays, and was comparable when stratified by duration of time from diagnosis to genotypic resistance assay.

Sulfadiazine-induced nephrolithiasis detected by spiral CT scan.

Nephrolithiasis is a known complication of the use of sulfadiazine in the treatment of cerebral toxoplasmosis. Radiographic diagnosis of this complication has historically been challenging. Between March 1999 and June 2002, 11 patients were treated for cerebral toxoplasmosis with sulfadiazine-containing therapy. Four of these patients (36.4%) developed nephrolithiasis during this period. Case patients had received sulfadiazine for a median of 35.5 days prior to nephrolithiasis. All cases were diagnosed by spiral CT scans. Although studies are needed to evaluate the sensitivity and specificity of this modality, spiral CT may aid in the diagnosis of sulfadiazine-induced nephrolithiasis.

Tenofovir-related nephrotoxicity: case report and review of the literature.

Tenofovir is a nucleotide reverse transcriptase inhibitor for treatment of human immunodeficiency virus (HIV) infection. Several cases of renal failure associated with tenofovir therapy recently have been reported. A 54-year-old man with HIV experienced decreasing renal function and Fanconi's syndrome secondary to tenofovir therapy. His condition gradually improved after discontinuation of the drug. The available medical literature for reported cases of tenofovir-related nephrotoxicity indicates that this complication is apparently rare. However, our case report and literature review underscore the importance of monitoring renal function when treating patients with any nucleotide reverse transcriptase inhibitor.

Smoking cessation: pharmacists helping patients kick the habit.

Nicotine is just as habit forming as "harder" drugs, and more deaths occur due to tobacco than other substances of abuse. Several treatments are available for pharmacists to recommend or dispense to patients attempting to stop smoking. The health benefits of quitting tobacco far outweigh the potential obstacles when beginning a smoking-cessation program. Pharmacists need to evaluate patients and their level of commitment to the program, provide education about behavioral modification, and follow-up with patients to support their efforts to quit smoking.

Enfuvirtide: a novel agent for the treatment of HIV-1 infection.

OBJECTIVE: To review the pharmacology, virology, pharmacokinetics, efficacy, safety, and clinical use of enfuvirtide. DATA SOURCES: English-language MEDLINE and AIDSline searches were performed (1966-January 2003) using enfuvirtide, T-20, gp41, and fusion inhibitors as key words. Abstracts from infectious diseases and HIV scientific meetings were identified. DATA EXTRACTION: All publications and meeting abstracts were reviewed and relevant items included. In vitro and preclinical studies were included, as well as Phase II and III clinical trials. DATA SYNTHESIS: Enfuvirtide is a fusion inhibitor used for the treatment of HIV-1 infection. Given its unique mechanism of action, most HIV-1 isolates are susceptible to enfuvirtide. Enfuvirtide is administered by subcutaneous injection twice daily. In clinical trials with antiretroviral-experienced patients, enfuvirtide was effective at suppressing HIV-RNA and increasing CD4+ T-cell counts. Enfuvirtide should be used in combination with other active antiretroviral agents to optimize its efficacy and limit resistance. Injection site reactions associated with administration of the drug are experienced in the majority of patients. Availability of enfuvirtide may be limited by a complex manufacturing procedure. CONCLUSIONS: Enfuvirtide is an effective treatment option for HIV-1-infected individuals when used in combination with other antiretroviral agents. It may be used as part of a regimen for treatment-experienced patients.

Survey of patient and clinician attitudes on adherence in a rural HIV clinic.

Adherence is critical to the success of antiretroviral therapy, with near perfect medication taking required for optimal results. Many factors may affect a patient's ability to adhere to antiretroviral therapy, including complexity of the regimen and adverse effects from medications. Previous research showed that some disparity may exist between clinicians' and patients' attitudes regarding characteristics of a regimen that are likely to affect adherence. The present survey was conducted in a rural HIV clinic and confirmed that similar differences were present in clinician and patient perceptions of adherence barriers. The patient population noted side effects and complexity of schedule as most likely to affect adherence, illustrating the need for thorough discussion of new regimens and involvement of the patient in treatment decisions.

Unusual presentations of primary human immunodeficiency virus infection.

Opportunistic infections during primary infection with human immunodeficiency virus (HIV) are rare, with the exception of oral and esophageal candidiasis. HIV-associated nephropathy (HIVAN) and Pneumocystis carinii pneumonia (PCP) typically occur during advanced HIV infection. We report two patients who developed HIVAN and a presumptive diagnosis of PCP, respectively, during primary HIV infection. Serologic testing demonstrated HIV seroconversion. Clinicians need to have a high index of suspicion when evaluating patients even when risk behaviors are not readily apparent.

Sexual dysfunction secondary to gemfibrozil.

Hypertriglyceridemia is a well-recognized complication of protease inhibitor therapy, specifically ritonavir. Fibrate derivatives are recommended as first-line therapy for isolated triglyceride elevations, and gemfibrozil has been successful for managing protease inhibitor-induced lipid changes. A 35-year-old man experienced sexual dysfunction 3 weeks after starting gemfibrozil. The temporal relationship and improvement in sexual function after the drug was discontinued suggest that gemfibrozil may have been responsible for his sexual dysfunction.