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Niewoehner D.,Minneapolis VA Health Care System | Niewoehner D.,University of Minnesota | Collins G.,University of Minnesota | Nixon D.,Virginia Commonwealth University | And 6 more authors.
HIV Medicine | Year: 2015

Objectives: The aim of the study was to describe the prevalence and correlates of chronic obstructive pulmonary disease (COPD) in a multicentre international cohort of persons living with HIV (PLWH). Methods: We performed a cross-sectional analysis of adult PLWH, naïve to HIV treatment, with baseline CD4 cell count >500 cells/μL enrolled in the Pulmonary Substudy of the Strategic Timing of AntiRetroviral Treatment (START) trial. We collected standardized, quality-controlled spirometry. COPD was defined as forced expiratory volume in 1s:forced vital capacity (FEV1:FVC) ratio less than the lower limit of normal. Results: Among 1026 participants from 80 sites and 20 countries, the median age was 36 [interquartile range (IQR) 30, 44] years, 29% were female, and the median time since HIV diagnosis was 1.2 (IQR 0.4, 3.5) years. Baseline median CD4 cell count was 648 (IQR 583, 767) cells/μL, median viral load was 4.2 (IQR 3.5, 4.7) log10 HIV-1 RNA copies/mL, and 10% had a viral load ≤400 copies/mL despite lack of HIV treatment. Current/former/never smokers comprised 28%/11%/61% of the cohort, respectively. COPD was present in 6.8% of participants, and varied by age, smoking status and region. Forty-eight per cent of those with COPD reported lifelong nonsmoking. In multivariable regression, age and pack-years of smoking had the strongest associations with FEV1:FVC ratio (P<0.0001). There was a significant effect of region on FEV1:FVC ratio (P=0.010). Conclusions: Our data suggest that, among PLWH who were naïve to HIV treatment and had CD4 cell counts >500 cells/μL, smoking and age were important factors related to COPD. Smoking cessation should remain a high global priority for clinical care and research in PLWH. © 2015 British HIV Association. Source


Lee M.,TU Munich | Eyer F.,TU Munich | Felgenhauer N.,TU Munich | Klinker H.H.F.,University of Wuerzburg Medical Center | Spinner C.D.,TU Munich
AIDS Research and Therapy | Year: 2015

A 21 year old MSM patient with newly diagnosed HIV infection was hospitalized in our department after ingestion of an overdose of his antiretroviral therapy (ART) comprising dolutegravir (DTG - Tivicay®) and tenofovir disaproxil fumarate/emtricitabine (Truvada®) in suicidal intention. On admission, the patient did not show any clinical signs of intoxication and laboratory findings were unremarkable. After 6 hours of intensive care monitoring, the patient was referred to a psychiatric clinic. 5 days after the day of intoxication, serum creatinine levels increased to high normal values (1.2 mg/dl). However, levels never exceeded the upper threshold. 8 and 12 weeks later, serum creatinine normalized to levels measured prior to the intoxication. No other adverse events occurred, and the patient does not suffer from permanent impairments. © 2015 Lee et al.; licensee BioMed Central. Source


Heinz W.J.,University of Wuerzburg Medical Center | Egerer G.,University of Heidelberg | Lellek H.,University of Hamburg | Boehme A.,Onkologikum Frankfurt am Museumsufer | Greiner J.,University of Ulm
Mycoses | Year: 2013

Invasive aspergillosis is an important cause of morbidity and mortality in haematological patients. Current guidelines recommend voriconazole as first-line therapy. A change in class of antifungal agent is generally recommended for salvage therapy. The focus of this analysis was to assess if posaconazole is suitable for salvage therapy following voriconazole treatment. This was a retrospective investigation on patients with sequential antifungal therapy of posaconazole after voriconazole identified at four German hospitals. Response rates at 30 and 60days following start of posaconazole application and toxicity of azoles by comparing liver enzymes and cholestasis parameters were evaluated. Data were analysed by descriptive statistics. Overall, the success rate was 72.2% [15 of 36 patients showed complete response (41.7%), 11 patients partial response (30.6%) at any time point], eight patients failed treatment and two were not evaluable. Mean laboratory values increased during voriconazole and decreased during posaconazole treatment: aspartate aminotransferase (increase: 31.9Ul-1 vs. decrease: 19.6Ul-1), alanine aminotransferase (32.4Ul-1 vs. 19.8Ul-1), gamma-glutamyl transferase (124.2Ul-1 vs. 152.3Ul-1) and alkaline phosphatase (71.5Ul-1 vs. 40.3Ul-1) respectively. No patient discontinued posaconazole therapy due to an adverse event. In this analysis posaconazole was a safe and effective antifungal salvage therapy in patients with prior administration of another triazole. © 2012 Blackwell Verlag GmbH. Source


Heinz W.J.,University of Wuerzburg Medical Center | Silling G.,University of Munster | Bohme A.,ONKOLOGIKUM
Current Medical Research and Opinion | Year: 2011

Objective: Invasive fungal infections (IFIs) are an important cause of morbidity and mortality, particularly in patients with cancer. The triazole voriconazole, given as oral or intravenous formulation, has a high bioavailability and proven efficacy against invasive aspergillosis, candidiasis and other fungi. We aimed to assess the utilisation, efficacy and safety of voriconazole with emphasis on the route of administration under standard clinical conditions. Methods: Prospective, observational study performed by 17 hospitals and office-based physicians in Germany. Results: A total of 264 patients received oral (53) or intravenous (22) voriconazole or both formulations sequentially (25). Of 228 patients with specified fungal diagnosis, 95 (36.0) had aspergillosis, 73 (27.7) candidiasis. Sixty (22.7) received voriconazole for other fungal indications (OFI). In 195 of 226 patients (86.2), treatment was successful (39.8 cured and 46.5 partial response). In terms of primary diagnoses, favourable responses were noted in 90 for pulmonary aspergillosis, 85 for candidiasis and 87 for OFI. Microbiological success was documented in 138 patients, of whom 105 (76.1) had complete eradication of fungi. Response rates by initial route were similar for oral and intravenous administration (86 and 87). Twenty-six of 264 patients died during the study, 53 patients experienced a serious adverse event (five treatment related), and 10 withdrew due to all-causality adverse events (AEs). Tolerability was assessed as very good in 55, and good in 40 of patients. Conclusions: Voriconazole as oral or intravenous formulation was well tolerated and equally effective in critically ill patients with IFIs. This study in daily care confirms the outcomes of controlled clinical trials. © 2011 Informa UK Ltd All rights reserved. Source


Schwab K.S.,University of Bonn | Hahn-Ast C.,University of Bonn | Heinz W.J.,University of Wuerzburg Medical Center | Germing U.,Heinrich Heine University Dusseldorf | And 7 more authors.
Infection | Year: 2014

Objectives: Tigecycline (TGC) is a first-in-class glycylcycline with an expanded spectrum of activity. Although TGC has not been prospectively studied in febrile neutropenia (FN), we observed that occasionally critically ill neutropenic patients unresponsive to other antibiotics were treated with TGC in our departments. The aim of our study was to analyse effectiveness and toxicity of TGC in FN. Methods: Data of infectious episodes treated with TGC were retrospectively collected. Baseline data of patients, haematological malignancy, infection and adverse events were documented. Success was defined as defervescence (≥7 days) in the absence of any sign of persistent infection. Results Data of 35 patients with haematological malignancies and FN were evaluated. Median duration of neutropenia was 25 days (range 6-69 days). The type of infection was pneumonia in 24 patients, four microbiologically documented infections, three clinically documented infections and four with fever of unknown origin. The TGC was administered after a median of two (range 1-5) prior antibiotic regimens. Treatment was successful in 15 (43%) patients. In patients with prolonged neutropenia (≥28 days), response was significantly lower (13 vs. 79%; p = 0.001). Eight (23%) patients died during the fever episode. Grade 3-4 toxicity occurred in five (14%) patients. Conclusion: Our results showed promising response rates to TGC and very low toxicity rates compared to the generally low response rate of third-line antibiotic therapies, indicating that TGC may be a successful alternative for salvage treatment of febrile neutropenia, but further study is needed. © Springer-Verlag 2013. Source

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