782 research outputs found
Discontinuation of secondary prophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection who have a response to antiretroviral therapy
No full textBackground: Patients with human immunodeficiency virus (HIV) infection and a history of Pneumocystis carinii pneumonia are at high risk for relapse if they are not given secondary prophylaxis. Whether secondary prophylaxis against P. carinii pneumonia can be safely discontinued in patients who have a response to highly active antiretroviral therapy is not known.
Methods: We analyzed episodes of recurrent P. carinii pneumonia in 325 HIV-infected patients (275 men and 50 women) in eight prospective European cohorts. Between October 1996 and January 2000, these patients discontinued secondary prophylaxis during treatment with at least three anti-HIV drugs after they had at least one peripheral-blood CD4 cell count of more than 200 cells per cubic millimeter.
Results: Secondary prophylaxis was discontinued at a median CD4 cell count of 350 per cubic millimeter; the median nadir CD4 cell count had been 50 per cubic millimeter. The median duration of the increase in the CD4 cell count to more than 200 per cubic millimeter after discontinuation of secondary prophylaxis was 11 months. The median follow-up period after discontinuation of secondary prophylaxis was 13 months, yielding a total of 374 person-years of follow-up; for 355 of these person-years, CD4 cell counts remained at or above 200 per cubic millimeter. No cases of recurrent P. carinii pneumonia were diagnosed during this period; the incidence was thus 0 per 100 patient-years (99 percent confidence interval, 0 to 1.2 per 100 patient-years, on the basis of the entire follow-up period, and 0 to 1.3 per 100 patient-years, on the basis of the follow-up period during which CD4 cell counts remained at or above 200 per cubic millimeter).
Conclusions: It is safe to discontinue secondary prophylaxis against P. carinii pneumonia in patients with HIV infection who have an immunologic response to highly active antiretroviral therapy
The Time Window for Generation of Dendritic Spikes by Coincidence of Action Potentials and EPSPs is Layer Specific in Somatosensory Cortex
No full textThe precise timing of events in the brain has consequences for intracellular processes, synaptic plasticity, integration and network behaviour. Pyramidal neurons, the most widespread excitatory neuron of the neocortex have multiple spike initiation zones, which interact via dendritic and somatic spikes actively propagating in all directions within the dendritic tree. For these neurons, therefore, both the location and timing of synaptic inputs are critical. The time window for which the backpropagating action potential can influence dendritic spike generation has been extensively studied in layer 5 neocortical pyramidal neurons of rat somatosensory cortex. Here, we re-examine this coincidence detection window for pyramidal cell types across the rat somatosensory cortex in layers 2/3, 5 and 6. We find that the time-window for optimal interaction is widest and shifted in layer 5 pyramidal neurons relative to cells in layers 6 and 2/3. Inputs arriving at the same time and locations will therefore differentially affect spike-timing dependent processes in the different classes of pyramidal neurons.© 2012 Ledergerber and Larkum. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Improved virological outcome in white patients infected with HIV-1 non-B subtypes compared to subtype B
No full text(See the Editorial Commentary by Gatell, on pages 1153-5.) Background. Antiretroviral compounds have been predominantly studied in human immunodeficiency virus type 1 (HIV-1) subtype B, but only ∼10% of infections worldwide are caused by this subtype. The analysis of the impact of different HIV subtypes on treatment outcome is important. Methods. The effect of HIV-1 subtype B and non-B on the time to virological failure while taking combination antiretroviral therapy (cART) was analyzed. Other studies that have addressed this question were limited by the strong correlation between subtype and ethnicity. Our analysis was restricted to white patients from the Swiss HIV Cohort Study who started cART between 1996 and 2009. Cox regression models were performed; adjusted for age, sex, transmission category, first cART, baseline CD4 cell counts, and HIV RNA levels; and stratified for previous mono/dual nucleoside reverse-transcriptase inhibitor treatment. Results. Included in our study were 4729 patients infected with subtype B and 539 with non-B subtypes. The most prevalent non-B subtypes were CRF02_AG (23.8%), A (23.4%), C (12.8%), and CRF01_AE (12.6%). The incidence of virological failure was higher in patients with subtype B (4.3 failures/100 person-years; 95% confidence interval [CI], 4.0-4.5]) compared with non-B (1.8 failures/100 person-years; 95% CI, 1.4-2.4). Cox regression models confirmed that patients infected with non-B subtypes had a lower risk of virological failure than those infected with subtype B (univariable hazard ratio [HR], 0.39 [95% CI, .30-.52; P < .001]; multivariable HR, 0.68 [95% CI, .51-.91; P = .009]). In particular, subtypes A and CRF02_AG revealed improved outcomes (multivariable HR, 0.54 [95% CI, .29-.98] and 0.39 [95% CI, .19-.79], respectively). Conclusions. Improved virological outcomes among patients infected with non-B subtypes invalidate concerns that these individuals are at a disadvantage because drugs have been designed primarily for subtype B infections
[The HIV-antibody positive patient in general practice. Guidelines for rational diagnosis and treatment]
No full textTrends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study.
No full textBrass instruments of the 19th and early 20th centuries between long-term conservation and use in historically informed performance practice
No full textThe presented project has a clearly defined object of research, namely the brass instruments used in a Parisian theatre orchestra in May 1913 for the world première of Igor Stravinsky’s Le sacre du printemps. Taking this as our starting point, one of the main goals is to examine the corrosion phenomena in historical instruments currently being used, and to present an appropriate set of recommendations for their conservation and usage. The project is an interdisciplinary collaboration between several institutions: the Collection Centre of the Swiss National Museum, the Paul Scherer Institute, the Swiss Federal Institute of Technology Zurich, the University of Cagliari, the Bern University of the Arts and the Burri Collection.
Among the 9 working packages of the project, 4 are dedicated to the development of a non-destructive methodology based on different analytical technics to assess the corrosion state of a corpus of 16 historical brass instruments (late 19th and early 20th centuries). Our main focus is the investigation of corrosion developed inside the instruments. In order to achieve this goal the project is structured upon the following tasks:
- Determine the chemical composition of the brass instrument alloys (μ-XRF), characterising the mineralogy of corrosion products (Raman spectroscopy); characterise and quantify the surface composition (X-ray photoelectron spectroscopy) [1].
- Perform a comprehensive visual inspection inside the tubes by endoscope;
- Apply electrochemical methods (potential and polarisation resistance –Rp- measure-ments) inside the instruments at specific locations (tuning slides, lead-pipe, etc.) [2];
- Obtain “cartographies” of the distribution of corrosion products inside the instruments by neutron imaging and X-Ray tomography.
16 brass instruments are daily played by the musicians. One group will be played according to specific preventive conservation guidelines; the second group will be played using common practice. All instruments are analysed by non-destructive methods at different times to evaluate the evolution of their corrosion condition. The comparison shall allow assessing the efficiency of the applied guidelines of preventive conservation. A concert using these instruments is planned at the end of the project.
[1] F. Cocco, M. Fantanzzi, B. Elsener, A. Rossi, this conference
[2] B. Elsener, M. Alter, T. Lombardo, M. Ledergerber, M. Wöhrle, F. Cocco, M. Fantauzzi, A. Rossi, this conferenc
Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study
No full textBACKGROUND:
Patterns of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals taking antiretroviral therapy are changing as a result of immune reconstitution and improved survival. We studied the influence of aging on the epidemiology of non-AIDS diseases in the Swiss HIV Cohort Study.
METHODS:
The Swiss HIV Cohort Study is a prospective observational cohort established in 1988 with continuous enrollment. We determined the incidence of clinical events (per 1000 person-years) from January 2008 (when a new questionnaire on non-AIDS-related morbidity was introduced) through December 2010. Differences across age groups were analyzed using Cox regression, adjusted for CD4 cell count, viral load, sex, injection drug use, smoking, and years of HIV infection.
RESULTS:
Overall, 8444 (96%) of 8848 participants contributed data from 40,720 semiannual visits; 2233 individuals (26.4%) were aged 50-64 years, and 450 (5.3%) were aged ≥65 years. The median duration of HIV infection was 15.4 years (95% confidence interval [CI], 9.59-22.0 years); 23.2% had prior clinical AIDS. We observed 994 incident non-AIDS events in the reference period: 201 cases of bacterial pneumonia, 55 myocardial infarctions, 39 strokes, 70 cases of diabetes mellitus, 123 trauma-associated fractures, 37 fractures without adequate trauma, and 115 non-AIDS malignancies. Multivariable hazard ratios for stroke (17.7; CI, 7.06-44.5), myocardial infarction (5.89; 95% CI, 2.17-16.0), diabetes mellitus (3.75; 95% CI, 1.80-7.85), bone fractures without adequate trauma (10.5; 95% CI, 3.58-30.5), osteoporosis (9.13; 95% CI, 4.10-20.3), and non-AIDS-defining malignancies (6.88; 95% CI, 3.89-12.2) were elevated for persons aged ≥65 years.
CONCLUSIONS:
Comorbidity and multimorbidity because of non-AIDS diseases, particularly diabetes mellitus, cardiovascular disease, non-AIDS-defining malignancies, and osteoporosis, become more important in care of HIV-infected persons and increase with older age
Stability of hepatitis C virus (HCV) RNA levels among interferon-naïve HIV/HCV-coinfected individuals treated with combination antiretroviral therapy.
No full textMolecular evidence of interhuman transmission in an outbreak of Pneumocystis jirovecii pneumonia among renal transplant recipients
No full textS. Gianella, L. Haeberli, B. Joos, B. Ledergerber, R.P. Wüthrich, R. Weber, H. Kuster, P.M. Hauser, T. Fehr, N.J. Mueller. Molecular evidence of interhuman transmission in an outbreak of Pneumocystis jirovecii pneumonia among renal transplant recipients. Transpl Infect Dis 2009. All rights reserved Abstract: Pneumocystis jirovecii pneumonia (PCP) remains an important cause of morbidity and mortality in immunocompromised individuals. The epidemiology and pathogenesis of this infection are poorly understood, and the exact mode of transmission remains unclear. Recent studies reported clusters of PCP among immunocompromised patients, raising the suspicion of interhuman transmission. An unexpected increase of the incidence of PCP cases in our nephrology outpatient clinic prompted us to conduct a detailed analysis. Genotyping of 7 available specimens obtained from renal transplant recipients was performed using multi-locus DNA sequence typing (MLST). Fragments of 4 variable regions of the P. jirovecii genome (ITS1, 26S, mt26S, beta-tubulin) were sequenced and compared with those of 4 independent control patients. MLST analysis revealed identical sequences of the 4 regions among all 7 renal allograft recipients with available samples, indicating an infection with the same P. jirovecii genotype. We observed that all but 1 of the 19 PCP-infected transplant recipients had at least 1 concomitant visit with another PCP-infected patient within a common waiting area. This study provides evidence that nosocomial transmission among immunocompromised patients may have occurred in our nephrology outpatient clinic. Our findings have epidemiological implications and suggest that prolonged chemoprophylaxis for PCP may be warranted in an era of more intense immunosuppression
Changes in alanine aminotransferase levels after switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in HIV‐positive people without viral hepatitis in the Swiss HIV Cohort Study
No full textOBJECTIVES
We previously demonstrated an association between tenofovir disoproxil fumarate (TDF) and chronic liver enzyme elevation in the D:A:D study. The objective of the study was to assess changes in alanine aminotransferase (ALT) levels after switching from TDF to tenofovir alafenamide (TAF).
METHODS
We included Swiss HIV Cohort Study participants who switched from TDF to TAF with two or more ALT values in the 24 months before and two or more values in the 24 months after replacing TDF with TAF. Individuals with replicating viral hepatitis were excluded. Uni- and multivariable linear mixed models were used to explore changes in ALT values associated with switching from TDF to TAF, and to assess potential modifying effects.
RESULTS
A total of 1712 participants were included, contributing 6169 ALT values before and 5482 after switching. Median (interquartile range, IQR) age was 50 (42-57) years, and 75% were male. Median (IQR) ALT was 28 (22-38) U/L before and 24 (19-32) U/L after replacing TDF with TAF. ALT values decreased by 3.7 U/L (95% confidence interval: 3.2-4.2) after the switch. The median drop was larger in patients with chronic ALT elevation (defined as two or more elevated values for ≥ 6 months) compared with patients with normal ALT values (17.8 vs. 3.3 U/L, P < 0.001). We did not identify any major effect modifications of the ALT change with any of the potential variables studied.
CONCLUSIONS
Replacing TDF with TAF in HIV-monoinfected people led to a significant decrease in ALT values. Findings were not significantly affected by known risk factors for hepatotoxicity
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