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Find video protocols related to scientific articles indexed in Pubmed.
[Middle-East respiratory syndrome].
Ned Tijdschr Geneeskd
PUBLISHED: 09-25-2014
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MERS-CoV is the sixth type of corona virus to cause disease in humans. This virus can cause severe respiratory infections, particularly in patients with underlying conditions. Although dromedary camels appear to be the most important source in primary cases, nosocomial transmission has proved to be a major cause of secondary infections. In accordance with the case definitions formulated by the Dutch National Institute for Public Health and the Environment (RIVM), in those patients who present with lower respiratory infections within 14 days of visiting the Arabian Peninsula, MERS-CoV should be considered.
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Development of a practice guideline for optimal symptom relief for patients with pneumonia and dementia in nursing homes using a Delphi study.
Int J Geriatr Psychiatry
PUBLISHED: 05-24-2014
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This study aimed to develop a practice guideline for a structured and consensus-based approach to relieve symptoms of pneumonia in patients with dementia in nursing homes.
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Activation of extrinsic apoptosis pathway in HCV monoinfected and HIV-HCV coinfected patients, irrespective of liver disease severity.
Apoptosis
PUBLISHED: 04-23-2014
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Chronic hepatitis C virus (HCV) infection is associated with increased levels of peripheral T cell apoptosis. We aimed to study whether T cell apoptosis markers indicate pathways that may contribute to clinical progression in HCV monoinfected and HIV-HCV coinfected patients. Activation of the extrinsic apoptosis pathways was measured by levels of death receptor Fas, initiator caspase 8 and effector caspases 3 and 7 activity and Annexin V binding on peripheral CD4 and CD8 T cells of HCV monoinfected and HIV/HCV coinfected patients, as well as healthy controls and HIV-infected, hepatitis B virus-infected and primary biliary cirrhosis disease controls. Association with liver fibrosis was assessed by biopsy or by transient elastography. HCV monoinfected and HIV-HCV coinfected patients displayed enhanced peripheral CD4 and CD8 T cell apoptosis. Caspase 8 activity was highest in HIV-HCV coinfection, without enhanced downstream activity of caspases 3 and 7. Level of peripheral T cell apoptosis was independent of liver fibrosis or other disease parameters in all disease groups. The extrinsic apoptosis pathway is upregulated in HCV monoinfection and HIV-HCV coinfection, but this is independent of liver disease severity.
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Chronic Q fever in the Netherlands 5 years after the start of the Q fever epidemic: results from the Dutch chronic Q fever database.
J. Clin. Microbiol.
PUBLISHED: 03-05-2014
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Coxiella burnetii causes Q fever, a zoonosis, which has acute and chronic manifestations. From 2007 to 2010, the Netherlands experienced a large Q fever outbreak, which has offered a unique opportunity to analyze chronic Q fever cases. In an observational cohort study, baseline characteristics and clinical characteristics, as well as mortality, of patients with proven, probable, or possible chronic Q fever in the Netherlands, were analyzed. In total, 284 chronic Q fever patients were identified, of which 151 (53.7%) had proven, 64 (22.5%) probable, and 69 (24.3%) possible chronic Q fever. Among proven and probable chronic Q fever patients, vascular infection focus (56.7%) was more prevalent than endocarditis (34.9%). An acute Q fever episode was recalled by 27.0% of the patients. The all-cause mortality rate was 19.1%, while the chronic Q fever-related mortality rate was 13.0%, with mortality rates of 9.3% among endocarditis patients and 18% among patients with a vascular focus of infection. Increasing age (P=0.004 and 0.010), proven chronic Q fever (P=0.020 and 0.002), vascular chronic Q fever (P=0.024 and 0.005), acute presentation with chronic Q fever (P=0.002 and P<0.001), and surgical treatment of chronic Q fever (P=0.025 and P<0.001) were significantly associated with all-cause mortality and chronic Q fever-related mortality, respectively.
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CD4/CD8 ratio is a promising candidate for non-invasive measurement of liver fibrosis in chronic HCV-monoinfected patients.
Eur. J. Clin. Microbiol. Infect. Dis.
PUBLISHED: 01-06-2014
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The extent of liver fibrosis is an important factor in prognosis and clinical decision-making in chronic hepatitis C virus (HCV) infection. We investigated CD4/CD8 ratio in HCV-monoinfected and HIV/HCV-coinfected patients, in order to reveal its relation with liver fibrosis. CD4/CD8 ratio in the peripheral blood was assessed by flow cytometry in a cohort of 19 HCV-monoinfected, 14 HIV/HCV-coinfected, ten HIV-monoinfected patients and 15 healthy controls. Liver fibrosis was assessed by transient elastography (n?=?25) or by liver biopsy (n?=?8). Coinfection with HIV was associated with decreased CD4/CD8 ratios in chronic HCV-infected patients, despite adequate antiretroviral treatment. Furthermore, HCV-monoinfected patients with F3-F4 liver fibrosis demonstrated much lower CD4/CD8 ratios than patients with F0-F2 fibrosis (1.4 versus 2.5, p?=?0.023). Similarly, we observed a strong negative correlation between the CD4/CD8 ratio and liver stiffness measured by transient elastography (R?=?-0.78, p?=?0.0006). ROC analysis revealed that CD4/CD8 ratio as a non-invasive marker for fibrosis is very promising (area under the curve 0.8). Although our study was performed with a relatively small number of patients, our findings suggest that the CD4/CD8 ratio is a promising candidate for non-invasive evaluation of liver fibrosis in HCV-monoinfected patients.
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HIV-HBV coinfection in Southern Africa and the effect of lamivudine- versus tenofovir-containing cART on HBV outcomes.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 07-30-2013
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This study assessed HIV-hepatitis B virus (HBV) coinfection in southern Africa in terms of prevalence, viral characteristics, occult HBV, and the effect of lamivudine- versus tenofovir-containing first-line combination antiretroviral treatment (cART) on HBV-related outcomes.
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Impact of transient elastography on clinical decision-making in patients with chronic viral hepatitis.
Scand. J. Gastroenterol.
PUBLISHED: 07-25-2013
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Transient elastography is a noninvasive tool to quantify liver fibrosis by liver stiffness measurements (LSMs). Previous studies have extensively evaluated the accuracy of LSMs compared to liver biopsy. In this retrospective study we explore potential impact of LSMs on clinical decisions in chronic viral hepatitis.
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Maraviroc treatment in non-R5-HIV-1-infected patients results in the selection of extreme CXCR4-using variants with limited effect on the total viral setpoint.
J. Antimicrob. Chemother.
PUBLISHED: 05-14-2013
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Using deep sequencing methods, we intensively investigated the selective pressure of maraviroc on the viral population in four patients with dual/mixed HIV-1 experiencing treatment failure.
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Peripheral T-cell apoptosis is not differentially affected by antiretroviral regimens in HIV-infected patients.
Antivir. Ther. (Lond.)
PUBLISHED: 04-28-2013
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BACKGROUND: HIV-induced CD4(+) and CD8(+) T cell apoptosis decreases upon start of combination antiretroviral therapy (cART). Although in vitro evidence suggests an anti-apoptotic effect of protease inhibitors (PI) as opposed to non-nucleoside reverse transcriptase inhibitors (NNRTI), in vivo studies are inconclusive about effects of differential cART-regimens on T cell apoptosis. METHODS: Peripheral T cell apoptosis was evaluated in a cross-sectional study including 20 patients on PI- and 19 on NNRTI-based combination antiretroviral therapy (cART), all with backbone therapy of tenofovir and emtricitabine and undetectable viral loads 6 months before inclusion. Spontaneous T cell apoptosis was measured in freshly isolated peripheral blood mononuclear cells (<4 hours after venipuncture) using Annexin V, propidium iodide and staining for caspase activity and levels of the anti-apoptotic protein Bcl-2. RESULTS: The groups were comparable in general- and HIV-specific characteristics. In addition, T cell activation was similar in both groups. We observed no difference in T cell apoptosis as measured by annexin V, propidium iodide or caspase staining between PI- and NNRTI-treated patients. Interestingly, the level of anti-apoptotic protein Bcl-2 was higher in PI-treated than in NNRTI-treated patients. CONCLUSIONS: In this cross-sectional study on HIV-infected patients, direct ex vivo spontaneous T cell apoptosis rates are not differentially affected by NNRTI- or PI-based cART.
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Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques.
PLoS ONE
PUBLISHED: 02-26-2013
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Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay.
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Risk of tuberculosis after antiretroviral treatment initiation: a comparison between efavirenz and nevirapine using inverse probability weighting.
Antivir. Ther. (Lond.)
PUBLISHED: 02-19-2013
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There is a high incidence of tuberculosis (TB) early after antiretroviral therapy (ART) initiation. This historical cohort study evaluated the association of efavirenz (EFV) compared to nevirapine (NVP) with post-ART TB among patients initiated on first-line ART from 2005 to 2009 in a large, urban HIV clinic in Uganda.
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Complementary role of HCV and HIV in T-cell activation and exhaustion in HIV/HCV coinfection.
PLoS ONE
PUBLISHED: 02-13-2013
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To investigate whether T-cell activation and exhaustion is linked to HCV- and HIV disease parameters in HIV/HCV infected individuals, we studied T-cell characteristics in HIV/HCV coinfected patients and controls.
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Sustained virological response on second-line antiretroviral therapy following virological failure in HIV-infected patients in rural South Africa.
PLoS ONE
PUBLISHED: 02-05-2013
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This study aims to describe the virological, immunological and clinical efficacy of protease inhibitor (PI)-based second-line antiretroviral therapy (ART) in rural South Africa.
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Lower incidence of Pneumocystis jirovecii pneumonia among Africans in the Netherlands host or environmental factors?
AIDS
PUBLISHED: 01-02-2013
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HIV-associated Pneumocystis jirovecii pneumonia (PJP) remains one of the commonest opportunistic infections in Western countries. Although it has been suggested that racial differences in PJP incidence exist, early studies report conflicting results. This study aimed to investigate differences in PJP incidence in a developed country among patients originating from sub-Saharan Africa compared with other regions of origin.
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Increased use of antimicrobial agents and hospital admission for infections in patients with primary adrenal insufficiency: a cohort study.
Eur. J. Endocrinol.
PUBLISHED: 01-01-2013
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Previous studies have suggested that infections are an important cause of death in patients with Addisons disease, but epidemiological studies on the frequency of infections in this population are lacking.
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Immunomodulatory effects of macrolides during community-acquired pneumonia: a literature review.
J. Antimicrob. Chemother.
PUBLISHED: 12-21-2011
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Macrolides are known to possess immunomodulatory properties, next to their antimicrobial effects. These immunomodulatory activities have been proven beneficial in chronic pulmonary inflammatory diseases. Whether macrolides also exert favourable immunomodulatory effects during acute inflammation, and therefore can act as adjuvant therapy in community-acquired pneumonia (CAP), is less clear. We aimed to give an overview of the existing evidence from in vitro and in vivo studies on the immunomodulatory effects of macrolides during CAP. A comprehensive search in the PubMed/MEDLINE and Embase databases was performed. Two investigators independently examined the eligible literature. Studies that dealt with the effects of macrolides on the immune response, in terms of cytokine secretion and the number or function of inflammatory and structural cells during acute inflammation, were included. A total of 27 studies were included, of which 15 were in vitro studies, 9 in vivo, 2 both in vivo and in vitro, and 1 was in human subjects. Although the methods and experimental model systems used in these studies are very heterogeneous, macrolides in general tempered inflammation caused by viable and non-viable bacteria or their products. Cytokine secretion decreased, as did inflammatory and structural cell activation and histological inflammatory signs. Not all data, however, are consistent and sometimes pro-inflammatory effects were found. To conclude, the available literature suggests that macrolides can temper the inflammatory response during CAP, independent of their antimicrobial activity. However, because the studies differ in their methodology, no definite conclusions can be drawn.
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Telbivudine exerts no antiviral activity against HIV-1 in vitro and in humans.
Antivir. Ther. (Lond.)
PUBLISHED: 10-26-2011
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HIV-HBV-coinfected individuals who need to be treated only for their HBV infection have limited therapeutic options, since most approved anti-HBV agents have a risk of selecting for drug-resistant HIV mutants. In vivo data are inconclusive as to whether telbivudine (LdT) may exert antiviral effects against HIV. Thus, we investigated in further detail the antiviral activity and the biochemical properties of LdT against HIV-1.
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Pegylated interferon-? monotherapy leads to low response rates in HIV-infected patients with acute hepatitis C.
Antivir. Ther. (Lond.)
PUBLISHED: 10-26-2011
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Despite a rising incidence of acute HCV in patients infected with HIV, the optimal therapeutic strategy (pegylated interferon-? [PEG-IFN-?] monotherapy or in combination with ribavirin) is still under debate.
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Accumulation of drug resistance and loss of therapeutic options precede commonly used criteria for treatment failure in HIV-1 subtype-C-infected patients.
Antivir. Ther. (Lond.)
PUBLISHED: 06-24-2011
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Virological monitoring is essential to identify antiretroviral treatment (ART) failure, but not widely available. Here, accumulation of resistance and consequences for second-line therapy were investigated in African HIV-1 subtype-C-infected patients.
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CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia.
J. Allergy Clin. Immunol.
PUBLISHED: 06-14-2011
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CD27 is a lymphocyte costimulatory molecule that regulates T-cell, natural killer (NK) cell, B-cell, and plasma cell function, survival, and differentiation. On the basis of its function and expression pattern, we considered CD27 a candidate gene in patients with hypogammaglobulinemia.
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Presence of occult HBV, but near absence of active HBV and HCV infections in people infected with HIV in rural South Africa.
J. Med. Virol.
PUBLISHED: 04-20-2011
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Human immunodeficiency (HIV), hepatitis B (HBV), and hepatitis C (HCV) viruses are endemic in Sub-Saharan Africa, but data regarding the prevalence of hepatitis co-infections in HIV-positive individuals residing there are limited. The aim of the study was to determine the prevalence of HBV, HCV, and occult HBV (presence of HBV-DNA in the absence of HBsAg) in a rural, South African cohort. The results were compared to various ethnic groups in a Dutch cohort of people infected with HIV. Antiretroviral-naïve individuals with HIV from both a rural South African clinic (n?=?258), and a Dutch University hospital (n?=?782), were included. Both serological (HBV and HCV) and molecular (occult HBV) assays were performed. Logistic regression analysis was used to define independent predictors of a hepatitis co-infection. HBV and HCV prevalence rates in the South African cohort were exceptionally low (0.4%, 1/242 and 0.8%, 2/242, respectively), compared to those observed in Caucasians (HBV 4.4% and HCV 10.9%) and African immigrants (HBV 8.9% and HCV 4.8%). Conversely, occult HBV was observed in a considerable proportion (10%, 6/60) of South African patients who were anti-HBc-positive but HBsAg-negative. Occult infections were less frequent in Caucasians and Africans in the Dutch cohort (3.2% and 1.4%, respectively). Independent predictors for occult HBV were not identified, but a trend towards more occult HBV at lower CD4 counts was observed. Local HBV/HCV prevalence data are needed to optimize vaccination and antiretroviral treatment strategies. Occult HBV in patients with HIV may be missed regularly when molecular analyses are not available.
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Association between IL28B polymorphisms and first-phase viral load decrease in chronic hepatitis C virus-infected patients treated with peginterferon alfa-2b/ribavirin.
Int. J. Antimicrob. Agents
PUBLISHED: 03-24-2011
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Host polymorphisms in the IL28B region have recently been associated with outcome of treatment for hepatitis C virus (HCV) infection. This study clearly shows an association between first-phase viral load decrease and the IL28B rs12979860 polymorphism in chronic HCV-infected patients. Furthermore, a higher treatment efficiency factor (?) was found in those HCV-infected patients with a CC genotype compared with those with a CT and TT genotype. This study highlights the importance of host response mechanisms in relation to favourable clearance of HCV.
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Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates.
PLoS ONE
PUBLISHED: 03-15-2011
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Resistance mutations to the HIV-1 fusion inhibitor enfuvirtide emerge mainly within the drugs target region, HR1, and compensatory mutations have been described within HR2. The surrounding envelope (env) genetic context might also contribute to resistance, although to what extent and through which determinants remains elusive. To quantify the direct role of the env context in resistance to enfuvirtide and in viral infectivity, we compared enfuvirtide susceptibility and infectivity of recombinant viral pairs harboring the HR1-HR2 region or the full Env ectodomain of longitudinal env clones from 5 heavily treated patients failing enfuvirtide therapy. Prior to enfuvirtide treatment onset, no env carried known resistance mutations and full Env viruses were on average less susceptible than HR1-HR2 recombinants. All escape clones carried at least one of G36D, V38A, N42D and/or N43D/S in HR1, and accordingly, resistance increased 11- to 2800-fold relative to baseline. Resistance of full Env recombinant viruses was similar to resistance of their HR1-HR2 counterpart, indicating that HR1 and HR2 are the main contributors to resistance. Strictly X4 viruses were more resistant than strictly R5 viruses, while dual-tropic Envs featured similar resistance levels irrespective of the coreceptor expressed by the cell line used. Full Env recombinants from all patients gained infectivity under prolonged drug pressure; for HR1-HR2 viruses, infectivity remained steady for 3/5 patients, while for 2/5 patients, gains in infectivity paralleled those of the corresponding full Env recombinants, indicating that the env genetic context accounts mainly for infectivity adjustments. Phylogenetic analyses revealed that quasispecies selection is a step-wise process where selection of enfuvirtide resistance is a dominant factor early during therapy, while increased infectivity is the prominent driver under prolonged therapy.
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Human African trypanosomiasis: a review of non-endemic cases in the past 20 years.
Int. J. Infect. Dis.
PUBLISHED: 03-10-2011
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Human African trypanosomiasis (HAT) is caused by sub-species of the parasitic protozoan Trypanosoma brucei and is transmitted by tsetse flies, both of which are endemic only to sub-Saharan Africa. Several cases have been reported in non-endemic areas, such as North America and Europe, due to travelers, ex-patriots or military personnel returning from abroad or due to immigrants from endemic areas. In this paper, non-endemic cases reported over the past 20 years are reviewed; a total of 68 cases are reported, 19 cases of Trypanosoma brucei gambiense HAT and 49 cases of Trypanosoma brucei rhodesiense HAT. Patients ranged in age from 19 months to 72 years and all but two patients survived. Physicians in non-endemic areas should be aware of the signs and symptoms of this disease, as well as methods of diagnosis and treatment, especially as travel to HAT endemic areas increases. We recommend extension of the current surveillance systems such as TropNetEurop and maintaining and promotion of existing reference centers of diagnostics and expertise. Important contact information is also included, should physicians require assistance in diagnosing or treating HAT.
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To bead or not to bead? Treatment of osteomyelitis and prosthetic joint-associated infections with gentamicin bead chains.
Int. J. Antimicrob. Agents
PUBLISHED: 03-04-2011
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Gentamicin-containing polymethylmethacrylate (PMMA) beads are frequently used to prevent and treat orthopaedic infections. The beads are typically inserted to fill anatomical defects secondary to surgical debridement. Local gentamicin use results in low serum levels whilst achieving high concentrations at the site of infection. However, a systematic review of the available literature showed that, despite these theoretical advantages, no prospective study has thus far proven gentamicin-containing PMMA beads to be effective in treating orthopaedic infections. Available studies are based on small patient numbers and do not show significantly better results when local and parenteral antibiotics are combined compared with systemic therapy alone. These poor results may be explained partially by reduced aminoglycoside efficacy when biofilms or gentamicin-resistant bacteria are present. Moreover, little is known regarding the potential side effects of gentamicin-containing beads. In this paper, the pros and cons regarding the use of gentamicin-containing PMMA beads are discussed. It is concluded that more well-executed, prospective studies are needed to settle the discussion on the use of gentamicin-containing beads in the treatment of orthopaedic infections.
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No influence of haemodialysis on interferon production in the QuantiFERON-TB Gold-In-Tube test.
J. Nephrol.
PUBLISHED: 02-08-2011
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Immunodeficiency in end-stage renal disease (ESRD) can be aggravated by haemodialysis (HD). This results in an increased incidence of reactivation of tuberculosis (TB) in HD patients. The tuberculin skin test to detect a latent TB infection (LTBI) has its limitations in these patients because of a high rate of false negative results due to anergy of T cells. Data on the influence of HD on the performance of interferon-gamma release assays are limited. The aim of this study was to determine the effect of HD on the performance of the QuantiFERON-TB Gold (QFT-G) assay in ESRD patients before, during and after the HD session.
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Maraviroc is able to inhibit dual-R5 viruses in a dual/mixed HIV-1-infected patient.
J. Antimicrob. Chemother.
PUBLISHED: 01-28-2011
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Maraviroc is the first licensed chemokine co-receptor 5 (CCR5) co-receptor antagonist in clinical practice. It is currently being used in patients harbouring exclusively CCR5-tropic virus. The objective of the study was to investigate the impact of maraviroc on viruses with different co-receptor preferences in a patient with a dual/mixed (D/M) infection.
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Differential effects of rosiglitazone and metformin on postprandial lipemia in patients with HIV-lipodystrophy.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 10-14-2010
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To compare the effects of rosiglitazone (8 mg/d, n=19) and metformin (2 g/d, n=18) on postprandial lipemia in patients with HIV-lipodystrophy.
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Hepatic safety and tolerability in the maraviroc clinical development program.
AIDS
PUBLISHED: 10-12-2010
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Maraviroc is the first CCR5 antagonist to be approved for the treatment of HIV-1 infection. It is generally well tolerated, with a similar side-effect profile to placebo in controlled studies. Many agents used to treat HIV disease are associated with the potential for hepatotoxicity. The hepatic effects of maraviroc were analyzed across all Pfizer-sponsored maraviroc clinical trials, in which 2350 volunteers received maraviroc. Although sporadic hepatic enzyme abnormalities were reported in 34 phase 1/2a studies of up to 28-day duration, they demonstrated no dose relationship or association with hyperbilirubinemia. In the four phase 2b/3 studies in antiretroviral -naive and antiretroviral-experienced patients, there was no significant imbalance in hepatic enzyme abnormalities or hepatobiliary adverse events in maraviroc versus comparator arms up to week 96. The findings were similar in patients coinfected with hepatitis B and/or C virus, although the number of coinfected patients was small. No patient met the strict definition for Hys Law. Two participants reported severe hepatotoxicity and although other potential causes were present, the contribution of maraviroc to these events could not be excluded. This analysis suggests that maraviroc does not present significant risks to hepatic safety when taken at the recommended doses in the populations studied.
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Impact of different empirical antibiotic treatment regimens for community-acquired pneumonia on the emergence of Clostridium difficile.
J. Antimicrob. Chemother.
PUBLISHED: 09-07-2010
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Treatment of community-acquired pneumonia (CAP) with newer fluoroquinolones may contribute to selection for Clostridium difficile. We studied the prevalence of C. difficile carriage and C. difficile infection (CDI) on admission, and nosocomial acquisition rates in patients hospitalized for CAP and compared different empirical treatment strategies.
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Long-Term Outcome of an HIV-Treatment Programme in Rural Africa: Viral Suppression despite Early Mortality.
AIDS Res Treat
PUBLISHED: 06-10-2010
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Objective. To define the long-term (2-4 years) clinical and virological outcome of an antiretroviral treatment (ART) programme in rural South Africa. Methods. We performed a retrospective observational cohort study, including 735 patients who initiated ART. Biannual monitoring, including HIV-RNA testing, was performed. Primary endpoint was patient retention; virological suppression (HIV-RNA ?1000 copies/mL) were secondary endpoints. Moreover, possible predictors of treatment failure were analyzed. Results. 63% of patients (466/735) have a fully suppressed HIV-RNA, a median of three years after treatment initiation. Early mortality was high: 14% died within 3 months after treatment start. 16% of patients experienced virological failure, but only 4% was switched to second-line ART. Male gender and a low performance score were associated with treatment failure; immunological failure was a poor predictor of virological failure. Conclusions. An "all or nothing" phenomenon was observed in this rural South African ART programme: high early attrition, but good virological control in those remaining in care. Continued efforts are needed to enrol patients earlier. Furthermore, the observed viro-immunological dissociation emphasises the need to make HIV-RNA testing more widely available.
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Abacavir/lamivudine/zidovudine maintenance after standard induction in antiretroviral therapy-naïve patients: FREE randomized trial interim results.
AIDS Patient Care STDS
PUBLISHED: 06-03-2010
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Maintenance with a triple nucleoside reverse transcriptase Inhibitor (NRTI) regimen after successful induction with a dual NRTI/protease inhibitor (PI) combination may be advantageous, because of low pill burden, favorable lipids, and less drug interactions. This strategy to become free of PI-related problems without losing viral efficacy has not been formally tested. We performed a randomized, open-label, multicenter, 96-week comparative study in antiretroviral therapy (ART)-naïve patients with CD4 50 copies per milliliter). Two hundred seven patients had similar baseline (BL) characteristics: median CD4 180 cells/mm(3), median VL 5.19 log(10) copies per milliliter. One hundred twenty subjects (58%) met randomization criteria. Baseline VL differed significantly between dropouts and randomized subjects (median 5.41 versus 5.06 log(10) copies per milliliter, p = 0.017), as did CD4 cells (median 160 and 200 cells/mm(3), p = 0.044). Sixty-one subjects received TZV and 59 subjects continued NRTIs/PI. At week 48, 2 patients in the TZV group and 5 in the PI group did not have a sustained virologic suppression (log rank test; p = 0.379). CD4 counts increased significantly in both arms. In ART-naïve patients, TZV maintenance had similar antiviral efficacy compared to continued standard ART at 48 weeks after baseline. Patients on successful standard ART can be safely switched to a NRTI-only regimen, at least for the tested time period.
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Risk of recurrent acute lower urinary tract infections and prescription pattern of antibiotics in women with and without diabetes in primary care.
Fam Pract
PUBLISHED: 05-12-2010
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Women with diabetes have an increased risk of urinary tract infections (UTIs), especially recurrences. Aim. To investigate diabetes characteristics associated with the risk of recurrent lower UTIs and the antibiotic prescription pattern.
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Incident tuberculosis during antiretroviral therapy contributes to suboptimal immune reconstitution in a large urban HIV clinic in sub-Saharan Africa.
PLoS ONE
PUBLISHED: 04-02-2010
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Antiretroviral therapy (ART) effectively decreases tuberculosis (TB) incidence long-term, but is associated with high TB incidence rates in the first 6 months. We sought to determine the incidence and the long-term effects of TB during ART on HIV treatment outcome, and the risk factors for incident TB during ART in a large urban HIV clinic in Uganda.
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T-cell responses at baseline and during therapy with peginterferon-alpha and ribavirin are not associated with outcome in chronic hepatitis C infected patients.
Antiviral Res.
PUBLISHED: 03-31-2010
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Since the association between hepatitis C virus (HCV)-specific T-cell responses both pre-treatment and during interferon-alpha based therapy and viral clearance is unresolved, a combined analysis of distinctive T-cell characteristics (proliferation and interferon-gamma production) is important to clarify this issue.
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Strategies to promote adherence to antiretroviral therapy applied by Dutch HIV nurse consultants: a descriptive qualitative study.
J Assoc Nurses AIDS Care
PUBLISHED: 03-11-2010
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This study describes strategies used by Dutch HIV nurse consultants to promote adherence to antiretroviral therapy (ART) and the assumptions on which these strategies were based. The study used a descriptive qualitative design with individual and focus group interviews. Individual semi-structured interviews (n = 23) focusing on adherence-supporting procedures and case-based focus groups (3 groups with 5-7 participants each) focusing on adherence strategies were held with HIV nurse consultants (n = 19). The strategies described were mainly based on experience. Theoretical principles were rarely discussed and participants seldom referred to the literature. Adherence-promoting strategies were identified for two phases: (a) before beginning ART and (b) during follow-up care while on ART. Strategies that were not used in one specific phase were categorized under "all phases." Data yielded useful ideas for the care of HIV-infected patients, and findings can be applied to the development and use of adherence-promoting strategies.
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Long-term therapy with tenofovir is effective for patients co-infected with human immunodeficiency virus and hepatitis B virus.
Gastroenterology
PUBLISHED: 03-09-2010
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We investigated the long-term efficacy and renal safety of tenofovir disoproxil fumarate (TDF), administered to patients co-infected with human immunodeficiency virus and hepatitis B virus (HBV) as part of an antiretroviral therapy.
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Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review.
Lancet Infect Dis
PUBLISHED: 02-27-2010
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Following large-scale roll-out of antiretroviral therapy in sub-Saharan Africa, the non-clinical efficacy of antiretroviral therapy has received little attention. We aimed to systematically review virological efficacy and drug-resistance outcomes of programmes of antiretroviral therapy in sub-Saharan Africa. 89 studies with heterogeneous design, definitions, and methods were identified. Overall, in on-treatment analysis, 10 351 (78%) of 13 288 patients showed virological suppression after 6 months of antiretroviral therapy, 7413 (76%) of 9794 after 12 months, and 3840 (67%) of 5690 after 24 months. Long-term virological data are scarce. Genotyping results were available for patients with virological failure (HIV-1 RNA greater than 1000 copies per mL). Most patients (839 of 849; 99%) were infected with a non-B HIV-1 subtype. However, drug-resistance patterns were largely similar to those in subtype B. Resistance profiles were associated with the antiretroviral drugs commonly used: the lamivudine-associated M184V mutation was most common, followed by K103N which is associated with non-nucleoside reverse transcriptase inhibitors. Thymidine-analogue mutations and the K65R mutation were less common. First-line antiretroviral therapy regimens used in sub-Saharan Africa are effective. Profiles of drug resistance suggest that a second-line treatment regimen based on protease inhibitors, with a backbone of nucleoside reverse transcriptase inhibitors, is a reasonable option for patients with HIV in sub-Saharan Africa who experience first-line treatment failure.
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Hepatitis B/C and HIV in sub-Saharan Africa: an association between highly prevalent infectious diseases. A systematic review and meta-analysis.
Int. J. Infect. Dis.
PUBLISHED: 01-06-2010
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Hepatitis B virus (HBV), hepatitis C virus (HCV), and the human immunodeficiency virus (HIV) are endemic in Africa. However, hepatitis co-infection rates among HIV-infected individuals remain controversial. The aim of this review was to determine the prevalence of HBV and HCV in HIV-infected patients in sub-Saharan Africa and to analyze whether HIV is associated with a higher HBV/HCV prevalence in that region.
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The role of HIV nursing consultants in the care of HIV-infected patients in Dutch hospital outpatient clinics.
Patient Educ Couns
PUBLISHED: 01-05-2010
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In the Netherlands HIV nursing consultants have participated in HIV-care since 1985; their profession has changed with developments in HIV-treatment over time. The study goal was to gather information about their role in HIV-care and to provide an useful example to other (HIV-)care settings over the world.
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Escherichia coli bacteriuria in female adults is associated with the development of hypertension.
Int. J. Infect. Dis.
PUBLISHED: 04-26-2009
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To investigate whether Escherichia coli bacteriuria is associated with the development of hypertension during a long-term follow-up.
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Pneumonia recovery: discrepancies in perspectives of the radiologist, physician and patient.
J Gen Intern Med
PUBLISHED: 04-24-2009
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Chest radiographs are often used to diagnose community-acquired pneumonia (CAP), to monitor response to treatment and to ensure complete resolution of pneumonia. However, radiological exams may not reflect the actual clinical condition of the patient.
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Adherence to HAART: processes explaining adherence behavior in acceptors and non-acceptors.
AIDS Care
PUBLISHED: 03-07-2009
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In order to explore and clarify the underlying processes which lead to (non)-adherence behavior in patients treated with highly active antiretroviral therapy (HAART), a qualitative study was conducted. Thirty-seven in-depth interviews were held with 30 Caucasian HIV-positive patients. Additional data were collected by diaries kept by some participants. The analysis took place in a cyclic process; selection of themes was alternated with input of new material. Adherence to HAART is mainly influenced by the experience of being HIV positive. Acceptance or non-acceptance of HIV leads to one of two basic stances toward adherence: "being determined to be adherent" or "medication is subordinate to other priorities in life". This stance determines the commitment to therapy and influences how patients cope with adherence. Patients who are determined to be adherent find solutions to adherence problems. Patients who are not determined to be adherent solve problems only if the solution does not compromise important aspects of their lives. Insight is provided into the manner in which prevalent themes; "start of HAART", "attitude toward medication", "HAART in daily life", "contextual factors", "health and HAART" and "being informed", influence adherence behavior. Before starting HAART the focus should be on helping the patient to accept HIV as a part of life. The findings need to be taken into account in adherence-promoting interventions.
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Occult hepatitis B in persons infected with HIV is associated with low CD4 counts and resolves during antiretroviral therapy.
J. Med. Virol.
PUBLISHED: 01-20-2009
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Occult hepatitis B virus (HBV) is defined by the presence of plasma HBV DNA in individuals with HBV core antibodies (anti-HBc), but without HBV surface antigen (HBsAg). The prevalence of occult HBV in HIV-infected patients remains controversial, and the risk factors, clinical significance and effect of highly active antiretroviral therapy (HAART) are unknown. The aim of this study was to determine prevalence, risk factors, and clinical significance of occult HBV in HIV-infected patients and to evaluate the effect of HAART. Plasma HBV DNA levels were determined in 191 HIV positive, antiretroviral naïve patients, who were anti-HBc positive and HBsAg negative. Quantitative HBV DNA was determined using a Taqman real-time nested PCR. Additionally, plasma HIV RNA levels, CD4 cell counts, anti-HBs-antibodies, anti-HCV-antibodies, ALT, AST, and gammaGT were determined. Occult HBV (a plasma HBV DNA level >50 copies/ml) was detected in 9/191 (4.7%) of the patients. Among 45 anti-HBs-negative patients (isolated anti-HBc positive), the prevalence was 11.1%. Patients with occult HBV had significantly lower CD4 count compared to anti-HBc-positive/HBsAg negative/HBV DNA-negative patients (105 +/- 157 (median +/- SD) vs. 323 +/- 299 cells/mm(3), P = 0.019). When HAART (including lamivudine) was initiated in the patients with occult HBV, HBV DNA was no longer detectable in any of the patients during 3 years of follow-up. In conclusion, occult HBV was associated with low CD4 counts and may be viewed as opportunistic reactivation of HBV that resolves as a consequence of HAART induced immune reconstitution and/or the effect of lamivudine.
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[Fatigue after Q fever: nothing new].
Ned Tijdschr Geneeskd
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New guidelines for the diagnosis and treatment of Q-fever related fatigue syndrome have been proposed. However, we argue that Q-fever related fatigue syndrome is only just another description of a chronic fatigue syndrome in which a specific micro-organism is implicated. We feel that development of this guideline comes too soon and may be redundant, as relevant diagnosis and treatment protocols for patients with chronic fatigue, without somatic or psychiatric cause, are already available and current evidence does not support a distinct guideline for fatigue after Q fever. Rather, chronic infection with Coxiella Burnetii should be ruled out. Introducing the term Q-fever related fatigue syndrome may only cause confusion, may lead to increased health-care costs, rather than improve patient management.
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Unrecognised tuberculosis at antiretroviral therapy initiation is associated with lower CD4+ T cell recovery.
Trop. Med. Int. Health
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To investigate whether an unrecognised diagnosis of tuberculosis (TB) at the start of antiretroviral therapy (ART) influences subsequent CD4+ T cell (CD4) count recovery in an urban HIV clinic in Uganda.
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The MOTIVATE trials: maraviroc therapy in antiretroviral treatment-experienced HIV-1-infected patients.
Expert Rev Anti Infect Ther
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Although the use of combination antiretroviral therapy has resulted in spectacular improvements in morbidity and mortality of HIV-1 infected patients, a need for the development of antiretroviral compounds with new mechanisms of action remains. Maraviroc (Celsentri(®); ViiV Healthcare, Middlesex, UK) is the only drug of the class of chemokine (C-C motif) receptor 5 antagonists registered for treatment for HIV-1-infected antiretroviral therapy-experienced patients. Registration was based on the MOTIVATE-1 and -2 studies, which compared the efficacy and tolerability of maraviroc in combination with optimized background therapy with placebo. The aim of this paper is to review the MOTIVATE studies and to discuss issues related to maraviroc therapy in clinical practice such as assessment of HIV-1 coreceptor tropism.
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No advantage of quadruple- or triple-class antiretroviral therapy as initial treatment in patients with very high viraemia.
Antivir. Ther. (Lond.)
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We assessed whether quadruple or triple-class therapy for the initial treatment of HIV-1 infection provides a virological benefit over standard triple therapy in patients with very high plasma viraemia. The assessment was made based on a national observational HIV cohort in the Netherlands.
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Implementation and effect of intensified case finding on diagnosis of tuberculosis in a large urban HIV clinic in Uganda: a retrospective cohort study.
BMC Public Health
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Increased detection of tuberculosis (TB) using intensified or active case finding (ICF) is one of the cornerstones of the Stop TB Strategy, and contrasts with passive case finding (PCF) which relies on self-reported symptoms. There is no clear guidance on implementation strategies. We implemented ICF in addition to ongoing PCF in our large urban HIV clinic in July 2010 using a twice-daily announcement screen method by a trained peer educator, asking waiting patients to self-refer to a trained peer supporter for screening of TB symptoms. We sought to determine the associated effect on TB case detection.
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Prevalence of chronic Q fever in patients with a history of cardiac valve surgery in an area where Coxiella burnetii is epidemic.
Clin. Vaccine Immunol.
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Chronic Q fever develops in 1 to 5% of patients infected with Coxiella burnetii. The risk for chronic Q fever endocarditis has been estimated to be ? 39% in case of preexisting valvulopathy and is potentially even higher for valvular prostheses. Since 2007, The Netherlands has faced the largest Q fever outbreak ever reported, allowing a more precise risk estimate of chronic Q fever in high-risk groups. Patients with a history of cardiac valve surgery were selected for microbiological screening through a cardiology outpatient clinic in the area where Q fever is epidemic. Blood samples were analyzed for phase I and II IgG against C. burnetii, and if titers were above a defined cutoff level, C. burnetii PCR was performed. Chronic Q fever was considered proven if C. burnetii PCR was positive and probable if the phase I IgG titer was ? 1:1,024. Among 568 patients, the seroprevalence of C. burnetii antibodies (IgG titer greater than or equal to 1:32) was 20.4% (n = 116). Proven or probable chronic Q fever was identified among 7.8% of seropositive patients (n = 9). Valve characteristics did not influence the risk for chronic Q fever. Patients with chronic Q fever were significantly older than patients with past Q fever. In conclusion, screening of high-risk groups is a proper instrument for early detection of chronic Q fever cases. The estimated prevalence of chronic Q fever is 7.8% among seropositive patients with a history of cardiac valve surgery, which is substantially higher than that in nonselected populations but lower than that previously reported. Older age seems to increase vulnerability to chronic Q fever in this population.
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Barriers to an early switch from intravenous to oral antibiotic therapy in hospitalised patients with CAP.
Eur. Respir. J.
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Do physicians apply an early-switch strategy (from intravenous to oral antibiotics) in clinically stable patients hospitalised with community-acquired pneumonia (CAP)? If not, why not? In a multicentre prospective cohort study, adult patients admitted for i.v. CAP treatment were included. On day 3 of antibiotic treatment, clinical stability was assessed and treating resident physicians were interviewed on their switch strategies. Additionally, treating physicians were interviewed to evaluate their knowledge of and adherence to guideline advice. 149 (92%) out of 162 patients were included and 97 (91%) out of 107 physicians were interviewed. A switch to oral antibiotics was possible in 68 (46%) out of 149 patients on day 3 of treatment but not performed in 27 (40%) out of 68. Patient factors delaying the switch were high CURB-65 (confusion of new onset, urea >7 mmol · L(-1), respiratory rate of ? 30 breaths · min(-1), blood pressure <90 mmHg or diastolic blood pressure ? 60 mmHg, and age ? 65 yrs) score (on admission) (p=0.04) and oxygen treatment (p=0.04), high temperature (p=0.00) and high respiration rate (p=0.04) (day 3). Physicians barriers to an early switch in clinically stable patients included misconceptions (26 (55%) out of 47), practical considerations (13 (28%) out of 47) and organisational factors (eight (17%) out of 47). Strikingly, 91 (94%) out of 97 interviewed physicians were not aware of guideline advice. The switch from i.v. to oral antibiotics is often unnecessarily delayed in patients hospitalised with CAP due to different types of barriers.
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Identification of risk factors for chronic Q fever, the Netherlands.
Emerging Infect. Dis.
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Since 2007, the Netherlands has experienced a large Q fever outbreak. To identify and quantify risk factors for development of chronic Q fever after Coxiella burnetii infection, we performed a case-control study. Comorbidity, cardiovascular risk factors, medications, and demographic characteristics from 105 patients with proven (n = 44), probable (n = 28), or possible (n = 33) chronic Q fever were compared with 201 patients who had acute Q fever in 2009 but in whom chronic Q fever did not develop (controls). Independent risk factors for development of proven chronic Q fever were valvular surgery, vascular prosthesis, aneurysm, renal insufficiency, and older age.
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Extensive genetic diversity within the Dutch clinical Cryptococcus neoformans population.
J. Clin. Microbiol.
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A set of 300 Dutch Cryptococcus neoformans isolates, obtained from 237 patients during 1977 to 2007, was investigated by determining the mating type, serotype, and AFLP and microsatellite genotype and susceptibility to seven antifungal compounds. Almost half of the studied cases were from HIV-infected patients, followed by a patient group of individuals with other underlying diseases and immunocompetent individuals. The majority of the isolates were mating type ? and serotype A, followed by ?D isolates and other minor categories. The most frequently observed genotype was AFLP1, distantly followed by AFLP2 and AFLP3. Microsatellite typing revealed a high genetic diversity among serotype A isolates but a lower diversity within the serotype D set of isolates. One patient was infected by multiple AFLP genotypes. Fluconazole and flucytosine had the highest geometric mean MICs of 2.9 and 3.5 ?g/ml, respectively, while amphotericin B (0.24 ?g/ml), itraconazole (0.08 ?g/ml), voriconazole (0.07 ?g/ml), posaconazole (0.06 ?g/ml), and isavuconazole (0.03 ?g/ml) had much lower geometric mean MICs. One isolate had a high flucytosine MIC (>64 ?g/ml), while decreased susceptibility (?16 ?g/ml) for flucytosine and fluconazole was found in 9 and 10 C. neoformans isolates, respectively.
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Microbiological challenges in the diagnosis of chronic Q fever.
Clin. Vaccine Immunol.
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Diagnosis of chronic Q fever is difficult. PCR and culture lack sensitivity; hence, diagnosis relies mainly on serologic tests using an immunofluorescence assay (IFA). Optimal phase I IgG cutoff titers are debated but are estimated to be between 1:800 and 1:1,600. In patients with proven, probable, or possible chronic Q fever, we studied phase I IgG antibody titers at the time of positive blood PCR, at diagnosis, and at peak levels during chronic Q fever. We evaluated 200 patients, of whom 93 (46.5%) had proven, 51 (25.5%) had probable, and 56 (28.0%) had possible chronic Q fever. Sixty-five percent of proven cases had positive Coxiella burnetii PCR results for blood, which was associated with high phase I IgG. Median phase I IgG titers at diagnosis and peak titers in patients with proven chronic Q fever were significantly higher than those for patients with probable and possible chronic Q fever. The positive predictive values for proven chronic Q fever, compared to possible chronic Q fever, at titers 1:1,024, 1:2,048, 1:4,096, and ?1:8,192 were 62.2%, 66.7%, 76.5%, and ?86.2%, respectively. However, sensitivity dropped to <60% when cutoff titers of ?1:8,192 were used. Although our study demonstrated a strong association between high phase I IgG titers and proven chronic Q fever, increasing the current diagnostic phase I IgG cutoff to >1:1,024 is not recommended due to increased false-negative findings (sensitivity < 60%) and the high morbidity and mortality of untreated chronic Q fever. Our study emphasizes that serologic results are not diagnostic on their own but should always be interpreted in combination with clinical parameters.
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Biomarkers define the clinical response to dexamethasone in community-acquired pneumonia.
J. Infect.
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Adjuvant dexamethasone treatment in patients with community-acquired pneumonia (CAP) can reduce length of hospital stay. Whether there are subgroups of patients that especially might benefit from corticosteroids is unknown. We hypothesized that a discrepancy between systemic inflammation and cortisol level can define a subgroup that lacks a sufficient cortisol response during CAP, and therefore particularly might benefit from corticosteroids.
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Integration of HIV and TB services results in improved TB treatment outcomes and earlier prioritized ART initiation in a large urban HIV clinic in Uganda.
J. Acquir. Immune Defic. Syndr.
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The World Health Organization recommends that treatment of tuberculosis (TB) in HIV-infected patients should be integrated with HIV care. In December 2008, a separate outdoor-integrated TB/HIV clinic was instituted for attendees of a large urban HIV clinic in Uganda. We sought to evaluate associated TB and HIV treatment outcomes.
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Hepatitis B viral load and risk of HBV-related liver disease: from East to West?
Ann Hepatol
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Chronic hepatitis B has a variable course in disease activity with a risk of clinical complications like liver cirrhosis and hepatocellular carcinoma. As clinical symptoms present in a late stage of the disease, identification of risk factors is important for early detection and therefore improvement of prognosis. Recently, two REVEAL-HBV studies from Taiwan have shown a positive correlation between viral load at any point in time and the development of cirrhosis and hepatocellular carcinoma. Due to differences in viral and host factors between Asians and other populations, it is unclear whether these results can be extrapolated to different populations. This manuscript will discuss viral predictors of hepatitis B related liver disease in relation to ethnic origin.
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