Publications by authors named "Andy I M Hoepelman"

148 Publications

The prognostic value of serological titers for clinical outcomes during treatment and follow-up of patients with chronic Q fever.

Clin Microbiol Infect 2021 Apr 1. Epub 2021 Apr 1.

Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Objectives: We assessed the prognostic value of phase I IgG titers during treatment and follow-up of chronic Q fever.

Methods: We performed a retrospective cohort study to analyze the course of phase I IgG titers in chronic Q fever. We used a multivariable time-varying Cox regression to assess our primary (first disease-related event) and secondary (therapy failure) outcomes. In a second analysis, we evaluated serological characteristics after one year of therapy (fourfold decrease in phase I IgG titer, absence of phase II IgM, and reaching phase I IgG titer of ≤1:1,024) with multivariable Cox regression.

Results: In total, 337 patients that were treated for proven (n=284, 84.3%) or probable (n=53, 15.7%) chronic Q fever were included. Complications occurred in 190 (56.4%), disease-related mortality in 71 (21.1%), and therapy failure in 142 (42.1%) patients. The course of phase I IgG titers was not associated with first disease-related event (HR 1.00, 95% CI 0.86-1.15) or therapy failure (HR 1.02, 95% CI 0.91-1.15). Similar results were found for the serological characteristics for the primary (HR 0.97, 95% CI 0.62-1.51; HR 1.12, 95% CI 0.66-1.90; HR 0.99, 95% CI 0.57-1.69, respectively) and secondary outcomes (HR 0.86, 95% CI 0.57-1.29; HR 1.37, 95% CI 0.86-2.18; HR 0.80, 95% CI 0.48-1.34, respectively).

Conclusions: C. burnetii serology does not reliably predict disease-related events or therapy failure during treatment and follow-up of chronic Q fever. Alternative markers for disease management are needed, but for now, management should be based on clinical factors, PCR results, and imaging results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmi.2021.03.016DOI Listing
April 2021

Dual Antiretroviral Therapy-All Quiet Beneath the Surface?

Front Immunol 2021 12;12:637910. Epub 2021 Feb 12.

Department of Internal Medicine and Infectious Diseases, University Medical Centre Utrecht, Utrecht, Netherlands.

Infection with the human immunodeficiency virus (HIV) is characterized by progressive depletion of CD4+ lymphocytes cells as a result of chronic immune activation. Next to the decreases in the number of CD4+ cells which leads to opportunistic infections, HIV-related immune activation is associated with several prevalent comorbidities in the HIV-positive population such as cardiovascular and bone disease. Traditionally, combination antiretroviral therapy (cART) consists of three drugs with activity against HIV and is highly effective in diminishing the degree of immune activation. Over the years, questions were raised whether virological suppression could also be achieved with fewer antiretroviral drugs, i.e., dual- or even monotherapy. This is an intriguing question considering the fact that antiretroviral drugs should be used lifelong and their use could also induce cardiovascular and bone disease. Therefore, the equilibrium between drug-induced toxicity and immune activation related comorbidity is delicate. Recently, two large clinical trials evaluating two-drug cART showed non-inferiority with respect to virological outcomes when compared to triple-drug regimens. This led to adoption of dual antiretroviral therapy in current HIV treatment guidelines. However, it is largely unknown whether dual therapy is also able to suppress immune activation to the same degree as triple therapy. This poses a risk for an imbalance in the delicate equilibrium. This mini review gives an overview of the current available evidence concerning immune activation in the setting of cART with less than three antiretroviral drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.637910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906996PMC
February 2021

Long-term serological follow-up after primary Coxiella burnetii infection in patients with vascular risk factors for chronic Q fever.

Eur J Clin Microbiol Infect Dis 2021 Feb 10. Epub 2021 Feb 10.

Department of Surgery, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.

We evaluated the long-term serological follow-up of patients with vascular risk factors for chronic Q fever that were previously Coxiella burnetii seropositive. C. burnetii phase I IgG titers were reevaluated in patients that gave informed consent or retrospectively collected in patients already deceased or lost to follow-up. Of 107 patients, 25 (23.4%) became seronegative, 77 (72.0%) retained a profile of past resolved Q fever infection, and five (4.7%) developed chronic Q fever. We urge clinicians to stay vigilant for chronic Q fever beyond two years after primary infection and perform serological testing based on clinical presentation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10096-021-04179-5DOI Listing
February 2021

Decreased All-Cause and Liver-Related Mortality Risk in HIV/Hepatitis B Virus Coinfection Coinciding With the Introduction of Tenofovir-Containing Combination Antiretroviral Therapy.

Open Forum Infect Dis 2020 Jul 25;7(7):ofaa226. Epub 2020 Jun 25.

Department of Internal Medicine & Infectious Diseases, University Medical Centre Utrecht, Utrecht, the Netherlands.

Background: The development of efficacious combination antiretroviral therapy (cART) has led to a dramatic decrease in mortality in HIV-positive patients. Specific data on the impact in HIV/hepatitis B virus (HBV)-coinfected patients are lacking. In this study, all-cause and cause-specific mortality risks stratified per era of diagnosis are investigated.

Methods: Data were analyzed from HIV/HBV-coinfected patients enrolled in the ATHENA cohort between January 1, 1998, and December 31, 2017. Risk for (cause-specific) mortality was calculated using Cox proportional hazard regression analysis, comparing patients diagnosed before 2003 with those diagnosed ≥2003. Risk factors for all-cause and liver-related mortality were also assessed using Cox proportional hazard regression analysis.

Results: A total of 1301 HIV/HBV-coinfected patients were included (14 882 person-years of follow-up). One-hundred ninety-eight patients (15%) died during follow-up. The adjusted hazard ratio (aHR) for all-cause mortality in patients diagnosed in or after 2003 was 0.50 (95% CI, 0.35-0.72) relative to patients diagnosed before 2003. Similar risk reduction was observed for liver-related (aHR, 0.29; 95% CI, 0.11-0.75) and AIDS-related mortality (aHR, 0.44; 95% CI, 0.22-0.87). Use of a tenofovir-containing regimen was independently associated with a reduced risk of all-cause and liver-related mortality. Prior exposure to didanosine/stavudine was strongly associated with liver-related mortality. Ten percent of the population used only lamivudine as treatment for HBV.

Conclusions: All-cause, liver-related, and AIDS-related mortality risk in HIV/HBV-coinfected patients has markedly decreased over the years, coinciding with the introduction of tenofovir. Tenofovir-containing regimens, in absence of major contraindications, should be strongly encouraged in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofaa226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340797PMC
July 2020

Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency.

Blood 2020 12;136(23):2638-2655

Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.

Biallelic mutations in the genes encoding CD27 or its ligand CD70 underlie inborn errors of immunity (IEIs) characterized predominantly by Epstein-Barr virus (EBV)-associated immune dysregulation, such as chronic viremia, severe infectious mononucleosis, hemophagocytic lymphohistiocytosis (HLH), lymphoproliferation, and malignancy. A comprehensive understanding of the natural history, immune characteristics, and transplant outcomes has remained elusive. Here, in a multi-institutional global collaboration, we collected the clinical information of 49 patients from 29 families (CD27, n = 33; CD70, n = 16), including 24 previously unreported individuals and identified a total of 16 distinct mutations in CD27, and 8 in CD70, respectively. The majority of patients (90%) were EBV+ at diagnosis, but only ∼30% presented with infectious mononucleosis. Lymphoproliferation and lymphoma were the main clinical manifestations (70% and 43%, respectively), and 9 of the CD27-deficient patients developed HLH. Twenty-one patients (43%) developed autoinflammatory features including uveitis, arthritis, and periodic fever. Detailed immunological characterization revealed aberrant generation of memory B and T cells, including a paucity of EBV-specific T cells, and impaired effector function of CD8+ T cells, thereby providing mechanistic insight into cellular defects underpinning the clinical features of disrupted CD27/CD70 signaling. Nineteen patients underwent allogeneic hematopoietic stem cell transplantation (HSCT) prior to adulthood predominantly because of lymphoma, with 95% survival without disease recurrence. Our data highlight the marked predisposition to lymphoma of both CD27- and CD70-deficient patients. The excellent outcome after HSCT supports the timely implementation of this treatment modality particularly in patients presenting with malignant transformation to lymphoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2020006738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735164PMC
December 2020

High efavirenz levels but not neurofilament light plasma levels are associated with poor neurocognitive functioning in asymptomatic HIV patients.

J Neurovirol 2020 08 10;26(4):572-580. Epub 2020 Jun 10.

Department of Internal Medicine, section Infectious Diseases, University Medical Center (UMC) Utrecht, Utrecht University, PO Box 85500, 3508, GA, Utrecht, the Netherlands.

The aim of this study is to assess the effect of efavirenz exposure on neurocognitive functioning and investigate plasma neurofilament light (Nfl) as a biomarker for neurocognitive damage. Sub-analysis of the ESCAPE-study, a randomised controlled trial where virologically suppressed, cognitively asymptomatic HIV patients were randomised (2:1) to switch to rilpivirine or continue on efavirenz. At baseline and week 12, patients underwent an extensive neuropsychological assessment (NPA), and serum efavirenz concentration and plasma Nfl levels were measured. Subgroups of elevated (≥ 4.0 mg/L) and therapeutic (0.74 to< 4.0 mg/L) baseline efavirenz concentration were made. Differences between these groups in baseline NPA Z-scores and in delta scores after efavirenz discontinuation were assessed. Nfl level was measured using an ELISA analysis using single molecule array (Simoa) technology. Correlation of plasma NFL with NPA Z-scores was evaluated using a linear mixed model. The elevated group consisted of 6 patients and the therapeutic group of 48. At baseline, the elevated group showed lower composite Z-scores (median - 1.03; IQR 0.87 versus 0.27; 0.79. p 0.02). This effect was also seen on the subdomains verbal (p 0.01), executive functioning (p 0.02), attention (p < 0.01) and speed (p 0.01). In the switch group, the elevated group improved more on composite scores after discontinuing efavirenz (mean 0.58; SD 0.32 versus 0.22; 0.54, p 0.15). No association between plasma Nfl and composite Z-score was found. High efavirenz exposure is associated with worse cognitive functioning compared with patients with therapeutic concentrations. Plasma Nfl is not a suitable biomarker to measure cognitive damage in this group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13365-020-00860-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438296PMC
August 2020

An open-label cluster-randomized controlled trial of chloroquine, hydroxychloroquine or only supportive care in patients admitted with moderate to severe COVID-19 (ARCHAIC)-Protocol publication.

Eur J Clin Invest 2020 Jul 19;50(7):e13297. Epub 2020 Jun 19.

Department of Infectious Diseases, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eci.13297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300462PMC
July 2020

The balancing perspective of hard-to-reach hepatitis C patients who were lost to follow-up: A qualitative study.

PLoS One 2020 13;15(4):e0230756. Epub 2020 Apr 13.

Cancer Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Background: In the foreseeable future, patients with hepatitis C virus (HCV) with good healthcare access will all have been cured and the lost to follow-up (LFU) HCV-population will increasingly exist of hard-to-reach patients. Efforts to retrieve these individuals with HCV have been moderately successful so far. A deeper understanding of the reasons for loss to follow-up and the underlying processes is lacking.

Aims: To explore reasons for previous loss to follow-up in patients with HCV who have been brought back into care.

Methods: In 2017, fifteen patients with HCV who were evaluated at the University Medical Center Utrecht (UMCU) Infectious diseases outpatient clinic as part of the "REtrieval And cure of Chronic Hepatitis C" (REACH)-project were included in this study through convenience sampling. Face-to-face semi-structured in-depth interviews were conducted and a qualitative analysis based on the grounded theory was applied.

Results: A basic socio- psychological process named "maintaining the achieved balance" was uncovered in patients with HCV who were LFU. This "achieved balance" is the result of a transformative process following the initial HCV diagnosis. It is a steadfast stance in which participants keep HCV out of sight and in the margin of their lives in order to reestablish an optimal state of well-being. The balancing perspective is subsequently defended by repeated evasive behavioral patterns to avoid confrontation with the disease.

Conclusion: The balancing perspective gives insight into why individuals with HCV were not retained in care but also why they remained LFU thereafter. Physicians should realize that this mindset can be persistent and repeated efforts may be needed to finally trace and retrieve these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230756PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153871PMC
July 2020

Immune reconstitution inflammatory syndrome in HIV infected late presenters starting integrase inhibitor containing antiretroviral therapy.

EClinicalMedicine 2019 Dec 13;17:100210. Epub 2019 Dec 13.

Department of Internal Medicine and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, 3015 CE, Rotterdam, the Netherlands.

Background: Integrase inhibitors (INI) induce a rapid decline of HIV-RNA in plasma and CD4 T-cell recovery in blood. Both characteristics are also associated with immune reconstitution inflammatory syndrome (IRIS). Whether the use of INI-containing combination antiretroviral therapy (cART) increases the risk of IRIS is being questioned.

Methods: Study within the Dutch ATHENA HIV observational cohort. HIV-1 infected late presenters initiating cART after March 2009 were included if they had <200 CD4 T-cells per μL were diagnosed with an opportunistic infection. IRIS was defined either according to the criteria by French et al. (IRIS) or by a clinical IRIS diagnosis of the physician (IRIS). The primary outcomes were the association between INI and the occurrence of IRIS and IRIS in multivariable logistic regression.

Findings: 672 patients with a median CD4 T-cell count of 35 cells per μL were included. Treatment with INI was independently associated with IRIS as well as IRIS (OR 2·43, 95%CI:1·45-4·07, and OR 2·17, 95%CI:1·45-3·25). When investigating INI separately, raltegravir (RAL) remained significantly associated with IRIS (OR 4·04 (95%CI:1·99-8·19) as well as IRIS (OR 3·07, 95%CI:1·66-5·69), while dolutegravir (DTG) became associated with IRIS after it replaced RAL as preferred INI in the cohort after 2015 (OR 4·08, 95%CI:0·99-16·82, =0·052). Too few patients used elvitegravir to draw meaningful conclusions. Steroid initiation for IRIS was more likely in those who initiated INI versus in those who did not, but no increased hospital (re)admission or mortality rates were observed.

Interpretation: In HIV late presenters from a resource rich setting, INI based treatment initiation increased the risk of IRIS. This was observed for RAL and DTG when being initiated as preferential INI in the presence of specific AIDS-conditions, indicative of channeling bias. Although we controlled for all relevant measured confounders, we cannot exclude that the observed association is partially explained by residual confounding. INI use was not associated with mortality nor hospitalization. Therefore, our observation is no reason to avoid INI in late presenters.

Funding: The ATHENA database is maintained by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2019.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933261PMC
December 2019

Brief Report: Low Sensitivity of the Fracture Risk Assessment Tool in Young HIV-Infected Patients: Time to Revise Our Screening Strategy.

J Acquir Immune Defic Syndr 2019 12;82(5):439-442

Department of Internal Medicine and Infectious Diseases, University Medical Centre Utrecht, Utrecht, the Netherlands.

Objectives: The burden of reduced bone mineral density (BMD) is high among HIV-infected patients. As a screening strategy, current guidelines recommend calculating a Fracture Risk Assessment Tool (FRAX) score in patients aged 40-49 years. Patients with a 10-year risk of a major osteoporotic fracture ≥10% should undergo dual-energy x-ray absorptiometry (DXA) to assess BMD. The aim of this study was to establish the sensitivity of this threshold to identify patients with risk of osteoporosis in this age category-as a surrogate marker for high fracture risk.

Methods: The study group consisted of patients aged 50-59 years and living with HIV for at least 10 years who recently underwent dual-energy x-ray absorptiometry (DXA). A clinical risk factor-based FRAX score was calculated using patient characteristics from 10 years earlier. In this way, we assessed which patients would have undergone DXA while they were 40-49 year old.

Results: The cohort consisted of 126 patients; 23 patients (18.3%) had osteoporosis. Ten years before the DXA, none of them met the guideline threshold of a 10-year major osteoporotic fracture probability of ≥10%, resulting in a sensitivity of 0% in this cohort. There was no difference between the median FRAX score between patients who developed osteoporosis and those who did not (3.3% vs. 3.4%. P = 0.55).

Conclusions: FRAX lacks sensitivity to determine which HIV-infected patients aged 40-49 years should undergo BMD testing to identify reduced BMD. Its role should be limited to treatment decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000002177DOI Listing
December 2019

External validation and update of a prognostic model to predict mortality in hospitalized adults with RSV: A retrospective Dutch cohort study.

J Med Virol 2019 12 28;91(12):2117-2124. Epub 2019 Aug 28.

Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.

Respiratory syncytial virus (RSV) causes significant mortality in hospitalized adults. Prediction of poor outcomes improves targeted management and clinical outcomes. We externally validated and updated existing models to predict poor outcome in hospitalized RSV-infected adults. In this single center, retrospective, observational cohort study, we included hospitalized adults with respiratory tract infections (RTIs) and a positive polymerase chain reaction for RSV (A/B) on respiratory tract samples (2005-2018). We validated existing prediction models and updated the best discriminating model by revision, recalibration, and incremental value testing. We included 192 RSV-infected patients (median age 60.7 years, 57% male, 65% immunocompromised, and 43% with lower RTI). Sixteen patients (8%) died within 30 days. During hospitalization, 16 (8%) died, 30 (16%) were admitted to intensive care unit, 21 (11%) needed invasive mechanical ventilation, and 5 (3%) noninvasive positive pressure ventilation. Existing models performed moderately at external validation, with C-statistics 0.6 to 0.7 and moderate calibration. Updating to a model including lower RTI, chronic pulmonary disease, temperature, confusion and urea, increased the C-statistic to 0.76 (95% confidence interval, 0.61-0.91) to predict in-hospital mortality. In conclusion, existing models to predict poor prognosis among hospitalized RSV-infected adults perform moderately at external validation. A prognostic model may help to identify and treat RSV-infected adults at high-risk of death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.25568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851775PMC
December 2019

Introducing hepatitis C virus healthcare pathways in addiction care in the Netherlands with a Breakthrough project: a mixed method study.

Harm Reduct J 2019 07 15;16(1):45. Epub 2019 Jul 15.

Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Background: People who inject drugs (PWID) are disproportionally affected by the hepatitis C virus (HCV) infection. In the Netherlands, active HCV transmission in PWID has practically been halted but uptake of HCV testing and linkage to care remains insufficient in this risk group. A national HCV in Addiction Care (HAC) quality improvement project based on the Breakthrough methodology (i.e. Breakthrough project) aimed to secure proper linkage to care in PWID by introducing local HCV healthcare screening and treatment pathways in addiction care units.

Aim: To qualitatively appraise the local HCV healthcare pathways; to evaluate the yield in terms of number of PWID screened, diagnosed, referred, and treated; and to identify best practices and barriers to successful participation in the HAC Breakthrough project.

Methods: Between 2013 and 2016, 12 units of addiction care centers throughout the Netherlands participated in two series of a HAC Breakthrough project. Local multidisciplinary teams created HCV healthcare pathways. Quality assessment of HCV healthcare pathways was performed retrospectively and data on screening results was collected. In-depth interviews were conducted to elucidate best practices and essential elements for successful participation.

Results: In total, six HCV healthcare pathways were submitted by ten teams of which 83% was judged to be of "good" or "sufficient" quality. Uptake of HCV-antibody screening was 40% (N = 487/1219) and uptake of HCV-RNA in HCV-antibody positives was 59% (N = 107/181). The project resulted in 76 (6%) newly detected cases of persistent HCV viremia. Of all HCV-RNA positives, 92% was referred to a hepatitis treatment center. In 39% (N = 27/70) of those referred, treatment initiation was documented and 82% (N = 22/27) achieved a sustained virological response. Teams identified several best practices including motivational counseling training, oral swabs for anti-HCV testing, facilitating complementary HCV RNA testing, and supervised hospital visits.

Conclusion: The HAC Breakthrough project has brought about good quality HCV healthcare pathways in the majority of participating addiction care centers and has successfully linked PWID with ongoing HCV viremia to care. Uptake of HCV screening and treatment after referral were identified as the main gaps to be closed in the HCV cascade of care to achieve final HCV elimination in Dutch PWID (i.e. micro-elimination).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12954-019-0316-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631626PMC
July 2019

The use of corticosteroids does not influence CD4 lymphocyte recovery in HIV-infected patients with advanced immunodeficiency.

AIDS Care 2020 06 27;32(6):701-704. Epub 2019 May 27.

Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, Netherlands.

Corticosteroids inhibit HIV-related immune activation and seem to have a mild favorable effect on immunological recovery in patients with CD4 counts ≥200 cells/mm. Data in patients with advanced immunodeficiency are lacking. We analyzed whether corticosteroids negatively influence the short-term CD4 lymphocyte recovery in patients with CD4 cell counts <200 cells/mm started on combination antiretroviral therapy (cART). We performed a retrospective cohort analysis including all HIV-infected patients under follow-up in our hospital with a documented episode of Pneumocystis Jirovecii Pneumonia (PJP) in the cART era. CD4 lymphocyte recovery was assessed at three months after the episode of PJP and subsequent start of cART, comparing patients that received adjunctive corticosteroids (AC) versus patients that did not receive corticosteroids (standard care (SC)). In total, 66 patients with an episode of PJP were identified with 38 patients in the AC-group versus 28 patients in the SC-group. Almost all baseline characteristics were similar, including mean CD4 lymphocyte counts. After three months, the mean CD4 cell count did not differ; 222 cells/mm for the SC-group versus 259 cells/mm for the AC-group ( = .29). The use of corticosteroids does not alter CD4 lymphocyte recovery in HIV-infected patients with advanced immunodeficiency in the first months of antiretroviral therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09540121.2019.1623376DOI Listing
June 2020

Pitfalls of molecular diagnostic testing for Coxiella burnetii DNA on throat swabs.

J Microbiol Methods 2019 07 14;162:16-20. Epub 2019 May 14.

Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, Henri Dunantlaan 1, 5223 GZ 's-Hertogenbosch, the Netherlands.

Introduction: Coxiella burnetii, the causative pathogen of Q fever, is regularly detected in throat swabs from patients without serological evidence of Q fever infection. C. burnetii is also frequently found in bulk tank milk from dairy cows. We evaluated the false positivity rate of polymerase chain reaction (PCR) for C. burnetii DNA on throat swabs and investigated whether recent consumption of C. burnetii DNA-positive cow milk could contribute to this phenomenon.

Methods: C. burnetii PCR was performed on throat swabs obtained from patients in whom a throat swab was ordered for other diagnostic purposes; patients with community-acquired pneumonia (CAP); and healthy volunteers after consumption of commercial C. burnetii-containing cow milk products.

Results: C. burnetii DNA was found in 5.0% of throat swabs ordered for other diagnostic purposes and in 15.3% of throat swabs from CAP patients without serological evidence of Q fever pneumonia. The positive and negative predictive value of C. burnetii PCR on throat swabs for Q fever pneumonia were 66.7% (95% CI, 38.0-88.2) and 48.9% (95% CI, 41.3-54.6), respectively. After consumption of commercial C. burnetii-containing cow milk products, C. burnetii DNA could be detected in throat swabs for as long as 30 min after ingestion.

Conclusion: C. burnetii PCR on throat swabs is of low diagnostic value for Q fever pneumonia and was false positive in 15.3% of CAP patients without Q fever pneumonia. Recent consumption of C. burnetii-containing products can influence the outcome of C. burnetii PCR on throat swabs. Therefore, diagnosis of C. burnetii infection should be made in combination with serology or PCR performed on blood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mimet.2019.05.006DOI Listing
July 2019

Switching tenofovir disoproxil fumarate to tenofovir alafenamide results in a significant decline in parathyroid hormone levels: uncovering the mechanism of tenofovir disoproxil fumarate-related bone loss?

AIDS 2019 07;33(9):1531-1534

Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.

: An increasing number of patients have been switched from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide because of its improved bone safety profile, although the pathophysiological mechanism is not fully understood. We show that serum parathyroid hormone levels drop significantly after the switch from TDF to tenofovir alafenamide. This observation supports the theories that TDF-related bone loss is parathyroid hormone-driven and that this effect is dose-dependent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAD.0000000000002238DOI Listing
July 2019

More targeted use of oseltamivir and in-hospital isolation facilities after implementation of a multifaceted strategy including a rapid molecular diagnostic panel for respiratory viruses in immunocompromised adult patients.

J Clin Virol 2019 07 7;116:11-17. Epub 2019 Apr 7.

Department of Infectious Diseases, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Background: Immunocompromised adults are more vulnerable to a complicated course of viral respiratory tract infections (RTI).

Objectives: Provide evidence on the effect of implementation of rapid molecular diagnostics for viruses on use of in-hospital isolation facilities, oseltamivir and antibiotic usage, and other clinical outcomes in immunocompromised patients.

Study Design: A before-after study during two consecutive respiratory viral seasons, including immunocompromised adult patients presenting at a tertiary care emergency department with clinical suspicion of RTI. During the first season (2016/2017), respiratory viruses were detected using inhouse real-time PCR. The second season (2017/2018), we implemented a diagnostic flowchart including a rapid molecular test for 15 respiratory viruses (FilmArray®). We assessed the effect of this implementation on need for isolation, antivirals and empirical antibiotics.

Results: We included 192 immunocompromised adult patients during the first and 378 during the second season. Respiratory viral testing was performed in 135 patients (70%) during the first and 284 (75%) during the second season (p = 0.218) of which 213 (75%) using the rapid test. After implementation, use of in-hospital isolation facilities was reduced (adjusted odds ratio 0.35, 95%CI 0.19-0.64). Furthermore, adequate use of oseltamivir improved, with fewer prescriptions in influenza negative patients (0.15, 95%CI 0.08-0.28) and more in influenza positive patients (11.13, 95%CI 1.75-70.86). No effect was observed on empirical antibiotic use, hospital admissions, length of hospital stay or safety outcomes.

Conclusions: Implementation of rapid molecular testing for respiratory viruses in adult immunocompromised patients results in more adequate use of oseltamivir and in-hospital isolation facilities without compromising safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcv.2019.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185605PMC
July 2019

New filovirus disease classification and nomenclature.

Nat Rev Microbiol 2019 05;17(5):261-263

World Health Organization Regional Office for Africa, Brazzaville, Democratic Republic of the Congo.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41579-019-0187-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637750PMC
May 2019

High epidemic burden of RSV disease coinciding with genetic alterations causing amino acid substitutions in the RSV G-protein during the 2016/2017 season in The Netherlands.

J Clin Virol 2019 03 23;112:20-26. Epub 2019 Jan 23.

University Medical Center Utrecht, Utrecht University, Department of Medical Microbiology, Utrecht 3584 CX, The Netherlands.

Background: We found amino acid substitutions in the Gglycoprotein of respiratory syncytial virus (RSV) A during the 2016/2017 epidemic in The Netherlands.

Objectives: We evaluated whether these alterations led to increased RSV incidence and disease burden.

Study Design: We sequenced the gene encoding the G-protein of prospectively collected clinical specimens from secondary care adult patients testing positive for RSV during the 2016/2017 and 2017/2018 epidemic RSV season. We evaluated associations between genetic, clinical and epidemiological data.

Results: We included 49 RSV strains. In 2016/2017 28 strains were included, 20 community acquired RSV-A, 5 hospital acquired RSV-A and 3 community acquired RSV-B. In 2017/2018 21 strains were included, 8 community acquired RSV-A and 13 community acquired RSV-B. G-proteins of 10 out of the 20 community acquired 2016/2017 RSV-A strains shared a set of eight novel amino acid substitutions of which seven in mucin-like regions 1 and 2 and one in the heparin binding domain. This genetic variant was no longer detected among 2017/2018 RSV-A strains. Among patients carrying the novel RSV-A strain-type, 30% died.

Conclusions: A set of eight amino acid substitutions was found in 50% of the 2016/2017 community acquired RSV-A G-proteins. This combination of substitutions was globally never observed before. The appearance of this new strain-type coincided with an increased RSV peak in The Netherlands and was associated with higher disease severity. The transient character of this epidemic strain-type suggests rapid clearance of this lineage in our study community.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcv.2019.01.007DOI Listing
March 2019

Rapid Molecular Tests for Influenza, Respiratory Syncytial Virus, and Other Respiratory Viruses: A Systematic Review of Diagnostic Accuracy and Clinical Impact Studies.

Clin Infect Dis 2019 09;69(7):1243-1253

Department of Infectious Diseases, University Medical Center Utrecht, Utrecht University, The Netherlands.

We systematically reviewed available evidence from Embase, Medline, and the Cochrane Library on diagnostic accuracy and clinical impact of commercially available rapid (results <3 hours) molecular diagnostics for respiratory viruses as compared to conventional molecular tests. Quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies criteria for diagnostic test accuracy (DTA) studies, and the Cochrane Risk of Bias Assessment and Risk of Bias in Nonrandomized Studies of Interventions criteria for randomized and observational impact studies, respectively. Sixty-three DTA reports (56 studies) were meta-analyzed with a pooled sensitivity of 90.9% (95% confidence interval [CI], 88.7%-93.1%) and specificity of 96.1% (95% CI, 94.2%-97.9%) for the detection of either influenza virus (n = 29), respiratory syncytial virus (RSV) (n = 1), influenza virus and RSV (n = 19), or a viral panel including influenza virus and RSV (n = 14). The 15 included impact studies (5 randomized) were very heterogeneous and results were therefore inconclusive. However, we suggest that implementation of rapid diagnostics in hospital care settings should be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciz056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108200PMC
September 2019

Coxiella burnetii in non-Hodgkin lymphoma tissue samples: Innocent until proven otherwise?

Immunobiology 2019 03 5;224(2):254-261. Epub 2018 Dec 5.

Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital,' s-Hertogenbosch, the Netherlands. Electronic address:

Purpose: Coxiella burnetii has been suggested as a potential cause of B-cell non-Hodgkin lymphoma (B-NHL), as C. burnetii was detected in B-NHL tissues. To further investigate this potential relationship, we hypothesized that among subjects previously exposed to C. burnetii, the bacterium is more frequently detectable in tissues of patients with B-NHL (cases) compared to patients without B-NHL (controls).

Methods: We aimed to evaluate this hypothesis by assessing the presence of C. burnetii with polymerase chain reaction (PCR), immunofluorescence staining (IF) and fluorescent in-situ hybridization (FISH). Eligible patients were those previously exposed to C. burnetii.

Results: Samples were available for 13 cases and 16 controls. C. burnetii was demonstrated in tissues of 8/29 patients in total (28%), with either PCR, IF or FISH: in 5/13 cases (38%) and 3/16 controls (19%), p = 0.41. Negative and positive control samples were all negative and positive appropriately for all three diagnostic methods.

Conclusions: In patients previously exposed to C. burnetii the bacterium was detected in tissue samples from subjects with and without B-NHL, without significant differences in the proportion positive samples. Therefore, we conclude that detection of C. burnetii in tissues of patients previously exposed to C. burnetii is a non-specific finding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imbio.2018.11.012DOI Listing
March 2019

A Review of Non-Alcoholic Fatty Liver Disease in HIV-Infected Patients: The Next Big Thing?

Infect Dis Ther 2019 Mar 3;8(1):33-50. Epub 2019 Jan 3.

Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht (UMCU) Utrecht, Utrecht, The Netherlands.

The burden of liver-related morbidity remains high among HIV-infected patients, despite advances in the treatment of HIV and viral hepatitis. Especially, the impact of non-alcoholic fatty liver disease (NAFLD) is significant with a prevalence of up to 50%. The pathogenesis of NAFLD and the reasons for progression to non-alcoholic steatohepatitis (NASH) are still not fully elucidated, but insulin resistance, mitochondrial dysfunction and dyslipidemia seem to be the main drivers. Both HIV-infection itself and combination antiretroviral therapy (cART) can contribute to the development of NAFLD/NASH in various ways. As ongoing HIV-related immune activation is associated with insulin resistance, early initiation of cART is needed to limit its duration. In addition, the use of early-generation nucleoside reverse transcriptase inhibitors and protease inhibitors is also associated with the development of NAFLD/NASH. Patients at risk should therefore receive antiretroviral drugs with a more favorable metabolic profile. Only weight reduction is considered to be an effective therapy for all patients with NAFLD/NASH, although certain drugs are available for specific subgroups. Since patients with NASH are at risk of developing liver cirrhosis and hepatocellular carcinoma, several non-antifibrotic and antifibrotic drugs are under investigation in clinical trials to broaden the therapeutic options. The epidemiology and etiology of NAFLD/NASH in HIV-positive patients is likely to change in the near future. Current guidelines recommend early initiation of cART that is less likely to induce insulin resistance, mitochondrial dysfunction and dyslipidemia. In contrast, as a result of increasing life expectancy in good health, this population will adopt the more traditional risk factors for NAFLD/NASH. HIV-treating physicians should be aware of the etiology, pathogenesis and treatment of NAFLD/NASH in order to identify and treat the patients at risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40121-018-0229-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374241PMC
March 2019

Overcoming Obstacles in Lipid-lowering Therapy in Patients with HIV - A Systematic Review of Current Evidence.

AIDS Rev 2018 ;20(4):205-219

Department of Internal Medicine and Infectious Diseases. University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.

Cardiovascular risk management in human immunodeficiency virus (HIV)-infected individuals is gaining increased attention due to the rising incidence and prevalence of cardiovascular disease in this population. Despite the availability of efficacious treatment strategies, implementation of guideline advocated preventive therapy, such as lipid-lowering therapy with statins, is hampered by perceived, expected, and real side effects as well as by expected interactions with combination antiretroviral therapy. These obstacles to optimal treatment have resulted in a large gap between the number of patients in whom lipid-lowering therapy is indicated and those actually taking lipid-lowering medication. In the past few years, research has shown that the majority of patient-reported side effects is not causally related to statin therapy but is attributable to the nocebo effect. Furthermore, excessive caution due to expected drug interactions between statins and antiretroviral therapy is often unnecessary, especially with novel classes of antiretroviral therapy. The main aim of this review is to discuss the causes and consequences of this lipid-lowering treatment gap in HIV-infected patients together with a practical guide on how to overcome these obstacles. In addition, new treatment options on the optimal cardiovascular management focusing primarily on novel classes of antiretroviral therapy and lipid-lowering medication will be discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.24875/AIDSRev.18000016DOI Listing
May 2019

Oral fosfomycin versus ciprofloxacin in women with E.coli febrile urinary tract infection, a double-blind placebo-controlled randomized controlled non-inferiority trial (FORECAST).

BMC Infect Dis 2018 Dec 5;18(1):626. Epub 2018 Dec 5.

University Medical Centre Utrecht, University of Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands.

Background: Febrile Urinary Tract Infection (FUTI) is frequently treated initially with intravenous antibiotics, followed by oral antibiotics guided by clinical response and bacterial susceptibility patterns. Due to increasing infection rates with multiresistant Enterobacteriaceae, antibiotic options for stepdown treatment decline and patients more frequently require continued intravenous antibiotic treatment for FUTI. Fosfomycin is an antibiotic with high bactericidal activity against Escherichia coli and current resistance rates are low in most countries. Oral Fosfomycin-Trometamol 3000 mg (FT) reaches appropriate antibiotic concentrations in urine and blood and is considered safe. As such, it is a potential alternative for stepdown treatment.

Methods: The FORECAST study (Fosfomycin Randomized controlled trial for E.coli urinary tract infections as Alternative Stepdown Treatment) is a randomized, double-blind, double-dummy, non-inferiority trial in which 240 patients will be randomly allocated to a stepdown treatment with FT or ciprofloxacin (standard of care) for FUTI, caused by Escherichia coli with in vitro susceptibility to both antibiotics. The study population consists of consenting female patients (≥18 years) with community acquired E. coli FUTI. After intravenous antibiotic treatment during at least 48 (but less than 120) hours, and if eligibility criteria for iv-oral switch are met, patients receive either FT (3 g every 24 h) or ciprofloxacin (500 mg every 12 h) for a total antibiotic duration of 10 days. The primary endpoint is clinical cure (resolution of symptoms) 6-10 days post-treatment. Secondary endpoints are microbiological cure 6-10 days post-treatment, clinical cure, mortality, ICU admittance, relapse, reinfection, readmission, additional antibiotic use for UTI, early study discontinuation, adverse events, days of hospitalization and days of absenteeism within 30-35 days post-treatment. The sample size is based on achieving non-inferiority on the primary endpoint, applying a non-inferiority margin of 10%, a two-sided p-value of < 0.05 and a power of 80%.

Discussion: The study aims to demonstrate non-inferiority of oral fosfomycin, compared to oral ciprofloxacin, in the stepdown treatment of E. coli FUTI.

Trial Registration: Registered at the Nederlands trial register (Dutch trial register) on 4-10-2017.

Trial Registration Number: NTR6449 . Secondary ID (national authority): NL60186.041.17.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-018-3562-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280543PMC
December 2018

Liver decompensation in HIV/Hepatitis B coinfection in the combination antiretroviral therapy era does not seem increased compared to hepatitis B mono-infection.

Liver Int 2019 03 2;39(3):470-483. Epub 2018 Dec 2.

Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.

Background & Aims: HIV/hepatitis B virus (HBV) coinfected subjects are thought to have faster progression to end-stage liver disease (ESLD) than HBV mono-infected subjects. We assessed whether this remains in the current cART-era.

Methods: Data from subjects with follow-up completion post-2003 were compared between HIV/HBV coinfected subjects in the Dutch HIV Monitoring database and HBV mono-infected subjects from two centres. The primary outcomes of composite ESLD included portal hypertension, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation and liver-related mortality. Outcomes were analysed using time-dependent cause-specific Cox regression models adjusted for follow-up time and relevant covariates. Subset-analyses were done in subjects with follow-up pre-2003.

Results: In the 1336 co- vs 742 mono-infected subjects, coinfected subjects had no increased probability for ESLD compared to mono-infected subjects (cHR 0.7 (95% CI 0.4-1.1), but had increased probabilities for all-cause (cHR 7.4 [4.9-11.1]) and liver-related mortality (cHR 3.4 [1.6-7.5]). In the current combined cohort, treatment with tenofovir or entecavir was inversely associated with ESLD, all-cause and liver-related mortality (cHR 0.4 [95% CI 0.3-0.7], cHR 0.003 [0.001-0.01]), cHR 0.007 [0.001-0.05]). Other predictors for ESLD were older age, being of Sub-Sahara African descent, increased alanine aminotransferase levels and hepatitis C virus coinfection. While the probability for all-cause mortality was increased in coinfected subjects, this rate decreased compared to pre-2003 (HR 40.2 (95% CI: 8.7-186.2).

Conclusions: HIV/HBV coinfected patients no longer seem to be at increased risk for progression to ESLD compared to HBV mono-infected patients, likely due to widespread use of highly effective cART with dual HBV and HIV activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14000DOI Listing
March 2019

Objective and Subjective Improvement of Cognition After Discontinuing Efavirenz in Asymptomatic Patients: A Randomized Controlled Trial.

J Acquir Immune Defic Syndr 2019 01;80(1):e14-e22

Department of Internal Medicine, Section Infectious Diseases, University Medical Center Utrecht (UMCU), Utrecht University, Utrecht, the Netherlands.

Background: Efavirenz is well known for its clinical cognitive side effects. Even asymptomatic patients who switch for other reasons than neurocognitive complaints have reported a subjective improvement in cognitive functioning after discontinuing efavirenz. The aim of this study was to assess the effect on cognition of switching Atripla (TDF/FTC/EFV) to Eviplera (TDF/FTC/RPV), hypothesizing an improvement when discontinuing efavirenz.

Setting: A randomized controlled design with a highly comparable comparator drug was used to minimize bias and to differentiate drug versus learning effects. An extensive sensitive neuropsychological assessment (NPA) was used to detect subtle changes.

Methods: Virologically suppressed, cognitively asymptomatic male HIV-infected patients on Atripla were included and randomized (2:1) to switch to Eviplera (switch group) or continue on Atripla (control group) for 12 weeks. At baseline and week 12, patients underwent an extensive NPA.

Results: Fourteen control and 34 switch subjects completed the study. There were no differences at baseline. Group analysis demonstrated a significantly better improvement for the switch group on the domains attention (P = 0.041) and speed of information processing (P = 0.014). Normative comparison analyses showed that 5 of the 34 patients who switched (15%) improved on NPA score as compared to the control group. Interestingly, subjective improvement after discontinuing efavirenz made 74% of the switch group chose for a regime without efavirenz after study completion.

Conclusions: Switching from Atripla to Eviplera resulted in objective cognitive improvement on the group level in cognitively asymptomatic patients. Discrepancies in objective and subjective cognitive complaints make it challenging to identify patients who would benefit from discontinuing efavirenz.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000001876DOI Listing
January 2019

REtrieval And cure of Chronic Hepatitis C (REACH): Results of micro-elimination in the Utrecht province.

Liver Int 2019 03 16;39(3):455-462. Epub 2018 Oct 16.

University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Background: The Netherlands is one of the six European countries considered on track to eliminate hepatitis C virus by 2030. To achieve this goal, continuous efforts have to be put into designing efficient case-finding strategies, including the retrieval of previously diagnosed hepatitis C virus-infected who are lost to follow-up.

Aims: To trace and treat all lost to follow-up hepatitis C virus patients in the Utrecht region and create an efficient retrieval strategy that can be used in future (national) retrieval initiatives.

Methods: Positive hepatitis C virus diagnostic tests (anti-hepatitis C virus IgG or hepatitis C virus-RNA) from the laboratory of all four hospitals and one central laboratory for primary care diagnostics in the province of Utrecht from 2001 to 2015 were linked to clinical records. Untreated patients with available contact information were deemed eligible for retrieval and invited for reevaluation with (virology) blood tests, fibroscan measurement and possible direct-acting antiviral therapy.

Main Results: After screening all hepatitis C virus diagnostics, 1913 chronic hepatitis C virus-infected were identified of which 14.1% (n = 269) were invited back into care. Overall, 17.4% was traced with the highest yield (28.3%) in those who lived in the Utrecht province. Through renewed patient assessments, 42 chronic hepatitis C virus infections were re-identified (76% with a history of intravenous drug use, 24% with Metavir F3-F4). Until now, 59% has either scheduled or initiated direct-acting antiviral therapy.

Conclusion: The retrieval of previously diagnosed hepatitis C virus patients through screening of laboratory diagnostics from the past is feasible and should be pursued for further control and reduction of hepatitis C virus infection. Retrieval is most successful when performed regionally.

Lay Summary: To completely eliminate chronic hepatitis C virus (HCV) infection and prevent complications, undiagnosed and also previously diagnosed but lost to follow-up (LFU) HCV patients have to be brought (back) into care for therapy. Retrieval of LFU HCV patients through screening of laboratory diagnostics from the past is feasible and most successful when performed regionally.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.13959DOI Listing
March 2019

The Impact of Hepatitis C Virus Direct-Acting Antivirals on Patient-Reported Outcomes: A Dutch Prospective Cohort Study.

Infect Dis Ther 2018 Sep 3;7(3):373-385. Epub 2018 Aug 3.

Department of Gastroenterology and Hepatology, University Medical Center Utrecht Affiliated to Utrecht University, Utrecht, The Netherlands.

Introduction: Pegylated interferon-based therapy for hepatitis C virus (HCV) negatively impacts nutritional state and patient-reported outcomes (PROs) such as health-related quality of life (HRQL). Clinical trials with direct-acting antivirals (DAAs) report significant PRO improvement but real-world data are still scarce.

Methods: Prospective cohort study recruiting HCV patients treated with DAAs in 2015-2016. Data at baseline, end of treatment (EOT) and 12 weeks thereafter (FU) included: patient-reported medication adherence; SF-36; Karnofsky Performance Status; paid labour productivity; physical exercise level; nutritional state [by body mass index (BMI) and Jamar hand grip strength (HGS)] and Beliefs about Medicines Questionnaire. Potential factors predicting these PROs were evaluated with multiple regression analysis.

Results: A total of 68 patients were enrolled: 85% male, median age 57 years, 80% genotype 1, 40% cirrhotics, 46% haemophilia. Both cure rate and patient-reported adherence were 97%. SF-36 Physical Component Summary did not change (43.2 ± 11.9, 44.9 ± 10.3 and 44.7 ± 10.9 at baseline, EOT and FU, p = 0.71). In contrast, SF-36 mental component summary (MCS) decreased transiently during therapy (49.2 ± 11.9, 44.6 ± 10.3 and 49.9 ± 12.6 at baseline, EOT and FU, p < 0.01). Concomitant ribavirin-use was the only independent predictor of decreased SF-36 MCS. BMI (25.7 ± 4.5 and 25.6 ± 4.4 at baseline and EOT, p = 0.8) and Jamar HGS (39.7 ± 13.0, 37.4 ± 11.9 and 37.9 ± 13.8 at baseline, EOT and FU, p = 0.56) did not change.

Conclusion: Our study reveals concomitant ribavirin as the only independent predictor of transient decrease in SF-36 mental HRQL during DAA therapy. In contrast to interferon-based therapy, DAAs do not affect BMI or Jamar HGS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40121-018-0208-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098748PMC
September 2018

The effect of switching protease inhibitors to raltegravir on endothelial function, in HIV-infected patients.

HIV Clin Trials 2018 04;19(2):75-83

a Department of Internal Medicine and Infectious Diseases , University Medical Centre Utrecht , Utrecht , The Netherlands.

Objective Lipid management is one of the cornerstones of cardiovascular risk reduction. Treatment of HIV infection with protease inhibitors (PIs) may cause dyslipidaemia, whilst the integrase inhibitor raltegravir (RAL) has a relatively favorable effect on plasma lipids. We examined the effect of switching from PIs to RAL on endothelial function, and its effect on immunological and inflammatory parameters. Methods We performed a 16-week open-label prospective crossover study: 8 weeks intervention (switch PIs to RAL) and 8 weeks control (unchanged cART regimen). Flow-mediated dilatation (FMD), inflammatory plasma, and cellular markers of immune activation were measured at weeks 0, 8, and 16. Results Study participants (n = 22) with a median age of 50 years (IQR 42-60) and known HIV infection of 6.5 years (IQR 5.0-17.3) were on stable cART with undetectable HIV viral loads. After 8 weeks of RAL therapy, a reduction in FMD of -0.81% was seen, compared to +0.54% control (pairwise, p = 0.051), while fasting total cholesterol (-17% versus +10%; p < 0.001), LDL cholesterol (-21% versus -3%; p = 0.026), and triglycerides (-41% versus +18%; p = 0.001) significantly decreased during RAL therapy compared to the control. Furthermore, a relation between the change in percentage of B-1 cells and the change in FMD was found (β 0.40, 95%CI 0.16; 0.64, p = 0.005) during treatment with RAL. Finally, during RAL therapy, 27% of the patients experienced an increased ALT rise. Conclusions We present an overall negative study, where switching from PIs to RAL slightly reduced the endothelial function while decreasing plasma lipids, thus possibly decreasing the CVD risk in the long term. A transient elevation of ALT was seen upon switch to RAL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15284336.2018.1455366DOI Listing
April 2018

Primary and secondary arterial fistulas during chronic Q fever.

J Vasc Surg 2018 12;68(6):1906-1913.e1

Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.

Objective: After primary infection with Coxiella burnetii, patients may develop acute Q fever, which is a relatively mild disease. A small proportion of patients (1%-5%) develop chronic Q fever, which is accompanied by high mortality and can be manifested as infected arterial or aortic aneurysms or infected vascular prostheses. The disease can be complicated by arterial fistulas, which are often fatal if they are left untreated. We aimed to assess the cumulative incidence of arterial fistulas and mortality in patients with proven chronic Q fever.

Methods: In a retrospective, observational study, the cumulative incidence of arterial fistulas (aortoenteric, aortobronchial, aortovenous, or arteriocutaneous) in patients with proven chronic Q fever (according to the Dutch Chronic Q Fever Consensus Group criteria) was assessed. Proven chronic Q fever with a vascular focus of infection was defined as a confirmed mycotic aneurysm or infected prosthesis on imaging studies or positive result of serum polymerase chain reaction for C. burnetii in the presence of an arterial aneurysm or vascular prosthesis.

Results: Of 253 patients with proven chronic Q fever, 169 patients (67%) were diagnosed with a vascular focus of infection (42 of whom had a combined vascular focus and endocarditis). In total, 26 arterial fistulas were diagnosed in 25 patients (15% of patients with a vascular focus): aortoenteric (15), aortobronchial (2), aortocaval (4), and arteriocutaneous (5) fistulas (1 patient presented with both an aortocaval and an arteriocutaneous fistula). Chronic Q fever-related mortality was 60% for patients with and 21% for patients without arterial fistula (P < .0001). Primary fistulas accounted for 42% and secondary fistulas for 58%. Of patients who underwent surgical intervention for chronic Q fever-related fistula (n = 17), nine died of chronic Q fever-related causes (53%). Of patients who did not undergo any surgical intervention (n = 8), six died of chronic Q fever-related causes (75%).

Conclusions: The proportion of patients with proven chronic Q fever developing primary or secondary arterial fistulas is high; 15% of patients with a vascular focus of infection develop an arterial fistula. This observation suggests that C. burnetii, the causative agent of Q fever, plays a role in the development of fistulas in these patients. Chronic Q fever-related mortality in patients with arterial fistula is very high, in both patients who undergo surgical intervention and patients who do not.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvs.2018.01.044DOI Listing
December 2018

Exposure to Coxiella burnetii and risk of non-Hodgkin lymphoma: a retrospective population-based analysis in the Netherlands.

Lancet Haematol 2018 May 9;5(5):e211-e219. Epub 2018 Apr 9.

Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht and Utrecht University, Utrecht, Netherlands.

Background: An association between Coxiella burnetii and non-Hodgkin lymphoma has been suggested. After a large Q fever epidemic in the Netherlands (2007-10), we postulated that the incidence of non-Hodgkin lymphoma would be increased during and after the epidemic in areas with a high endemicity of Q fever compared with those with low endemicity.

Methods: We did a retrospective population-based analysis and calculated relative risks (RRs) of non-Hodgkin lymphoma during 1-year periods before, during, and after the Q fever epidemic, for areas with intermediate and high endemicity of Q fever compared with low endemic areas. We also calculated the RR of non-Hodgkin lymphoma in people with chronic Q fever compared with the general population.

Findings: Between Jan 1, 2002, and Dec 31, 2013, 48 760 cases of non-Hodgkin lymphoma were diagnosed. The incidence of non-Hodgkin lymphoma ranged from 21·4 per 100 000 per year in 2002 to 26·7 per 100 000 per year in 2010. A significant association with non-Hodgkin lymphoma was noted in 2009 for areas with a high endemicity of Q fever compared with low endemic areas (RR 1·16, 95% CI 1·02-1·33; p=0·029); no further associations were noted in any other year or for areas with intermediate Q fever endemicity. Among 439 individuals with chronic Q fever, five developed non-Hodgkin lymphoma, yielding a crude absolute risk of 301·0 cases per 100 000 per year (RR 4·99, 95% CI 2·07-11·98; p=0·0003) compared with the general population in the Netherlands.

Interpretation: These findings do not support the hypothesis that Q fever has a relevant causal role in the development of non-Hodgkin lymphoma. Several limitations, inherent to the design of this study, might lead to both underestimation and overestimation of the studied association.

Funding: Foundation Q-support and Institut Mérieux.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-3026(18)30038-3DOI Listing
May 2018