Has the Rate of CD4 Cell Count Decline before Initiation of Antiretroviral Therapy Changed over the Course of the Dutch HIV Epidemic among MSM?

Introduction:Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline.Methods:Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

Costs and effects of MRSA control in Dutch hospitals

In the Netherlands the prevalence of MRSA among S. aureus bloodstream isolates was as low as 0.7% in 2008. This low prevalence is maintained by a nationwide MRSA policy (also called search and destroy), that has been employed in Dutch hospitals since 1984. In the last years we have witnessed major changes in the Dutch MRSA epidemiology. Since 2003 a new MRSA strain (ST398), which originated from livestock, emerged in the Netherlands. Importantly, there is now a substantial number of MRSA carriers in the Netherlands with persistent (professional) exposure to ST398 MRSA in whom MRSA eradication will not be effective, due to repeated exposure. We performed a large Dutch multicenter study and calculated that the relative risk on transmission of MRSA ST398 in the hospital, as compared to healthcare associated (HA)-MRSA, was only 0.28. The calculated RA ratio between HA-MRSA and livestock associated MRSA was 5.9 (95% CI 2.2-23.8), suggesting livestock associated MRSA is almost six times less transmissible than HA-MRSA. Also, the MRSA prevalence among admitted patients suspected for MRSA carriage because of treatment in foreign hospitals appeared lower than previously reported: 1.6% and 1.9% in two Dutch multicenter trial we executed between 2005 and 2008. Besides changes in MRSA epidemiology, new rapid diagnostic tests (RDT) have become available that allow more rapid detection for MRSA carriage. The most important advantage of RDT is the reduction in unnecessary pre-emptive isolation days. RDT of MRSA reduced the number of pre-emptive isolation days with 48% and 60% when using chromogenic agar and MRSA PCR, respectively. Infection control policies to prevent S. aureus infections, both MSSA and MRSA, in the Netherlands are cost-saving, despite the costs to execute preventive control policies. Yet, cost-effectiveness of RDT for MRSA is unknown. In the Dutch multicenter trial the extra costs of screening and pre-emptive isolation of high risk patients were €95.77, €125.43 and €6.74 per isolation day avoided, using IDI PCR, GeneXpert PCR and chromogenic agar for MRSA screening, respectively. Since the additional costs of one extra isolation day on a regular ward in a non-outbreak situation were estimated to be €26.34, chromogenic screening, but not PCR-based screening, is a cost saving procedure. In conclusion, there is no need to pre-emptively isolate patients with a high risk for MRSA carriage on hospital admission. These patients can be screened using both RDT and conventional microbiological cultures. Closure of wards for new admissions is rarely necessary anymore when using PCR-based testing

The nosocomial transmission rate of animal-associated ST398 meticillin-resistant Staphylococcus aureus

The global epidemiology of meticillin-resistant Staphylococcus aureus (MRSA) is characterized by different clonal lineages with different epidemiological behaviour. There are pandemic hospital clones (hospital-associated (HA-)MRSA), clones mainly causing community-acquired infections (community-associated (CA-)MRSA, mainly USA300) and an animal-associated clone (ST398) emerging in European and American livestock with subsequent spread to humans. Nosocomial transmission capacities (RA) of these different MRSA types have never been quantified. Using two large datasets from MRSA outbreaks in Dutch hospitals (dataset 1, the UMC Utrecht for 144 months; dataset 2, 51 hospitals for six months) and a recently developed mathematical model, we determined the genotype-specific RA for ST398 and non-ST398 isolates (categorized as HA-MRSA), using observational data, the detection rate of MRSA carriage and the discharge rate from hospital as the input. After detection of 42 MRSA index cases in dataset 1 (all non-ST398 MRSA) 5076 people were screened, yielding 30 secondary cases. In dataset 2, 75 index cases (51 non-ST398 MRSA and 24 ST398) resulted in 7892 screened individuals and 56 and three secondary cases for non-ST398 MRSA and ST398, respectively. The ratio between discharge and the detection rate was 2.7. RA values (95% confidence interval (CI)) were 0.68 (0.47–0.95) for non-ST398 MRSA in dataset 1, 0.93 (0.71–1.21) for non-ST398 MRSA in dataset 2 and 0.16 (0.04–0.40) for ST398. The RA ratio between non-ST398 MRSA and ST398 was 5.90 (95% CI 2.24–23.81). ST398 is 5.9 times less transmissible than non-ST398 MRSA in Dutch hospitals, which may allow less stringent transmission-control measures for ST398 MRS

Transmissibility of livestock-associated methicillin-resistant Staphylococcus aureus (ST398) in Dutch hospitals

We quantified nosocomial transmission rates of sequence type (ST) 398 methicillin-resistant Staphylococcus aureus (MRSA) (an emerging livestock-associated MRSA clone) and non-ST398 MRSA isolates in patients hospitalized without infection control measures in 51 Dutch hospitals. Identification of 174 index patients initiated 139 post-exposure screenings of 9925 persons. There were 65 genotype-confirmed secondary cases (three and 62 for ST398 and non-ST398 MRSA, respectively), yielding a relative transmission risk for ST398 MRSA of 0.28 (95% CI 0.09–0.90), which was not sensitive to adjustment for duration of hospitalization at time of detection. Nosocomial transmission of ST398 MRSA is 72% less likely than that of non-ST398 MRSA strain

Rapid diagnostic testing of methicillin-resistant Staphylococcus aureus carriage at different anatomical sites: costs and benefits of less extensive screening regimens

Item does not contain fulltextMultiple body site screening and pre-emptive isolation of patients at risk for methicillin-resistant Staphylococcus aureus (MRSA) carriage are considered essential for control of nosocomial spread. The relative importance of extranasal screening when using rapid diagnostic testing (RDT) is unknown. Using data from a multicentre study evaluating BD GeneOhm MRSA PCR (IDI), Xpert MRSA (GeneXpert) and chromogenic agar, added to conventional cultures, we determined cost-effectiveness assuming isolation measures would have been based on RDT results of different hypothetical screening regimes. Costs per isolation day avoided were calculated for regimes with single or less extensive multiple site RDT, regimes without conventional back-up cultures and when PCR would have been performed with pooling of swabs. Among 1764 patients at risk, MRSA prevalence was 3.3% (n = 59). In all scenarios the negative predictive value is above 98.4%. With back-up cultures of all sites as a reference, the costs per isolation day avoided were euro15.19, euro30.83 and euro45.37 with 'nares only' screening using chromogenic agar, IDI and GeneXpert, respectively, as compared with euro19.95, euro95.77 and euro125.43 per isolation day avoided when all body sites had been screened. Without back-up cultures costs per isolation day avoided using chromogenic agar would range from euro9.24 to euro76.18 when costs per false-negative RDT range from euro5000 up to euro50 000; costs for molecular screening methods would be higher in all scenarios evaluated. In conclusion, in a low endemic setting chromogenic agar screening added to multiple site conventional cultures is the most cost-effective MRSA screening strategy

Rapid screening of methicillin-resistant Staphylococcus aureus using PCR and chromogenic agar: a prospective study to evaluate costs and effects

Contains fulltext : 89508.pdf (publisher's version ) (Closed access)Pre-emptive isolation of suspected methicillin-resistant Staphylococcus aureus (MRSA) carriers is considered essential for controlling the spread of MRSA, but noncolonized patients will be isolated unnecessarily as a result of a delay in diagnosis of 3-5 days with conventional cultures. We determined costs per isolation day avoided, and incremental costs of rapid MRSA screening tests when added to conventional screening, but with decisions on isolation measures based on PCR results. A prospective multicentre study evaluating BD GeneOhm MRSA PCR (`IDI') (BD Diagnostics, San Diego, CA, USA), Xpert MRSA (`GeneXpert') (Cepheid, Sunnyvale, CA, USA) and chromogenic agar (MRSA-ID) (bioMerieux, Marcy-l'Etoile, France) was performed in 14 Dutch hospitals. Among 1764 patients at risk, MRSA prevalence was 3.3% (n=59). Duration of isolation was 19.7 and 16.1 h with IDI and GeneXpert, respectively, and would have been 30.0 and 76.2 h when based on chromogenic agar and conventional cultures, respectively. Negative predictive values (at a patient level) were 99.5%, 99.1% and 99.5% for IDI, GeneXpert and chromogenic agar, respectively. Numbers of isolation days were reduced by 60% and 47% with PCR-based and chromogenic agar-based screening, respectively. The cost per test was euro56.22 for IDI, euro69.62 for GeneXpert and euro2.08 for chromogenic agar, and additional costs per extra isolation day were euro26.34. Costs per isolation day avoided were euro95.77 (IDI) and euro125.43 (GeneXpert). PCR-based decision-making added euro153.64 (IDI) and euro193.84 (GeneXpert) per patient to overall costs and chromogenic testing would have saved euro30.79 per patient. Rapid diagnostic testing safely reduces the number of unnecessary isolation days, but only chromogenic screening, and not PCR-based screening, can be considered as cost saving.1 december 201

Predictive Performance of Cardiovascular Disease Risk Prediction Algorithms in People Living With HIV

Immunogenetics and cellular immunology of bacterial infectious disease