Soluble urokinase plasminogen activator receptor (suPAR) is a novel, independent predictive marker of myocardial infarction in HIV-1-infected patients: a nested case-control study.

OBJECTIVES: Patients infected with HIV are at increased risk of myocardial infarction (MI). Increased plasma levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) have been associated with increased risk of cardiovascular diseases (CVD), including MI in the general population. We tested suPAR as a predictive biomarker of MI in HIV-1-infected individuals. METHODS: suPAR levels were investigated in a nested case-control study of 55 HIV-1-infected cases with verified first-time MI and 182 HIV-1-infected controls with no known CVD. Controls were matched for age, gender, duration of antiretroviral therapy (ART), smoking and no known CVD. suPAR was measured in the four plasma samples available for each patient at different time-points; 1, Before initiation of ART; 2, 3 months after initiation of ART; 3, 1 year before the case's MI; and 4, The last sample available before the case's MI. RESULTS: In unadjusted conditional regression analysis, higher levels of suPAR were associated with a significant increase in risk of MI at all time-points. Patients in the third and fourth suPAR quartiles had a three- to 10-fold higher risk of MI compared to patients in the lowest suPAR quartile at all time-points. suPAR remained a strong significant predictor of MI, when adjusting for HIV-1 RNA, total cholesterol, triglycerides and high-density lipoprotein. CONCLUSION: Elevated suPAR levels were associated with increased risk of MI in HIV-infected patients, suggesting that suPAR could be a useful biomarker for prediction of first-time MI in this patient group, even years before the event.

Utilization of psychotropic drugs prescribed to persons with and without HIV infection: a Danish nationwide population-based cohort study.

OBJECTIVES: The objective was to estimate the utilization of psychotropic drugs in HIV-infected individuals compared with that in the background population. METHODS: Using data obtained from the Danish HIV Cohort Study and the Danish National Prescription Registry, we analysed aggregated data on redeemed prescription of psychotropic drugs during 1995-2009. We primarily focused our analyses on HIV-infected individuals with no history of injecting drug use (IDU) or hepatitis C virus (HCV) infection. Drug utilization was expressed as defined daily doses per 1000 person-days (DDD/1000PD). The utilization rate ratio (URR) was calculated as utilization in the HIV-infected cohort compared with that in the comparison cohort. We estimated longitudinal trends in utilization and potential associations with HIV and exposure to highly active antiretroviral therapy (HAART), especially efavirenz. RESULTS: During 1995-2009, 54.5% of the HIV-infected cohort (3615 non-IDU/non-HCV-infected HIV-infected individuals) and 29.2% of the comparison cohort (32 535 individuals) had at least one prescription of a psychotropic drug. HIV infection was associated with a URR of 1.13 for antipsychotics, 1.76 for anxiolytics, 4.42 for hypnotics and sedatives, and 2.28 for antidepressants. Antidepressants were confined primarily to men who have sex with men (MSM). Older age, more recent calendar time, and increased time after HIV diagnosis were associated with increased drug utilization. However, no association with exposure to HAART or efavirenz was found. CONCLUSIONS: HIV-infected individuals had a higher utilization of psychotropic drugs than the background population, which was not confined to individuals with a history of IDU or HCV infection. This emphasizes the need to focus on diagnosis of, and appropriate psychopharmacological interventions for, mental disorders in this population.

Laboratory exposure to Brucella melitensis in Denmark: a prospective study.

Brucella species are a frequent cause of laboratory-acquired infections. This report describes the handling of a laboratory exposure of 17 laboratory staff members exposed to Brucella melitensis in a large microbiology laboratory in a brucella-non-endemic area. We followed the US Centers for Disease Control and Prevention guidelines, but, of 14 staff members classified as high-risk exposure, none accepted post-exposure prophylaxis. However, in a period of 6 months of follow-up, none of the exposed laboratory workers developed brucellosis and all obtained sera were negative for antibrucella antibodies. We therefore question the value of routine serological follow-up.

No change in viral set point or CD4 cell decline among antiretroviral treatment-naïve, HIV-1-infected individuals enrolled in the Danish HIV Cohort Study in 1995-2010.

OBJECTIVES: Recent studies have reported faster progression of HIV infection than anticipated based on results from earlier studies. The aim of the present study was to examine if the virulence of HIV-1 infection changed in the period 1995-2010 among chronically HIV-infected individuals in Denmark. METHODS: We included all patients registered in the Danish HIV Cohort Study, who were diagnosed in 1995-2009, had a CD4 count > 100 cells/µL at diagnosis and had at least two CD4 measurements prior to initiation of antiretroviral therapy (ART). Changes in viral set point and rate of CD4 cell decline from enrolment until the initiation of ART by calendar year of HIV diagnosis were analysed. Time to first CD4 count < 350 cells/µL was compared among patients diagnosed in 1995-2000, 2001-2005 and 2006-2010. RESULTS: We followed 1469 HIV-infected patients for a total of 5783 person-years. The median viral set point was 4.27 log10 HIV-1 RNA copies/mL [interquartile range (IQR) 3.58-4.73 log10 copies/mL]. The median CD4 cell decline per year was 57 cells/µL (IQR 10-139 cells/µL). In analyses adjusted for age, gender, origin, route of transmission and CD4 count at diagnosis, there were no associations between year of diagnosis and viral set point or CD4 cell decline. Time to first CD4 count < 350 cells/µL did not change in the study period [incidence rate ratio (IRR) 0.90 (95% confidence interval (CI) 0.76-1.06) for 2001-2005 and 1.09 (95% CI 0.79-1.34) for 2006-2010 compared with 1995-2000]. CONCLUSIONS: We found no evidence of changing trends in viral set point, CD4 cell decline or time to CD4 count < 350 cells/µL during the period 1995-2010 in a cohort of chronically HIV-infected individuals.

Causes of death among Danish HIV patients compared with population controls in the period 1995-2008.

PURPOSE: To compare the mortality and causes of death in human immunodeficiency syndrome (HIV) patients with the background population. METHODS: All adult HIV patients treated in Danish HIV centers from 1995 to 2008 and 14 controls for each HIV patient were included. Age-adjusted mortality rates (MR) and mortality rate ratios (MRR) were estimated using direct standardization and Poisson regression analyses. Up to four contributory causes of death for each person were included in analyses of cause-specific MR. RESULTS: A total of 5,137 HIV patients and 71,918 controls were followed for 37,838 and 671,339 person-years (PY), respectively. Among non-injection drug use (IDU) HIV patients, the acquired immune deficiency syndrome (AIDS)-related MR/1,000 PY declined dramatically from 122.9 [95 % confidence interval (CI) 106.8-141.4] in 1995 to 5.0 (95 % CI 3.1-8.1) in 2008. The non-AIDS-related MR did not change substantially from 6.9 (95 % CI 3.8-12.5) to 5.6 (95 % CI 3.6-8.8). The MR of unnatural causes declined from 6.9 (95 % CI 3.8-12.5) to 2.7 (95 % CI 1.4-5.1). The MRR of infections declined from 46.6 (95 % CI 19.6-110.9) to 3.3 (95 % CI 1.6-6.6). The MRR of other natural causes of death remained constant. CONCLUSIONS: After the introduction of highly active antiretroviral therapy (HAART), the AIDS-related mortality has decreased substantially, but the long-term exposure to HIV and HAART has not translated into increasing mortality from malignancy, cardiovascular, and hepatic diseases.

Major but differential decline in the incidence of Staphylococcus aureus bacteraemia in HIV-infected individuals from 1995 to 2007: a nationwide cohort study*.

OBJECTIVES: Incidence rates (IRs) of Staphylococcus aureus bacteraemia (SAB) are known to be higher in HIV-infected individuals than in the general population, but have not been assessed in the era of highly active antiretroviral therapy. METHODS: From 1 January 1995 to 31 December 2007, all Danish HIV-infected individuals (n=4871) and population controls (n=92 116) matched on age and sex were enrolled in a cohort and all cases of SAB were registered. IRs and risk factors were estimated using time-updated Poisson regression analysis. RESULTS: We identified 329 cases of SAB in 284 individuals, of whom 132 individuals were infected with HIV and 152 were not [crude IR ratio (IRR) 24.2; 95% confidence interval (CI) 19.5-30.0, for HIV-infected vs. non-HIV-infected individuals]. Over time, IR declined for HIV-infected individuals (IRR 0.40). Injecting drug users (IDUs) had the highest incidence and the smallest decline in IR, while men who have sex with men (MSM) had the largest decline over time. Among HIV-infected individuals, a latest CD4 count <100 cells/µL was the strongest independent predictor of SAB (IRR 10.2). Additionally, HIV transmission group was associated with risk of SAB. MSM were more likely to have hospital-acquired SAB, a low CD4 cell count and AIDS at the time of HIV acquisition compared with IDUs. CONCLUSIONS: We found that the incidence of SAB among HIV-infected individuals declined during the study period, but remained higher than that among HIV-uninfected individuals. There was an unevenly distributed burden of SAB among HIV transmission groups (IDU>MSM). Low CD4 cell count and IDU were strong predictors of SAB among HIV-infected individuals.

The rate of accumulation of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in patients kept on a virologically failing regimen containing an NNRTI*.

BACKGROUND: Virological failure of first-generation nonnucleoside reverse transcriptase inhibitors (NNRTIs) can compromise the efficacy of etravirine as a result of the accumulation of NNRTI resistance mutations. How quickly NNRTI resistance accumulates in patients with a delayed switch from nevirapine or efavirenz despite virological failure, when these drugs are used as a component of combination antiretroviral therapy (cART), remains unclear. METHODS: The rate of NNRTI resistance accumulation was estimated in patients in EuroSIDA with at least two available genotypic resistance tests (GRTs), provided that (1) the date of the first GRT (t0) was after the date of the first virological failure (VF) of an NNRTI, and (2) patients were receiving an NNRTI and HIV RNA was >500 HIV-1 RNA copies/mL in all measurements between GRTs. RESULTS: A total of 227 patients were included in the study, contributing 467 GRT pairs. At baseline-t0, a median of 3 months after VF, 66% of patients had at least one NNRTI mutation: 103N (34%), 181C (22%) and 190A (20%) were the most common mutations. Overall, 180 additional NNRTI mutations were found to have accumulated over 295 years [1 new/1.6 years; 95% confidence interval (CI) 1.5-1.8]. The rate of accumulation was faster in the first 6 months from VF (1 new/1.1 years), and slower in patients exposed to nevirapine vs. those receiving efavirenz [relative risk (RR) 0.66; 95% CI 0.46-0.95; P=0.03]. CONCLUSIONS: There is an initial phase of rapid accumulation of NNRTI mutations close to the time of VF followed by a phase of slower accumulation. We predict that it should take approximately one year of exposure to a virologically failing first-generation NNRTI-based cART regimen to reduce etravirine activity from fully susceptible to intermediate resistant, and possibly longer in patients kept on a failing nevirapine-containing regimen.

HIV and risk of venous thromboembolism: a Danish nationwide population-based cohort study.

OBJECTIVE: The association between HIV infection and the risk of venous thromboembolism (VTE) is controversial. We examined the risk of VTE in HIV-infected individuals compared with the general population and estimated the impact of low CD4 cell count, highly active antiretroviral therapy (HAART) and injecting drug use (IDU). METHODS: We identified 4333 Danish HIV-infected patients from the Danish HIV Cohort Study and a population-based age- and gender-matched comparison cohort of 43,330 individuals. VTE diagnoses were extracted from the Danish National Hospital Registry. Cumulative incidence curves were constructed for time to first VTE. Incidence rate ratios (IRRs) and impact of low CD4 cell count and HAART were estimated by Cox regression analyses. Analyses were stratified by IDU, adjusted for comorbidity and disaggregated by overall, provoked and unprovoked VTE. RESULTS: The 5-year risk of VTE was 8.0% [95% confidence interval (CI) 5.78-10.74%] in IDU HIV-infected patients, 1.5% (95% CI 1.14-1.95%) in non-IDU HIV-infected patients and 0.3% (95% CI 0.29-0.41%) in the population comparison cohort. In non-IDU HIV-infected patients, adjusted IRRs for unprovoked and provoked VTE were 3.42 (95% CI 2.58-4.54) and 5.51 (95% CI 3.29-9.23), respectively, compared with the population comparison cohort. In IDU HIV-infected patients, the adjusted IRRs were 12.66 (95% CI 6.03-26.59) for unprovoked VTE and 9.38 (95% CI 1.61-54.50) for provoked VTE. Low CD4 cell count had a minor impact on these risk estimates, while HAART increased the overall risk (IRR 1.93; 95% CI 1.00-3.72). CONCLUSION: HIV-infected patients are at increased risk of VTE, especially in the IDU population. HAART and possibly low CD4 cell count further increase the risk.

Abacavir and risk of myocardial infarction in HIV-infected patients on highly active antiretroviral therapy: a population-based nationwide cohort study.

OBJECTIVE: The aim of the study was to examine whether exposure to abacavir increases the risk for myocardial infarction (MI). DESIGN, SETTING AND SUBJECTS: This was a prospective nationwide cohort study which included all Danish HIV-infected patients on highly active antiretroviral therapy (HAART) from 1995 to 2005 (N = 2952). Data on hospitalization for MI and comorbidity were obtained from Danish medical databases. Hospitalization rates for MI after HAART initiation were calculated for patients who used abacavir and those who did not. We used Cox's regression to compute incidence rate ratios (IRR) as a measure of relative risk for MI, while controlling for potential confounders (as separate variables and via propensity score) including comorbidity. MAIN OUTCOME: Relative risk of hospitalization with MI in abacavir users compared with abacavir nonusers. RESULTS: Hospitalization rates for MI were 2.4/1000 person-years (PYR) [95% confidence interval (CI) 1.7-3.4] for abacavir nonusers and 5.7/1000 PYR (95% CI 4.1-7.9) for abacavir users. The risk of MI increased after initiation of abacavir [unadjusted IRR = 2.22 (95% CI 1.31-3.76); IRR adjusted for confounders = 2.00 (95% CI 1.10-3.64); IRR adjusted for propensity score = 2.00 (95% CI 1.07-3.76)]. This effect was also observed among patients initiating abacavir within 2 years after the start of HAART and among patients who started abacavir as part of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen. CONCLUSIONS: We confirmed the association between abacavir use and increased risk of MI. Further studies are needed to control for potential confounding not measured in research to date.

Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV-1-infected individuals receiving combination antiretroviral therapy.

OBJECTIVES: To investigate, using a longitudinal design, whether biomarkers of cardiovascular risk change after a switch to an abacavir (ABC)-containing regimen in HIV-1-infected individuals already receiving combination antiretroviral therapy (ART). METHODS: Thirty-five HIV-1-infected individuals who switched ART to an ABC-containing regimen were identified. Twenty-two HIV-1-infected individuals who switched ART from and to a non-ABC-containing regimen served as controls. Plasma concentrations of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), matrix metallopeptidase 9 (MMP9), myeloperoxidase (MPO) and high sensitivity C-reactive protein (hs-CRP) were measured in blood samples before the switch in ART, and 3 months and 12 months afterwards. Log10-transformed data were compared with paired t-tests. RESULTS: Median MMP9 increased from 45.5 to 64.4 microg/mL after 3 months of ABC exposure (P = 0.011) and remained increased after 12 months (64.2 microg/mL; P = 0.013). MPO increased from median 8.8 to 10.4 microg/mL (P = 0.036) after 3 months of ABC exposure but was not increased after 12 months of exposure (9.1 microg/mL). hs-CRP increased from 3.3 to 4.2 microg/mL after 3 months (P = 0.031) but was not increased after 12 months of exposure (2.8 microg/mL). Neither sVCAM-1 nor sICAM-1 changed after the initiation of ABC. No changes were observed in the control group. CONCLUSIONS: MMP9, MPO and hs-CRP all increased after a switch in ART to an ABC-containing regimen. This indicates increased cardiovascular risk in viral load-suppressed HIV-1-infected individuals switching to ABC and proposes a proinflammatory potential as the underlying pathogenetic mechanism.

Reduction in circulating markers of endothelial dysfunction in HIV-infected patients during antiretroviral therapy.

OBJECTIVES: Antiretroviral therapy (ART) in HIV-infected patients is associated with increased cardiovascular risk. Circulating markers of endothelial dysfunction may be used to study early atherogenesis. The aim of our study was to investigate changes in such markers during initiation of ART. METHODS: In 115 HIV-positive treatment-naïve patients, plasma lipids, E-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), tissue-type plasminogen activator inhibitor 1 (tPAI-1) and high-sensitivity C-reactive protein (hsCRP) were measured before and after 2 and 14 months of ART. A control group of 30 healthy subjects was included. Values are mean+/-standard error of the mean. RESULTS: Prior to treatment, HIV-infected patients had elevated levels of sICAM-1 (296+/-24 vs. 144+/-12 ng/mL), tPAI-1 (18 473+/-1399 vs. 5490+/-576 pg/mL) and hsCRP (28 060+/-5530 vs. 6665+/-2063 ng/mL) compared with controls (P<0.001). In contrast, sVCAM-1 and E-selectin did not differ between the groups. Initiation of ART resulted in significantly lower levels of E-selectin (15.1+/-0.8; P<0.01), sICAM-1 (248+/-12 ng/mL; P<0.05), sVCAM-1 (766+/-33 ng/mL; P<0.001) and hsCRP (14 708+/-2358 ng/mL; P<0.001) after 2 months, which remained reduced at 14 months. tPAI-1 was not influenced by initiation of ART. CONCLUSIONS: Markers of endothelial dysfunction were elevated in treatment-naïve HIV-infected patients and were related to HIV RNA viral load. Initiation of ART reduced the levels of the majority of these markers. The positive effect of ART initiation was dependent on the duration of HIV infection prior to treatment.

Predictive value of soluble haemoglobin scavenger receptor CD163 serum levels for survival in verified tuberculosis patients.

Pre-treatment serum levels of sCD163 were measured in a cohort of 236 suspected tuberculosis (TB) cases from Guinea-Bissau, with a median follow-up period of 3.3 years (range 0-6.4 years). In 113 cases, the diagnosis of TB was verified by positive sputum microscopy and/or culture. Among the verified TB cases, a decreased survival rate was found in 27 patients with sCD163 levels above the upper reference limit (3.95 microg/mL). The difference in survival was significant during TB treatment (log rank, p<0.02) and after long-term follow-up (log rank, p<0.001). The decrease in survival rate during TB treatment remained significant in a multivariate Cox model controlling for human immunodeficiency virus (HIV) status, age and gender, with a mortality increase of 1.19 (95% CI, 1.04-1.36) per microg of sCD163, and a hazard ratio (HR) for sCD163 levels above the upper reference limit of 4.18 (95% CI, 1.06-16.4). The difference was not significant after excluding patients with concomitant HIV-1 and HIV-2 infection in Kaplan-Meier analyses (log rank, p 0.11). In contrast, the difference in survival remained significant in Kaplan-Meier analyses after long-term follow-up, even after excluding patients with concomitant HIV-1 and HIV-2 infection (log rank, p 0.002). In the Cox model, the mortality increase per microg of sCD163 was 1.27 (95% CI, 1.14-1.40), with an HR for elevated sCD163 levels of 2.85 (95% CI, 1.44-5.63). The HRs for concomitant HIV-1 and HIV-2 infection were 6.92 (95% CI, 3.28-14.58) and 2.48 (95% CI, 1.09-5.67), respectively. Thus, sCD163 levels appeared to be an independent predictor of survival in verified TB patients.

The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality.

This multicentre prospective study was conducted to investigate whether the level of the soluble form of urokinase-type plasminogen activator receptor (suPAR) is elevated during pneumococcal bacteraemia and is of predictive value in the early stage of the disease. Plasma levels of suPAR were increased significantly (median 5.5; range 2.4-21.0 ng/mL) in 141 patients with pneumococcal bacteraemia, compared to 31 healthy controls (median 2.6, range 1.5-4.0 ng/mL, p 0.001). Furthermore, suPAR levels were elevated significantly in patients who died from the infection (n = 24) compared to survivors (n = 117; p < 0.001). No correlation was found between suPAR levels and C-reactive protein. In univariate logistic regression analysis, hypotension, renal failure, cerebral symptoms and high serum concentrations of protein YKL-40 and suPAR were associated significantly with mortality (p < 0.05). In multivariate analysis, only suPAR remained a significant predictor of death (mortality rate of 13 for suPAR levels of > 10 ng/mL; 95% CI: 1.1-158). The increase in suPAR levels may reflect increased expression by vascular or inflammatory cells in the setting of pneumococcal sepsis. This plasma protein may be used to identify patients who are severely ill with pneumococcal bacteraemia.

[Is polysaccharide pneumococcal vaccine effective in adults?]. / Er der klinisk effekt af polysakkaridbaseret pneumokokvaccine hos voksne?

Pneumococcal (PC) infections are common and dangerous. Polysaccharide PC vaccine is recommended in some countries for use in adults who have an increased risk of PC infection. Randomised studies of the clinical effect of polysaccharide PC vaccine in healthy adults reported a protective effect, which, in general, was not reproduced in subsequent studies of risk groups. Case-control studies showed a protective effect, but were potentially biased. Two meta-analyses found that the vaccine had an effect on the incidence of PC bacteraemia and pneumonia in healthy adults, but had no effect in risk groups; one meta-analysis found no evidence of less effect in risk groups. There is insufficient evidence to support mass vaccination of risk groups, including elderly people, with polysaccharide PC vaccine.

[Sample size and number needed to treat--a statistical case study]. / Sample size og number needed to treat--en statistisk kasuistik.

The sample size necessary in each group to detect a significant effect of a vaccine on a given disease in a randomised clinical trial (RCT) can be calculated from the observed disease incidence without vaccine, the expected incidence with vaccine, and the desired level of significance and statistical power of the study. In this example, sample size is calculated for an RCT of the effect of pneumococcal vaccine on the incidence of pneumococcal sepsis. The number of persons needed to be vaccinated to prevent one episode of pneumococcal sepsis can be similarly calculated from the observed incidences with and without vaccine.

Hypotension during endotoxemia in aged humans.

BACKGROUND: and objective The aim of this study was to determine possible age-associated differences in human blood pressure regulation during an immunological challenge in healthy subjects. METHODS: Eight healthy young volunteers (median age 24 yr) and nine healthy elderly volunteers (median age 66 yr) received an intravenous bolus injection of Escherichia coli endotoxin (2 ng kg(-1)). Blood pressure, heart rate and core temperature were monitored during the first 7 h. Plasma catecholamine concentrations were measured at hourly intervals. RESULTS: The elderly showed a significantly more pronounced decrease in mean arterial pressure 4-7 h after endotoxin administration compared with the young controls (ANOVA; age x time; P < 0.0005). This mainly reflected a decrease in the systolic blood pressure in the elderly. The heart rate of both groups increased without difference between groups. Increased plasma epinephrine concentrations were found 2-3 h after endotoxin administration in both groups. Five hours after the endotoxin challenge, the epinephrine concentration had returned to control values in the elderly group only, in spite of decreased blood pressure. CONCLUSION: In conclusion, healthy elderly subjects fail to maintain a constant mean arterial pressure in response to the immunological challenge of endotoxemia.

Ageing is associated with a prolonged fever response in human endotoxemia.

The purpose of this study was to investigate whether an age-associated impaired acute-phase response exists. Nine healthy elderly volunteers (median, 66 years; range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to 27 years) were given an intravenous bolus of endotoxin (2 ng/kg). The rectal temperature was monitored continuously, and blood samples for cytokine measurements were obtained before endotoxin administration as well as 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 24 h after the injection. The elderly subjects showed a more prolonged fever response compared to the young controls. Levels of tumor necrosis factor alpha (TNF-alpha), soluble TNF receptors (sTNFR-I), interleukin-6 (IL-6), IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) in plasma increased markedly following endotoxin administration in both groups. The elderly group showed larger initial increases in TNF-alpha and sTNFR-I levels and prolonged increased levels of sTNFR-I. Monocyte concentrations decreased in both groups, with the elderly group showing a more rapid decrease and a slower subsequent increase than did the young group. Furthermore, the elderly group had a more rapid increase in C-reactive protein levels than did the young group. In conclusion, ageing is associated with an altered acute-phase response including initial hyperreactivity, prolonged inflammatory activity, and prolonged fever response.

[Non-antibiotic treatment of sepsis]. / Non-antibiotisk behandling af sepsis.

Treatment of patients with sepsis with monoclonal antibodies against lipopolysaccharide, tumour necrosis factor or treatment with soluble TNF-receptors or interleukin-1 receptor antagonist have not had any effect on mortality. Treatment with intravenous polyclonal nonspecific immunoglobulin has been shown to have beneficial efficacy on mortality. However, the number of patients included in the latter treatment studies are limited, the patients studied are heterogeneous and do not allow to conclude that sepsis patients should be routinely treated with immunoglobulins.

Mannose-binding lectin polymorphisms and susceptibility to infection in systemic lupus erythematosus.

OBJECTIVE: To determine whether variant alleles in the coding portion of the mannose-binding lectin (MBL) gene are associated with increased susceptibility to systemic lupus erythematosus (SLE) and concomitant infections. METHODS: MBL alleles and serum concentrations were determined by polymerase chain reaction and enzyme-linked immunosorbent assay, respectively, in 91 Danish patients with SLE and in 250 controls. RESULTS: Homozygosity for MBL variant alleles was observed in 7.7% of the SLE patients compared with 2.8% of the controls (P = 0.06), while no difference was seen for heterozygosity (33.0% versus 34.4%). Homozygotes had an increased risk of acquiring serious infections compared with patients who were heterozygous or homozygous for the normal allele (odds ratio 8.6, 95% confidence interval 1.5-47.6, P = 0.01). The time interval from the diagnosis of SLE to the first infectious event was shorter (P = 0.017), and the annual number of infectious events was 4 times higher, among homozygotes (P = 0.00002). They were especially prone to acquire pneumonia (P = 0.00004). CONCLUSION; Homozygosity for MBL variant alleles may explain much of the increased risk of complicating infections seen in SLE patients. Additionally, it is a minor risk factor for acquiring SLE.