Summary Objectives Smaller studies indicate that the incidence of pyogenic spondylodiscitis is increasing, possible related to a growing elderly population. Data supporting this is sparse, and we ...therefore studied patient characteristics and changes in spondylodiscitis incidence 1995–2008. Methods In a population-based study we identified all patients aged ≥18 years treated for pyogenic spondylodiscitis in Funen County, Denmark (population 483 123). Annual incidences were determined. Demographics, symptoms and diagnostic methods were recorded. Results We found 192 cases: median age 66.6 years; 57.3% men; 76.6% culture positive cases . Staphylococcus aureus was the most common pathogen (55.1%). During 1995–2008 the overall incidence, incidence of culture negative cases, and incidence of cases due to S. aureus increased 2.2–5.8, 0.3–1.8, and 1.6–2.5 cases per 100 000 person years, respectively. The elderly had the highest incidence compared to those aged ≤70 years (rate ratio for men 5.9 (95% CI: 4.2–8.5) and for women 3.5 (95% CI: 2.3–5.3)). Conclusions During 1995–2008 the overall incidence of S. aureus and culture negative cases of spondylodiscitis increased and remained highest among the elderly. Whether the increase is real or is a result of improved diagnostic methods and workup remains unknown.
Background. Chronic human immunodeficiency virus (HIV) infection is associated with intestinal permeability and microbial translocation that contributes to systemic immune activation, which is an ...independent predictor of HIV disease progression. The association of microbial translocation with clinical outcome remains unknown. Methods. This nested case-control study included 74 subjects who died, 120 of whom developed cardiovascular disease and 81 of whom developed AIDS during the Strategies for Management of Anti-Retroviral Therapy (SMART) study with matched control subjects. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), soluble CD14 (sCD14), endotoxin core antibody (EndoCAb), and 16S ribosomal DNA (rDNA) were measured in baseline plasma samples. Results. Subjects with the highest quartile of sCD14 levels had a 6-fold higher risk of death than did those in the lowest quartile (95% confidence interval, 2.2-16.1; P<. 001), with minimal change after adjustment for inflammatory markers, CD4⁺ T cell count, and HIV RNA level. No other marker was significantly associated with clinical outcomes. I-FABP, LPS, and sCD14 were increased and EndoCAb was decreased in study subjects, compared with healthy volunteers. sCD14 level correlated with levels of IL-6, C-reactive protein, serum amyloid A and D-dimer. Conclusions. sCD14, a marker of monocyte response to LPS, is an independent predictor of mortality in HIV infection. Therapeutic attenuation of innate immune activation may improve survival in patients with HIV infection.
•SIRS versus Sepsis-3 regarding mortality in medical patients with acute infectious disease.•SOFA score of at least 2 predicts 28-day mortality in medical patients with acute infectious disease.•SOFA ...score of at least 2 is a better prognostic marker than qSOFA and SIRS in medical patients with acute infectious disease.
Evaluating the use of sequential organ failure assessment (SOFA) ≥ 2 compared to quick SOFA (qSOFA) and to systemic inflammatory response syndrome (SIRS) in assessing 28-days mortality in medical patients with acute infection.
In total, 323 patients with verified infection were stratified in accordance to Sepsis-3. SOFA, qSOFA and SIRS were calculated using registered variables. Adverse outcome was death within 28-days of admission.
In total, 190 (59%) patients had a SOFA score≥2 and the overall in-hospital mortality was 21 (6%). Scores of SOFA and qSOFA were both significantly elevated in non-survivors. SOFA showed good accuracy (Area under the receiver operating characteristic (AUROC)=0.83, 95% CI, 0.76 - 0.90) for 28-days mortality compared with qSOFA (AUROC=0.67, 95% CI, 0.54 - 0.80) and SIRS (AUROC=0.62, 95% Cl 0.49 - 0.74). SOFA was≥2 in all patients who died, while qSOFA and SIRS was≥2 in 8 (38%) and 17 (81%) of the patients who died, respectively.
SOFA score≥2 was better than SIRS and qSOFA to predict mortality within 28-days of admission among patients with acute infectious disease.
We determined the impact of three factors on mortality in HIV-infected patients who had been on highly active antiretroviral therapy (HAART) for at least one year: (1) insufficient response to ...(HAART) and presence of AIDS-defining diseases, (2) comorbidity, and (3) drug and alcohol abuse and compared the mortality to that of the general population.
In a Danish nationwide, population-based cohort study, we used population based registries to identify (1) all Danish HIV-infected patients who started HAART in the period 1 January 1998-1 July 2009, and (2) a comparison cohort of individuals matched on date of birth and gender (N = 2,267 and 9,068, respectively). Study inclusion began 1 year after start of HAART. Patients were categorised hierarchically in four groups according to the three risk factors, which were identified before study inclusion. The main outcome measure was probability of survival from age 25 to 65 years. The probability of survival from age 25 to age 65 was substantially lower in HIV patients 0.48 (95% confidence interval (CI) 0.42-0.55) compared to the comparison cohort 0.88 (0.86 to 0.90). However, in HIV patients with no risk factors (N = 871) the probability of survival was equivalent to that of the general population 0.86 (95% CI 0.77-0.92). In contrast, the probability of survival was 0.58 in patients with HIV risk factors (N = 704), 0.30 in patients with comorbidities (N = 479), and 0.03 in patients with drug or alcohol abuse (N = 313).
The increased risk of death in HIV-infected individuals is mainly attributable to risk factors that can be identified prior to or in the initial period of antiretroviral treatment. Mortality in patients without risk factors on a successful HAART is almost identical to that of the non-HIV-infected population.
In a nationwide, population-based cohort study we assessed the risk of diabetes mellitus (DM) in HIV-infected individuals compared with the general population, and evaluated the impact of risk ...factors for DM in HIV-infected individuals.
We identified 4,984 Danish-born HIV-infected individuals from the Danish HIV Cohort Study and a Danish born population-based age- and gender-matched comparison cohort of 19,936 individuals (study period: 1996-2009). Data on DM was obtained from the Danish National Hospital Registry and the Danish National Prescription Registry. Incidence rate ratios (IRR) and impact of risk factors including exposure to Highly Active Antiretroviral Therapy (HAART) and antiretroviral drugs were estimated by Poisson regression analyses.
In the period 1996-1999 risk of DM was higher in HIV-infected individuals compared to the comparison cohort (adjusted IRR: 2.83; 95%CI: 1.57-5.09), both before (adjusted IRR: 2.40; 95%CI: 1.03-5.62) and after HAART initiation (adjusted IRR: 3.24; 95% CI: 1.42-7.39). In the period 1999-2010 the risk of DM in HIV-infected individuals did not differ from that of the comparison cohort (adjusted IRR: 0.90; 95% CI: 0.72-1.13), although the risk was decreased before HAART-initiation (adjusted IRR: 0.45; 95%CI: 0.21-0.96). Increasing age, BMI and the presence of lipoatrophy increased the risk of DM, as did exposure to indinavir, saquinavir, stavudine and didanosine.
Native HIV-infected individuals do not have an increased risk of developing DM compared to a native background population after year 1998. Some antiretroviral drugs, not used in modern antiretroviral treatment, seem to increase the risk of DM.
Whether the reported high risk of age-related diseases in HIV-infected people is caused by biological ageing or HIV-associated risk factors such as chronic immune activation and low-grade ...inflammation is unknown. We assessed time trends in age-standardised and relative risks of nine serious age-related diseases in a nationwide cohort study of HIV-infected individuals and population controls.
We identified all HIV-infected individuals in the Danish HIV Cohort Study who had received HIV care in Denmark between Jan 1, 1995, and June 1, 2014. Population controls were identified from the Danish Civil Registration System and individually matched in a ratio of nine to one to the HIV-infected individuals for year of birth, sex, and date of study inclusion. Individuals were included in the study if they had a Danish personal identification number, were aged 16 years or older, and were living in Denmark at the time of study inclusion. Data for study outcomes were obtained from the Danish National Hospital Registry and the Danish National Registry of Causes of Death and were cardiovascular diseases (myocardial infarction and stroke), cancers (virus associated, smoking related, and other), severe neurocognitive disease, chronic kidney disease, chronic liver disease, and osteoporotic fractures. We calculated excess and age-standardised incidence rates and adjusted incidence rate ratios of outcomes for time after HIV diagnosis, highly active antiretroviral therapy (ART) initiation, and calendar time. The regression analyses were adjusted for age, sex, calendar time, and origin.
We identified 5897 HIV-infected individuals and 53,073 population controls; median age was 36·8 years (IQR 30·6-44·4), and 76% were men in both cohorts. Dependent on disease, the HIV cohort had 55,050-57,631 person-years of follow-up and the population controls had 638,204-659,237 person-years of follow-up. Compared with the population controls, people with HIV had high excess and relative risk of all age-related diseases except other cancers. Overall, the age-standardised and relative risks of cardiovascular diseases, cancers, and severe neurocognitive disease did not increase substantially with time after HIV diagnosis or ART initiation. Except for chronic kidney diseases, the age-standardised and relative risks of age-related diseases did not increase with calendar time.
Severe age-related diseases are highly prevalent in people with HIV, and continued attention and strategies for risk reduction are needed. The findings from our study do not suggest that accelerated ageing is a major problem in the HIV-infected population.
Preben og Anna Simonsens Fond, Novo Nordisk Foundation, Danish AIDS Foundation, Augustinus Foundation, and Odense University Hospitals Frie Fonds Midler.
Acute patients presenting with hypotension in the prehospital or emergency department (ED) setting are in need of focused management and knowledge of the epidemiology characteristics might help the ...clinician. The aim of this review was to address prevalence, etiology and mortality of nontraumatic hypotension (SBP ≤ 90 mmHg) with or without the presence of shock in the prehospital and ED setting.
We performed a systematic literature search up to August 2013, using Medline, Embase, Cinahl, Dare and The Cochrane Library. The analysis and eligibility criteria were documented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-guidelines) and The Cochrane Collaboration. No restrictions on language, publication date, or status were imposed. We used the Newcastle-Ottawa quality assessment scale (NOS-scale) and the Strengthening the Reporting of Observational studies in Epidemiology (STROBE-statement) to assess the quality.
Six observational studies were considered eligible for analysis based on the evaluation of 11,880 identified papers. Prehospital prevalence of hypotension was 19.5/1000 emergency medicine service (EMS) contacts, and the prevalence of hypotensive shock was 9.5-19/1000 EMS contacts with an inhospital mortality of shock between 33 to 52%. ED prevalence of hypotension was 4-13/1000 contacts with a mortality of 12%. Information on mortality, prevalence and etiology of shock in the ED was limited. A meta-analysis was not feasible due to substantial heterogeneity between studies.
There is inadequate evidence to establish concise estimates of the characteristics of nontraumatic hypotension and shock in the ED or in the prehospital setting. The available studies suggest that 2% of EMS contacts present with nontraumatic hypotension while 1-2% present with shock. The inhospital mortality of prehospital shock is 33-52%. Prevalence of hypotension in the ED is 1% with an inhospital mortality of 12%. Prevalence, etiology and mortality of shock in the ED are not well described.
Background. Human immunodeficiency virus (HIV) infection predisposes to progressive multifocal leukoencephalopathy (PML). Here, we describe the incidence, presentation, and prognosis of PML in ...HIV-1-infected patients during the period before highly active antiretroviral therapy (HAART) (1995–1996) and during the early HAART (1997–1999) and late HAART (2000–2006) periods. Methods. Patients from a nationwide population-based cohort of adult HIV-1-infected individuals were included. We calculated incidence rates of PML and median survival times after diagnosis. We also described neurological symptoms at presentation and follow-up. Results. Among 4649 patients, we identified 47 patients with PML. The incidence rates were 3.3, 1.8, and 1.3 cases per 1000 person-years at risk in 1995–1996, 1997–1999, and 2000–2006, respectively. The risk of PML was significantly associated with low CD4+ cell count, and 47% of cases were diagnosed by means of brain biopsy or polymerase chain reaction analysis for JC virus. The predominant neurological symptoms at presentation were coordination disturbance, cognitive defects, and limb paresis. Thirty-five patients died; the median survival time was 0.4 years (95% confidence interval CI, 0.0–0.7) in 1995–1996 and 1.8 years (95% CI, 0.6–3.0) in both 1997–1999 and 2000–2006. CD4+ cell count >50 cells/µL at diagnosis of PML was significantly associated with reduced mortality. Conclusions. The incidence of PML in HIV-infected patients decreased after the introduction of HAART. Survival after PML remains poor. In the management of PML, the main focus should be on prophylactic measures to avoid immunodeficiency.
Abstract Background context Information on short- and especially long-term mortality among patients with infectious spondylodiscitis is sparse. Purpose To analyze mortality, factors associated with ...death, and cause-specific mortality rates among patients with infectious nonpostoperative spondylodiscitis. Study design A case-cohort study. Patient sample We identified all patients aged 18 years or older treated for infectious spondylodiscitis from January 1994 to May 2009 at hospitals in Funen County, Denmark. Outcome measures Overall and cause-specific mortality. Methods Mortality rates among patients were compared with rates among a reference population using Kaplan-Meier plots and mortality rate ratios (MRRs). Short-term mortality was defined as deaths within first year after admission and long-term mortality was deaths thereafter. Factors associated with death were determined. Results Among 298 identified patients, 61 (20%) died within the first year. Adjusted MRRs were 16.8 (95% confidence interval: 9.9–28.5) for 0 to 90 days; 4.2 (2.5–7.0) for 91 to 365 days; 2.2 (1.6–2.9) for 1 to 4 years; and 1.7 (1.2–2.5) for 5 to 14 years. Mortality rate ratios stratified on microbiological etiology were 8.8 (3.3–22.1) for 0 to 90 days; 1.4 (0.3–5.8) for 91 to 365 days; 3.2 (2.0–5.1) for 1 to 4 years; and 1.1 (0.5–2.4) for 5 to 14 years for unknown etiology and 24.0 (13.0–44.2) for 0 to 90 days; 6.0 (3.1–11.5) for 91 to 365 days; 1.9 (1.1–3.2) for 1 to 4 years; and 2.7 (1.5–4.7) for 5 to 14 years among Staphylococcus aureus infections. The main factors associated with short-term mortality were severe neurologic deficits at the time of admission, epidural abscess, and comorbidities. Long-term mortality seemed independent of microbiological etiology. Conclusions Mortality remained high the first year after admission and thereafter decreased with time to a level close to the reference population. Short-term mortality was especially related to infection with abscess formation and neurologic deficits and long-term mortality was related to alcohol dependency.
Abstract Background During the last few years many new human picornaviruses have been discovered due to advances in metagenomics and other molecular biological approaches. The clinical significance ...and the occurrence are only sparsely described. Objectives To determine the epidemiology and clinical significance of infections with the novel human picornaviruses, aichi virus, cosavirus, salivirus, and saffold virus in infants in Denmark. Study design We tested 1393 stool samples from a birth cohort of 454 children for these viruses. Samples were collected at ages 6, 10 and 15 months, and at episodes of gastroenteritis. Samples were tested by real-time reverse-transcriptase polymerase chain reaction assays. Each study participant had a diary, where the parents reported episodes of disease, including gastroenteritis. Results Aichi virus, salivirus and saffold virus were detected in 6, 9 and 38 of the children, respectively, but cosavirus was not detected in any of the children. There was a clear seasonal variation with most infections occurring in autumn and winter. A statistically significant association between the findings of salivirus and gastrointestinal disease was demonstrated. There was no association between gastrointestinal disease and the presence of aichi virus or saffold virus. Conclusions The newly discovered human picornaviruses aichi virus, saffold virus, and salivirus are circulating in Danish children, with the most common being saffold virus. Saffold virus was seen almost exclusively in the autumn and winter period. Salivirus was the only virus, which was significantly associated with gastroenteritis, although the number of positive samples was rather low.
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