Casper Roed

Incidence and Impact on Mortality of Severe Neurocognitive Disorders in Persons With and Without HIV Infection: A Danish Nationwide Cohort Study

OBJECTIVE The risk of neurocognitive disorders in human immunodeficiency virus (HIV)-infected patients in the era of highly active antiretroviral therapy (HAART) is controversial. We aimed to compare the incidence and impact on mortality of severe neurocognitive disorders (SNCDs) in HIV-infected patients with that of the background population. METHODS The method used was a nationwide, population-based cohort study using Danish registries. We calculated incidence rates, incidence rate ratios, mortality rate ratios, and Kaplan-Meier tables to estimate the incidence of and survival after SNCD in HIV-infected patients, compared with a general population control cohort matched by age and sex. RESULTS We observed 32 cases of SNCDs among 4452 HIV-infected patients and 120 cases of SNCDs among 62 328 population control subjects. The overall risk of SNCD among HIV-infected patients was 1.0 case per 1000 person-years (PYR), compared with 0.23 cases per 1000 PYR for population control subjects but became 0.35 cases/1000 PYR after 2004, compared with 0.27 cases/1000 PYR in population control subjects. The absence of HAART and a low CD4 lymphocyte count increased the risk of SNCD. The mortality among HIV-infected patients with SNCD was higher than that among population controls with SNCD (median survival, 4.3 years vs 9.7 years [P = .02]). CONCLUSION HIV-infected patients have an increased risk of SNCD, but the risk is low and has, in recent years, become comparable to that seen in the background population. In contrast, the mortality remains high among HIV-infected patients diagnosed with SNCD.

Microbiological and therapeutic challenges in infectious spondylodiscitis: a cohort study of 100 cases, 2006–2011

Abstract Background: The microbiological diagnosis of infectious spondylodiscitis is often difficult to establish and the disease requires prolonged antibiotic treatment. We analyzed the medical records of 100 patients admitted for infectious spondylodiscitis from 2006 to 2011 with an emphasis on (1) the diagnostic utility of blood cultures and invasive biopsies in the microbiological diagnosis, (2) clinical features differentiating Staphylococcus aureus infections from those with other aetiologies, and (3) evaluation of the outcome of the antimicrobial therapy. Methods: A retrospective chart review was performed. Results: Patients were diagnosed a median of 32 days after symptom onset and treated for a median of 91 days; 68% had abscesses, 65% experienced sequelae, and the 1-y crude mortality was 11%. Blood cultures yielded a diagnosis in 67%. Among blood culture-positive cases, no other culture or polymerase chain reaction results yielded further diagnoses. S. aureus infections comprised 58%. These cases compared to those with other aetiologies were younger, more frequently female, had a higher C-reactive protein, and more often had neutrocytosis, bacteraemia, and abscess formation. Presumed side effects mediated a change in treatment 33 times in 23 patients. Four patients experienced relapse. Conclusions: This contemporary case-series on infectious spondylodiscitis mostly concurs with previous studies. We emphasize the importance of thorough blood culture sampling before more invasive tests are considered. S. aureus infections exhibit, in particular, prominent pyogenic characteristics. Prospective studies evaluating the choice and duration of antimicrobial treatment are needed.

Fever of unknown origin: A retrospective study of 52 cases with evaluation of the diagnostic utility of FDG-PET/CT

Abstract Objectives: Fever of unknown origin (FUO) is dynamic in its origin and will be an ongoing challenge to the clinician because of shifting disease epidemiology. Here we present a series of patients with classical FUO admitted to an infectious diseases department during a 5-y period, with an emphasis on the diagnostic utility of 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) in present-day cases of FUO. Methods: Patient records were reviewed retrospectively. Results: A final diagnosis was achieved for 31 of the 52 cases (60%). The final diagnoses of these 31 cases and their distribution in the respective diagnostic categories were: infections 32% (10/31), non-infectious inflammatory disease 55% (17/31), and malignancy 13% (4/31). In our study PET/CT successfully identified an infectious, inflammatory, or neoplastic cause of fever in 10 of the 22 patients (45%) who underwent this scan. Conclusions: During the past decade the proportion of non-infectious inflammatory diseases in FUO series has increased. Based on our findings we recommend: (1) a PET/CT scan be performed early in the diagnostic work-up of patients with FUO, and (2) restraint in performing invasive procedures in patients with FUO in whom no cause of fever has been determined during diagnostic work-up.

Socioeconomic status in HCV infected patients – risk and prognosis

Background and aims It is unknown whether socioeconomic status (SES) is a risk factor for hepatitis C virus (HCV) infection or a prognostic factor following infection. Methods From Danish nationwide registries, we obtained information on three markers of SES: employment, income, and education. In a case control design, we examined HCV infected patients and controls; conditional logistic regression was employed to obtain odds ratios (ORs) for HCV infection for each of the three SES markers, adjusting for the other two SES markers, comorbidity, and substance abuse. In a cohort design, we used Cox regression analysis to compute mortality rate ratios (MRRs) for each of the three SES markers, adjusting for the other two SES markers, comorbidity level, age, substance abuse, and gender. Results When compared to employed persons, ORs for HCV infection were 2.71 (95% confidence interval [CI]: 2.24–3.26) for disability pensioners and 2.24 (95% CI: 1.83–2.72) for the unemployed. When compared to persons with a high income, ORs were 1.64 (95% CI: 1.34–2.01) for low income persons and 1.19 (95% CI: 1.02–1.40) for medium income persons. The OR was 1.35 (95% CI: 1.20–1.52) for low education (no more than basic schooling). When compared to employed patients, MRRs were 1.71 (95% CI: 1.22–2.40) for unemployed patients and 2.24 (95% CI: 1.63–3.08) for disability pensioners. When compared to high income patients, MRRs were 1.47 (95% CI: 1.05–2.05) for medium income patients and 1.64 (95% CI: 1.13–2.34) for low income patients. Educational status was not associated with mortality. Conclusion Low SES was associated with an increased risk of HCV infection and with poor prognosis in HCV infected patients.

Long-term prognosis and causes of death after spondylodiscitis: A Danish nationwide cohort study.

Abstract Background: Data on long-term prognosis after spondylodiscitis are scarce. The purpose of this study was to determine long-term mortality and the causes of death after spondylodiscitis. Methods: A nationwide, population-based cohort study using national registries of patients diagnosed with non-post-operative pyogenic spondylodiscitis from 1994–2009, alive 1 year after diagnosis (n = 1505). A comparison cohort from the background population individually matched for sex and age was identified (n = 7525). Kaplan-Meier survival curves were constructed and Poisson regression analyses used to estimate mortality rate ratios (MRR). Results: Three hundred and sixty-five patients (24%) and 1115 individuals from the comparison cohort (15%) died. Unadjusted MRR for spondylodiscitis patients was 1.76 (95% CI = 1.57–1.98) and 1.47 (95% CI = 1.30–1.66) after adjustment for comorbidity. No deaths were observed in 128 patients under the age of 16 years. Siblings of patients did not have increased long-term mortality compared with siblings of the individuals from the comparison cohort. This study observed increased mortality due to infections (MRR = 2.57), neoplasms (MRR = 1.40), endocrine (MRR = 3.72), cardiovascular (MRR = 1.62), respiratory (MRR = 1.71), gastrointestinal (MRR = 3.35), musculoskeletal (MRR = 5.39) and genitourinary diseases (MRR = 3.37), but also due to trauma, poisoning and external causes (MRR = 2.78), alcohol abuse-related diseases (MRR = 5.59) and drug abuse-related diseases (6 vs 0 deaths, MRR not calculable). Conclusions: Patients diagnosed with spondylodiscitis have increased long-term mortality, mainly due to comorbidities, particularly substance abuse.

Educational Achievement and Economic Self-sufficiency in Adults After Childhood Bacterial Meningitis

IMPORTANCE To our knowledge, no previous study has examined functioning in adult life among persons who had bacterial meningitis in childhood. OBJECTIVE To study educational achievement and economic self-sufficiency in adults diagnosed as having bacterial meningitis in childhood. DESIGN, SETTING, AND PARTICIPANTS Nationwide population-based cohort study using national registries of Danish-born children diagnosed as having meningococcal, pneumococcal, or Haemophilus influenzae meningitis in the period 1977-2007 (n=2784 patients). Comparison cohorts from the same population individually matched on age and sex were identified, as were siblings of all study participants. End of study period was 2010. MAIN OUTCOMES AND MEASURES Cumulative incidences of completed vocational education, high school education, higher education, time to first full year of economic self-sufficiency, and receipt of disability pension and differences in these outcomes at age 35 years among meningitis patients, comparison cohorts, and siblings. RESULTS By age 35 years, among persons who had a history of childhood meningococcal (n=1338), pneumococcal (n=455), and H. influenzae (n=991) meningitis, an estimated 11.0% (41.5% vs 52.5%; 95% CI, 7.3%-14.7%), 10.2% (42.6% vs 52.8%; 95% CI, 3.8%-16.6%), and 5.5% (47.7% vs 53.2%; 95% CI, 1.9%-9.1%) fewer persons, respectively, had completed high school and 7.9% (29.3% vs 37.2%; 95% CI, 1.6%-14.2%), 8.9% (28.1% vs 37.0%; 95% CI, 0.6%-17.2%), and 6.5% (33.5% vs 40.0%; 95% CI, 1.4%-11.6%) fewer had attained a higher education compared with individuals from the comparison cohort. Siblings of meningococcal meningitis patients also had lower educational achievements, while educational achievements of siblings of pneumococcal and H. influenzae meningitis patients did not differ substantially from those in the general population. At end of follow-up, 3.8% (90.3% vs 94.1%; 95% CI, 1.1%-6.5%), 10.6% (84.0% vs 94.6%; 95% CI, 5.1%-16.1%), and 4.3% (90.6% vs 94.9%; 95% CI, 2.0%-6.6%) fewer meningococcal, pneumococcal, and H. influenzae meningitis patients were economically self-sufficient and 1.5% (3.7% vs 2.3%; 95% CI, -0.2% to 3.2%), 8.7% (10.0% vs 1.3%; 95% CI, 5.0%-12.4%), and 3.7% (6.2% vs 2.5%; 95% CI, 1.6%-5.8%) more received disability pension compared with individuals from the comparison cohort. CONCLUSIONS AND RELEVANCE In a Danish population, bacterial meningitis in childhood was associated with lower educational achievement and economic self-sufficiency in adult life. This association may apply particularly to pneumococcal and H. influenzae meningitis, whereas for meningococcal meningitis the lower educational achievement may be family-related.

Long-term mortality in patients with tuberculous meningitis: a Danish nationwide cohort study.

Background With high short-term mortality and substantial excess morbidity among survivors, tuberculous meningitis (TBM) is the most severe manifestation of extra-pulmonary tuberculosis (TB). The objective of this study was to assess the long-term mortality and causes of death in a TBM patient population compared to the background population. Methods A nationwide cohort study was conducted enrolling patients notified with TBM in Denmark from 1972–2008 and alive one year after TBM diagnosis. Data was extracted from national registries. From the background population we identified a control cohort of individuals matched on gender and date of birth. Kaplan-Meier survival curves and Cox regression analysis were used to estimate mortality rate ratios (MRR) and analyse causes of death. Findings A total of 55 TBM patients and 550 individuals from the background population were included in the study. Eighteen patients (32.7%) and 107 population controls (19.5%) died during the observation period. The overall MRR was 1.79 (95%CI: 1.09–2.95) for TBM patients compared to the population control cohort. TBM patients in the age group 31–60 years at time of diagnosis had the highest relative risk of death (MRR 2.68; 95%CI 1.34–5.34). The TBM patients had a higher risk of death due to infectious disease, but not from other causes of death. Conclusion Adult TBM patients have an almost two-fold increased long-term mortality and the excess mortality stems from infectious disease related causes of death.

Long-term mortality after Staphylococcus aureus spondylodiscitis: A Danish nationwide population-based cohort study

OBJECTIVES To determine the long-term mortality and the causes of death after Staphylococcus aureus spondylodiscitis. METHODS Nationwide, population-based cohort study using national registries of adults diagnosed with non postoperative S. aureus spondylodiscitis from 1994-2009 and alive 1 year after diagnosis (n Z 313). A comparison cohort from the background population individually matched on sex and age was identified (n Z 1565). Kaplan-Meier survival curves were constructed and Poisson regression analyses used to estimate mortality rate ratios (MRR) adjusted for comorbidity. RESULTS 88 patients (28.1%) and 267 individuals from the population-based comparison cohort (17.1%) died. Un-adjusted MRR for S. aureus spondylodiscitis patients was 1.77 (95% CI, 1.39-2.25) and 1.32 (95% CI, 1.02-1.71) after adjustment for comorbidity. We observed increased mortality due to infectious (MRR 8.57; 95% CI, 2.80-26.20), endocrine (MRR 3.57; 95%CI, 1.01-12.66), cardiovascular (MRR 1.59; 95% CI, 1.02-2.49), gastrointestinal (MRR 3.21; 95% CI, 1.178.84) and alcohol and drug abuse-related (MRR 10.71; 95% CI, 3.23-35.58) diseases. CONCLUSIONS Patients diagnosed with S. aureus spondylodiscitis have substantially increased long-term mortality, mainly due to comorbidity. To improve survival after S. aureus spondylodiscitis these patients should be screened for comorbidity and substance abuse predisposing to the disease [corrected].

Long-term mortality in patients diagnosed with Listeria monocytogenes meningitis: a Danish nationwide cohort study.

OBJECTIVES To determine the long-term mortality, the causes of death and the incidence of cancer in listeria meningitis patients. METHODS Nationwide, population-based cohort study including all adult patients diagnosed with listeria meningitis from 1977 to 2006 and alive 1 year after diagnosis, and an age-and gender-matched, population control cohort. Kaplan-Meier tables, Cox regression analysis and cumulative incidence function were used as outcome analyses. RESULTS We identified 114 listeria meningitis patients and 1026 population controls. The adjusted mortality rate ratio (MRR) for listeria meningitis patients the first 5 years of follow-up was 2.35(95% confidence interval (CI) 1.60-3.45) thereafter the MRR was 0.93(95% CI: 0.56-1.55). Listeria meningitis patients had an increased risk of death due to cancer the first 5 years of follow-up, and in the same period patients above 50 years of age had a 2-fold increased risk of being diagnosed with cancer, thereafter the risks declined to that of the background population. CONCLUSIONS The long-term mortality in adult patients diagnosed with listeria meningitis was increased the first 5 years of follow-up, mainly due to death from cancer, thereafter the mortality did not differ from the background population. To improve survival this patient population should be meticulously screened for predisposing conditions, mainly underlying malignant diseases.

Imported melioidosis in Danish travellers: A diagnostic challenge

Abstract Infections with Burkholderia pseudomallei (melioidosis) are rare events in Scandinavian countries, but the bacterium may be contracted during travel to endemic areas, i.e. Southeast Asia (especially Thailand) and northern Australia. Here, 5 travel-related cases occurring within the last 3 y in Denmark are reported, with particular emphasis on diagnostic and therapeutic challenges posed to health staff with little experience in the management of melioidosis. A newly developed B. pseudomallei-specific polymerase chain reaction test was applied and was able to correctly identify all isolates.