Survival among people with HIV and their families in Denmark 1995-2021: a nationwide population-based cohort study.

Background: Survival among people with HIV (PWH) has vastly improved globally over the last few decades but remains lower than among the general population. We aimed to estimate time trends of survival among PWH and their families from 1995 to 2021. Methods: We conducted a registry-based, nationwide, population-based, matched cohort study. We included all Danish-born PWH from 1995 to 2021 who had been on antiretroviral therapy for 90 days, did not report intravenous drug use, and were not co-infected with hepatitis C (n = 4168). We matched population controls from the general population 10:1 to PWH by date of birth and sex (n = 41,680). For family cohorts, we identified siblings, mothers, and fathers of PWH and population controls. From Kaplan-Meier tables with age as time scale, we estimated survival from age 25. We compared PWH with population controls and families of PWH with families of population controls to calculate mortality rate ratios adjusted for sex, age, comorbidities, and education (aMRR). Findings: The median age of death among PWH increased from 27.5 years in 1995-1997 to 73.9 years (2010-2014), but thereafter survival increased only marginally. From 2015 to 2021, mortality was increased among PWH (aMRR 1.87 (95% CI: 1.65-2.11)) and siblings (aMRR: 1.25 (95% CI: 1.07-1.47)), mothers (aMRR: 1.30 (95% CI: 1.17-1.43)), and fathers (aMRR: 1.15 (95% CI: 1.03-1.29)) of PWH compared to their respective control cohorts. Mortality among siblings of PWH who reported heterosexual route of HIV transmission (aMRR: 1.51 (95% CI: 1.16-1.96)) was higher than for siblings of PWH who reported men who have sex with men as route of HIV transmission (aMRR 1.19 (95% CI: 0.98-1.46)). Interpretation: Survival among PWH improved substantially until 2010, after which it increased only marginally. This may partly be due to social and behavioural factors as PWH families also had higher mortality. Funding: Preben and Anna Simonsen's Foundation and Independent Research Fund Denmark.

Risk Factors and Prognosis of Epilepsy Following Brain Abscess: A Nationwide Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Epilepsy in patients with brain abscess is frequent, but risk factors and prognosis remain undetermined. This study examined risk factors of epilepsy among survivors of brain abscess and associated prognosis. METHODS: Nationwide, population-based healthcare registries were used to compute cumulative incidences and cause-specific adjusted hazard rate ratios (adj. HRRs) with 95% CIs for epilepsy among 30-day survivors of brain abscess from 1982 through 2016. Data were enriched with clinical details by medical record review of patients hospitalized from 2007 through 2016. Adjusted mortality rate ratios (adj. MRRs) were examined using epilepsy as a time-dependent variable. RESULTS: The study included 1,179 30-day survivors of brain abscess among whom 323 (27%) developed new-onset epilepsy after a median of 0.76 years (interquartile range [IQR] 0.24-2.41). At admission for brain abscess, the median age was 46 years (IQR 32-59) in patients with epilepsy compared with 52 years (IQR 33-64) in those without epilepsy. The proportion of female individuals was similar in patients with and without epilepsy (37%). Adj. HRRs for epilepsy were 2.44 (95% CI 1.89-3.15) for aspiration or excision of brain abscess, 2.37 (1.56-3.60) for alcohol abuse, 1.75 (1.27-2.40) for previous neurosurgery or head trauma, 1.62 (1.17-2.25) for stroke, and 1.55 (1.04-2.32) for age group 20-39 years. Cumulative incidences were increased in patients with alcohol abuse (52% vs 31%), aspiration or excision of brain abscess (41% vs 20%), previous neurosurgery or head trauma (41% vs 31%), and stroke (46% vs 31%). Analysis using clinical details from medical record review of patients from 2007 through 2016 demonstrated adj. HRRs of 3.70 (2.24-6.13) for seizures at admission for brain abscess and 1.80 (1.04-3.11) for frontal lobe abscess. By contrast, adj. HRR was 0.42 (0.21-0.86) for occipital lobe abscess. Using the entire registry-based cohort, patients with epilepsy had an adj. MRR of 1.26 (1.01-1.57). DISCUSSION: Important risk factors of epilepsy were seizures during admission for brain abscess, neurosurgery, alcoholism, frontal lobe abscess, and stroke. Epilepsy was associated with an increased mortality. Antiepileptic treatment may be guided by individual risk profiles, and a specialized follow-up is highlighted by an increased mortality in survivors with epilepsy.

Impact of pre-antiretroviral treatment HIV-RNA on time to successful virological suppression and subsequent virological failure - two nationwide, population-based cohort studies.

BACKGROUND: The impact of pre-antiretroviral treatment (ART) HIV-RNA on time to successful virological suppression and subsequent failure in HIV patients remains poorly investigated. METHODS: We used the Swedish InfCareHIV database and the Danish HIV Cohort Study to evaluate impact of pre-ART HIV-RNA on primary virological suppression (HIV-RNA < 50 copies/ml) and risk of secondary virological failure (two consecutive HIV-RNA > 200 copies/ml or one >1000 copies/ml). The study included 3366 Swedish and 2050 Danish ART naïve individuals who initiated ART in the period 2000-2018. We used Kaplan-Meier estimates and Cox regression analyses to estimate absolute risks and hazard ratios. RESULTS: In both cohorts, more than 95% of patients with a pre-ART HIV-RNA <100 000 copies/ml obtained virological suppression within the first year after ART initiation contrasting 74% (Sweden) and 86% (Denmark) in those with HIV-RNA >1 000 000 copies/ml. Almost all patients obtained virological suppression after four years irrespective of pre-ART HIV-RNA. In contrast, we observed no substantial impact of pre-ART HIV-RNA on risk of virological failure once virological suppression was obtained. CONCLUSION: High pre-ART HIV-RNA is strongly associated with increased time to successful virological suppression, but pre-ART HIV-RNA has no impact on risk of subsequent virological failure.

Clinical features and prognostic factors in adults with brain abscess.

Studies on brain abscess are hampered by single-centre design with limited sample size and incomplete follow-up. Thus, robust analyses on clinical prognostic factors remain scarce. This Danish nationwide, population-based cohort study included clinical details of all adults (≥18 years) diagnosed with brain abscess in the Danish National Patient Registry from 2007 through 2014 and the prospective clinical database of the Danish Study Group of Infections of the Brain covering all Danish departments of infectious diseases from 2015 through 2020. All patients were followed for 6 months after discharge. Prognostic factors for mortality at 6 months after discharge were examined by adjusted modified Poisson regression to compute relative risks with 95% confidence intervals (CI). Among 485 identified cases, the median age was 59 years [interquartile range (IQR 48-67)] and 167 (34%) were female. The incidence of brain abscess increased from 0.4 in 2007 to 0.8 per 100 000 adults in 2020. Immuno-compromise was prevalent in 192/485 (40%) and the clinical presentation was predominated by neurological deficits 396/485 (82%), headache 270/411 (66%), and fever 208/382 (54%). The median time from admission until first brain imaging was 4.8 h (IQR 1.4-27). Underlying conditions included dental infections 91/485 (19%) and ear, nose and throat infections 67/485 (14%), and the most frequent pathogens were oral cavity bacteria (59%), Staphylococcus aureus (6%), and Enterobacteriaceae (3%). Neurosurgical interventions comprised aspiration 356/485 (73%) or excision 7/485 (1%) and was preceded by antibiotics in 377/459 (82%). Fatal outcome increased from 29/485 (6%) at discharge to 56/485 (12%) 6 months thereafter. Adjusted relative risks for mortality at 6 months after discharge was 3.48 (95% CI 1.92-6.34) for intraventricular rupture, 2.84 (95% CI 1.45-5.56) for immunocompromise, 2.18 (95% CI 1.21-3.91) for age >65 years, 1.81 (95% CI 1.00-3.28) for abscess diameter >3 cm, and 0.31 (95% CI 0.16-0.61) for oral cavity bacteria as causative pathogen. Sex, neurosurgical treatment, antibiotics before neurosurgery, and corticosteroids were not associated with mortality. This study suggests that prevention of rupture of brain abscess is crucial. Yet, antibiotics may be withheld until neurosurgery, if planned within a reasonable time period (e.g. 24 h), in some clinically stable patients. Adjunctive corticosteroids for symptomatic perifocal brain oedema was not associated with increased mortality.

Risk of Psychiatric Disorders, Use of Psychiatric Hospitals, and Receipt of Psychiatric Medication in Patients With Brain Abscess in Denmark.

BACKGROUND: It is unknown whether patients diagnosed with brain abscess have an increased risk of psychiatric disorders. METHODS: In this nationwide, population-based matched cohort study from Denmark, we compared the incidence of psychiatric disorders, use of psychiatric hospitals, and receipt of psychiatric medications between patients diagnosed with brain abscess and individuals from the general population, matched on date of birth, sex, and residential area. RESULTS: We included 435 patients diagnosed with brain abscess and 3909 individuals in the comparison cohort: 61% were male and median age was 54 years. Patients diagnosed with brain abscess were more likely to suffer from comorbidity. The risk of a hospital diagnosis of psychiatric disorders was increased the first 5 years of observation. In the subpopulation, who had never been in contact with psychiatric hospitals or received psychiatric medication before study inclusion, the risk of developing psychiatric disorders was close to that of the background population, especially when we excluded dementia from this outcome. There was a substantial increase in the receipt of anxiolytics and antidepressants. The difference in the proportion of individuals who received anxiolytics and antidepressants increased from 4% (95% confidence interval [CI], 0%-7%) and 2% (95% CI, -1% to 5%) 2 years before study inclusion to 17% (95% CI, 12%-21%) and 11% (95% CI, 7%-16%) in the year after study inclusion. CONCLUSIONS: Patients with brain abscess without prior psychiatric disorders or receipt of psychiatric medicine are not at increased risk psychiatric disorders diagnosed in psychiatric hospitals, but they have an increased receipt of psychiatric medication.

Herpes Simplex Virus 2 Meningitis in Adults: A Prospective, Nationwide, Population-Based Cohort Study.

BACKGROUND: Data on the clinical presentation are scarce and prognostic factors of herpes simplex virus type 2 (HSV-2) meningitis remain unknown. METHODS: Prospective, nationwide, population-based database identifying all adults treated for HSV-2 meningitis at departments of infectious diseases in Denmark from 2015 to 2020. Unfavorable outcome was defined as Glasgow Outcome Scale (GOS) scores of 1-4 and Extended GOS scores of 1-6. Modified Poisson regression was used to compute relative risks with 95% confidence intervals for unfavorable outcome. RESULTS: HSV-2 meningitis was diagnosed in 205 patients (76% female; median age [interquartile range (IQR)], 35 [27-49] years) yielding an incidence of 0.7/100 000 population/y. Common symptoms were headache (195 of 204 patients [95%]), photophobia or phonophobia (143 of 188 [76%]), and neck stiffness (106 of 196 [54%]). The median (IQR) time to lumbar puncture was 2.0 (1-4.8) hours, and the median cerebrospinal fluid (CSF) leukocyte count was 360 (166-670) × 10 × 6/L, with a mononuclear predominance of 97% (91%-99%). Lumbar puncture was preceded by brain imaging in 61 of 205 patients (30%). Acyclovir or valacyclovir was administered in 197 of 205 patients (96%) for a median (IQR) of 10 (7-14) days. Unfavorable outcome was observed in 64 of 205 patients (31%) at discharge and 19 of 181 (11%) after 6 months and was not associated with female sex (relative risk [95% confidence interval], 1.08 [.65-1.79]), age ≥35 years (1.28 [.83-1.97]), immunocompromise (1.07 [.57-2.03]), or CSF leukocyte count >1000 × 10 × 6/L (0.78 [.33-1.84]). CONCLUSIONS: HSV-2 meningitis often presented as meningeal symptoms in younger women. Unfavorable outcome at discharge was common and was not associated with sex, age, immunocompromise, or CSF leukocyte count. Sequelae persisted beyond 6 months in one-tenth of patients.