Repeated doxycycline treatment among patients with neuroborreliosis: a nationwide, population-based, registry-based, matched cohort study.

OBJECTIVES: To investigate receipt of antibiotics among patients with neuroborreliosis after initial antibiotic treatment, likely attributable to posttreatment symptoms. METHODS: We performed a nationwide, matched, population-based cohort study in Denmark (2009-2021). We included all Danish patients with neuroborreliosis, i.e. a positive Borrelia burgdorferi intrathecal antibody index test and a cerebrospinal fluid leukocyte count ≥10 × 106/l, and initially treated with doxycycline. To form a comparison cohort, we randomly extracted individuals from the general population matched 1:10 to patients with neuroborreliosis on date of birth and sex. The main outcome was receipt of doxycycline, and the secondary outcome was receipt of phenoxymethylpenicillin. We calculated short-term (<1 year) and long-term (≥1 year) hazard ratios (HR) with 95% confidence intervals (95%CI). RESULTS: We included 463 patients with neuroborreliosis and 2,315 comparison cohort members. Compared with the comparison cohort members, patients with neuroborreliosis initially treated with doxycycline had increased receipt of additional doxycycline within 1 year (HR: 38.6, 95%CI: 17.5-85.0) and ≥1 years (HR: 3.5, 95%CI: 1.9-6.3). Compared with comparison cohort members, patients with neuroborreliosis had no increased receipt of phenoxymethylpenicillin (<1 year HR 1.0, 95%CI: 0.7-1.3; ≥1 years HR 1.2, 95%CI: 0.9-1.5). CONCLUSIONS: After initial antibiotic treatment, patients with neuroborreliosis have increased receipt of doxycycline particularly within one year after initial antibiotic therapy but also subsequently. The lack of increased receipt of phenoxymethylpenicillin suggests that the receipt of doxycycline was not merely due to differences in healthcare-seeking behaviour, increased risk of early Lyme borreliosis due to exposure, or differences in antibacterial usage in general.

Colorectal cancer and association with anaerobic bacteraemia: A Danish nationwide population-based cohort study.

OBJECTIVES: We aimed to identify specific anaerobic bacteria causing bacteraemia and a subsequent diagnosis of colorectal cancer. METHODS: A nationwide population-based cohort study, which included all episodes of defined specific anaerobic bacteraemia from 2010 (5,534,738 inhabitants) through 2020 (5,822,763 inhabitants) and all cases of colorectal cancer diagnosed from 2010 through 2021 in Denmark. We calculated the incidence and risk of colorectal cancer after bacteraemia with specific anaerobic bacteria using Escherichia coli bacteraemia as reference. RESULTS: Nationwide data on colorectal cancer and specific anaerobic bacteraemia (100% complete, representing 11,124 episodes). The frequencies of colorectal cancer within one year following anaerobic bacteraemia were higher for species, which almost exclusively reside in the colon, such as Phocaeicola vulgatus/dorei (5.5%), Clostridium septicum (24.2%), and Ruminococcus gnavus (4.6%) compared to 0.6% in 50,650 E. coli bacteraemia episodes. Bacteroides spp. had a subhazard ratio for colorectal cancer of 3.9 (95% confidence interval [CI], 3.0 to 5.1) and for Clostridium spp. it was 8.9 (95% CI, 6.7 to 11.8, with C. septicum 50.0 [95% CI, 36.0 to 69.5]) compared to E. coli (reference). CONCLUSION: This nationwide study identified specific colorectal cancer-associated anaerobic bacteria, which almost exclusively reside in the colon. Bacteraemia with these bacteria could be an indicator of colorectal cancer.

Obtainment of prescribed analgesics among patients with Lyme neuroborreliosis; a nationwide, population-based matched cohort study.

BACKGROUND: Radicular pain is the most predominant symptom among adults with Lyme neuroborreliosis (LNB) but the duration preceding and following diagnosis remains unknown. We aimed to investigate whether patients with LNB have increased obtainment of analgesics before and after diagnosis and for how long. METHODS: We performed a nationwide, population-based, matched cohort study (2009-2021). all Danish residents with LNB (positive Borrelia burgdorferi intrathecal antibody index test and cerebrospinal fluid pleocytosis) were included. To form a comparison cohort, individuals from the general population were randomly extracted and matched 10:1 to patients with LNB on age and sex. Outcomes were obtainment of simple analgesics, antiepileptics, tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, tramadol, and other opioids. We calculated monthly and six-monthly proportions of individuals with obtainment of analgesics and absolute risk differences. RESULTS: 1,056 patients with LNB and 10,560 comparison cohort members were included. An increased proportion of patients with LNB obtained analgesics from 3 months before study inclusion, especially simple analgesics, tramadol, and other opioids. Within the 0-1-month period after study inclusion, patients with LNB most frequently obtained simple analgesics (15 %), antiepileptics (11 %), and tramadol (10 %). Thereafter, obtainment of analgesics declined within a few months. A slightly larger proportion of patients with LNB obtained antiepileptics up to 2.5 years after diagnosis. CONCLUSIONS: Up to 3 months preceding diagnosis, LNB was preceded by increased obtainment of analgesics, which suggests diagnostic delay. Importantly, most patients with LNB did not obtain analgesics after the immediate disease course, although obtainment remained more frequent up to 2.5 years after.

Risk of heart failure among individuals tested for Borrelia burgdorferi sensu lato antibodies, and serum Borrelia burgdorferi sensu lato seropositive individuals; a nationwide population-based, registry-based matched cohort study.

BACKGROUND: Lyme borreliosis is a tick-borne disease caused by the bacterium Borrelia burgdorferi (Bb) sensu lato complex. Previous studies have suggested an association between Lyme borreliosis and heart failure, which have been suggested to be a possible manifestation of Lyme carditis. We aimed to investigate the risk of heart failure among individuals tested for serum Bb antibodies, and serum Bb seropositive individuals. METHODS: We performed a matched nationwide cohort study (Denmark, 1993-2020) and included 52,200 Bb seropositive individuals, and two age- and sex-matched comparison cohorts: 1) 104,400 Bb seronegative comparison cohort members, and 2) 261,000 population controls. We investigated the risk associated with 1) being tested for serum Bb antibodies, and 2) being Bb seropositive. Outcomes were: 1) a composite of heart failure, cardiomyopathy, and/or myocarditis diagnosis, and 2) redemption of cardiovascular medicine used for treatment of heart failure. We calculated short-term odds ratios (aOR) (within 1 month) and long-term hazard rates (aHR) (after 1 month) adjusted for age, sex, diabetes, pre-existing heart failure, and kidney disease. RESULTS: Compared with the population controls, individuals tested for Bb antibodies, regardless of the test result, had increased short-term risk of heart failure, cardiomyopathy, and myocarditis (aOR 8.3, 95 %CI: 6.7-10.2), and both increased short- and long-term risk of redemption of cardiovascular medicine (aOR 4.3, 95 %CI: 3.8-4.8, aHR 1.13, 95 % CI: 1.11-1.15). The Bb seropositive individuals had no increased short- or long-term risk of any outcome compared with Bb seronegative comparison cohort members. CONCLUSIONS: In conclusion, Bb antibody tests seemed to be performed in the diagnostic work-up of heart failure, but Bb seropositivity was not associated with heart failure.

Risk of cardiac conduction disorders, and pacemaker implantations among individuals tested for serum Borrelia burgdorferi antibodies, a nationwide, matched, population-based cohort study.

OBJECTIVES: To investigate the short- and long-term risks of atrioventricular block and other cardiac conduction disorders associated with being tested for Borrelia burgdorferi (Bb) antibodies or Bb seropositivity as measures of confounding by indication and Bb infection, respectively. METHODS: We performed a nationwide population-based matched cohort study (Denmark, 1993-2021). We included 52 200 Bb-seropositive individuals (stratified as only Bb-IgM-seropositive [n = 26 103], only Bb-IgG-seropositive [n = 18 698], and Bb-IgM-and-IgG-seropositive [n = 7399]) and two age- and sex-matched comparison cohorts: 104 400 Bb-seronegative individuals and 261 000 population controls. We investigated the risk associated with being tested for serum Bb antibodies and being Bb seropositive. Outcomes were atrioventricular block and other conduction disorders. We calculated short-term odds ratios (aOR) (within 1 month), and long-term hazard ratios (aHR) (after 1 month) adjusted for age, sex, diabetes, chronic heart failure, and kidney disease with 95% CI. RESULTS: Compared with population controls, individuals tested for Bb antibodies had increased short- and long-term risks of atrioventricular block (aOR 47.9, 95% CI: 30.0-76.7, aHR 1.3, 95% CI:1.2-1.3), and other conduction disorders (aOR 18.2, 95% CI: 10.1-32.8, aHR 1.2, 95% CI: 1.1-1.4). Compared with Bb-seronegative individuals, only Bb-IgM-and-IgG-seropositive individuals had increased short-term risk of atrioventricular block (aOR: 2.1, 95% CI: 1.5-3.1). DISCUSSION: The results suggest that Bb antibody testing is included in the diagnostic work-up of conduction disorders. Finally, that Bb seropositivity is not associated with other conduction disorders than atrioventricular block or with increased long-term risk of conduction disorders.

Increase in invasive group A streptococcal infections and emergence of novel, rapidly expanding sub-lineage of the virulent Streptococcus pyogenes M1 clone, Denmark, 2023.

A highly virulent sub-lineage of the Streptococcus pyogenes M1 clone has been rapidly expanding throughout Denmark since late 2022 and now accounts for 30% of the new invasive group A streptococcal infections. We aimed to investigate whether a shift in variant composition can account for the high incidence rates observed over winter 2022/23, or if these are better explained by the impact of COVID-19-related restrictions on population immunity and carriage of group A Streptococcus.

First molecular documented case of a rarely reported parasite: Plasmodium knowlesi infection in Denmark in a traveller returning from Malaysian Borneo.

Plasmodium knowlesi has been reported as an emerging infection throughout the Southeast Asian region, especially in the Malaysian state of Sabah, where it accounts for the majority of the malaria cases reported. This is in contrast to Europe, where imported P. knowlesi is a rarely reported infection. We present a case of P. knowlesi infection in a Danish woman returning from a short trip to Malaysian Borneo. Microscopy of blood smears revealed 0.8% infected erythrocytes, but due to the atypical morphological presentation, a conclusive species identification was made by molecular methods. Plasmodium knowlesi is a potentially fatal infection and taking the increasing travel activity into consideration after the coronavirus disease 2019 (COVID-19) pandemic, P. knowlesi should be a differential diagnosis in patients with travel-associated illness returning from highly endemic Southeast Asian areas.

Use of Inhaled Corticosteroids and Risk of Acquiring Haemophilus influenzae in Patients with Chronic Obstructive Pulmonary Disease.

Background: Inhaled corticosteroids (ICS) are widely used in chronic obstructive pulmonary disease (COPD), despite the known risk of severe adverse effects including pulmonary infections. Research Question: Our study investigates the risk of acquiring a positive Haemophilus influenzae airway culture with use of ICS in outpatients with COPD. Study Design and Methods: We conducted an epidemiological cohort study using data from 1 January 2010 to 19 February 2018, including 21,218 outpatients with COPD in Denmark. ICS use 365 days prior to cohort entry was categorised into low, moderate, and high, based on cumulated ICS dose extracted from a national registry on reimbursed prescriptions. A Cox proportional hazards regression model was used to assess the future risk of acquiring H. Influenzae within 365 days from cohort entry, and sensitivity analyses were performed using propensity score matched models. Results: In total, 801 (3.8%) patients acquired H. Influenzae during follow-up. Use of ICS was associated with a dose-dependent increased risk of acquiring H. Influenzae with hazard ratio (HR) 1.2 (95% confidence interval (CI) 0.9−1.5, p value = 0.1) for low-dose ICS; HR 1.7 (95% CI 1.3−2.1, p value < 0.0001) for moderate dose; and HR 1.9 (95% CI 1.5−2.4, p value < 0.0001) for high-dose ICS compared to no ICS use. Results were confirmed in the propensity-matched model using the same categories. Conclusions: ICS use in outpatients with COPD was associated with a dose-dependent increase in risk of isolating H. Influenzae. This observation supports that high dose ICS should be used with caution.

Bacteremia With Anaerobic Bacteria and Association With Colorectal Cancer: A Population-based Cohort Study.

BACKGROUND: There is a well-described association between bacteremia with bovis group streptococci or Clostridium septicum and an increased probability of a colorectal cancer (CRC) diagnosis. We wanted to investigate the existence of a similar association between CRC and bacteremia with other bacteria belonging to the gut microbiota.. METHODS: A population based cohort study in a population about 2 million people including 45 774 bacteremia episodes and 231 387 blood culture negative cases was performed in the Region of Southern Denmark and Region Zealand from 2007-2016. Episodes of bacteremia were combined with the Danish central register for CRC. We performed Cox's regression analysis with hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The study results confirmed previous findings of an increased risk of a CRC diagnosis after bacteremia with the bovis group streptococci (risk within a year: 4.3%; HR [95% CI]: 8.46 [3.51-20.4]) or C. septicum (20.8%; 76.2 [42.0-138]). Furthermore, Bacteroides ovatus (6.7%; 20.3 [5.04-81.8]), Bacteroides uniformis (5.4%; 16.2 [4.02-65.7]), Clostridium tertium (3.6 %; 13.9 [1.96-99.4]), Fusobacterium spp. (excluding F. necrophorum) (3.0 %; 8.51 [2.73-26.5]), and Gram-positive anaerobic cocci (3.6 %; 10.9 [4.50-26.3]) were also associated with an increased risk of a CRC diagnosis compared to patients with negative blood cultures (0.4%). CONCLUSIONS: Bacteremia with specific gut microbiota anaerobic bacteria is associated with a high risk of a diagnosis of CRC, indicating the need for colorectal workup. Importantly, this strategy also holds the possible additional benefit of detecting adenomas or other premalignant conditions, which were not included in the present study.

Comparison of video and in-hospital consultations during early in-home care for premature infants and their families: A randomised trial.

INTRODUCTION: Early in-home care is increasingly being used in Scandinavian countries for clinically stable premature infants. Due to challenges with travel and hospital resources, alternative ways to support parents during early in-home care are being considered. The aim of this study was to test whether the proportion of mothers exclusively breastfeeding, parental confidence and mother-infant interaction increased after early in-home care with premature infants, and to compare the outcomes of in-home care involving the use of video communication and a mobile application with those of in-home care involving in-hospital consultations. METHODS: This study was conducted in four neonatal wards offering premature infant in-home care in Denmark. Premature infants were randomised using 1:1 block randomisation. During early in-home care, families had planned consultations two to three times a week, during which they received support from nurses: the intervention group had video consultations, while the control group had in-hospital consultations. RESULTS: The proportion of exclusively breastfeeding mothers at discharge was 66.7% in the intervention group vs 66% in the control group and decreased to 49.4% vs 55%, respectively, 1 month after discharge. No significant improvements were found in the intervention group compared with the control group. In the intervention group, some video consultations were changed to telephone consultations due to problems with the video function, or to in-hospital consultations due to infants' requirement for medical services. No significant differences in secondary outcomes were observed. DISCUSSION: The study showed similar breastfeeding proportions at discharge. No unfavourable effects of video consultation compared with in-hospital consultation were found, indicating that video consultation could be a viable option and an important supplement during early in-home care. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02581800.

Seroprevalence of SARS-CoV-2 antibodies and reduced risk of reinfection through 6 months: a Danish observational cohort study of 44 000 healthcare workers.

OBJECTIVES: Antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are a key factor in protecting against coronavirus disease 2019 (COVID-19). We examined longitudinal changes in seroprevalence in healthcare workers (HCWs) in Copenhagen and the protective effect of antibodies against SARS-CoV-2. METHODS: In this prospective study, screening for antibodies against SARS-CoV-2 (ELISA) was offered to HCWs three times over 6 months. HCW characteristics were obtained by questionnaires. The study was registered at ClinicalTrials.gov, NCT04346186. RESULTS: From April to October 2020 we screened 44 698 HCWs, of whom 2811 were seropositive at least once. The seroprevalence increased from 4.0% (1501/37 452) to 7.4% (2022/27 457) during the period (p < 0.001) and was significantly higher than in non-HCWs. Frontline HCWs had a significantly increased risk of seropositivity compared to non-frontline HCWs, with risk ratios (RRs) at the three rounds of 1.49 (95%CI 1.34-1.65, p < 0.001), 1.52 (1.39-1.68, p < 0.001) and 1.50 (1.38-1.64, p < 0.001). The seroprevalence was 1.42- to 2.25-fold higher (p < 0.001) in HCWs from dedicated COVID-19 wards than in other frontline HCWs. Seropositive HCWs had an RR of 0.35 (0.15-0.85, p 0.012) of reinfection during the following 6 months, and 2115 out of 2248 (95%) of those who were seropositive during rounds one or two remained seropositive after 4-6 months. The 133 of 2248 participants (5.0%) who seroreverted were slightly older and reported fewer symptoms than other seropositive participants. CONCLUSIONS: HCWs remained at increased risk of infection with SARS-CoV-2 during the 6-month period. Seropositivity against SARS-CoV-2 persisted for at least 6 months in the vast majority of HCWs and was associated with a significantly lower risk of reinfection.

Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark.

Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but being seronegative is observed in 1 to 9%. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. In a prospective cohort study, we screened health care workers (HCW) in the Capital Region of Denmark for SARS-CoV-2 antibodies. We performed three rounds of screening from April to October 2020 using an enzyme-linked immunosorbent assay (ELISA) method targeting SARS-CoV-2 total antibodies. Data on all participants' PCR for SARS-CoV-2 RNA were captured from national registries. The Kaplan-Meier method and Cox proportional hazards models were applied to investigate the probability of being seronegative and the related risk factors, respectively. Of 36,583 HCW, 866 (2.4%) had a positive PCR before or during the study period. The median (interquartile range [IQR]) age of 866 HCW was 42 (31 to 53) years, and 666 (77%) were female. After a median of 132 (range, 35 to 180) days, 21 (2.4%) of 866 were seronegative. In a multivariable model, independent risk factors for being seronegative were self-reported asymptomatic or mild infection hazard ratio (HR) of 6.6 (95% confidence interval [CI], 2.6 to 17; P < 0.001) and body mass index (BMI) of ≥30, HR 3.1 (95% CI, 1.1 to 8.8; P = 0.039). Only a few (2.4%) HCW were not seropositive. Asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges. IMPORTANCE Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but negative serology is observed in 1 to 9%. We found that asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges.

Comparison of 16 Serological SARS-CoV-2 Immunoassays in 16 Clinical Laboratories.

Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (Ab), immunoglobulin G (IgG), and IgM against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was a Danish national collaboration and evaluated 15 commercial and one in-house anti-SARS-CoV-2 assays in 16 laboratories. Sensitivity was evaluated using 150 samples from individuals with asymptomatic, mild, or moderate COVID-19, nonhospitalized or hospitalized, confirmed by nucleic acid amplification tests (NAAT); samples were collected 13 to 73 days either from symptom onset or from positive NAAT (patients without symptoms). Specificity and cross-reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from >586 blood donors and patients with autoimmune diseases, cytomegalovirus or Epstein-Barr virus infections, and acute viral infections. A specificity of ≥99% was achieved by all total-Ab and IgG assays except one, DiaSorin Liaison XL IgG (97.2%). Sensitivities in descending order were Wantai ELISA total Ab (96.7%), CUH-NOVO in-house ELISA total Ab (96.0%), Ortho Vitros total Ab (95.3%), YHLO iFlash IgG (94.0%), Ortho Vitros IgG (93.3%), Siemens Atellica total Ab (93.2%), Roche Elecsys total Ab (92.7%), Abbott Architect IgG (90.0%), Abbott Alinity IgG (median 88.0%), DiaSorin Liaison XL IgG (median 84.6%), Siemens Vista total Ab (81.0%), Euroimmun/ELISA IgG (78.0%), and Snibe Maglumi IgG (median 78.0%). However, confidence intervals overlapped for several assays. The IgM results were variable, with the Wantai IgM ELISA showing the highest sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity.

Characteristics and Long-term Prognosis of Danish Patients With Varicella Zoster Virus Detected in Cerebrospinal Fluid Compared With the Background Population.

BACKGROUND: Risk factors for, and long-term outcomes following, detection of varicella zoster virus (VZV) DNA in the cerebrospinal fluid (CSF) are unknown. METHODS: We performed a nationwide population-based cohort study of all Danish residents who had VZV DNA detected in the CSF by polymerase chain reaction (PCR) between 1 January 1997 and 1 March 2016 (VZV cohort; n = 517) and an age- and sex- matched comparison cohort from the general Danish population (n = 9823). We examined potential risk factors and mortality, neurologic morbidity, psychiatric morbidity, redemptiom of prescriptions for nervous system medicine prescribed for the nervous system, and social outcomes. RESULTS: Prior hospital admission, redemption of immunosuppressive medicine, comorbidity, and immunosuppressive conditions were associated with detection of VZV DNA in the CSF. Mortality was increased in the VZV cohort, especially during the first year of observation and among patients with encephalitis. Patients in the VZV cohort had an increased risk of dementia and epilepsy. The redemption of antiepileptics and antidepressants was increased in the VZV cohort. CONCLUSIONS: Immunosuppression and comorbidity are associated with increased risk of detection of VZV DNA in the CSF and the condition is associated with increased mortality and neurological morbidity.

Assessment of the Risk of Psychiatric Disorders, Use of Psychiatric Hospitals, and Receipt of Psychiatric Medication Among Patients With Lyme Neuroborreliosis in Denmark.

Importance: The association of Lyme neuroborreliosis with the development of psychiatric disease is unknown and remains a subject of debate. Objective: To investigate the risk of psychiatric disease, the percentage of psychiatric hospital inpatient and outpatient contacts, and the receipt of prescribed psychiatric medications among patients with Lyme neuroborreliosis compared with individuals in a matched comparison cohort. Design, Setting, and Participants: This nationwide population-based matched cohort study included all residents of Denmark who received a positive result on an intrathecal antibody index test for Borrelia burgdorferi (patient cohort) between January 1, 1995, and December 31, 2015. Patients were matched by age and sex to a comparison cohort of individuals without Lyme neuroborreliosis from the general population of Denmark. Data were analyzed from February 2019 to March 2020. Exposures: Diagnosis of Lyme neuroborreliosis, defined as a positive result on an intrathecal antibody index test for B burgdorferi. Main Outcomes and Measures: The 0- to 15-year hazard ratios for the assignment of psychiatric diagnostic codes, the difference in the percentage of psychiatric inpatient and outpatient hospital contacts, and the difference in the percentage of prescribed psychiatric medications received among the patient cohort vs the comparison cohort. Results: Among 2897 patients with Lyme neuroborreliosis (1646 men [56.8%]) and 28 970 individuals in the matched comparison cohort (16 460 men [56.8%]), the median age was 45.7 years (interquartile range [IQR], 11.5-62.0 years) for both groups. The risk of a psychiatric disease diagnosis and the percentage of hospital contacts for psychiatric disease were not higher among patients with Lyme neuroborreliosis compared with individuals in the comparison cohort. A higher percentage of patients with Lyme neuroborreliosis compared with individuals in the comparison cohort received anxiolytic (7.2% vs 4.7%; difference, 2.6%; 95% CI, 1.6%-3.5%), hypnotic and sedative (11.0% vs 5.3%; difference, 5.7%; 95% CI, 4.5%-6.8%), and antidepressant (11.4% vs 6.0%; difference, 5.4%; 95% CI, 4.3%-6.6%) medications within the first year after diagnosis, after which the receipt of psychiatric medication returned to the same level as the comparison cohort. Conclusions and Relevance: In this population-based matched cohort study, patients with Lyme neuroborreliosis did not have an increased risk of developing psychiatric diseases that required hospital care or treatment with prescription medication. The increased receipt of psychiatric medication among patients with Lyme neuroborreliosis within the first year after diagnosis, but not thereafter, suggests that most symptoms associated with the diagnosis subside within a short period.

Changes in Lyme neuroborreliosis incidence in Denmark, 1996 to 2015.

Lyme neuroborreliosis (LNB) has recently been added to the list of diseases under the European Union epidemiological surveillance in order to obtain updated information on incidence. The goal of this study was to identify temporal (yearly) variation, high risk geographical regions and risk groups, and seasonal variation for LNB in Denmark. This cohort-study investigated Danish patients (n = 2791) diagnosed with LNB (defined as a positive Borrelia burgdorferi sensu lato (s.l.) intrathecal antibody test) between 1996-2015. We calculated incidence and incidence ratios of LNB by comparing 4-yr groups of calendar-years, area of residency, sex and age, income and education groups, and the number of new LNB cases per month. The incidence of LNB was 2.2 per 100,000 individuals and year in 1996-1999, 2.7 in 2004-2007 and 1.1 per 100,000 individuals in 2012-2015. Yearly variations in LNB incidence were similar for most calendar-year groups. LNB incidence was highest in Eastern Denmark and among males and individuals who were 0-14 yrs old, who had a yearly income of >449,000 DKK, and who had a Master's degree or higher education. The number of LNB cases was highest from July to November (p < 0.001). In conclusion, based on Danish nationwide data of patients with positive B. burgdorferi s.l. intrathecal antibody index (1996-2015) the incidence of LNB was found to increase until 2004-2007 but thereafter to decline. European surveillance studies of Lyme borreliosis should be encouraged to monitor the incidence trend.

Long-Term Survival, Morbidity, Social Functioning and Risk of Disability in Patients with a Herpes Simplex Virus Type 1 or Type 2 Central Nervous System Infection, Denmark, 2000-2016.

BACKGROUND: The long-term prognosis following herpes simplex virus (HSV) central nervous system (CNS) infection is still debated. PATIENTS AND METHODS: We examined outcomes in all Danish residents who, during 2000-2016, tested PCR positive for HSV-1 (n=208) or HSV-2 (n=283) in the cerebrospinal fluid, compared to comparison cohorts from the general population (n=2080 and n=2830). RESULTS: One-year mortality was increased among HSV-1 patients (difference 19.3%; 95% CI: 13.6% to 25.0%) and HSV-2 patients (difference 5.3%; 95% CI: 2.5% to 8.1%), but thereafter mortality was not increased. After exclusion of persons diagnosed with cancer prior to study inclusion, one-year mortality difference for HSV-2 patients was 1.7% (-0.1% to 3.5%). After five years, HSV-1 patients had lower employment (difference -19.8%; 95% CI: -34.7% to -4.8%) and higher disability pension rates (difference 22.2%; 95% CI: 8.4% to 36.0%) than the comparison cohort, but similar number of inpatient days, outpatient visits, and sick leave. HSV-2 patients had employment and disability pension rates comparable to the comparison cohort, but more inpatient days (difference 1.5/year; 95% CI: -0.2 to 3.2), outpatient visits (difference 1.3/year; 95% CI: 0.3 to 3.2), and sick leave days (difference 9.1/year; 95% CI: 7.9 to 10.4). CONCLUSION: HSV-1 and HSV-2 CNS infections differ substantially with respect to prognosis. HSV-1 CNS infection is followed by increased short-term mortality and long-term risk of disability. HSV-2 CNS infection has no substantial impact on mortality or working capability but is associated with increased morbidity.

Rejection of the name Borreliella and all proposed species comb. nov. placed therein.

Rejection (nomen rejiciendum) of the name Borreliella and all new combinations therein is being requested on grounds of risk to human health and patient safety (Principle 1, subprinciple 2 and Rule 56a) and violation to aim for stability of names, to avoid useless creation of names (Principle 1, subprinciple 1 and 3) and that names should not be changed without sufficient reason (Principle 9 of the International Code of Nomenclature of Prokaryotes).

Long-Term Survival, Health, Social Functioning, and Education in Patients With an Enterovirus Central Nervous System Infection, Denmark, 1997-2016.

BACKGROUND: The long-term clinical course of patients with an enterovirus central nervous system infection (ECI) is poorly understood. METHODS: We performed a nationwide population-based cohort study of all Danish patients with ECI diagnosed 1997-2016 (n = 1745) and a comparison cohort from the general population individually matched on date of birth and sex (n = 17 450). Outcomes were categorized into mortality and risk of cancer and likely measures of neurological sequelae: neuropsychiatric morbidities, educational landmarks, use of hospital services, employment, receipt of disability pension, income, number of sick leave days, and nursing home residency. RESULTS: Mortality in the first year was higher among patients with ECI (mortality rate ratio [MRR] = 10.0; 95% confidence interval [CI], 4.17-24.1), but thereafter mortality was not higher (MMR = 0.94; 95% CI, 0.47-1.86). Long-term outcomes for patients with ECI were not inferior to those of the comparison cohort for risk of cancer, epilepsy, mental and behavioral disorders, dementia, depression, school start, school marks, high school education, use of hospital services, employment, receipt of disability pension, income, days of sick leave, or nursing home residency. CONCLUSIONS: Diagnosis of an ECI had no substantial impact on long-term survival, health, or social/educational functioning.

Risk of Neurological Disorders in Patients With European Lyme Neuroborreliosis: A Nationwide, Population-Based Cohort Study.

BACKGROUND: Lyme neuroborreliosis (LNB), caused by the tick-borne spirochetes of the Borrelia burgdorferi sensu lato species complex, has been suggested to be associated with a range of neurological disorders. In a nationwide, population-based cohort study, we examined the associations between LNB and dementia, Alzheimer's disease, Parkinson's disease, motor neuron disease, epilepsy, and Guillain-Barré syndrome. METHODS: We used national registers to identify all Danish residents diagnosed during 1986-2016 with LNB (n = 2067), created a gender- and age-matched comparison cohort from the general population (n = 20 670), and calculated risk estimates and hazard ratios. RESULTS: We observed no long-term increased risks of dementia, Alzheimer's disease, Parkinson's disease, motor neuron diseases, or epilepsy. However, within the first year, 8 (0.4%) of the LNB patients developed epilepsy, compared with 20 (0.1%) of the comparison cohort (difference, 0.3%; 95% confidence interval, .02-.6%). In the LNB group, 11 (0.5%) patients were diagnosed with Guillain-Barré syndrome within the first year after LNB diagnosis, compared with 0 (0.0%) in the comparison cohort. After the first year, the risk of Guillain-Barré was not increased. CONCLUSIONS: LNB patients did not have increased long-term risks of dementia, Alzheimer's disease, Parkinson's disease, motor neuron diseases, epilepsy, or Guillain-Barré. Although the absolute risk is low, LNB patients might have an increased short-term risk of epilepsy and Guillain-Barré syndrome.