Hospital-treated Infections Research Articles

Hospital-Treated Infections and Risk of Disability Worsening in Multiple Sclerosis.

To investigate the association between infections and disability worsening in people with multiple sclerosis (MS) treated with either B-cell depleting therapy (rituximab) or interferon-beta/glatiramer acetate (IFN/GA). This cohort study spanned from 2000 to 2021, using data from the Swedish MS Registry linked to national health care registries, comprising 8,759 rituximab and 7,561 IFN/GA treatment episodes. The risk of hospital-treated infection was estimated using multivariable Cox models. The association between infections and increase in Expanded Disability Status Scale (EDSS) scores was assessed using a doubly robust generalized estimating equations model. Additionally, a piece-wise exponential model analyzed events of increased disability beyond defined cut-off values, controlling for relapses, and MRI activity. Compared with IFN/GA, rituximab displayed increased risk of both inpatient- and outpatient-treated infections (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.50-2.90 and HR, 1.37; 95% CI, 1.13-1.67, respectively). An inpatient-treated infection was associated with a 0.19-unit increase in EDSS (95% CI, 0.12-0.26). Degree of worsening was greatest for progressive MS, and under IFN/GA treatment, which unlike rituximab, was more commonly associated with MRI activity. After controlling for relapses and MRI activity, inpatient-treated infections were associated with disability worsening in people with relapsing-remitting MS treated with IFN/GA (HR, 2.01; 95% CI, 1.59-2.53), but not in those treated with rituximab. Compared to IFN/GA, rituximab doubled the infection risk, but reduced the risk of subsequent disability worsening. Further, the risk of worsening after hospital-treated infection was greater with progressive MS than with relapsing-remitting MS. Infection risk should be considered to improve long term outcomes. ANN NEUROL 2024.

COMBAT-MS: A Population-Based Observational Cohort Study Addressing the Benefit-Risk Balance of Multiple Sclerosis Therapies Compared with Rituximab.

To assess comparative effectiveness, safety, and tolerability of off-label rituximab, compared with frequently used therapies approved for multiple sclerosis (MS). A Swedish cohort study of persons with relapsing-remitting MS, age 18 to 75 years at inclusion and with a first therapy start or a first therapy switch between 2011 and 2018. Low-dose rituximab was compared with MS-approved therapies. Primary outcomes were proportions with 12 months confirmed disability worsening and change in MS Impact Scale-29 (MSIS-29) scores, respectively. Secondary endpoints included relapses, therapy discontinuation, and serious adverse events. Analyses used an intention-to-treat approach and were adjusted for demographics, MS features, and health characteristics. We included 2,449 participants as first therapy start and 2,463 as first therapy switch. Proportions with disability worsening at 3 years were 9.1% for rituximab as first therapy and 5.1% after therapy switch, with no differences to MS-approved comparators. Worsening on rituximab was mostly independent of relapses. MSIS-29 with rituximab at 3 years improved by 1.3/8.4 points (physical/psychological) for first disease-modifying therapy (DMT) and 0.4/3.6 for DMT switch, and was mostly similar across therapies. Rituximab had lower relapse rates and higher therapy persistence in both groups. The rate of hospital-treated infections was higher with rituximab after a therapy switch, but not as a first therapy. This population-based real-world cohort study found low rates of disability progression, mostly independent of relapses, and without significant differences between rituximab and MS-approved comparators. Rituximab led to lower rates of inflammatory activity and higher treatment persistence, but was associated with an increased rate of serious infections. ANN NEUROL 2024.

Association of frailty with risk of incident hospital-treated infections in middle-aged and older adults: A large-scale prospective cohort study.

Although frailty is associated with a range of adverse health outcomes, its association with the risk of hospital-treated infections is uncertain. A total of 416220 participants from the UK Biobank were included in this prospective cohort study. Fried phenotype was adopted to evaluate frailty, which included five aspects (gait speed, physical activity, grip strength, exhaustion, and weight). More than 800 infectious diseases were identified based on electronic health records. Cox proportional models were used to estimate the associations. During a median 12.3 years (IQR 11.4-13.2) of follow-up (4747345 person-years), there occurred 77988 (18.7%) hospital-treated infections cases. In the fully adjusted model, compared with participants with non-frail, the HRs (95% CIs) of those with pre-frail and frail for overall hospital-treated infections were 1.22 (1.20, 1.24) and 1.78 (1.72-1.84), respectively. The attributable risk proportion of pre-frail and frail were 18.03% and 43.82%. Similarly, compared to those without frailty, the HRs (95% CIs) of those with frailty for bacterial infections were 1.76 (1.70-1.83), for viral infections were 1.62 (1.44-1.82), and for fungal infections were 1.75 (1.47-2.08). No association was found between frailty and parasitic infections (HR: 1.17, 95% CI: 0.62-2.20). Frailty was significantly associated with a higher risk of hospital-treated infections, except for parasitic infections. Studies evaluating the effectiveness of implementing frailty assessments are needed to confirm our results.

Heightened Prevalence of Common Hospital-Treated Infections Preceding Dementia Diagnosis with Accelerated Dementia Onset after Influenza

BackgroundSince the beginning of Alzheimer’s disease research, the hypothesis that infections are to some extent associated with neurodegenerative processes has been tested repeatedly. Epidemiological studies on the associations between infections and dementia have reported conflicting results.ObjectivesThis study analyses common hospital-treated infections (herpes, influenza, intestinal infections, pneumonia, sepsis, urinary tract infections) and their association with subsequent dementia and time until dementia onset.Design, Setting, and ParticipantsFor this nationwide population-based case-control study, the dataset of the Austrian National Health Insurance Association was used, including dementia patients (dementia cohort) and age- and gender-matched non-demented individuals (control cohort). Only subjects with data availability of at least 10 years prior to the index date (date of dementia diagnosis or date of censoring) were included.MeasurementsThe incidence of six common infections in older adults (herpes, influenza, intestinal infections, pneumonia, sepsis, and urinary tract infections) was analyzed over a period of 10 years before the censoring date.ResultsThe study population consists of 58208 subjects (29104 per study cohort), mean age: 81 years, 54% females. Patients of the dementia cohort had suffered from infections significantly more often than patients of the control cohort (6002, 20.6% vs. 4826, 16.6%; p < 0.001). Influenza, urinary tract infections, intestinal infections, and sepsis showed independent positive associations with subsequent dementia diagnosis, irrespective of other comorbidities (odds ratios: 1.26 (95% CI: 1.06–1.49), 1.23 (95% CI: 1.16–1.30), 1.16 (95% CI: 1.07–1.27), 1.17 (95% CI: 1.01–1.37), respectively). Time from infection to dementia diagnosis was shorter after influenza compared to all other infections (median: 3.4 years (95% CI: 3.1–3.7) vs. 6.6 years (95% CI: 6.4–6.8); p < 0.001).ConclusionThis is the first study to assess the association between infections and dementia over such a long minimum reporting period. These results, supported by consistent data from other epidemiological studies, emphasize the critical importance of infection prevention measures, especially for older adults. Further research is crucial to better understand the nature of the relationship between infections and dementia.

Associations of hospital-treated infections with subsequent dementia: nationwide 30-year analysis.

Infections, which can prompt neuroinflammation, may be a risk factor for dementia1-5. More information is needed concerning associations across different infections and different dementias, and from longitudinal studies with long follow-ups. This New Zealand-based population register study tested whether infections antedate dementia across three decades. We identified individuals born between 1929 and 1968 and followed them from 1989 to 2019 (n = 1,742,406, baseline age = 21-60 years). Infection diagnoses were ascertained from public hospital records. Dementia diagnoses were ascertained from public hospital, mortality and pharmaceutical records. Relative to individuals without an infection, those with an infection were at increased risk of dementia (hazard ratio 2.93, 95% confidence interval 2.68-3.20). Associations were evident for dementia diagnoses made up to 25-30 years after infection diagnoses. Associations held after accounting for preexisting physical diseases, mental disorders and socioeconomic deprivation. Associations were evident for viral, bacterial, parasitic and other infections, and for Alzheimer's disease and other dementias, including vascular dementia. Preventing infections might reduce the burden of neurodegenerative conditions.

Hospital-treated infections and subsequent Parkinson's disease risk: a register-based sibling comparison study.

Serious infections may result in greater risk of Parkinson's disease. However, high-quality cohort studies focusing on a potential causal role of different types and sites of infection are lacking. Gastrointestinal infections are of a particular interest due to growing evidence implicating gut dysbiosis in Parkinson's disease aetiology. This population-based cohort study used the Swedish Total Population Register to identify individuals born during 1944-77 and resident in Sweden between 1990 and 2018 (N = 3 698 319). Hospital-treated infections at ages 21-30 and 31-40 years were identified from the National Patient Register. Participants were followed to identify Parkinson's disease diagnoses from age 41 years up to December 31, 2018, when the oldest individual reached 75 years. Cox regression with a sibling comparison design to tackle familial genetic and environmental confounding was used to derive hazard ratios and 95% confidence intervals for each infection site, type, or any infections at ages 21-30 and 31-40 years. During a median follow-up of 15.4 years, 8815 unique Parkinson's disease diagnoses were accrued, with a crude rate of 17.3 (95% confidence interval 17.0, 17.7) per 100 000 person-years. After controlling for shared familial factors, hospital-treated gastrointestinal and respiratory infections between 21 and 30 years of age were associated with a greater risk of Parkinson's disease [hazard ratios 1.35 (95% confidence interval: 1.05, 1.75) and 1.45 (95% confidence interval: 1.08, 1.95), respectively]; no association was found for any infections at age 31-40 [hazard ratio 1.05 (95% confidence interval: 0.93, 1.19)]. After adjustment, no statistically significant associations were observed for other sites including genitourinary and skin. These findings suggest that hospital-treated infections of the gastrointestinal tract and lungs, both of which may have an influence on the gut microbiome, by age 30 years may be risk factors for Parkinson's disease.

Defining treatment success in children with surgical conditions

ObjectivesDevelop a score summarising how successfully a child with any surgical condition has been treated, and test the clinical validity of the score.DesignDiscrete choice experiment (DCE), and secondary analysis of...

Infection burden and its association with neurite orientation dispersion and density imaging markers in the UK Biobank

BackgroundInfection burden (IB), although linked to neurodegeneration, including Alzheimer’s Disease (AD), has not been examined against neurite orientation, dispersion, and density imaging (NODDI) measures. MethodsAmong 38,803 UK Biobank adults (Age:40–70 years), we tested associations of total IB (IBtotal, 47.5 %) and hospital-treated IB (IBhosp, 9.7 %) with NODDI measures (5–15 years later), including volume fraction of Gaussian isotropic diffusion (ISOVF), intra-cellular volume fraction (ICVF) and orientation dispersion (OD) indices, using multiple linear regression models. ResultsTotal and hospital-treated infection burdens (IBtotal and IBhosp) were associated with increased ISOVF, indicating increased free-water component. IBtotal was positively associated with OD, indicating that at higher IBtotal there was greater fanning of neurites. This was more evident in the lower cardiovascular health group. IBhosp was associated with higher OD, and lower ICVF at higher AD polygenic risk. Together, these findings indicate that both total and hospital-treated infections have effects on NODDI outcomes in the direction of poor brain health. These effects were largely homogeneous across cardiovascular health and AD polygenic risk groups, with some effects shown to be stronger at poor cardiovascular health and/or higher AD risk. ConclusionsTotal and hospital-treated infections were associated with poorer white matter microstructure (higher ISOVF or OD or lower ICVF), with some heterogeneity across cardiovascular health and AD risk. Longitudinal studies with multiple repeats on neuroimaging markers in comparable samples are needed.

Cardiovascular health, infection burden, and incident dementia in the UK Biobank.

Among older adults, total and hospitalized infection may be associated with incidence of all-cause and Alzheimer's disease (AD) dementias, with variation by cardiovascular health (CVH). We used Cox proportional hazards (PH) models to examine the relationships between International Classification of Diseases-10th revision(ICD-10)-specific viral and bacterial infectious agents and incident all-cause and AD dementia among 355,046 UK Biobank participants ≥50 years at baseline. Life's Essential 8 (LE8) index reflected CVH. In both sexes, total infection burden (yes vs. no) was associated with all-cause dementia, with significant interactions by LE8 tertiles, whereby this relationship was significant only in the lowest LE8 tertile. Hospital-treated infection burden (yes vs no) was significantly related to all-cause and AD dementia, with no significant interaction with LE8 tertile. Age group patterns were detected. AD and all-cause dementia were related to hospital-treated infections, while CVH modified the relationship of total infection burden with all-cause dementia. Highlights Secondary analysis on>355,000 UK Biobank participants ≥50 years at baseline. Alzheimer's disease and all-cause dementia are both related to hospital-treated infection. Cardiovascular health modifies association of infection burden with all-cause dementia.

Effect of single versus multiple prophylactic antibiotic doses on prosthetic joint infections following primary total hip arthroplasty in patients with osteoarthritis at public and private hospitals in Denmark: protocol for a nationwide cross-over, cluster randomised, non-inferiority trial [The Pro-Hip-Quality Trial]

IntroductionA feared complication after total hip arthroplasty (THA) is prosthetic joint infection (PJI), associated with high morbidity and mortality. Prophylactic antibiotics can reduce the risk of PJI. However, there is...

Cardiovascular health, infection burden and their interactive association with brain volumetric and white matter integrity outcomes in the UK Biobank

BackgroundCardiovascular health is associated with brain magnetic resonance imaging (MRI) markers of pathology and infections may modulate this association. MethodsUsing data from 38,803 adults (aged 40–70 years) and followed-up for 5–15 years, we tested associations of prevalent total (47.5%) and hospital-treated infection burden (9.7%) with brain structural and diffusion-weighted MRI (i.e., sMRI and dMRI, respectively) common in dementia phenome. Poor white matter tissue integrity was operationalized with lower global and tract-specific fractional anisotropy (FA) and higher mean diffusivity (MD). Volumetric sMRI outcomes included total, gray matter (GM), white matter (WM), frontal bilateral GM, white matter hyperintensity (WMH), and selected based on previous associations with dementia. Cardiovascular health was measured with Life’s Essential 8 score (LE8) converted to tertiles. Multiple linear regression models were used, adjusting for intracranial volumes (ICV) for subcortical structures, and for demographic, socio-economic, and the Alzheimer’s Disease polygenic risk score for all outcomes, among potential confounders. ResultsIn fully adjusted models, hospital-treated infections were inversely related to GM (β ± SE: −1042 ± 379, p = 0.006) and directly related to WMH as percent of ICV (Loge transformed) (β ± SE:+0.026 ± 0.007, p < 0.001). Both total and hospital-treated infections were associated with poor WMI, while the latter was inversely related to FA within the lowest LE8 tertile (β ± SE:-0.0011 ± 0.0003, p < 0.001, PLE8×IB < 0.05), a pattern detected for GM, Right Frontal GM, left accumbens and left hippocampus volumes. Within the uppermost LE8 tertile, total infection burden was linked to smaller right amygdala while being associated with larger left frontal GM and right putamen volumes, in the overall sample. Within that uppermost tertile of LE8, caudate volumes were also positively associated with hospital-treated infections. ConclusionsHospital-treated infections had more consistent deleterious effects on volumetric and white matter integrity brain neuroimaging outcomes compared with total infectious burden, particularly in poorer cardiovascular health groups. Further studies are needed in comparable populations, including longitudinal studies with multiple repeats on neuroimaging markers.

Comorbidity and risk of infection among patients with hip fracture: a Danish population-based cohort study

SummaryImpact of comorbidity on infection risk among hip fracture patients is unclear. We found high incidence of infection. Comorbidity was an important risk factor for infection up to 1 year after surgery. Results indicates a need for additional investment in pre- and postoperative programs that assist patients with high comorbidity.PurposeComorbidity level and incidence of infection have increased among older patients with hip fracture. The impact of comorbidity on infection risk is unclear. We conducted a cohort study examining the absolute and relative risks of infection in relation to comorbidity level among hip fracture patients.MethodsUtilizing Danish population-based medical registries, we identified 92,600 patients aged ≥ 65 years undergoing hip fracture surgery between 2004 and 2018. Comorbidity was categorized by Charlson comorbidity index scores (CCI): none (CCI = 0), moderate (CCI = 1–2), or severe (CCI ≥ 3). Primary outcome was any hospital-treated infection. Secondary outcomes were hospital-treated pneumonia, urinary tract infection, sepsis, reoperation due to surgical-site infection (SSI), and a composite of any hospital- or community-treated infection. We calculated cumulative incidence and hazard ratios (aHRs) adjusted for age, sex, and surgery year, including 95% confidence intervals (CIs).ResultsPrevalence of moderate and severe comorbidity was 40% and 19%, respectively. Incidence of any hospital-treated infection increased with comorbidity level within 0–30 days (none 13% vs. severe 20%) and 0–365 days (none 22% vs. 37% severe). Patients with moderate and severe comorbidity, compared to no comorbidity, had aHRs of 1.3 (CI: 1.3–1.4) and 1.6 (CI: 1.5–1.7) within 0–30 days, and 1.4 (CI: 1.4–1.5) and 1.9 (CI: 1.9–2.0) within 0–365, respectively. Highest incidence was observed for any hospital- or community-treated infection (severe 72%) within 0–365 days. Highest aHR was observed for sepsis within 0–365 days (severe vs. none: 2.7 (CI: 2.4–2.9)).ConclusionComorbidity is an important risk factor for infection up to 1 year after hip fracture surgery.

Association of social isolation and loneliness with risk of incident hospital-treated infections: an analysis of data from the UK Biobank and Finnish Health and Social Support studies

Although loneliness and social isolation have been linked to an increased risk of non-communicable diseases such as cardiovascular disease and dementia, their association with the risk of severe infection is uncertain. We aimed to examine the associations between loneliness and social isolation and the risk of hospital-treated infections using data from two independent cohort studies. We assessed the association between loneliness and social isolation and incident hospital-treated infections using data for participants from the UK Biobank study aged 38-73 years at baseline and participants from the nationwide population-based Finnish Health and Social Support (HeSSup) study aged 20-54 years at baseline. For inclusion in the study, participants had to be linked to national health registries, have no history of hospital-treated infections at or before baseline, and have complete data on loneliness or social isolation. Participants with missing data on hospital-treated infections, loneliness, and social isolation were excluded from both cohorts. The outcome was defined as a hospital admission with a primary diagnosis of infection, ascertained via linkage to electronic health records. After exclusion of 8·6 million participants for not responding or not providing appropriate consent, the UK Biobank cohort consisted of 456 905 participants (249 586 women and 207 319 men). 26 860 (6·2%) of 436 001 participants with available data were reported as being lonely and 40 428 (9·0%) of 448 114 participants with available data were socially isolated. During a median 8·9 years (IQR 8·0-9·6) of follow-up, 51 361 participants were admitted to hospital due to an infectious disease. After adjustment for age, sex, demographic and lifestyle factors, and morbidities, loneliness was associated with an increased risk of a hospital-treated infection (hazard ratio [HR] 1·12 [95% CI 1·07-1·16]), whereas social isolation was not (HR 1·01 [95% CI 0·97-1·04]). Of 64 797 individuals in the HeSSup cohort, 18 468 (11 367 women and 7101 men) were eligible for inclusion. 4466 (24·4%) of 18 296 were lonely and 1776 (9·7%) of 18 376 socially isolated. During a median follow-up of 10·0 years (IQR 10·0-10·1), 814 (4·4%) participants were admitted to hospital for an infectious disease. The HRs for the HeSSup study replicated those in the UK Biobank (multivariable-adjusted HR for loneliness 1·32 [95% CI 1·06-1·64]; 1·08 [0·87-1·35] for social isolation). Loneliness might increase susceptibility to severe infections, although the magnitude of this effect appears modest and residual confounding cannot be excluded. Interventional studies are required before policy recommendations can advance. Academy of Finland, the UK Medical Research Council, and Wellcome Trust UK.

Hospital-treated infections in early- and mid-life and risk of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis: A nationwide nested case-control study in Sweden.

Experimental observations have suggested a role of infection in the etiology of neurodegenerative disease. In human studies, however, it is difficult to disentangle whether infection is a risk factor or rather a comorbidity or secondary event of neurodegenerative disease. To this end, we examined the risk of 3 most common neurodegenerative diseases in relation to previous inpatient or outpatient episodes of hospital-treated infections. We performed a nested case-control study based on several national registers in Sweden. Cases were individuals newly diagnosed with Alzheimer's disease (AD), Parkinson's disease (PD), or amyotrophic lateral sclerosis (ALS) during 1970 to 2016 in Sweden, identified from the National Patient Register. For each case, 5 controls individually matched to the case on sex and year of birth were randomly selected from the general population. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) with adjustment for potential confounders, including sex, year of birth, area of residence, educational attainment, family history of neurodegenerative disease, and Charlson comorbidity index. Infections experienced within 5 years before diagnosis of neurodegenerative disease were excluded to reduce the influence of surveillance bias and reverse causation. The analysis included 291,941 AD cases (median age at diagnosis: 76.2 years; male: 46.6%), 103,919 PD cases (74.3; 55.1%), and 10,161 ALS cases (69.3; 56.8%). A hospital-treated infection 5 or more years earlier was associated with an increased risk of AD (OR = 1.16, 95% CI: 1.15 to 1.18, P < 0.001) and PD (OR = 1.04, 95% CI: 1.02 to 1.06, P < 0.001). Similar results were observed for bacterial, viral, and other infections and among different sites of infection including gastrointestinal and genitourinary infections. Multiple infections before age 40 conveyed the greatest risk of AD (OR = 2.62, 95% CI: 2.52 to 2.72, P < 0.001) and PD (OR = 1.41, 95% CI: 1.29 to 1.53, P < 0.001). The associations were primarily due to AD and PD diagnosed before 60 years (OR = 1.93, 95% CI: 1.89 to 1.98 for AD, P < 0.001; OR = 1.29, 95% CI: 1.22 to 1.36 for PD, P < 0.001), whereas no association was found for those diagnosed at 60 years or older (OR = 1.00, 95% CI: 0.98 to 1.01 for AD, P = 0.508; OR = 1.01, 95% CI: 0.99 to 1.03 for PD, P = 0.382). No association was observed for ALS (OR = 0.97, 95% CI: 0.92 to 1.03, P = 0.384), regardless of age at diagnosis. Excluding infections experienced within 10 years before diagnosis of neurodegenerative disease confirmed these findings. Study limitations include the potential misclassification of hospital-treated infections and neurodegenerative diseases due to incomplete coverage of the National Patient Register, as well as the residual confounding from unmeasured risk or protective factors for neurodegenerative diseases. Hospital-treated infections, especially in early- and mid-life, were associated with an increased risk of AD and PD, primarily among AD and PD cases diagnosed before 60 years. These findings suggest that infectious events may be a trigger or amplifier of a preexisting disease process, leading to clinical onset of neurodegenerative disease at a relatively early age. However, due to the observational nature of the study, these results do not formally prove a causal link.

Lower incidence of hospital-treated infections in infants under 3 months of age vaccinated with BCG

BackgroundLive vaccines potentially have non-specific effects that protect against other infections than those the vaccines are targeted against. The national vaccination program (NVP) in Finland was changed on September 1st, 2006: before BCG vaccine was given to all newborn babies and afterwards to babies in risk groups only. We used this natural experiment to study the non-specific effects of BCG in the frame of NVP using before-after design. MethodsWe compared the incidence of several outcomes obtained from Finnish health registers between children born between July 1st, 2004, and June 30th, 2006 (BCG-eligible) and an age- and season-matched reference cohort born between July 1st, 2007, and June 30th, 2009 (BCG-non-eligible) using Poisson regression. These cohorts were restricted to full-term children whose parents were born in Finland. Follow-up began at birth and lasted 3 months, which is the scheduled age for DTaP-IPV-Hib vaccination, and from 4 months until first birthday. The outcomes included all infections, pneumonia and injuries as a negative control outcome. ResultsThe incidence rate ratio (IRR) of the BCG-eligible cohort (N = 93,658) compared to BCG-non-eligible cohort (N = 94,712) for hospital-diagnosed infections was 0.89 (95 %Cl 0.86–0.93) for the 3-month follow-up. The decrease was mainly caused by respiratory infections. In 4–12 months follow-up the BCG-eligible had slightly more infections than BCG-non-eligible children (IRR 1.03, 1.01–1.06). ConclusionsBCG vaccination was associated with a lower incidence of all hospital-diagnosed infections during the first three months of life. The difference cannot be attributed to lung tuberculosis, since only few paediatric cases occurred in Finland during 2000s. The disappearance of non-specific effect after administration of an inactivated vaccine is compatible with previous studies.

Hospital-Treated Infections and Increased Risk of Two EBV-Related Malignancies: A Nested Case-Control Study.

Simple SummaryEpstein–Barr virus (EBV) is associated with the risk of several human malignancies, including Hodgkin’s lymphoma (HL) and nasopharyngeal carcinoma (NPC). However, as EBV infection is widely spread across human populations, whereas only a small proportion of the infected individuals eventually develop such malignancies, additional component causes are likely needed in the development of EBV-related malignancies. We performed a national register-based study in Sweden to examine the role of infections that required hospital treatment on the subsequent risk of HL and NPC. We found that previous hospital-treated infections were associated with a higher risk of HL and NPC and that a positive association was observed for both bacterial and viral infections, especially for respiratory and skin infections. A dose-response relationship was also noted between the number of infections and the risk of HL. These findings suggest that infectious events might contribute to the carcinogenesis of malignancies potentially related to EBV.Background: To assess the association of hospital-treated infections with the subsequent risk of two Epstein-Barr virus (EBV)-related malignancies, namely Hodgkin’s lymphoma (HL) and nasopharyngeal carcinoma (NPC). Methods: We performed a nested case-control study based on several national registers in Sweden. Cases were individuals newly diagnosed with HL or NPC during 1994–2016 in Sweden, according to the Swedish Cancer Register. For each case, we randomly selected five controls individually matched to the case on sex and year of birth from the general Swedish population. Hospital-treated infections (i.e., infections requiring either inpatient or outpatient hospital care) were identified from the Swedish Patient Register. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of HL and NPC, in relation to hospital-treated infections, after adjustment for age, sex, calendar period, educational achievement, and region of residence. Results: The study included a total of 890 cases of HL and 306 cases of NPC. A hospital-treated infection three years ago or earlier was associated with a higher risk of HL (OR = 1.49, 95%CI: 1.26–1.75) as well as NPC (OR = 1.36; 95%CI: 1.01–1.83). The positive association was noted for both bacterial and viral infections and primarily for respiratory and skin infections. A monotonous dose-response relationship was found between a number of hospital-treated infections and the risk of HL (p = 0.02) but less compelling for NPC (p = 0.06). Using a 5-year lag time rendered similar results (OR = 1.43, 95%CI: 1.21–1.70 for HL; OR = 1.43, 95%CI: 1.05–1.95 for NPC). Conclusions: These findings suggest that infections requiring hospital treatment might contribute to the carcinogenesis of malignancies potentially related to EBV.

Postoperative complications, mortality, and quality of in-hospital care among hip fracture patients with Parkinson's disease

AimThe aim of this study was to investigate the association between Parkinson's disease (PD) and postoperative complications, mortality, and quality of in-hospital care in patients with hip fracture. MethodsWe included patients aged 65+ years with an incident hip fracture from 2004-2017, registered in the Danish Multidisciplinary Hip Fracture Registry. Patients with PD were identified using diagnosis codes prior to hip fracture. Using log-binomial regression, we calculated both 30-day crude and adjusted risk ratios (aRR) with 95% confidence intervals (CIs) for the following outcomes: any hospital-treated infections, pneumonia, urinary tract infection, sepsis, community-treated infections, cardiovascular events, mortality, and fulfilment of quality indicators of in-hospital care. Analyses were adjusted for age, sex and Charlson comorbidity index score. ResultsWe identified 77,550 hip fracture patients of which 1,915 had PD. Compared to non-PD, patients with PD had higher risk of any hospital-treated - (aRR = 1.27 (CI: 1.10-1.45) and community-treated infection (aRR = 1.22 (CI: 1.13-1.32)), pneumonia (aRR = 1.38 (1.11-1.69)), urinary tract infection (aRR of 1.58 (CI: 1.28-1.92)) and sepsis (aRR = 1.18 (CI: 0.67-1.89)), but a reduced risk of cardiovascular events (aRR = 0.59 (CI: 0.41-0.82)). The aRR for 30-day mortality was 1.11 (CI: 0.97-1.27) for PD vs non-PD patients, and the aHR for 1-year mortality was 1.19 (CI: 1.09-1.30). The aRRs for fulfillment of all relevant quality indicators was about 1 for PD vs non-PD patients. ConclusionHip fracture patients with PD have a higher risk of infections and mortality within 30 days after surgery after adjustment for sex, age, and comorbidity. They do, however, receive comparable quality of in-hospital care after hip fracture compared to non-PD patients.

The association between socioeconomic status and the 30- and 90-day risk of infection after total hip arthroplasty : a registry-based cohort study of 103,901 patients with osteoarthritis.

The aim of this study was to examine whether socioeconomic status (SES) is associated with a higher risk of infections following total hip arthroplasty (THA) at 30 and 90 days. We obtained individual-based information on SES markers (cohabitation, education, income, and savings) on 103,901 THA patients from Danish health registries between 1 January 1995 and 31 December 2017. The primary outcome measure was any hospital-treated infection (i.e. all infections). The secondary outcomes were further specified to specific hospital-treated infections (pneumonia, urinary tract infection, and periprosthetic joint infection). The primary timepoint was within 90 days. In addition, the outcomes were further evaluated within 30 days. We calculated the cumulative incidence, and used the pseudo-observation method and generalized linear regression to estimate adjusted risk ratios (RRs) with 95% confidence intervals (CIs) for each marker. The cumulative incidence of any infection at 90 days was highest in patients who lived alone (1.5% (95% CI 1.3 to 1.6)) versus cohabitant (0.7% (95% CI 0.7 to 0.8)), had the lowest educational achievement (1.1% (95% CI 1.0 to 1.2)) versus highest (0.7% (95% CI 0.5 to 0.8)), had the lowest income (1.6% (95% CI 1.5 to 1.70)) versus highest (0.4% (95% CI 0.3 to 0.5)), or had lowest savings (1.3% (95% CI 1.2 to 1.4)) versus highest (0.7% (95% CI 0.6 to 0.8)). Within 90 days, the RRs for any infection were 1.3 (95% CI 1.2 to 1.4) for patients living alone versus cohabiting, 1.2 (95% CI 1.0 to 1.3) for low education achievement versus high, 1.7 (95% CI 1.4 to 2.1) for low income versus high income, and 1.5 (95% CI 1.4 to 1.8) for low savings versus high savings. The same trends were also seen for any infections within the first 30 days. Our study provides evidence that socioeconomic inequality adversely influences the risk of infection after THA, thus contributing to healthcare disparities and inequalities. We found that living alone, low educational achievement, low income, or low savings were associated with higher risks of infections within the first 30 and 90 days after THA. Therefore, the development of targeted intervention strategies with the aim of increasing awareness of patients identified as being at greatest risk is needed to mitigate the impact of SES on the risk of infections following THA. Cite this article: Bone Joint J2022;104-B(2):221-226.

Infections in temporal proximity to HPV vaccination and adverse effects following vaccination in Denmark: A nationwide register-based cohort study and case-crossover analysis.

BackgroundPublic trust in the human papilloma virus (HPV) vaccination programme has been challenged by reports of potential severe adverse effects. The reported adverse symptoms were heterogeneous and overlapping with those characterised as chronic fatigue syndrome (CFS) and have been described as CFS-like symptoms. Evidence suggests that CFS is often precipitated by an infection. The aim of the study was to examine if an infection in temporal proximity to HPV vaccination is a risk factor for suspected adverse effects following HPV vaccination.Methods and findingsThe study was a nationwide register-based cohort study and case-crossover analysis. The study population consisted of all HPV vaccinated females living in Denmark, born between 1974 and 2006, and vaccinated between January 1, 2006 and December 31, 2017. The exposure was any infection in the period ± 1 month around time of first HPV vaccination and was defined as (1) hospital-treated infection; (2) redemption of anti-infective medication; or (3) having a rapid streptococcal test done at the general practitioner. The outcome was referral to a specialised hospital setting (5 national HPV centres opened June 1, 2015) due to suspected adverse effects following HPV vaccination. Multivariable logistic regression was used to estimate the association between infection and later HPV centre referral. The participants were 600,400 HPV-vaccinated females aged 11 to 44 years. Of these, 48,361 (9.7%) females had a hospital-treated infection, redeemed anti-infective medication, or had a rapid streptococcal test ± 1 month around time of first HPV vaccination. A total of 1,755 (0.3%) females were referred to an HPV centre. Having a hospital-treated infection in temporal proximity to vaccination was associated with significantly elevated risk of later referral to an HPV centre (odds ratio (OR) 2.75, 95% confidence interval (CI) 1.72 to 4.40; P < 0.001). Increased risk was also observed among females who redeemed anti-infective medication (OR 1.56, 95% CI 1.33 to 1.83; P < 0.001) or had a rapid streptococcal test (OR 1.45, 95% CI 1.10 to 1.93; P = 0.010). Results from a case-crossover analysis, which was performed to adjust for potential unmeasured confounding, supported the findings. A key limitation of the study is that the HPV centres did not open until June 1, 2015, which may have led to an underestimation of the risk of suspected adverse effects, but stratified analyses by year of vaccination yielded similar results.ConclusionsTreated infection in temporal proximity to HPV vaccination is associated with increased risk for later referral with suspected adverse vaccine effects. Thus, the infection could potentially be a trigger of the CFS-like symptoms in a subset of the referred females. To our knowledge, the study is the first to investigate the role of infection in the development of suspected adverse effects after HPV vaccination and replication of these findings are needed in other studies.

Long working hours and risk of 50 health conditions and mortality outcomes: a multicohort study in four European countries.

SUMMARYBackgroundStudies on the association between long working hours and health have captured only a narrow range of outcomes (mainly cardiometabolic diseases and depression) and no outcome-wide studies on this topic are available. To achieve wider scope of potential harm, we examined long working hours as a risk factor for a wide range of disease and mortality endpoints.MethodsThe data of this multicohort study were from two population cohorts from Finland (primary analysis, n=59 599) and nine cohorts (replication analysis, n=44 262) from Sweden, Denmark, and the UK, all part of the Individual-participant Meta-analysis in Working Populations (IPD-Work) consortium. Baseline-assessed long working hours (≥55 hours per week) were compared to standard working hours (35-40 h). Outcome measures with follow-up until age 65 years were 46 diseases that required hospital treatment or continuous pharmacotherapy, all-cause, and three cause-specific mortality endpoints, ascertained via linkage to national health and mortality registers.Findings2747 (4·6%) participants in the primary cohorts and 3027 (6·8%) in the replication cohorts worked long hours. After adjustment for age, sex, and socioeconomic status, working long hours was associated with increased risk of cardiovascular death (hazard ratio 1·68; 95% confidence interval 1·08-2·61 in primary analysis and 1·52; 0·90-2·58 in replication analysis), infections (1·37; 1·13-1·67 and 1·45; 1·13-1·87), diabetes (1·18; 1·01-1·38 and 1·41; 0·98-2·02), injuries (1·22; 1·00-1·50 and 1·18; 0·98-1·18) and musculoskeletal disorders (1·15; 1·06-1·26 and 1·13; 1·00-1·27). Working long hours was not associated with all-cause mortality.InterpretationFollow-up of 50 health outcomes in four European countries suggests that working long hours is associated with an elevated risk of early cardiovascular death and hospital-treated infections before age 65. Associations, albeit weak, were also observed with diabetes, musculoskeletal disorders and injuries. In these data working long hours was not related to elevated overall mortality.FundingNordForsk, the Medical Research Council, the National Institute on Aging, the Wellcome Trust, Academy of Finland, and Finnish Work Environment Fund.