Pneumococcal disease is a leading cause of morbidity and mortality worldwide. The aim of this study was to investigate the association between specific pneumococcal serotypes and mortality from ...invasive pneumococcal disease (IPD).
In a nationwide population-based cohort study of IPD in Denmark during 1977-2007, 30-d mortality associated with pneumococcal serotypes was examined by multivariate logistic regression analysis after controlling for potential confounders. A total of 18,858 IPD patients were included. Overall 30-d mortality was 18%, and 3% in children younger than age 5 y. Age, male sex, meningitis, high comorbidity level, alcoholism, and early decade of diagnosis were significantly associated with mortality. Among individuals aged 5 y and older, serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A were associated with highly increased mortality as compared with serotype 1 (all: adjusted odds ratio >or=3, p<0.001). In children younger than 5 y, associations between serotypes and mortality were different than in adults but statistical precision was limited because of low overall childhood-related mortality.
Specific pneumococcal serotypes strongly and independently affect IPD associated mortality.
Health-care workers are thought to be highly exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to investigate the prevalence of antibodies against SARS-CoV-2 ...in health-care workers and the proportion of seroconverted health-care workers with previous symptoms of COVID-19.
In this observational cohort study, screening was offered to health-care workers in the Capital Region of Denmark, including medical, nursing, and other students who were associated with hospitals in the region. Screening included point-of-care tests for IgM and IgG antibodies against SARS-CoV-2. Test results and participant characteristics were recorded. Results were compared with findings in blood donors in the Capital Region in the study period.
Between April 15 and April 23, 2020, we screened 29 295 health-care workers, of whom 28 792 (98·28%) provided their test results. We identified 1163 (4·04% 95% CI 3·82–4·27) seropositive health-care workers. Seroprevalence was higher in health-care workers than in blood donors (142 3·04% of 4672; risk ratio RR 1·33 95% CI 1·12–1·58; p<0·001). Seroprevalence was higher in male health-care workers (331 5·45% of 6077) than in female health-care workers (832 3·66% of 22 715; RR 1·49 1·31–1·68; p<0·001). Frontline health-care workers working in hospitals had a significantly higher seroprevalence (779 4·55% of 16 356) than health-care workers in other settings (384 3·29% of 11 657; RR 1·38 1·22–1·56; p<0·001). Health-care workers working on dedicated COVID-19 wards (95 7·19% of 1321) had a significantly higher seroprevalence than other frontline health-care workers working in hospitals (696 4·35% of 15 983; RR 1·65 1·34–2·03; p<0·001). 622 53·5% of 1163 seropositive participants reported symptoms attributable to SARS-CoV-2. Loss of taste or smell was the symptom that was most strongly associated with seropositivity (377 32·39% of 1164 participants with this symptom were seropositive vs 786 2·84% of 27 628 without this symptom; RR 11·38 10·22–12·68). The study is registered at ClinicalTrials.gov, NCT04346186.
The prevalence of health-care workers with antibodies against SARS-CoV-2 was low but higher than in blood donors. The risk of SARS-CoV-2 infection in health-care workers was related to exposure to infected patients. More than half of seropositive health-care workers reported symptoms attributable to COVID-19.
Lundbeck Foundation.
Summary Background Uncertainty in the risk of reproductive complications (pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility) following chlamydia infection and repeat ...infection hampers the design of evidence-based chlamydia control programmes. We estimate the association between diagnosed chlamydia and episodes of hospital health care (inpatient, outpatient, and emergency department) for a reproductive complication. Methods We constructed and analysed a retrospective population-based cohort of women aged 15–44 years from administrative records in Denmark (1995–2012). We used a subset of the national Danish Chlamydia Study. The master dataset contains all residents of Denmark (including Greenland) who had a positive chlamydia test recorded by a public health microbiology laboratory from Jan 1, 1992, to Nov 2, 2011. Individuals were randomly matched (by age and sex) to four individuals drawn from the population register (Danish Civil Registration System) who did not have a positive chlamydia test during this interval. The outcomes in the study were hospital episodes of health-care (inpatient, outpatient, and emergency department) with a diagnosis of pelvic inflammatory disease, ectopic pregnancy, or tubal factor infertility. Findings The 516 720 women (103 344 positive, 182 879 negative, 230 497 never-tested) had a mean follow-up of 7·96 years. Compared with women with only negative tests, the risk of each complication was 30% higher in women with one or more positive tests (pelvic inflammatory disease, adjusted hazard ratio AHR 1·50 95% CI 1·43–1·57; ectopic pregnancy, AHR 1·31 1·25–1·38; tubal factor infertility, AHR 1·37 1·24–1·52) and 60% lower in women who were never-tested (pelvic inflammatory disease, AHR 0·33 0·31–0·35; ectopic pregnancy, AHR 0·42 0·39–0·44; tubal factor infertility AHR 0·29 0·25–0·33). A positive test had a minor absolute impact on health as the difference in the lifetime incidence of complications was small between women who tested positive and those who tested negative (pelvic inflammatory disease, 0·6%; ectopic pregnancy, 0·2%; tubal factor infertility, 0·1%). Repeat infections increased the risk of pelvic inflammatory disease by a further 20% (AHR 1·20, 95% CI 1·11–1·31). Interpretation A single diagnosed chlamydia infection increased the risk of all complications and a repeat diagnosed infection further increased the risk of pelvic inflammatory disease. Therefore, control programmes must prevent first and repeat infections to improve women's reproductive health. Funding Unrestricted partial funding from Frederiksberg Kommune, Frederiksberg, Denmark. BD held an Medical Research Council Population Health Scientist Fellowship (G0902120). KT held an National Institute for Health Research Post-Doctoral Fellowship 2009-02-055.
The Neutrophil-Lymphocyte Ratio (NLR) in blood has demonstrated its capability to predict bacteremia in emergency departments, and its association with mortality has been established in patients with ...sepsis in intensive care units. However, its potential concerning mortality and readmission in patients with Gram-negative bacteremia (GNB) is unexplored.
This retrospective cohort study included patients with GNB between 2018 and 2022 from six hospitals in the Capital Region of Denmark. Patients who were immunosuppressed or had missing NLR values on the day of blood culture were excluded. Logistic regression models were used to analyze the association between NLR levels and 90-day all-cause mortality, while the logit link interpretation of the cumulative incidence function was used to assess the association between NLR levels and 60-day readmission. Associations were quantified as odds ratios (OR) with corresponding 95% confidence intervals (CI).
The study included 1763 patients with a median age was 76.8 years and 51.3% were female. The median NLR was 17.3 and 15.8% of patients had a quick sequential organ failure assessment score of two or three. Urinary tract infection (UTI) was the most frequent focus and Escherichia coli the most frequent pathogen. Statistically significant differences in median NLR were found by age group and pathogen, and for patients with or without hypertension, liver disease, chronic obstructive pulmonary disease, dementia, and alcohol abuse. 378 patients (21.4%) died before 90 days. 526 (29.8%) patients were readmitted to the hospital within 60 days. For each doubling of the NLR, the OR for all-cause 90-day mortality was 1.15 (95% CI, 1.04-1.27) and 1.12 (95% CI, 1.02-1.24) for 60-day readmission. Analysis of subgroups did not show statistically significant differences between groups in relation to the association between NLR and mortality. The discriminatory ability of NLR for mortality was limited and comparable to blood neutrophil or lymphocyte count, producing receiver operating characteristic curves with an area under the curve of 0.59 (95% CI, 0.56-0.63), 0.60 (95% CI, 0.56-0.65) and 0.53 (95% CI, 0.49-0.56), respectively.
Blood neutrophil-lymphocyte ratio was associated with 90-day all-cause mortality and 60-day readmission in patients with GNB. However, the ratio has limited ability in predicting mortality or readmission.
Background. The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) at the population level is unclear. We explored PCV13's effect in reducing invasive pneumococcal disease (IPD)–related ...morbidity and mortality, and whether serotype-specific changes were attributable to vaccination or expected as a part of natural, cyclical variations. Methods. This was a Danish nationwide population-based cohort study based on the linkage of laboratory surveillance data and the Danish Civil Registration System. Changes in IPD incidence and mortality during baseline (2000–2007), 7-valent pneumococcal conjugate vaccine (PCV7) (2008–2010), and PCV13 (2011–2013) periods were estimated. Predicted incidences of serotypes were estimated controlling for cyclical trends from historical patterns observed during the past 20 years. Results. We observed a 21% reduction (95% confidence interval CI, 17%–25%) in IPD incidence in the total population after PCV13's introduction, and a 71% reduction (95% CI, 62%–79%) in children aged <2 years, considered as the vaccine effectiveness. We estimated a 28% reduction (95% CI, 18%–37%) in IPD-related 30-day mortality, from 3.4 deaths (95% CI, 3.2–3.6) per 100 000 population in the pre-PCV period to 2.4 (95% CI, 2.2–2.7) in the PCV13 period. The decline in mortality was observed across all age groups but was mainly related to mortality reductions in the nonvaccinated population. For serotypes 1 and 3, there were no significant changes in incidence beyond what would be expected from natural cyclical patterns. Serotype 19A significantly increased following PCV7's introduction, but the incidence declined toward baseline in 2012. Conclusions. PCV13 has brought greater benefits than we had expected in our setting. We observed a further decline on IPD incidence shortly after the shift from PCV7 to PCV13 in the national immunization program. This decline was accompanied by a substantial population-level decline in pneumococcal-related mortality of nearly 30% among nonvaccinated persons.
•Carriage rates of S. pneumoniae are high in low- and lower-middle-income countries.•Pneumococcal Conjugate Vaccine coverage is moderate in L-MICs compared to HICs.•Vaccine-type carriage has ...decreased in most countries with introduction of the PCV.•Non-vaccine-type pneumococcal carriage has increased due to serotype replacement.
Streptococcus pneumoniae is one of the most important causes of diseases leading to child mortality, especially in low- and lower-middle-income countries. This review aims to describe the prevalence of carriage of S. pneumoniae and the impact of vaccination among children aged under five years in low- and lower-middle-income countries since 2012.
The study is a systematic review of the literature. Relevant publications were searched in PubMed and screened systematically for information on the prevalence of carriage of S. pneumoniae among children aged under five years. 149 publications were identified, and 20 were included in the review.
The prevalence of S. pneumoniae ranged between 26.7% - 90.7%. The prevalence of vaccine-type carriage ranged between 4.4% - 57.6% but generally decreased in countries after the introduction of PCV, with a reduction of 15.6% - 65.7%. Half of the post- pneumococcal conjugate vaccine (PCV) studies reported a vaccine-type carriage rate below 15%.
Vaccine-type-carriage has decreased in most countries with the introduction of PCV. Still, coverage is only moderate, and carriage rates of S. pneumoniae vary significantly between countries. Continuous monitoring of carriage is needed to evaluate the effect of the further introduction of PCV10 and PCV13.
Staphylococcus aureus bacteremia (SAB) is a major cause of illness and death worldwide. We analyzed temporal trends of SAB incidence and death in Denmark during 2008-2015. SAB incidence increased ...48%, from 20.76 to 30.37 per 100,000 person-years, during this period (p<0.001). The largest change in incidence was observed for persons >80 years of age: a 90% increase in the SAB rate (p<0.001). After adjusting for demographic changes, annual rates increased 4.0% (95% CI 3.0-5.0) for persons <80 years of age, 8.4% (95% CI 7.0-11.0) for persons 80-89 years of age, and 13.0% (95% CI 9.0-17.5) for persons >90 years of age. The 30-day case-fatality rate remained stable at 24%; crude population death rates increased by 53% during 2008-2015 (p<0.001). Specific causes and mechanisms for this rapid increase in SAB incidence among the elderly population remain to be clarified.
Introduction Immune dysregulation with an excessive release of cytokines has been identified as a key driver in the development of severe COVID-19. The aim of this study was to evaluate the initial ...cytokine profile associated with 90-day mortality and respiratory failure in a cohort of patients hospitalized with COVID 19 that did not receive immunomodulatory therapy. Methods Levels of 45 cytokines were measured in blood samples obtained at admission from patients with confirmed COVID-19. Logistic regression analysis was utilized to determine the association between cytokine levels and outcomes. The primary outcome was death within 90 days from admission and the secondary outcome was need for mechanical ventilation. Results A total of 132 patients were included during the spring of 2020. We found that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with the odds of 90-day mortality, specifically: interleukin-1 receptor antagonist, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, macrophage inflammatory protein-3α, macrophage inflammatory protein-3β, and fractalkine. All but fractalkine were also associated with the odds of respiratory failure during admission. Monocyte chemoattractant protein-1 showed the strongest estimate of association with both outcomes. Conclusion We showed that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with 90-day mortality in patients hospitalized with COVID-19 that did not receive immunomodulatory therapy.
Background. Pneumococcal infections have historically played a major role in terms of morbidity and mortality. We explored historical trends of invasive pneumococcal disease (IPD) and pneumococcal ...serotypes in a population exposed to limited antibiotic selective pressure and conjugate pneumococcal vaccination (PCV). Methods. Retrospective cohort study based on nationwide laboratory surveillance data on IPD collected uninterruptedly in Denmark during 1938–2007. Changes in the reported incidence and trends of pneumococcal serotypes were explored using nonlinear regression analysis. Results. There were 25,502 IPD cases included in our study. The median incidence of IPD increased from 2.8 cases per 100,000 population (interquartile range IQR, 1.5–2.6) during the first 4 decades to 15.7 cases per 100,000 population (IQR, 7–20.4) during the 1980s and 1990s, mainly attributed to an increase in the number of bacteremia cases. The incidence of meningitis remained relatively stable, with a median of 1.3 cases per 100,000 population (IQR, 0.9–1.6). The proportions of serotypes/groups 4 and 9 increased; the proportion of serotype 18C decreased; the proportions of serotypes 6, 7F, 14, and 23F remained stable; and serotype 2 nearly disappeared. Before the 1960s, serotypes 1, 2, 3, and 5 presented peaks every 2–3 years, becoming less frequent during the 1970s with peaks every 7–10 years. Between 20% and 90% of IPD in children <5 years were caused by PCV serotypes during the last 4 decades. Cases of IPD caused by serotype 19A increased before introduction of PCV. Between 1993 and 2007, the level of resistance to macrolides and β-lactams was ⩽6%. Conclusions. The epidemiology of IPD and single serotypes has constantly changed over the past 7 decades. PCV serotypes appeared to dominate the pneumococcal population.
Gautret and colleagues reported the results of a non-randomised case series which examined the effects of hydroxychloroquine and azithromycin on viral load in the upper respiratory tract of Severe ...acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. The authors reported that hydroxychloroquine (HCQ) had significant virus reducing effects, and that dual treatment of both HCQ and azithromycin further enhanced virus reduction. In light of criticisms regarding how patients were excluded from analyses, we reanalysed the original data to interrogate the main claims of the paper. We applied Bayesian statistics to assess the robustness of the original paper's claims by testing four variants of the data: 1) The original data; 2) Data including patients who deteriorated; 3) Data including patients who deteriorated with exclusion of untested patients in the comparison group; 4) Data that includes patients who deteriorated with the assumption that untested patients were negative. To ask if HCQ monotherapy was effective, we performed an A/B test for a model which assumes a positive effect, compared to a model of no effect. We found that the statistical evidence was highly sensitive to these data variants. Statistical evidence for the positive effect model ranged from strong for the original data (BF+0 ~11), to moderate when including patients who deteriorated (BF+0 ~4.35), to anecdotal when excluding untested patients (BF+0 ~2), and to anecdotal negative evidence if untested patients were assumed positive (BF+0 ~0.6). The fact that the patient inclusions and exclusions are not well justified nor adequately reported raises substantial uncertainty about the interpretation of the evidence obtained from the original paper.
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