Pediatric health service utilization at tertiary hospitals in Denmark 2000-2018.

Pediatric health service differs between and within countries. To prioritize limited resources, data-driven studies on pediatric tertiary hospital contacts are warranted. This population-based register study identified all contacts with four Danish tertiary hospitals 2000-2018 by 0-17-year-old patients. During 2000-2018, 2,496,001 individuals resided in Denmark while 0-17 years old, and the study described 829,562 inpatient and 3,932,744 outpatient contacts at tertiary hospitals by hospital, sex, age, diagnosis, department, and residence. Male patients accounted for more contacts overall (inpatient 55.51%, outpatient 52.40%) and more contacts with severe chronic disease (inpatient 56.24%, outpatient 54.41%). Median (interquartile range) patient age was 3.09 (0.26-9.96) and 8.48 (2.78-13.70) years for in- and outpatient contacts. Overall, 28.23% and 21.02% of in- and outpatient contacts included a diagnosis of a severe chronic disease, but the proportions differed across hospitals. A pattern of pediatric healthcare directed towards less severe diseases was observed: While the total number of outpatient visits at tertiary hospitals increased from 2000 to 2018, the proportion of these contacts which had a diagnosis of a severe chronic disease decreased. Future comparisons between hospitals regarding pediatric outcomes should consider potential differences in terms of uptake and diagnosis severity. Such findings may have implications for future pediatric organization, nationally and internationally.

Inflammatory and endothelial host responses in community-acquired pneumonia: exploring the relationships with HbA1c, admission plasma glucose, and glycaemic gap-a cross-sectional study.

Introduction: Diabetes is associated with dysregulated immune function and impaired cytokine release, while transient acute hyperglycaemia has been shown to enhance inflammatory cytokine release in preclinical studies. Although diabetes and acute hyperglycaemia are common among patients with community-acquired pneumonia (CAP), the impact of chronic, acute, and acute-on-chronic hyperglycaemia on the host response within this population remains poorly understood. This study investigated whether chronic, acute, and acute-on- chronic hyperglycaemia are associated with distinct mediators of inflammatory, endothelial, and angiogenic host response pathways in patients with CAP. Methods: In a cross-sectional study of 555 patients with CAP, HbA1c, admission plasma (p)-glucose, and the glycaemic gap (admission p-glucose minus HbA1c- derived average p-glucose) were employed as measures of chronic, acute, and acute-on-chronic hyperglycaemia, respectively. Linear regression was used to model the associations between the hyperglycaemia measures and 47 proteins involved in inflammation, endothelial activation, and angiogenesis measured at admission. The models were adjusted for age, sex, CAP severity, pathogen, immunosuppression, comorbidity, and body mass index. Adjustments for multiple testing were performed with a false discovery rate threshold of less than 0.05. Results: The analyses showed that HbA1c levels were positively associated with IL-8, IL-15, IL-17A/F, IL-1RA, sFlt-1, and VEGF-C. Admission plasma glucose was also positively associated with these proteins and GM-CSF. The glycaemic gap was positively associated with IL-8, IL-15, IL-17A/F, IL-2, and VEGF-C. Conclusion: In conclusion, chronic, acute, and acute-on-chronic hyperglycaemia were positively associated with similar host response mediators. Furthermore, acute and acute-on-chronic hyperglycaemia had unique associations with the inflammatory pathways involving GM-CSF and IL-2, respectively.

The Influence of Size on the Intracranial Distribution of Biomedical Nanoparticles Administered by Convection-enhanced Delivery in Minipigs.

Because of the blood-brain barrier (BBB), successful drug delivery to the brain has long been a key objective for the medical community, calling for pioneering technologies to overcome this challenge. Convection-enhanced delivery (CED), a form of direct intraparenchymal microinfusion, shows promise but requires optimal infusate design and real-time distribution monitoring. The size of the infused substances appears to be especially critical, with current knowledge being limited. Herein, we examined the intracranial administration of polyethylene glycol (PEG)-coated nanoparticles (NPs) of various sizes using CED in groups of healthy minipigs (n = 3). We employed stealth liposomes (LIPs, 130 nm) and two gold nanoparticle designs (AuNPs) of different diameters (8 and 40 nm). All were labeled with copper-64 for quantitative and real-time monitoring of the infusion via positron emission tomography (PET). NPs were infused via two catheters inserted bilaterally in the putaminal regions of the animals. Our results suggest CED with NPs holds promise for precise brain drug delivery, with larger LIPs exhibiting superior distribution volumes and intracranial retention over smaller AuNPs. PET imaging alongside CED enabled dynamic visualization of the process, target coverage, timely detection of suboptimal infusion, and quantification of distribution volumes and concentration gradients. These findings may augment the therapeutic efficacy of the delivery procedure while mitigating unwarranted side effects associated with nonvisually monitored delivery approaches. This is of vital importance, especially for chronic intermittent infusions through implanted catheters, as this information enables informed decisions for modulating targeted infusion volumes on a catheter-by-catheter, patient-by-patient basis.

Implementation of the vaccination program in Guinea-Bissau: Coverage and missed opportunities for BCG at birth.

BACKGROUND: The Bacillus Calmette-Guérin (BCG) vaccine is recommended at birth in Guinea-Bissau but often given with delay. Delays are not evident in routine coverage estimates since coverage is measured by 12 months of age. Studies show that BCG protects against other infections than tuberculosis and lowers neonatal mortality. Hence, the timing of BCG is important since the children should benefit from these non-specific effects as early as possible. METHODS: Using data from a nationally representative health and demographic surveillance system in Guinea-Bissau, we assessed BCG coverage at birth (within the first 3 days of life), 1 month, and 12 months for children born in 2013-19. We measured the proportion of children who had a documented health system contact within the first 3 days of life, thus an opportunity for BCG at birth, and whether the opportunities were utilized. In binomial regression models, we investigated factors associated with missed opportunities for vaccination. RESULTS: Among the 22,178 children only 19 % were vaccinated at birth. By 1 month and 12 months, BCG coverages were 64 % and 93 %. The timeliness of BCG improved over time, with coverage at birth increasing from 16 % in 2013 to 25 % in 2019 and 1-month coverage from 63 % in 2013 to 75 % in 2019. If all vaccination opportunities had been utilized, the BCG coverage at birth could have reached 45 % (in the 1-month cohort) instead of the actual coverage of 19 %, as only 40 % of the vaccination opportunities were utilized. Region of residence was associated with having a missed opportunity for vaccination. CONCLUSION: The high coverage estimates at 12 months falsely imply that the vaccine is being administered according to the recommended schedule. Our findings suggest that early coverage could be markedly improved by ensuring that children are vaccinated at their first contact with the health system.

Tenascin-C in patients with central nervous system infections.

BACKGROUND: The extracellular matrix protein tenascin-C has been discovered to be an important regulator of the response to tissue injury and repair in cerebrovascular diseases. This study investigated if tenascin-C is released in response to infections in the central nervous system (CNS). METHODS: Tenascin-C concentration in the cerebrospinal fluid (CSF) was measured in patients, (>18 years) with and without CNS infections, admitted to a department of infectious diseases in Denmark. CSF tenascin-C was measured on the Meso-scale platform. RESULTS: 174 patients were included of which 140 were diagnosed with a CNS infection and 34 where this was ruled out (control group). Median CSF tenascin-C levels were significantly higher among patients with bacterial meningitis (147 pg/mL), viral meningitis (33 mg/mL), viral encephalitis (39 pg/mL) and Lyme neuroborreliosis (45 pg/mL) when compared to controls (21 pg/mL). Correlations between tenascin-C and CSF markers of inflammation and age were only moderate. CONCLUSION: Levels of CSF tenascin-C are higher among patients with bacterial and viral neuroinfections, already on admission, but exhibit only a modest correlation with baseline indices of neuroinflammation. CSF tenascin-C is highest among patients with bacterial meningitis compared to the other CNS infections. Patients with unfavorable outcomes presented with higher median CSF tenascin-C than their counterparts.

Corrigendum: Adiponectin as a predictor of mortality and readmission in patients with community-acquired pneumonia: a prospective cohort study.

[This corrects the article DOI: 10.3389/fmed.2024.1329417.].

Focal Traumatic Brain Injury Impairs the Integrity of the Basement Membrane of Hindlimb Muscle Fibers Revealed by Extracellular Matrix Immunoreactivity.

Traumatic brain injury (TBI) stands as a prominent global cause of disability, with motor deficits being a common consequence. Despite its widespread impact, the precise pathological mechanisms underlying motor deficits after TBI remain elusive. In this study, hindlimb postural asymmetry (HL-PA) development in rats subjected to focal TBI was investigated to explore the potential roles of collagen IV and laminin within the extracellular matrix (ECM) of selected hindlimb muscles in the emergence of motor deficits following TBI. A focal TBI was induced by ablating the left sensorimotor cortex in rats and motor deficits were assessed by measuring HL-PA. The expression of laminin and collagen IV in eight selected muscles on each side of the hindlimbs from both TBI- and sham-operated rats were studied using immunohistochemistry and semi-quantitatively analyzed. The results indicated that the TBI rats exhibited HL-PA, characterized by flexion of the contralateral (right) hindlimb. In the sham-operated rats, the immunoreactive components of laminin and collagen IV were evenly and smoothly distributed along the border of the muscle fibers in all the investigated muscles. In contrast, in the TBI rats, the pattern was broken into aggregated, granule-like, immunoreactive components. Such a labeling pattern was detected in all the investigated muscles both from the contra- and ipsilateral sides of the TBI rats. However, in TBI rats, most of the muscles from the contralateral hindlimb showed a significantly increased expression of these two proteins in comparison with those from the ipsilateral hindlimb. In comparison to sham-operated rats, there was a significant increase in laminin and collagen IV expression in various contralateral hindlimb muscles in the TBI rats. These findings suggest potential implications of laminin and collagen IV in the development of motor deficits following a focal TBI.

Adiponectin as a predictor of mortality and readmission in patients with community-acquired pneumonia: a prospective cohort study.

Background: Adiponectin is secreted by adipocytes and is inversely associated with obesity. Given the association between low body mass index (BMI) and higher mortality risk after community-acquired pneumonia (CAP), we hypothesized that high adiponectin levels are associated with a higher risk of adverse clinical outcomes in patients with CAP. Methods: In a prospective cohort study of 502 patients hospitalized with CAP, adiponectin was measured in serum at admission. The associations between adiponectin and clinical outcomes were estimated with logistic regression analyses adjusted for age, sex, and measures of obesity (BMI, waist circumference or body fat percentage). Results: Adiponectin was associated with higher 90-day mortality for each 1 µg/mL increase [OR 1.02, 95% CI (1.00, 1.04), p = 0.048] independent of age and sex. Likewise, adiponectin was associated with a higher risk of 90-day readmission for each 1 µg/mL increase [OR 1.02, 95% CI (1.01, 1.04), p = 0.007] independent of age and sex. The association between adiponectin and 90-day mortality disappeared, while the association with 90-day readmission remained after adjusting for adiposity. Conclusion: Adiponectin was positively associated with mortality and readmission. The association with mortality depended on low body fat, whereas the association with readmission risk was independent of obesity.

Investigation of imaging the somatostatin receptor by opening the blood-brain barrier with melittin - A feasibility study using positron emission tomography and [64Cu]Cu-DOTATATE.

DOTATATE is a somatostatin peptide analog used in the clinic to detect somatostatin receptors which are highly expressed on neuroendocrine tumors. Somatostatin receptors are found naturally in the intestines, pancreas, lungs, and brain (mainly cortex). In vivo measurement of the somatostatin receptors in the cortex has been challenging because available tracers cannot cross the blood-brain barrier (BBB) due to their intrinsic polarity. A peptide called melittin, a main component of honeybee venom, has been shown to disrupt plasma membranes and increase the permeability of biological membranes. In this study, we assessed the feasibility of using melittin to facilitate the passage of [64Cu]Cu-DOTATATE through the BBB and its binding to somatostatin receptors in the cortex. Evaluation included in vitro autoradiography on Long Evans rat brains to estimate the binding affinity of [64Cu]Cu-DOTATATE to the somatostatin receptors in the cortex and an in vivo evaluation of [64Cu]Cu-DOTATATE binding in NMRI mice after injection of melittin. This study found an in vitro Bmax = 89 ± 4 nM and KD = 4.5 ± 0.6 nM in the cortex, resulting in a theoretical binding potential (BP) calculated as Bmax/KD ≈ 20, which is believed suitable for in vivo brain PET imaging. However, the in vivo results showed no significant difference between the control and melittin injected mice, indicating that the honeybee venom failed to open the BBB. Additional experiments, potentially involving faster injection rates are required to verify that melittin can increase brain uptake of non-BBB permeable PET tracers. Furthermore, an evaluation of whether a venom with a narrow therapeutic range can be used for clinical purposes needs to be considered.

12-month follow-up of intensive outpatient treatment for PTSD combining prolonged exposure therapy, EMDR and physical activity.

BACKGROUND: Preliminary evidence shows promising treatment outcomes at short-term follow-up for intensive posttraumatic stress disorder (PTSD) treatment, but long-term follow-up studies are sparse. This study is a sequel to a previous pilot study and open trial, set out to investigate treatment outcomes at 12-month follow-up for outpatients completing an 8-day intensive treatment for PTSD. METHODS: All patients were diagnosed with PTSD and had multiple previous psychotherapy attempts (M = 3.1). Patients were assessed at pre-treatment, post-treatment, 3- and 12-month follow-up. Of 35 treated patients, 32 (91.4%) attended the long-term follow-up assessment. The treatment programme combined prolonged exposure therapy, eye movement desensitization and reprocessing, and physical activity. RESULTS: The effect sizes indicated large reductions in symptoms of PTSD, depression, anxiety, interpersonal problems, and well-being. Changes in functioning showed a small-medium effect. Results were stable across the follow-up period. The treatment response rates showed that 46-60% of patients achieved recovery with respect to PTSD symptoms, and that 44-48% no longer met diagnostic criteria for PTSD. CONCLUSIONS: Time-limited and concentrated outpatient treatment for PTSD can yield large and enduring positive outcomes. Controlled trials are needed to establish relative efficacy. TRIAL REGISTRATION: The study was registered in Current Research Information System In Norway (Cristin). Cristin-project-ID: 654,790. Date of registration: 18.03.2019.

Tracked and self-reported nighttime smartphone use, general health, and healthcare utilization: results from the SmartSleep Study.

STUDY OBJECTIVES: Nighttime smartphone use is an increasing public health concern. We investigated whether nighttime smartphone use is associated with general health and primary healthcare utilization. METHODS: Four thousand five hundred and twenty individuals (age 35.6 ±â€…9.7 years, 35% male) provided self-reported information on smartphone use frequency, symptoms of depression, and general health (one-item perceived health and cross-symptom composite score). A subset of the study sample (n = 3221) tracked their nighttime smartphone use. Primary healthcare utilization, i.e. the number of weeks in which at least one service from the patient's general practitioner (GP) was billed in 2020, was extracted from Danish population registries. Statistical analysis comprised logistic and multiple linear regression, controlling for sociodemographics. RESULTS: Three hundred and nineteen individuals (7%) reported using their smartphone almost every night or more. More frequent self-reported nighttime smartphone use was associated with poor general health across all measures. Using the smartphone almost every night or more was associated with 2.8 [95% CI: 1.9, 4.1] fold higher odds of reporting poor health and with an average of 1.4 [95% CI: 0.7, 2.1] additional GP utilizations per year compared to no use. Associations were also found for the cross-symptom composite score across all symptoms. Further adjustment for symptoms of depression attenuated some associations. Smartphone use towards the end of the sleep period (sleep-offset use) was associated with poorer self-reported general health, but not with healthcare utilization. CONCLUSIONS: Nighttime smartphone use frequency is associated with poor general health and healthcare utilization. Further studies should investigate the underlying causal structure and nighttime smartphone use as a transdiagnostic intervention target.

Effect of distributing locally produced cloth facemasks on COVID-19-like illness and all-cause mortality-a cluster-randomised controlled trial in urban Guinea-Bissau.

Facemasks have been employed to mitigate the spread of SARS-CoV-2. The community effect of providing cloth facemasks on COVID-19 morbidity and mortality is unknown. In a cluster randomised trial in urban Bissau, Guinea-Bissau, clusters (geographical areas with an average of 19 houses), were randomised to an intervention or control arm using computer-generated random numbers. Between 20 July 2020 and 22 January 2021, trial participants (aged 10+ years) living in intervention clusters (n = 90) received two 2-layer cloth facemasks, while facemasks were only distributed later in control clusters (n = 91). All participants received information on COVID-19 prevention. Trial participants were followed through a telephone interview for COVID-19-like illness (3+ symptoms), care seeking, and mortality for 4 months. End-of-study home visits ensured full mortality information and distribution of facemasks to the control group. Individual level information on outcomes by trial arm was compared in logistic regression models with generalised estimating equation-based correction for cluster. Facemasks use was mandated. Facemask use in public areas was assessed by direct observation. We enrolled 39,574 trial participants among whom 95% reported exposure to groups of >20 persons and 99% reported facemasks use, with no difference between trial arms. Observed use was substantially lower (~40%) with a 3%, 95%CI: 0-6% absolute difference between control and intervention clusters. Half of those wearing a facemask wore it correctly. Few participants (532, 1.6%) reported COVID-19-like illness; proportions did not differ by trial arm: Odds Ratio (OR) = 0.81, 95%CI: 0.57-1.15. 177 (0.6%) participants reported consultations and COVID-19-like illness (OR = 0.83, 95%CI: 0.56-1.24); 89 participants (0.2%) died (OR = 1.34, 95%CI: 0.89-2.02). Hence, though trial participants were exposed to many people, facemasks were mostly not worn or not worn correctly. Providing facemasks and messages about correct use did not substantially increase their use and had limited impact on morbidity and mortality. Trial registration: clinicaltrials.gov: NCT04471766.

Self-reported and tracked nighttime smartphone use and their association with overweight and cardiometabolic risk markers.

Nighttime smartphone use is associated with sleep problems, which in turn have a bidirectional association with overweight. We aim to investigate whether nighttime smartphone use and sleep are related to overweight and metabolic dysfunction in adult populations. We used data from three population samples (aged 16-89) from the SmartSleep Study, which included survey data (N = 29,838), high-resolution tracking data (N = 3446), follow-up data (N = 1768), and cardiometabolic risk markers (N = 242). Frequent self-reported nighttime smartphone use was associated with 51% higher odds (95% CI: 1.32; 1.70) of overweight compared with no use. Tracked nighttime smartphone use was also associated with overweight. Similar results were found for obesity as an outcome. No consistent associations were found between nighttime smartphone use and cardiometabolic risk markers in a small subsample of healthy young women. Poor sleep quality (vs. good sleep quality) was associated with overweight (OR = 1.19, 85% CI: 1.10; 1.28). Overall, frequent nighttime smartphone use was consistently associated with overweight and a higher BMI across diverse population samples. The bidirectional interplay between nighttime smartphone use, sleep, and overweight may create a vicious circle of metabolic dysfunction over time. Therefore, nighttime smartphone use may be a potential target point for public health interventions to reduce overweight at the population level.

Development and Preclinical Evaluation of [211At]PSAt-3-Ga: An Inhibitor for Targeted α-Therapy of Prostate Cancer.

The application of prostate-specific membrane antigen (PSMA)-targeted α-therapy is a promising alternative to ß--particle-based treatments. 211At is among the potential α-emitters that are favorable for this concept. Herein, 211At-based PSMA radiopharmaceuticals were designed, developed, and evaluated. Methods: To identify a 211At-labeled lead, a surrogate strategy was applied. Because astatine does not exist as a stable nuclide, it is commonly replaced with iodine to mimic the pharmacokinetic behavior of the corresponding 211At-labeled compounds. To facilitate the process of structural design, iodine-based candidates were radiolabeled with the PET radionuclide 68Ga to study their preliminary in vitro and in vivo properties before the desired 211At-labeled lead compound was formed. The most promising candidate from this evaluation was chosen to be 211At-labeled and tested in biodistribution studies. Results: All 68Ga-labeled surrogates displayed affinities in the nanomolar range and specific internalization in PSMA-positive LNCaP cells. PET imaging of these compounds identified [68Ga]PSGa-3 as the lead compound. Subsequently, [211At]PSAt-3-Ga was synthesized in a radiochemical yield of 35% and showed tumor uptake of 19 ± 8 percentage injected dose per gram of tissue (%ID/g) at 1 h after injection and 7.6 ± 2.9 %ID/g after 24 h. Uptake in off-target tissues such as the thyroid (2.0 ± 1.1 %ID/g), spleen (3.0 ± 0.6 %ID/g), or stomach (2.0 ± 0.4 %ID/g) was low, indicating low in vivo deastatination of [211At]PSAt-3-Ga. Conclusion: The reported findings support the use of iodine-based and 68Ga-labeled variants as a convenient strategy for developing astatinated compounds and confirm [211At]PSAt-3 as a promising radiopharmaceutical for targeted α-therapy.

The importance of nonobstructive plaque characteristics in symptomatic and asymptomatic coronary artery disease.

BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.

Immunogenicity and reactogenicity following MMR vaccination in 5-7-month-old infants: a double-blind placebo-controlled randomized clinical trial in 6540 Danish infants.

Background: Measles is a highly contagious viral disease. Vaccinated mothers transfer fewer antibodies during pregnancy, resulting in shortened infant immunity. Earlier primary vaccination might avert the gap in protection. Methods: Healthy 5-7-month-old Danish infants were assigned in a 1:1 ratio to M-M-RVaxPro or placebo (solvent) in a double-blind, randomized trial between April 15, 2019 and November 1, 2021 (ClinicalTrials.govNCT03780179, EudraCT 2016-001901-18). Eligibility criteria were birth weight >1000 g and gestational age ≥32 weeks.Immunogenicity was measured by plaque reduction neutralization test (PRNT) and IgG ELISA before intervention, four weeks after intervention and routine MMR. Reactogenicity data were collected for six weeks and measured by hazard ratios (HR). Findings: 647 and 6540 infants participated in the immunogenicity and reactogenicity study, respectively; 87% and 99% completed follow-up. After early MMR, seroprotection rates (SPRs) were 47% (13%) in measles PRNT; 28% (2%), 57% (8%) in mumps and rubella IgG (placebo). For measles PRNT, geometric mean ratio was 4.3 (95% CI: 3.4-5.3) between randomization groups after intervention and 1.5 (95% CI: 1.3-1.9) after routine MMR.Reactogenicity was independent of randomization (HR, 1.0; 95% CI: 0.9-1.1). Severe adverse events occurred in 25 infants (HR, 1.8; 95% CI: 0.8-4.0); none deemed vaccine related. Interpretation: Early MMR elicited low SPRs but did not negatively impact short-term responses to a subsequent MMR. MMR at 5-7 months was safe and not associated with higher rates of reactogenicity than placebo. Funding: Innovation Fund Denmark.

Bacterial aerobic respiration is a major consumer of oxygen in sputum from patients with acute lower respiratory tract infection.

Bacterial aerobic respiration may determine the outcome of antibiotic treatment in experimental settings, but the clinical relevance of bacterial aerobic respiration for the outcome of antibiotic treatment has not been tested. Therefore, we hypothesized that bacterial aerobic respiration is higher in sputum from patients with acute lower respiratory tract infections (aLRTI), than in sputum from patients with chronic LRTI (cLRTI), where the bacteria persist despite antibiotic treatment. The bacterial aerobic respiration was determined according to the dynamics of the oxygen (O2 ) concentration in sputum from aLRTI patients (n = 52). This result was evaluated by comparison to previously published data from patients with cLRTI. O2 consumption resulting in anoxic zones was more frequent in sputum with detected bacterial pathogens. The bacterial aerobic respiration in aLRTI sputum approximated 55% of the total O2 consumption, which was significantly higher than previously published for cLRTI. The bacterial aerobic respiration in sputum was higher in aLRTI patients than previously seen in cLRTI patients, indicating the presence of bacteria with a sensitive physiology in aLRTI. These variations in bacterial physiology between aLRTI patients and cLRTI patients may contribute the huge difference in treatment success between the two patient groups.

Application of life course trajectory methods to public health data: A comparison of sequence analysis and group-based multi-trajectory modeling for modelling childhood adversity trajectories.

There is increasing awareness of the importance of modelling life course trajectories to unravel how social, economic and health factors relate to health over time. Different methods have been developed and applied in public health to classify individuals into groups based on characteristics of their life course. However, the application and results of different methods are rarely compared. We compared the application and results of two methods to classify life course trajectories of individuals, i.e. sequence analysis and group-based multi-trajectory modeling (GBTM), using public health data. We used high-resolution Danish nationwide register data on 926,160 individuals born between 1987 and 2001, including information on the yearly occurrence of 7 childhood adversities in 2 dimensions (i.e. family poverty and family dynamics). We constructed childhood adversity trajectories from 0 to 15 years by applying (1) sequence analysis using optimal matching and cluster analysis using Ward's method and (2) GBTM using logistic and zero-inflated Poisson regressions. We identified 2 to 8 cluster solutions using both methods and determined the optimal solution for both methods. Both methods generated a low adversity, a poverty, and a consistent or high adversity cluster. The 5-cluster solution using sequence analysis additionally included a household psychiatric illness and a late adversity cluster. The 4-group solution using GBTM additionally included a moderate adversity cluster. Compared with the solution obtained through sequence analysis, the solution obtained through GBTM contained fewer individuals in the low adversity cluster and more in the other clusters. We find that the two methods generate qualitatively similar solutions, but the quantitative distributions of children over the groups are different. The method of choice depends on the type of data available and the research question of interest. We provide a comprehensive overview of important considerations and benefits and drawbacks of both methods.

NatIonal Danish endocarditis stUdieS - Design and objectives of the NIDUS registry.

AIMS: The NatIonal Danish endocarditis stUdieS (NIDUS) registry aims to investigate the mechanisms contributing to the increasing incidence of infective endocarditis (IE) and to discover risk factors associated to the course, treatment and clinical outcomes of the disease. METHODS: The NIDUS registry was created to investigate a nationwide unselected group of patients hospitalized for IE. The National Danish healthcare registries have been queried for validated IE diagnosis codes (International Classification of Disease, 10th edition [ICD-10]: DI33, DI38, and DI398). Subsequently, a team of 28 healthcare professionals, including experts in endocarditis, will systematically review and evaluate all identified patient records using the modified Duke Criteria and the 2015 European Society of Cardiology modified diagnostic criteria. The registry will contain all cases with definite or possible IE found in primary data sources in Denmark between January 1, 2016, and December 31, 2021. We will gather individual patient data, such as clinical, microbiological, and echocardiographic characteristics, treatment regimens, and clinical outcomes. A digital data collection form will be used to the gathering of data. A sample of approximately 4,300 individual patients will be evaluated using primary data sources. CONCLUSIONS AND PERSPECTIVES: The NIDUS registry will be the first comprehensive nationwide IE registry, contributing critical knowledge about the course, treatment, and clinical outcomes of the disease. Additionally, it will significantly aid in identifying areas in which future research is needed.