Risk factors associated with short-term adverse events after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases.

BACKGROUND: Studies have suggested incremental short-term adverse events (AE) after repeated vaccination. In this report, we assessed occurrence and risk factors for short-term AEs following repeated SARS-CoV-2 vaccination in patients with various immune-mediated inflammatory diseases (IMIDs). METHODS: Self-reported daily questionnaires on AEs during the first 7 days after vaccination were obtained of 2259 individuals (2081 patients and 178 controls) participating in an ongoing prospective multicenter cohort study on SARS-CoV-2 vaccination in patients with various IMIDs in the Netherlands (T2B-COVID). Relative risks were calculated for potential risk factors associated with clinically relevant AE (rAE), defined as AE lasting longer than 2 days or impacting daily life. RESULTS: In total, 5454 vaccinations were recorded (1737 first, 1992 second and 1478 third vaccinations). Multiple sclerosis, Crohn's disease and rheumatoid arthritis were the largest disease groups. rAEs were reported by 57.3% (95% CI 54.8-59.8) of patients after the first vaccination, 61.5% (95% CI 59.2-63.7) after the second vaccination and 58% (95% CI 55.3-60.6) after the third vaccination. At day 7 after the first, second and third vaccination, respectively, 7.6% (95% CI 6.3-9.1), 7.4% (95% CI 6.2-8.7) and 6.8% (95% CI 5.4-8.3) of patients still reported AEs impacting daily life. Hospital admissions and allergic reactions were uncommon (<0.7%). Female sex (aRR 1.43, 95% CI 1.32-1.56), age below 50 (aRR 1.14, 95% CI 1.06-1.23), a preceding SARS-CoV-2 infection (aRR 1.14, 95% CI 1.01-1.29) and having an IMID (aRR 1.16, 95% CI 1.01-1.34) were associated with increased risk of rAEs following a vaccination. Compared to the second vaccination, the first vaccination was associated with a lower risk of rAEs (aRR 0.92, 95% CI 0.84-0.99) while a third vaccination was not associated with increased risk on rAEs (aRR 0.93, 95% CI 0.84-1.02). BNT162b2 vaccines were associated with lower risk on rAEs compared to CX-024414 (aRR 0.86, 95% CI 0.80-0.93). CONCLUSIONS: A third SARS-CoV-2 vaccination was not associated with increased risk of rAEs in IMID patients compared to the second vaccination. Patients with an IMID have a modestly increased risk of rAEs after vaccination when compared to controls. Most AEs are resolved within 7 days; hospital admissions and allergic reactions were uncommon. TRIAL REGISTRATION: NL74974.018.20 , Trial ID: NL8900. Registered on 9 September 2020.

Treatment and Coronary Artery Aneurysm Formation in Kawasaki Disease: A Per-Day Risk Analysis.

OBJECTIVE: To assess whether 'treatment day' is a significant predicting factor in Kawasaki disease and imposes a risk for coronary artery aneurysms (CAAs) in a per-day analysis. CAA formation can be reduced from 25% to 10% when treated with intravenous immunoglobulin (IVIG). STUDY DESIGN: Patient data from (n = 1016) a single center were collected for an observational cohort study. After exclusions, we retrospectively analyzed 776 patients in total. A multivariate analysis was performed with treatment day as a continuous variable (n = 691). Patients were categorized as no enlargement, small CAA, medium CAA, and giant CAA. RESULTS: Late treatment per-day was a significant predicting factor for the development of larger CAAs. ORs for medium and giant CAAs per delayed day were 1.1 (95% CI 1.1-1.2) P < .05 and 1.2 (95% CI 1.1-1.2) P < .05, respectively. CONCLUSION: We showed that every day of delay in treatment of patients with Kawasaki disease inherently carries a risk of medium and giant aneurysm formation. There was no cut-off point for treatment day that could mark a safe zone.

Interferon Gamma-Induced Protein (IP-10) as Potential Biomarker for Cancer-Related-Fatigue: Results from a 6-month Randomized Controlled Trial.

We examined if serum concentrations Interferon gamma-induced protein (IP-10) is a potential clinical biomarker for cancer-related-fatigue (CRF). Fatigue scores and IP-10 concentrations were measured from curatively treated fatigued cancer patients randomized to either cognitive behavioral therapy (CBT, n = 26) or waiting-list (WL, n = 13). No correlation was found between baseline IP-10 level and fatigue severity and no significant differences in IP-10 serum levels were observed between fatigued and matched non-fatigued patients (n = 22). Relative changes in IP-10 concentrations from baseline to six-month follow-up were not significantly different between the CBT and WL conditions. In this study, IP-10 showed low potential as clinical CRF biomarker. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT01096641).

Volatile organic compounds in exhaled breath are independent of systemic inflammatory syndrome caused by intravenous lipopolysaccharide infusion in humans: results from an experiment in healthy volunteers.

Systemic inflammatory response syndrome (SIRS) is observed during critical illness in most patients. It is defined by a clinical definition. The composition of volatile organic compounds (VOCs) in exhaled breath may change during SIRS and may thus serve as a diagnostic tool. We investigated whether exhaled breath VOCs can serve as biomarker for SIRS in a human model of endotoxemia. Eighteen healthy volunteers received 2 ng Eschericia coli lipopolysaccharide (LPS) kg-1 body weight intravenously. Venous blood and exhaled breath were collected before infusion of LPS and every 2 h thereafter, up to 8 h after infusion. The interleukin (IL)-6 concentration was measured in plasma. VOCs in the exhaled breath were measured by gas chromatography and mass spectrometry. A mixed effects model was fitted to examine the relation between the measured compounds in exhaled breath and time after LPS infusion or IL-6 levels in plasma. Partially-least squares discriminant analysis (PLS-DA) was used to investigate whether we could discriminate between samples collected before and after LPS infusion. The exhaled concentrations of 3-methyl-pentane, 4-methyl-pentanol, 1-hexanol, 2,4-dimethyl-heptane, decane and one unknown compound changed after LPS infusion. However, the false-discovery rate was 43% for the total set of 52 compounds that were present in all samples. Of these VOCs only the unknown compound was associated with systemic levels of IL-6. The PLS-DA algorithm resulted in a moderate discriminatory accuracy. SIRS induced by endotoxemia in human volunteers resulted in minor changes in exhaled VOCs. We therefore conclude that LPS infusion in healthy volunteers does not induce metabolic effects that can be detected through VOC analysis of the exhaled breath. This trial is registered at the Dutch Trial Register: NTR4455.

Thresholds for Arterial Wall Inflammation Quantified by 18F-FDG PET Imaging: Implications for Vascular Interventional Studies.

OBJECTIVES: This study assessed 5 frequently applied arterial 18fluorodeoxyglucose (18F-FDG) uptake metrics in healthy control subjects, those with risk factors and patients with cardiovascular disease (CVD), to derive uptake thresholds in each subject group. Additionally, we tested the reproducibility of these measures and produced recommended sample sizes for interventional drug studies. BACKGROUND: 18F-FDG positron emission tomography (PET) can identify plaque inflammation as a surrogate endpoint for vascular interventional drug trials. However, an overview of 18F-FDG uptake metrics, threshold values, and reproducibility in healthy compared with diseased subjects is not available. METHODS: 18F-FDG PET/CT of the carotid arteries and ascending aorta was performed in 83 subjects (61 ± 8 years) comprising 3 groups: 25 healthy controls, 23 patients at increased CVD risk, and 35 patients with known CVD. We quantified 18F-FDG uptake across the whole artery, the most-diseased segment, and within all active segments over several pre-defined cutoffs. We report these data with and without background corrections. Finally, we determined measurement reproducibility and recommended sample sizes for future drug studies based on these results. RESULTS: All 18F-FDG uptake metrics were significantly different between healthy and diseased subjects for both the carotids and aorta. Thresholds of physiological 18F-FDG uptake were derived from healthy controls using the 90th percentile of their target to background ratio (TBR) value (TBRmax); whole artery TBRmax is 1.84 for the carotids and 2.68 in the aorta. These were exceeded by >52% of risk factor patients and >67% of CVD patients. Reproducibility was excellent in all study groups (intraclass correlation coefficient >0.95). Using carotid TBRmax as a primary endpoint resulted in sample size estimates approximately 20% lower than aorta. CONCLUSIONS: We report thresholds for physiological 18F-FDG uptake in the arterial wall in healthy subjects, which are exceeded by the majority of CVD patients. This remains true, independent of readout vessel, signal quantification method, or the use of background correction. We also confirm the high reproducibility of 18F-FDG PET measures of inflammation. Nevertheless, because of overlap between subject categories and the relatively small population studied, these data have limited generalizability until substantiated in larger, prospective event-driven studies. (Vascular Inflammation in Patients at Risk for Atherosclerotic Disease; NTR5006).

Interventions to prevent needle stick injuries among health care workers.

Needle stick injuries (NSIs) are frequently reported as occupational injuries among health care workers. The health effects of a NSI can be significant when blood-to-blood contact occurs from patient to health care worker. The objective of this study was to evaluate whether the number of NSIs decreased among health care workers at risk in one Dutch academic hospital after introduction of injection needles with safety devices in combination with an interactive workshop. In a cluster three-armed randomized controlled trial, 23 hospital divisions (n=796 health care workers) were randomly assigned to a group that was subjected to the use of a 'safety device plus workshop', to a group that was subjected to a 'workshop only' or to a control group with no intervention. The combined intervention of the introduction of needle safety devices and an interactive workshop led to the highest reduction in the number of self-reported NSIs compared to a workshop alone or no intervention. For practice, the use of relatively simple protective needle safety devices and interactive communication are effective measures for reducing NSI's.

Blood volume measurement with indocyanine green pulse spectrophotometry: dose and site of dye administration.

BACKGROUND: (1) To determine the optimal administration site and dose of indocyanine green (ICG) for blood volume measurement using pulse spectrophotometry, (2) to assess the variation in repeated blood volume measurements for patients after subarachnoid hemorrhage and (3) to evaluate the safety and efficacy of this technique in patients who were treated for an intracranial aneurysm. METHODS: Four repeated measurements of blood volume (BV) were performed in random order of bolus dose (10 mg or 25 mg ICG) and venous administration site (peripheral or central) in eight patients admitted for treatment of an intracranial aneurysm. Another five patients with subarachnoid hemorrhage underwent three repeated BV measurements with 25 mg ICG at the same administration site to assess the coefficient of variation. FINDINGS: The mean +/- SD in BV was 4.38 +/- 0.88 l (n=25) and 4.69 +/- 1.11 l (n=26) for 10 mg and 25 mg ICG, respectively. The mean +/- SD in BV was 4.59 +/- 1.15 l (n= 26) and 4.48 +/- 0.86 l (n=25) for central and peripheral administration, respectively. No significant difference was found. The coefficient of variance of BV measurement with 25 mg of ICG was 7.5% (95% CI: 3-12%). CONCLUSIONS: There is no significant difference between intravenous administration of either 10 or 25 mg ICG, and this can be injected through either a peripheral or central venous catheter. The 7.5% coefficient of variation in BV measurements determines the detectable differences using ICG pulse spectrophotometry.

Quality of life and self-esteem in children treated for idiopathic short stature.

OBJECTIVE: Changes in health-related quality of life (HRQOL) and self-esteem were studied in children with idiopathic short stature (ISS) participating in a study on the effect of growth hormone treatment. STUDY DESIGN: Prepubertal children (n = 36) with ISS were randomly assigned to a treatment or control group. Children with ISS, their parents, and the pediatrician completed HRQOL and self-esteem questionnaires 3 times in 2 years. RESULTS: At the start, children with ISS did not have lower scores than the norm population, except for social functioning HRQOL. The pediatrician reported an improvement of HRQOL in the treatment group, the parents reported no change, and the children in the treatment group reported the same, or sometimes even worse, HRQOL or self-esteem than the control group. Changes related to the child's satisfaction with height and hardly to growth itself. CONCLUSION: The assumption that growth hormone treatment improves HRQOL in children with ISS could not be supported in this study.