Analyzing the immunogenicity of bivalent booster vaccinations in healthcare workers: The SWITCH ON trial protocol.

Vaccination against coronavirus disease 2019 (COVID-19) has contributed greatly to providing protection against severe disease, thereby reducing hospital admissions and deaths. Several studies have reported reduction in vaccine effectiveness over time against the Omicron sub-lineages. However, the willingness to receive regular booster doses in the general population is declining. To determine the need for repeated booster vaccinations in healthy individuals and to aid policymakers in future public health interventions for COVID-19, we aim to gain insight into the immunogenicity of the additional bivalent booster vaccination in a representative sample of the healthy Dutch population. The SWITCH ON study was initiated to investigate three main topics: i) immunogenicity of bivalent vaccines after priming with adenovirus- or mRNA-based vaccines, ii) immunological recall responses and reactivity with relevant variants after booster vaccination, and iii) the necessity of booster vaccinations for the healthy population in the future. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05471440.

Evaluation of the importance of mixing during preparation of antibiotic infusions.

BACKGROUND: The mixing step after medication addition to the infusion bag is frequently omitted during the preparation of drug infusions. However, the importance of mixing when preparing antibiotic infusions is still unknown. METHODS: The primary aim of this study was to assess the importance of the mixing step by comparing the concentrations of unmixed antibiotic infusions (cefuroxime, flucloxacillin, meropenem, and vancomycin) with the declared concentration at regular intervals during infusion. The secondary aim was to compare concentrations between preparation sites (hospital pharmacy versus clinical ward). Infusion bags were run through electronic infusion pumps. For cefuroxime, flucloxacillin, and meropenem, samples were collected 1, 15, and 20 min after starting the administration (infusion duration: 30 min). For vancomycin, samples were collected after 1, 60, and 110 min (infusion duration: 120 min). Vancomycin concentrations were measured using the Architect c4000 analyser and other concentrations using a validated UPC2-MS-MS multimethod. RESULTS: The median concentrations of the four antibiotics were comparable to the declared concentration at all three time points. No significant differences were found between preparation sites. CONCLUSIONS: Spontaneous mixing occurred in the examined antibiotic solutions during normal handling.

Progression of skin autofluorescence of AGEs over 4 years in patients with type 1 diabetes.

BACKGROUND: The deposit of advanced glycation end-products is involved in diabetic complications. It can be evaluated by measuring the skin autofluorescence (sAF). We searched whether sAF progressed over 4 years in type 1 diabetes and analysed its relationship with the development of nephropathy. METHODS: Two measurements of skin autofluorescence (sAF) were completed on 154 patients during years 2009 and 2013. Baseline factors associated with the progression of sAF were analysed by multivariate regression analysis. The relations among sAF progression, microalbuminuria, and impaired estimated glomerular filtration rate (eGFR) were analysed by logistic regression analysis. RESULTS: The patients were 51 ± 16 years old, with duration of diabetes of 23 ± 13 years, HbA1c: 7.7 ± 1.0%, 20.7% were treated by continuous subcutaneous insulin infusion (CSII). The sAF progressed by +18.1% over 4 years. Two interacting (P = .04) variables were associated with the later progression of sAF: mildly impaired eGFR and treatment by CSII. The patients with mildly impaired eGFR had the highest progression of sAF (+11.5% P = .01). Continuous subcutaneous insulin infusion was associated with a reduced progression of sAF in patients without kidney impairment (ß = -7.2%, P = .01). A +10% progression of sAF during the follow-up was associated with more microalbuminuria: OR = 1.45, P = .02, and more mildly impaired eGFR (<90 mL/min/1.73 m2 ): OR 1.22, P = .03 at 4 years of follow-up. CONCLUSIONS: The skin autofluorescence of advanced glycation end-products progresses in patients with type 1 diabetes, more if they have diabetic nephropathy, less if they are treated by continuous subcutaneous insulin infusion. This progression is associated with the development of nephropathy.

Skin autofluorescence, renal insufficiency and retinopathy in patients with type 2 diabetes.

OBJECTIVES: Advanced glycation end-products (AGEs) are involved in diabetic retinopathy (DR). Their accumulation in tissues can be analyzed by measuring the skin autofluorescence (sAF). We hypothesized that renal insufficiency, another cause of high sAF, may disturb the relation between sAF and DR. RESEARCH DESIGN AND METHODS: We measured sAF with an AGE-Reader in 444 patients with type 2 diabetes (T2D), and we analyzed their retinal status. The associations of sAF with DR, and interaction with renal insufficiency were estimated by multivariate logistic regression analysis. RESULTS: Mean age was 62years (standard deviation (SD) 10years), diabetes duration 13 (9) years and mean HbA1C 8.9% (1.8). The prevalence of DR was 21.4% and increased with age, diabetes duration, arterial hypertension, renal parameters (serum creatinine and albumin excretion rates), and sAF. The prevalence of macular edema (ME) was 8.6% and increased with the duration of diabetes, but not with sAF (p=0.11). There was a significant interaction between renal insufficiency and sAF for the relation with DR or ME (p=0.02). For the 83% patients without renal insufficiency (estimated GFR>60mL/min/1.73m2), sAF was related to DR or ME after multivariate adjustment: OR 1.87 (1.09-3.19). The 17% patients with renal insufficiency had the highest rates of DR or ME (38.6%) and the highest sAF, unrelated to each other. CONCLUSIONS: In T2D patients with renal insufficiency, the high sAF does not relate to retinopathy, which should be systematically searched due to its high frequency. For other patients, a high sAF argues for DR screening.

Skin autofluorescence predicts cardio-renal outcome in type 1 diabetes: a longitudinal study.

BACKGROUND: We aimed to analyze the relationships between skin autofluorescence (SAF) and incident macrovascular events and renal impairment after 4 years of follow-up in patients with type 1 diabetes (T1D). METHODS: Two hundred and forty-three patients (51.2 ± 16.7 years old) with T1D participated. SAF was measured by AGE-Reader-TM at inclusion. Macrovascular events (MVE), estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER) were recorded then and 4 years later. Multivariate logistic regression was used to analyze the relationships between SAF and incident MVE and renal profile 4 years later. RESULTS: Patients with incident MVE had a higher SAF (p = 0.003). SAF predicted incident MVE after adjustment for age, sex, body mass index, tobacco, diabetes duration, hypertension, HbA1c, AER, eGFR (OR 4.84 [95 % CI 1.31-17.89], p = 0.018). However, this relation was no longer significant after adjustment for history of MVE. An inverse relation was found between SAF and incident eGFR (p = 0.0001). Patients with incident eGFR <60 ml/min/1.73 m(2) had a SAF higher than patients with normal eGFR. After adjustment for the previous criteria, SAF remained associated with the risk of impaired incident eGFR (OR 7.42 [95 % CI 1.59-34.65], p = 0.018). No relation was found between SAF and increased AER 4 years later. CONCLUSIONS: SAF predicts MVE in patients with T1D, adjusted for cardiovascular risk factors but the most powerful predictive factor remains history of MVE. SAF also predicts eGFR impairment, adjusted for initial AER and renal function. SAF could be a useful non-invasive tool for estimating risk of cardiovascular or renal impairment in patients with T1D.

Energy expenditure and nutritional complications of metabolic syndrome and rheumatoid cachexia in rheumatoid arthritis: an observational study using calorimetry and actimetry.

OBJECTIVE: Altered energy expenditure may contribute to the nutritional complications of RA, metabolic syndrome (MS) and rheumatoid cachexia (RC). The main aim of this study was to evaluate whether the altered resting energy expenditure (REE) and physical activity (PA)-related energy expenditure (EE) are related to the duration of RA and inflammatory activity and nutritional complications in RA. METHODS: Among patients with well-characterized RA (duration, activity: DAS28 ESR), we measured REE by indirect calorimetry, and PA-EE by actimetry (SenseWear Armband). MS was defined according to the International Diabetes Federation criteria and RC from DXA body composition analysis. The relations between the characteristics and nutritional complications, and EE were analysed by linear regression. RESULTS: Fifty-seven patients were included [73% women, age 57 (10) years] with a wide range of disease duration: 3.8 (3.0) years, and DAS28 ESR: 3.9 (1.4). The mean REE was 1486 (256) kcal/day, associated with the DAS28 ESR (ß = +0.21, P = 0.02 after adjusting for gender and fat free mass). The prevalence of MS and RC was, respectively, 24 and 18%, and they were unrelated to each other. The patients with MS and/or RC had double the longstanding RA score (P < 0.05), twice the homeostasis model assessment of insulin resistance values (P = 0.052) and halved levels of PA (P < 0.05 for metabolic equivalent tasks (METs) and number of steps/day). Two modifiable factors were associated with the presence of MS and/or RC: a low level of PA as METs [exp(B) = 0.03, P = 0.009] and the use of glucocorticoids [exp(B) = 4.08, P = 0.046]. CONCLUSION: Low levels of PA and treatment by glucocorticoids are associated with the nutritional complications of RA, suggesting the potential for therapeutic interventions.