The main aim of our study was to investigate the specific contribution of a 9-valent human papillomavirus vaccine (9vHPV) to the recurrence risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women vaccinated post-excision. Therefore, we conducted a retrospective monocentric cohort study in women aged 22-49 years undergoing conization between 2014 and 2023. The 9vHPV-vaccinated women were matched to unvaccinated women for age and follow-up duration in a 1:2 ratio to eliminate allocation bias. The risk of CIN2+ recurrence was estimated by the incidence rate ratio using Poisson regression with adjustment for comorbidities, smoking status, nulliparity, CIN grade, positive cone margin, and HPV genotypes. The CIN2+ recurrence rates in 147 women enrolled in the analysis were 18 and 2 cases per 100,000 person-days for unvaccinated and vaccinated women, respectively, during a mean follow-up period of 30 months (±22 months). A reduction in CIN2+ recurrences by 90% (95% confidence interval: 12-99%) was documented in 9vHPV-vaccinated participants compared to women undergoing only surgical excision. Moreover, vaccinated women with a positive cone margin showed a 42% (though non-significant) reduction in relapse (p = .661). Full post-conization vaccination with the 9vHPV contributed to an additional reduction in the risk of CIN2+ recurrence. This finding is consistent with current knowledge and suggests a high adjuvant effect of the 9vHPV vaccine.
- Klíčová slova
- Human papillomavirus, cervical intraepithelial neoplasia, conization, recurrence reduction, vaccination,
- MeSH
- dospělí MeSH
- dysplazie děložního hrdla * prevence a kontrola virologie MeSH
- infekce papilomavirem * prevence a kontrola MeSH
- konizace děložního čípku metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * prevence a kontrola MeSH
- mladý dospělý MeSH
- nádory děložního čípku * prevence a kontrola virologie MeSH
- retrospektivní studie MeSH
- vakcinace MeSH
- vakcíny proti papilomavirům * aplikace a dávkování imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- vakcíny proti papilomavirům * MeSH
OBJECTIVES: The COVID-19 pandemic required rapid development of vaccines within a short period of time which did not allow to assess vaccine effectiveness (VE) in the long-term. METHODS: A computerized literature search was undertaken to identify eligible studies, with no language restrictions, published between 1 December 2020 and 30 June 2023. RESULTS: Out of a total of 27,597 publications, 761 studies were included. Early VE of 87.2% decreased to 55.1% after 9 months among populations fully immunized not only with mRNA (proxy mRNA) vaccines, and 66.3% decreased to 23.5% in populations immunized exclusively with non-mRNA vaccines. Protection against severe COVID-19 declined to 80.9% for proxy mRNA vaccines and 67.2% for non-mRNA vaccines. Omicron variants significantly diminished VE. Within 6-8 months of receiving a single booster of an mRNA vaccine, VE declined to 14.0% and 67.7% for any and severe COVID-19, respectively. Multiple mRNA booster doses restored protection that declined to 29.5% and 70.6% for any and severe COVID-19, respectively, within 5-7 months. CONCLUSION: Outcomes of this meta-regression underscore the evolving nature of COVID-19 in response to vaccination, dosing schedules, and emerging variants, and provide crucial insights for public health interventions and vaccination strategies.
- Klíčová slova
- COVID-19, Meta-regression, Persistence, Protection, Vaccine effectiveness,
- MeSH
- COVID-19 * epidemiologie prevence a kontrola MeSH
- lidé MeSH
- messenger RNA MeSH
- pandemie MeSH
- SARS-CoV-2 genetika MeSH
- účinost vakcíny MeSH
- vakcinace MeSH
- vakcíny * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- messenger RNA MeSH
- vakcíny * MeSH
BACKGROUND: COVID-19, an infectious disease caused by SARS-CoV-2, was shown to be associated with an increased risk of new-onset diabetes. Mechanisms contributing to the development of hyperglycemia are still unclear. We aimed to study whether hyperglycemia is related to insulin resistance and/or beta cell dysfunction. MATERIALS AND METHODS: Survivors of severe COVID-19 but without a known history of diabetes were examined at baseline (T0) and after 3 (T3) and 6 (T6) months: corticosteroids use, indirect calorimetry, and OGTT. Insulin response and sensitivity (IS) were expressed as insulinogenic (IGI), disposition (DI), and Matsuda insulin sensitivity index (ISI). Resting energy expenditure (REE) and respiratory quotient (RQ) was calculated from the gas exchange and nitrogen losses. RESULTS: 26 patients (out of 37) with complete outcome data were included in the analysis (age ~59.0 years; BMI ~ 30.4, 35% women). Patients were hypermetabolic at T0 (30.3 ± 4.0 kcal/kg lean mass/day, ~120% predicted) but REE declined over 6 months (ΔT6-T0 mean dif. T6-T0 (95% CI): -5.4 (-6.8, -4.1) kcal/kg FFM/day, p < 0.0001). 17 patients at T0 and 13 patients at T6 had hyperglycemia. None of the patients had positive islet autoantibodies. Insulin sensitivity in T0 was similarly low in hyperglycemic (H) and normoglycemic patients (N) (T0 ISIH = 3.12 ± 1.23, ISIN = 3.47 ± 1.78, p = 0.44), whereas insulin response was lower in the H group (DIH = 3.05 ± 1.79 vs DIN = 8.40 ± 5.42, p = 0.003). Over 6 months ISI (ΔT6-T0 mean dif. T6-T0 for ISI (95% CI): 1.84 (0.45, 3.24), p = 0.01)) increased in the H group only. CONCLUSIONS: Patients with severe COVID-19 had increased REE and insulin resistance during the acute phase due to the infection and corticosteroid use, but these effects do not persist during the follow-up period. Only patients with insufficient insulin response developed hyperglycemia, indicating that beta cell dysfunction, rather than insulin resistance, was responsible for its occurrence.
- MeSH
- COVID-19 * komplikace MeSH
- hyperglykemie * MeSH
- inzulin MeSH
- inzulinová rezistence * fyziologie MeSH
- krevní glukóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- SARS-CoV-2 MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- inzulin MeSH
- krevní glukóza MeSH
OBJECTIVES: This study assessed trends in tobacco use in students of the Third Faculty of Medicine of Charles University in the Czech Republic between academic years 2012/13 and 2019/2020. METHODS: Two cross-sectional surveys designed to obtain information on smoking history, smoking status, tobacco products use, and cessation were conducted among 382 students of the 6-year Master's Study Programme (General Medicine) and the 3-year Bachelor's Study Programme (Public Health) in 2012/2013; and among 580 students of General Medicine and of the Bachelor's Study Programmes (Public Health, Dental Hygiene and Nursing) in 2019/2020. RESULTS: Regular/daily smoking was reported by 4.4 ± 2.4% (with 95% CI) of General Medicine students and 4.8 ± 4.1% of Public Health students in 2012/2013, and 1.3 ± 1.1% of General Medicine students and 14.4 ± 4.8% of students of bachelor studies in 2019/2020. The share of regular and occasional smokers was higher among junior students in both academic years (23.9 ± 5.1% and 20.1 ± 4.7%, respectively) compared to senior students (23.6 ± 9.8% and 9.6 ± 5.7%). Cigarettes were the most common products used in both academic years (67.0 ± 4.7% and 45.5 ± 4.0%). There was a significant increase in proportion of students using more tobacco products in the course of the time (from 12.1 ± 3.1% to 53.7 ± 4.1%). The proportion of students who quitted smoking has risen from 11.4 ± 3.2% to 16.1 ± 3.0%. On the contrary, the proportion of students who started smoking has dropped from 15.9 ± 3.7% to 2.9 ± 1.4%. The proportion of non-smokers has risen from 57.6 ± 5.0% to 65.3 ± 3.9%. CONCLUSIONS: The study revealed some positive trends concerning tobacco use in students (decline in regular smokers among students of General Medicine, senior students, cigarette smokers, water pipe smokers; rise in non-smokers), but also negative ones (rise in regular smokers among students of Public Health, students who used more tobacco products).
- Klíčová slova
- health professions students, tobacco use, trend,
- MeSH
- akademický sbor MeSH
- lidé MeSH
- prevalence MeSH
- průřezové studie MeSH
- průzkumy a dotazníky MeSH
- studenti * MeSH
- tabákové výrobky * MeSH
- univerzity MeSH
- užívání tabáku MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
Riociguat is novel antihypertensive drug for treatment of pulmonary hypertension. As such, it is still being tested in many clinical and pharmacokinetic trials. Existing methods that determine serum riociguat and desmethylriociguat (DMR) are based solely on liquid chromatography with mass spectrometry. Therefore, we present a novel capillary electrophoresis with mass spectrometry method (CE-MS) for their determination in human serum as alternative method for ongoing trials. Complete resolution of both analytes was achieved by means of pH optimization of ammonium formate background electrolytes that are fully compatible with ESI/MS detection. Simple liquid-liquid extraction was used as sample pretreatment. The calibration dependence of the method was linear (in the range of 10-1000 ng/mL), with adequate accuracy (90.1-114.9%) and precision (13.4%). LOD and LOQ were arbitrarily set at 10 ng/mL for both analytes. Clinical applicability was validated using serum samples from patients treated with riociguat in pharmacokinetic study and the results corresponded with reference HPLC-MS/MS values. Capillary electrophoresis proved to be sensitive and selective tool for the analysis of riociguat and DMR.
- Klíčová slova
- Capillary electrophoresis, Desmethylriociguat, Determination, Mass spectrometry, Riociguat,
- MeSH
- elektroforéza kapilární metody MeSH
- elektrolyty MeSH
- extrakce kapalina-kapalina MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody MeSH
- lidé MeSH
- limita detekce MeSH
- lineární modely MeSH
- pyrazoly krev chemie izolace a purifikace farmakokinetika MeSH
- pyrimidiny krev chemie izolace a purifikace farmakokinetika MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- elektrolyty MeSH
- pyrazoly MeSH
- pyrimidiny MeSH
- riociguat MeSH Prohlížeč
Capillary electrophoresis (CE) with contactless conductivity detection (C4D) represents a strong tool for determining amino acids in clinical samples. This chapter provides detailed instructions for CE/C4D determination of the branched-chain amino acids (BCAAs) valine, isoleucine, and leucine in human plasma, which can be readily employed in physiological studies. Baseline separation of all the BCAAs is achieved on a short separation length equal to 18 cm in optimized background electrolyte consisting of 3.2 M acetic acid dissolved in 20% v/v methanol with addition of 1.0% v/v INST-coating solution. The analysis time does not exceed 3 min and the limit of detection is 0.4 μM for all BCAAs. The pretreatment of human plasma is very simple and is based on fourfold plasma dilution by acetonitrile and subsequent filtration. Only 50 μL of plasma is used for the analysis. The high sensitivity of the CE/C4D method is achieved by injecting a large volume of sample, combined with application of negative pressure to flush the acetonitrile zone out of the capillary.
- Klíčová slova
- Branched-chain amino acids, Capillary electrophoresis, Contactless conductivity detection, Human plasma, Large-volume sample stacking, Pressure-assisted analysis, Rapid determination,
- MeSH
- elektrická vodivost * MeSH
- elektroforéza kapilární metody MeSH
- fyziologie * MeSH
- kalibrace MeSH
- lidé MeSH
- referenční standardy MeSH
- větvené aminokyseliny krev MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- větvené aminokyseliny MeSH
Two methods of capillary electrophoresis with contactless conductivity detection have been developed for monitoring the levels of glucose and lactate in clinical samples. The separations are performed in uncoated fused silica capillaries with inner diameter 10 or 20 μm, total length 31.5 cm, length to detector 18 cm, using an Agilent electrophoretic instrument with an integrated contactless conductivity detector. Glucose is determined in optimized background electrolyte, 50 mM NaOH with pH 12.6 and 2-deoxyglucose is used as an internal standard; the determination of lactate is performed in 40 mM CHES/NaOH with pH 9.4 and lithium cations as an internal standard. Both substances are determined in minimal volumes of (1) nutrient media after cell incubation, and (2) microdialysates of human adipose tissue; after dilution and filtration as the only treatment of the sample. The migration time of glucose is 2.5 min and that of lactate is 1.5 min with detection limits at the micromolar concentration level. The developed techniques are suitable for sequential monitoring of glucose and lactate over time during metabolic experiments.
- Klíčová slova
- Capillary electrophoresis, Cell incubation, Contactless conductivity detection, Glucose, Lactate, Microdialysis, Rapid determination,
- MeSH
- elektrická vodivost * MeSH
- elektroforéza kapilární metody MeSH
- glukosa analýza MeSH
- kalibrace MeSH
- kultivační média chemie MeSH
- kultivované buňky MeSH
- kyselina mléčná analýza MeSH
- lidé MeSH
- mikrodialýza metody MeSH
- tuková tkáň MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- glukosa MeSH
- kultivační média MeSH
- kyselina mléčná MeSH