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Background A new adjuvanted subunit vaccine (HZ/su), with higher vaccine efficacy than live-attenuated vaccine (ZVL), has been licensed in Europe since March 2018. Therefore, Belgian decision-makers might need to re-assess their recommendations for vaccination against herpes zoster (HZ). Methods We conducted a cost-effectiveness analysis, using a Markov decision tree, of vaccinating 50- to 85-year-old immunocompetent Belgian cohorts with no vaccination, HZ/su, ZVL, and ZVL with booster after 10 years. Due to the uncertainty in vaccine waning of HZ/su vaccine beyond 4 years, we used a logarithmic and 1-minus-exponential function to model respectively a long and short duration of protection. We used a lifetime time horizon and implemented the health care payer perspective throughout the analysis. Results HZ/su had the greatest impact in avoiding health and economic burden. However, it would never become cost-effective at a willingness-to-pay threshold of €40,000 per quality-adjusted life year (QALY) gained at its market price set by the manufacturer in the USA. Depending on the waning function assumed for HZ/su, the price per dose needs to drop 60% or 83% such that vaccination with HZ/su, assuming respectively a long or short duration of protection, would become cost-effective in 50- and 80-year-old individuals. At €40,000 per QALY gained, ZVL or ZVL with booster was never found cost-effective compared with HZ/su, even if only administration cost was considered. Conclusion HZ/su is cost-effective in the 50-year-old age cohort at the unofficial Belgian threshold of €40,000 per QALY gained, if its price drops to €55.40 per dose. This result is, however, very sensitive to the assumed duration of protection of the vaccine, and the assumed severity and QALY loss associated with HZ and post-herpetic neuralgia (PHN).

The immune response in patients with Coronavirus Disease 2019 (COVID-19) is highly variable and is linked to disease severity and mortality. However, antibody and cytokine responses in the early disease stage and their association with disease course and outcome are still not completely understood. In this large, multi-centre cohort study, blood samples of 434 Belgian COVID-19 hospitalized patients with different disease severities (ranging from asymptomatic/mild to critically ill) from the first wave of the COVID-19 pandemic were obtained. Baseline antibody and cytokine responses were characterized and associations with several clinical outcome parameters were determined. Anti-spike immunoglobulin (Ig)G and IgM levels were elevated in patients with a more severe disease course. This increased baseline antibody response however was associated with decreased odds for hospital mortality. Levels of the pro-inflammatory cytokines IL-6, IP-10 and IL-8, the anti-inflammatory cytokine IL-10 and the antiviral cytokines IFN-α, IFN-β and IFN-λ1 were increased with disease severity. Remarkably, we found significantly lower levels of IFN-λ2,3 in critically ill patients compared to patients of the moderate and severe disease category. Finally, levels of IL-8, IL-6, IP-10, IL-10, IFN-α, IFN-β, IFN-γ and IFN-λ1 at baseline were positively associated with mortality, whereas higher IFN-λ2,3 levels were negatively associated with mortality.

We conducted a systematic literature review and meta-analysis and estimated the case fatality rate of enteric fever to be 2.49% (95% confidence interval, 1.65%-3.75%; n = 44), 2.5 times higher than what was assumed up until now. Abstract Enteric fever is a febrile illness, occurring mostly in Asia and Africa, which can present as a severe and possibly fatal disease. Currently, a case fatality rate (CFR) of 1% is assumed when evaluating the global burden of enteric fever. Until now, no meta-analysis has been conducted to summarize mortality from enteric fever. Therefore, we conducted a systematic review and meta-analysis to aggregate all available evidence. We estimated an overall CFR of 2.49% (95% confidence interval, 1.65%-3.75%; n = 44), and a CFR in hospitalized patients of 4.45% (2.85%-6.88%; n = 21 of 44). There was considerably heterogeneity in estimates of the CFR from individual studies. Neither age nor antimicrobial resistance were significant prognostic factors, but limited data were available for these analyses. The combined estimate of the CFR for enteric fever is higher than previously estimated, and the evaluation of prognostic factors, including antimicrobial resistance, urgently requires more data.

Background Although effective in reducing relapse rate and delaying progression, current therapies for multiple sclerosis (MS) do not completely halt disease progression. T cell autoimmunity to myelin antigens is considered one of the main mechanisms driving MS. It is characterized by autoreactivity to disease-initiating myelin antigen epitope(s), followed by a cascade of epitope spreading, which are both strongly patient-dependent. Targeting a variety of MS-associated antigens by myelin antigen-presenting tolerogenic dendritic cells (tolDC) is a promising treatment strategy to re-establish tolerance in MS. Electroporation with mRNA encoding myelin proteins is an innovative technique to load tolDC with the full spectrum of naturally processed myelin-derived epitopes. Methods In this study, we generated murine tolDC presenting myelin oligodendrocyte glycoprotein (MOG) using mRNA electroporation and we assessed the efficacy of MOG mRNA-electroporated tolDC to dampen pathogenic T cell responses in experimental autoimmune encephalomyelitis (EAE). For this, MOG 35–55 -immunized C57BL/6 mice were injected intravenously at days 13, 17, and 21 post-disease induction with 1α,25-dihydroxyvitamin D 3 -treated tolDC electroporated with MOG-encoding mRNA. Mice were scored daily for signs of paralysis. At day 25, myelin reactivity was evaluated following restimulation of splenocytes with myelin-derived epitopes. Ex vivo magnetic resonance imaging (MRI) was performed to assess spinal cord inflammatory lesion load. Results Treatment of MOG 35–55 -immunized C57BL/6 mice with MOG mRNA-electroporated or MOG 35–55 -pulsed tolDC led to a stabilization of the EAE clinical score from the first administration onwards, whereas it worsened in mice treated with non-antigen-loaded tolDC or with vehicle only. In addition, MOG 35–55 -specific pro-inflammatory pathogenic T cell responses and myelin antigen epitope spreading were inhibited in the peripheral immune system of tolDC-treated mice. Finally, magnetic resonance imaging analysis of hyperintense spots along the spinal cord was in line with the clinical score. Conclusions Electroporation with mRNA is an efficient and versatile tool to generate myelin-presenting tolDC that are capable to stabilize the clinical score in EAE. These results pave the way for further research into mRNA-electroporated tolDC treatment as a patient-tailored therapy for MS.

Consumer-oriented wearable devices (CWDs) such as smartphones and smartwatches have gained prominence for their ability to detect atrial fibrillation (AF) through proprietary algorithms using electrocardiography or photoplethysmography (PPG)-based digital recordings. Despite numerous individual validation studies, a direct comparison of interdevice performance is lacking. This study aimed to evaluate and compare the ability of CWDs to distinguish between sinus rhythm and AF. Patients exhibiting sinus rhythm or AF were enrolled through a cardiology outpatient clinic. The participants were instructed to perform heart rhythm measurements using a handheld 6-lead electrocardiogram (ECG) device (KardiaMobile 6L), a smartwatch-derived single-lead ECG (Apple Watch), and two PPG-based smartphone apps (FibriCheck and Preventicus) in a random sequence, with simultaneous 12-lead reference ECG as the gold standard. A total of 122 participants were included in the study: median age 69 (IQR 61-77) years, 63.9% (n=78) men, 25% (n=30) with AF, 9.8% (n=12) without prior smartphone experience, and 73% (n=89) without experience in using a smartwatch. The sensitivity to detect AF was 100% for all devices. The specificity to detect sinus rhythm was 96.4% (95% CI 89.5%-98.8%) for KardiaMobile 6L, 97.8% (95% CI 91.6%-99.5%) for Apple Watch, 98.9% (95% CI 92.5%-99.8%) for FibriCheck, and 97.8% (95% CI 91.5%-99.4%) for Preventicus (P=.50). Insufficient quality measurements were observed in 10.7% (95% CI 6.3%-17.5%) of cases for both KardiaMobile 6L and Apple Watch, 7.4% (95% CI 3.9%-13.6%) for FibriCheck, and 14.8% (95% CI 9.5%-22.2%) for Preventicus (P=.21). Participants preferred Apple Watch over the other devices to monitor their heart rhythm. In this study population, the discrimination between sinus rhythm and AF using CWDs based on ECG or PPG was highly accurate, with no significant variations in performance across the examined devices.

Typhoid fever is a major cause of morbidity and mortality in low-income and middle-income countries. In 2017, WHO recommended the programmatic use of typhoid Vi-conjugate vaccine (TCV) in endemic settings, and Gavi, The Vaccine Alliance, has pledged support for vaccine introduction in these countries. Country-level health economic evaluations are now needed to inform decision-making. In this modelling study, we compared four strategies: no vaccination, routine immunisation at 9 months, and routine immunisation at 9 months with catch-up campaigns to either age 5 years or 15 years. For each of the 54 countries eligible for Gavi support, output from an age-structured transmission-dynamic model was combined with country-specific treatment and vaccine-related costs, treatment outcomes, and disability weights to estimate the reduction in typhoid burden, identify the strategy that maximised average net benefit (ie, the optimal strategy) across a range of country-specific willingness-to-pay (WTP) values, estimate and investigate the uncertainties surrounding our findings, and identify the epidemiological conditions under which vaccination is optimal. The optimal strategy was either no vaccination or TCV immunisation including a catch-up campaign. Routine vaccination with a catch-up campaign to 15 years of age was optimal in 38 countries, assuming a WTP value of at least US$200 per disability-adjusted life-year (DALY) averted, or assuming a WTP value of at least 25% of each country's gross domestic product (GDP) per capita per DALY averted, at a vaccine price of $1·50 per dose (but excluding Gavi's contribution according to each country's transition phase). This vaccination strategy was also optimal in 48 countries assuming a WTP of at least $500 per DALY averted, in 51 with assumed WTP values of at least $1000, in 47 countries assuming a WTP value of at least 50% of GDP per capita per DALY averted, and in 49 assuming a minimum of 100%. Vaccination was likely to be cost-effective in countries with 300 or more typhoid cases per 100 000 person-years. Uncertainty about the probability of hospital admission (and typhoid incidence and mortality) had the greatest influence on the optimal strategy. Countries should establish their own WTP threshold and consider routine TCV introduction, including a catch-up campaign when vaccination is optimal on the basis of this threshold. Obtaining improved estimates of the probability of hospital admission would be valuable whenever the optimal strategy is uncertain. Bill & Melinda Gates Foundation, Research Foundation–Flanders, and the Belgian–American Education Foundation.

The performance and acceptability of first-void urine as specimen for the detection of HPV DNA in a Belgian referral population was evaluated using an optimized sample collection and processing protocol. One hundred ten first-void urine and cervical samples were collected from 25- to 64-year-old women who were referred for colposcopy (January–November 2016). Paired samples were analyzed by the Riatol qPCR HPV genotyping assay. Acceptability data were gathered through questionnaires (NCT02714127). A higher high-risk HPV DNA prevalence was observed in first-void urine (n = 76/110) compared to cervical samples (n = 73/110), with HPV31 and HPV16/31 being most prevalent correspondingly. For both any and high-risk HPV DNA, good agreement was observed between paired samples (Cohen’s Kappa of 0.660 (95% CI: 0.486–0.833) and 0.688 (95% CI: 0.542–0.835), respectively). In addition, significant positive correlations in HPV copies (per microliter of DNA extract) between paired samples were observed for HPV16 (rs = 0.670; FDR (false discovery rate)-adjusted p = 0.006), HPV18 (rs = 0.893; FDR-adjusted p = 0.031), HPV31 (rs = 0.527; FDR-adjusted p = 0.031), HPV53 (rs = 0.691; FDR-adjusted p = 0.017), and HPV68 (rs = 0.569; FDR-adjusted p = 0.031). First-void urine sampling using a first-void urine collection device was preferred over a clinician-collected cervical sample. And mostly, first-void urine sampling at home was favored over collection at the clinic or the general practitioner’s office. First-void urine sampling is a highly preferred, non-invasive method that ensures good agreement in HPV DNA (copies) with reference cervical samples. It is particularly interesting as a screening technique to reach non-participants, and its clinical performance should be further evaluated.

To guide and assist applicants for the preparation and presentation of genetically modified (GM) plant market authorization applications, the GMO Panel of EFSA has developed guidance for the risk assessment of GM plants and derived food and feed, which describes principles, concepts, data requirements and issues to be considered when performing the risk assessment of GM plants and derived food and feed. The objective of this framework contract is to provide statistical support to the EFSA GMO Panel for the evaluation of GMO application dossiers with respect to the statistical analysis of collected data from field trials carried out for the comparative assessment according to the requirements described in the EFSA guidance on statistical considerations for the safety evaluation of GMOs and EFSA guidance on the risk assessment of food and feed from genetically modified plants. This annual report describes the different tasks performed in 2021 under the framework contract and summarises their outcome. The evaluations of the statistical analysis of applications during 2021 met to a large extent the requirements reported in the guidance documents. Only a few minor non-compliances were recurrently reported in most of the applications.

To guide and assist applicants for the preparation and presentation of genetically modified (GM) plant market authorization applications, the GMO Panel of EFSA has developed guidance for the risk assessment of GM plants and derived food and feed, which describes principles, concepts, data requirements and issues to be considered when performing the risk assessment of GM plants and derived food and feed. The objective of this framework contract is to provide statistical support to the EFSA GMO Panel for the evaluation of GMO application dossiers with respect to the statistical analysis of collected data from field trials carried out for the comparative assessment according to the requirements described in the EFSA guidance on statistical considerations for the safety evaluation of GMOs and EFSA guidance on the risk assessment of food and feed from genetically modified plants. This annual report describes the different tasks performed in 2022 and 2023 under the framework contract and summarizes their outcome. The majority of the applications received during 2022, for the evaluation of the statistical analysis, contained a few minor non-compliances and met to a large extent the requirements described in the EFSA guidance documents.

To guide and assist applicants for the preparation and presentation of genetically modified (GM) plant market authorization applications, the GMO Panel of EFSA has developed guidance for the risk assessment of GM plants and derived food and feed, which describes principles, concepts, data requirements and issues to be considered when performing the risk assessment of GM plants and derived food and feed. The objective of this framework contract is to provide statistical support to the EFSA GMO Panel for the evaluation of GMO application dossiers with respect to the statistical analysis of collected data from field trials carried out for the comparative assessment according to the requirements described in the EFSA guidance on statistical considerations for the safety evaluation of GMOs and EFSA guidance on the risk assessment of food and feed from genetically modified plants. This annual report describes the different tasks performed in 2020 under the framework contract and summarizes their outcome. The evaluations of the statistical analysis of applications during 2020 met to a large extent the requirements reported in the guidance documents. Only a few minor non-compliances were recurrently reported in most of the applications.