Design and Development of Tools for Risk Evaluation of Diabetes and Cardiovascular Disease in Community Pharmacy.

There is an increasing motivation to implement pharmacist-led screening services in community pharmacies. This study aims to develop tools to support the pharmacist in the context of a diabetes and cardiovascular disease risk assessment service. Our development involved a multistep process using a user-centred approach, including a need assessment phase (14 patients, 17 pharmacists) and a creative design phase, followed by the evaluation of the materials (10 patients, 16 pharmacists). Three following themes covering educational needs emerged from stakeholders' discussions: "content", "layout", and "form", with three additional themes regarding the practical organisation: "software", "awareness", and "referral". Based on the need assessment, tools for patient education purposes and awareness campaigns were created. During the development, special attention was paid to the writing style and structure with less text and more graphical colourful elements to suit patients with different health literacy and educational levels. The evaluation phase allowed researchers to observe participants engaging with the materials. Overall, participants were satisfied with the tools. The contents were considered valuable and relevant. However, adaptations were necessary to ensure their understanding and long-term usability. Finally, future research is required to evaluate the materials' impact on patients' behaviour towards their identified risk factors and ensure their effectiveness.

Diabetes and Cardiovascular Diseases Risk Assessment in Community Pharmacies: An Implementation Study.

The implementation of a new service is often challenging when translating research findings into routine clinical practices. This paper presents the results of the implementation study of a pilot project for a diabetes and cardiovascular diseases risk-assessment service in Belgian community pharmacies. To evaluate the implementation of the service, a mixed method was used that follows the RE-AIM framework. During the testing stage, 37 pharmacies participated, including five that dropped out due to a lack of time or COVID-19-related temporary obligations. Overall, 502 patients participated, of which 376 (74.9%) were eligible for according-to-protocol analysis. Of these, 80 patients (21.3%) were identified as being at high risk for the targeted diseases, and 100 (26.6%) were referred to general practice for further investigation. We presented the limited effectiveness and the key elements influencing optimal implementation. Additional strategies, such as interprofessional workshops, a data-sharing platform, and communication campaigns, should be considered to spread awareness of the new role of pharmacists. Such strategies could also promote collaboration with general practitioners to ensure the follow-up of patients at high risk. Overall, this service was considered easy to perform and feasible in practice but would require financial and external support to ensure its effectiveness, sustainability, and larger-scale implementation.

Clinical-grade manufacturing of autologous mature mRNA-electroporated dendritic cells and safety testing in acute myeloid leukemia patients in a phase I dose-escalation clinical trial.

BACKGROUND AIMS: RNA-electroporated dendritic cell (DC)-based vaccines are rapidly gaining interest as therapeutic cancer vaccines. We report on a phase I dose-escalation trial using clinical-grade manufactured mature RNA-electroporated DC in acute myeloid leukemia (AML) patients. METHODS: CD14(+) cells were isolated from leukapheresis products by immunomagnetic CliniMACS separation and differentiated into mature DC (mDC). mDC were electroporated with clinical-grade mRNA encoding the Wilm's tumor (WT1) antigen, and tested for viability, phenotype, sterility and recovery. To test product safety, increasing doses of DC were administered intradermally four times at 2-week intervals in 10 AML patients. RESULTS: In a pre-clinical phase, immunomagnetic monocyte isolation proved superior over plastic adherence in terms of DC purity and lymphocyte contamination. We also validated a simplified DC maturation protocol yielding a consistent phenotype, migration and allogeneic T-cell stimulatory capacity in AML patients in remission. In the clinical trial, highly purified CD14(+) cells (94.5+/-3.4%) were obtained from all patients. A monocyte-to-mDC conversion factor of 25+/-10% was reached. All DC preparations exhibited high expression of mDC markers. Despite a decreased cell recovery of mDC after a combination of mRNA electroporation and cryopreservation, successful vaccine preparations were obtained in all AML patients. DC injections were well tolerated by all patients. CONCLUSIONS: Our method yields a standardized, simplified and reproducible preparation of multiple doses of clinical-grade mRNA-transfected DC vaccines from a single apheresis with consistent mature phenotype, recovery, sterility and viability. Intradermal injection of such DC vaccines in AML patients is safe.

Coverage of recommended vaccines during pregnancy in Flanders, Belgium. Fairly good but can we do better?

BACKGROUND: In Flanders, Belgium, pertussis vaccination is recommended since 2013 and available free-of-charge in every pregnancy between 24 and 32 weeks of gestation. Influenza vaccination is recommended for more than 10 years with a co-payment system in the second or third trimester of pregnancy, when pregnancy coincides with the influenza season. This study aims to estimate the coverage of pertussis and influenza vaccination during pregnancy in 2016 and to determine predictors for missing vaccination. METHODS: Postpartum women were visited at home for a vaccination coverage survey using an Expanded Program on Immunization (EPI)-based two-stage cluster sampling design. Predictors for missed vaccination were identified using a multiple logistic regression model. RESULTS: Among 481 participating women, 69.3% were vaccinated against pertussis and 47.2% were vaccinated against influenza. Moreover, 65.3% of pertussis vaccine recipients and 96.9% of influenza vaccine recipients were vaccinated within the recommended gestational window. Surprisingly, among women who were completely informed (i.e. on disease-associated risks, maternal vaccination costs and recommendations), still 12.4% were unvaccinated against pertussis and 23.9% against influenza. In the final models, the only common predictor of missing maternal pertussis and influenza vaccination was multiparity. Significant predictors of maternal pertussis vaccination were family income (less likely if unknown or low (< €3000) than if moderate (€3001-€4000)) and hospital of delivery (less likely if >800 annual deliveries than <800). Significant predictors of maternal influenza vaccination, though with less straight-forward associations, were maternal ethnicity and educational level, involvement of a gynaecologist in pregnancy follow-up, and characteristics of the hospital of delivery. CONCLUSION: In Flanders, more than two-third of pregnant women receives pertussis vaccination but less than half of them receives the influenza vaccine. Further improvement for both maternal vaccination programs can be achieved by targeting the underserved populations and diminishing vaccination hurdles.

Maternal pertussis and influenza immunization coverage and attitude of health care workers towards these recommendations in Flanders, Belgium.

In Belgium, pertussis vaccination is recommended for all pregnant women in every pregnancy. Adults in close contact with young infants are equally advised to receive a pertussis containing booster dose. Maternal influenza vaccination is likewise recommended in Belgium in the second or third trimester of pregnancy, within the influenza season. A quantitative multicenter survey study has been performed between October 2014 and May 2015 in both postpartum women (N=823, response rate=89.2%) and health care workers (HCWs) (N=261) to assess the coverage of both vaccines during pregnancy along with the coverage of the pertussis cocoon strategy, and to evaluate the knowledge and recommending attitude of HCWs towards the maternal vaccination strategies and the cocoon strategy among surveyed women and HCWs. Overall coverage of pertussis vaccination during pregnancy was 64.0%. Most women were vaccinated by their general practitioner (GP) (82.4%), and most often in the third trimester (74.0%) of pregnancy. Overall coverage of influenza vaccination during pregnancy was 45.0%. Again the GP administered most vaccines (67.6%); vaccines were equally administered in the second or third trimester of pregnancy. Educational level had a significant influence on both the pertussis and influenza vaccination coverage during pregnancy while working situation and parity had only an influence on the maternal pertussis vaccination coverage and country of birth only on the maternal influenza vaccination coverage. Overall, 78.4% of gynecologists and GPs recommends both maternal pertussis and influenza vaccination and 67.0% recommends both maternal vaccination strategies and the cocoon strategy. Within the group of the midwives, only 23.7% recommends both maternal pertussis and influenza vaccination and 10.5% recommends both maternal vaccination strategies and the cocoon strategy. High coverage is reached among pregnant women for pertussis and influenza vaccination. Several underserved populations of pregnant women regarding maternal immunization, are identified.

Anchor profiles of HLA-specific peptides: analysis by a novel affinity scoring method and experimental validation.

The study of intermolecular interactions is a fundamental research subject in biology. Here we report on the development of a quantitative structure-based affinity scoring method for peptide-protein complexes, named PepScope. The method operates on the basis of a highly specific force field function (CHARMM) that is applied to all-atom structural representations of peptide-receptor complexes. Peptide side-chain contributions to total affinity are scored after detailed rotameric sampling followed by controlled energy refinement. A de novo approach to estimate dehydration energies was developed, based on the simulation of individual amino acids in a solvent box filled with explicit water molecules. Transferability of the method was demonstrated by its application to the hydrophobic HLA-A2 and -A24 receptors, the polar HLA-A1, and the sterically ruled HLA-B7 receptor. A combined theoretical and experimental study on 39 anchor substitutions in FxSKQYMTx/HLA-A2 and -A24 complexes indicated a prediction accuracy of about two thirds of a log-unit in Kd. Analysis of free energy contributions identified a great role of desolvation and conformational strain effects in establishing a given specificity profile. Interestingly, the method rightly predicted that most anchor profiles are less specific than so far assumed. This suggests that many potential T-cell epitopes could be missed with current prediction methods. The results presented in this work may therefore significantly affect T-cell epitope discovery programs applied in the field of peptide vaccine development.

Induction of cytomegalovirus-specific T cell responses in healthy volunteers and allogeneic stem cell recipients using vaccination with messenger RNA-transfected dendritic cells.

BACKGROUND: Infection with human cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ and hematopoietic stem cell transplant (HSCT) recipients. METHODS: The present study explored the safety, feasibility, and immunogenicity of CMV pp65 messenger RNA-loaded autologous monocyte-derived dendritic cells (DC) as a cellular vaccine for active immunization in healthy volunteers and allogeneic HSCT recipients. Four CMV-seronegative healthy volunteers and three allogeneic HSCT recipients were included in the study. Four clinical-grade autologous monocyte-derived DC vaccines were prepared after a single leukapheresis procedure and administered intradermally at a weekly interval. RESULTS: De novo induction of CMV-specific T-cell responses was detected in three of four healthy volunteers without serious adverse events. Of the HSCT recipients, none developed CMV disease and one of two patients displayed a remarkable threefold increase in CMV pp65-specific T cells on completion of the DC vaccination trial. CONCLUSION: In conclusion, our DC vaccination strategy induced or expanded a CMV-specific cellular response in four of six efficacy-evaluable study subjects, providing a base for its further exploration in larger cohorts.

Timeliness of infant vaccination and factors related with delay in Flanders, Belgium.

Achieving high vaccination coverage is a necessary, but not a sufficient indicator of the quality of a vaccination programme, in terms of control and prevention of childhood infectious diseases. For optimal protection of infants, timeliness of vaccination is increasingly recognized as another important target. The aim of this study was to assess the timeliness of measles-mumps-rubella (MMR) and diphtheria-tetanus-pertussis (DTP) vaccination in infants in Flanders (Belgium), and to identify predictors of vaccination delay. The timeliness was assessed using the Kaplan-Meier estimator in three consecutive vaccination coverage surveys among children aged 18-24 months, conducted in 2005, 2008 and 2012, respectively. Factors associated with delayed administration of the vaccines were identified using Cox regression analysis. Over the time period, vaccination coverage for the first dose of MMR ranged from 94.0 to 96.6% and for the third dose of DTP from 97.9 to 98.7%. However, up to 32% (for MMR1) and 95% (for DTP3) of infants received vaccine doses delayed according to the recommended schedule. Although some improvement was achieved over the last decade, further efforts are needed to reach risk groups with delays, more specifically children vaccinated outside the baby well clinics, born from a mother originating from outside the European Union, children with a higher ranking or in families with a lower income.

Assessing vaccination coverage in infants, survey studies versus the Flemish immunisation register: achieving the best of both worlds.

Infant immunisation coverage in Flanders, Belgium, is monitored through repeated coverage surveys. With the increased use of Vaccinnet, the web-based ordering system for vaccines in Flanders set up in 2004 and linked to an immunisation register, this database could become an alternative to quickly estimate vaccination coverage. To evaluate its current accuracy, coverage estimates generated from Vaccinnet alone were compared with estimates from the most recent survey (2012) that combined interview data with data from Vaccinnet and medical files. Coverage rates from registrations in Vaccinnet were systematically lower than the corresponding estimates obtained through the survey (mean difference 7.7%). This difference increased by dose number for vaccines that require multiple doses. Differences in administration date between the two sources were observed for 3.8-8.2% of registered doses. Underparticipation in Vaccinnet thus significantly impacts on the register-based immunisation coverage estimates, amplified by underregistration of administered doses among vaccinators using Vaccinnet. Therefore, survey studies, despite being labour-intensive and expensive, currently provide more complete and reliable results than register-based estimates alone in Flanders. However, further improvement of Vaccinnet's completeness will likely allow more accurate estimates in the nearby future.

Prevalence of rotavirus antibodies in breast milk and inhibitory effects to rotavirus vaccines.

Rotavirus (RV) is the most common cause of childhood diarrhea worldwide, and several vaccines have been successfully developed to reduce the burden of disease. However, lower vaccine immunogenicity and efficacy in developing countries might be related to the virus-neutralizing activity of breast milk. We examined possible differences in breast milk antibody levels (total IgA antibody, RV-specific antibodies, and RV-neutralizing antibodies) between healthy mothers living in a rural area (n=145) and mothers living in an urban area (n=147) of Vietnam. Total IgA concentration was significantly higher in samples from mothers in the rural region than in samples from mothers in the urban region, whereas urban mothers had significantly higher RV-specific IgA antibody titers than did rural mothers. Neutralizing antibodies against RV strain G1P[8] were undetected in nearly one-half of the breast milk samples (45-48%), whereas the majority of the remaining samples had low antibody titers (2-16). Despite these low titers, the breast milk still reduced vaccine strain titers (2×10(6) plaque forming units/mL) up to 80% or more, even at a milk-to-virus ratio of 1:8. An increase in neutralizing anti-G1P[8] antibody titers (P<0.05) in rural infants over time suggests a continuous exposure to circulating RV. These results contribute to the understanding of the potential interference of breast milk with RV vaccine efficacy and immunogenicity in Vietnamese infants.

Breastfeeding after maternal immunisation during pregnancy: providing immunological protection to the newborn: a review.

Vaccination during pregnancy results in an augmentation of disease specific maternal antibodies. Immunoglobulin G (IgG) is mainly transferred through the placenta during the third trimester of pregnancy, while secretory Immunoglobulin A (sIgA) is passed through breast milk. At birth, newborns are partially protected against infectious diseases by these antibodies. This review aims to provide an overview of the effect of vaccination during pregnancy on the immunological protection of the newborn by the presence of disease specific sIgA antibodies in breast milk and their possible protective function against disease. Our search produced 11 relevant papers; 1 on pertussis, 7 on pneumococcus, 2 on influenza and 1 on meningococcus. All of the studies in this review that measured disease specific antibodies in breast milk (n=8 papers), stressed the beneficial effect of maternal vaccination during pregnancy on the amount of disease specific sIgA in breast milk. Only a few studies demonstrated a potential protective effect, particularly with influenza vaccines. In an era where maternal vaccination is increasingly considered as a valuable strategy to protect both the mother and infant, further research is needed to assess the effect on breast milk sIgA and to understand the potentially beneficial effects to the infant.

Two decades of hepatitis B vaccination in mentally retarded patients: effectiveness, antibody persistence and duration of immune memory.

INTRODUCTION: Institutionalized mentally retarded subjects are well-known to be at-risk for HBV infection. We studied the persistence of vaccine-induced anti-HBs antibodies and the robustness of the HBsAg-specific immune memory in this population, 18-20 years after the first vaccine dose. MATERIALS AND METHODS: Non-immune residents of 4 institutions were immunized in 1984-1986. In 2004, 207 subjects were bled to determine humoral and cellular immune memory. Immune response to a booster dose was evaluated in subjects with anti-HBs level <100 IU/L. RESULTS: Four subjects showed anti-HBc seroconversion, without clinical implications. Pre-booster anti-HBs levels <100 IU/L were found in 45 subjects (22%); 34/39 (87%) responded with a rapid and high anti-HBs titer to the booster dose. Robust T and B cell memory was present pre- and post-booster. DISCUSSION AND CONCLUSION: Overall results confirm that hepatitis B vaccines are highly effective and immunogenic, and confer long-term persistence of antibodies and immune memory in an at-risk population.

Effectiveness of rotavirus vaccination in prevention of hospital admissions for rotavirus gastroenteritis among young children in Belgium: case-control study.

OBJECTIVE: To evaluate the effectiveness of rotavirus vaccination among young children in Belgium. DESIGN: Prospective case-control study. SETTING: Random sample of 39 Belgian hospitals, February 2008 to June 2010. PARTICIPANTS: 215 children admitted to hospital with rotavirus gastroenteritis confirmed by polymerase chain reaction and 276 age and hospital matched controls. All children were of an eligible age to have received rotavirus vaccination (that is, born after 1 October 2006 and aged ≥ 14 weeks). MAIN OUTCOME MEASURE: Vaccination status of children admitted to hospital with rotavirus gastroenteritis and matched controls. RESULTS: 99 children (48%) admitted with rotavirus gastroenteritis and 244 (91%) controls had received at least one dose of any rotavirus vaccine (P<0.001). The monovalent rotavirus vaccine accounted for 92% (n=594) of all rotavirus vaccine doses. With hospital admission as the outcome, the unadjusted effectiveness of two doses of the monovalent rotavirus vaccine was 90% (95% confidence interval 81% to 95%) overall, 91% (75% to 97%) in children aged 3-11 months, and 90% (76% to 96%) in those aged ≥ 12 months. The G2P[4] genotype accounted for 52% of cases confirmed by polymerase chain reaction with eligible matched controls. Vaccine effectiveness was 85% (64% to 94%) against G2P[4] and 95% (78% to 99%) against G1P[8]. In 25% of cases confirmed by polymerase chain reaction with eligible matched controls, there was reported co-infection with adenovirus, astrovirus and/or norovirus. Vaccine effectiveness against co-infected cases was 86% (52% to 96%). Effectiveness of at least one dose of any rotavirus vaccine (intention to vaccinate analysis) was 91% (82% to 95%). CONCLUSIONS: Rotavirus vaccination is effective for the prevention of admission to hospital for rotavirus gastroenteritis among young children in Belgium, despite the high prevalence of G2P[4] and viral co-infection.

Rotavirus vaccines in Belgium: policy and impact.

BACKGROUND: : The current Belgian experience with rotavirus vaccination provides a unique perspective to look at the effect of vaccination. Shortly after introduction, a nation-wide recommendation was issued and despite the fact that both rotavirus vaccines are offered through partial reimbursement, vaccine uptake has already reached a high level (at least 90%). METHODS: : For the purpose of looking at the effectiveness of the Belgian rotavirus vaccination policy, 3 years after introduction, we retrospectively collated the publicly available data on the number of laboratory-confirmed rotavirus cases reported to a national network of sentinel laboratories during 1999 to 2010 and compared them with the available data on hospitalizations due to rotavirus gastroenteritis. RESULTS: : Both data sources (reported laboratory-diagnosed cases to a sentinel network as well as data on hospitalizations due to rotavirus gastroenteritis) show a decrease in the number of rotavirus infections and a 4- to 6-week delay in the onset of disease and the peak of incidence in the postvaccination period. CONCLUSIONS: : Because this decline coincides with the increased vaccine uptake and is sustained during consecutive rotavirus seasons, the effect is mainly attributed to the rotavirus vaccination. The rapid increase in vaccine coverage, despite the partial reimbursement for the vaccines, is remarkable. Continued postlicensure surveillance is necessary to further investigate the effectiveness of the vaccines and to document the public health impact of the vaccination in reducing disease burden.