Perspectives of European Patient Advocacy Groups on Volunteer Registries and Vaccine Trials: VACCELERATE Survey Study.

BACKGROUND: The VACCELERATE Pan-European Scientific network aims to strengthen the foundation of vaccine trial research across Europe by following the principles of equity, inclusion, and diversity. The VACCELERATE Volunteer Registry network provides access to vaccine trial sites across the European region and supports a sustainable volunteer platform for identifying potential participants for forthcoming vaccine clinical research. OBJECTIVE: The aim of this study was to approach members of patient advocacy groups (PAGs) across Europe to assess their willingness to register for the VACCELERATE Volunteer Registry and their perspectives related to participating in vaccine trials. METHODS: In an effort to understand how to increase recruitment for the VACCELERATE Volunteer Registry, a standardized survey was developed in English and translated into 8 different languages (Dutch, English, French, German, Greek, Italian, Spanish, and Swedish) by the respective National Coordinator team. The online, anonymous survey was circulated, from March 2022 to May 2022, to PAGs across 10 European countries (Belgium, Cyprus, Denmark, France, Germany, Greece, Ireland, Italy, Spain, and Sweden) to share with their members. The questionnaire constituted of multiple choice and open-ended questions evaluating information regarding participants' perceptions on participating in vaccine trials and their willingness to become involved in the VACCELERATE Volunteer Registry. RESULTS: In total, 520 responses were collected and analyzed. The PAG members reported that the principal criteria influencing their decision to participate in clinical trials overall are (1) the risks involved, (2) the benefits that will be gained from their potential participation, and (3) the quality and quantity of information provided regarding the trial. The survey revealed that, out of the 520 respondents, 133 individuals across all age groups were "positive" toward registering in the VACCELERATE Volunteer Registry, with an additional 47 individuals reporting being "very positive." Respondents from Northern European countries were 1.725 (95% CI 1.206-2.468) times more likely to be willing to participate in the VACCELERATE Volunteer Registry than respondents from Southern European countries. CONCLUSIONS: Factors discouraging participants from joining vaccine trial registries or clinical trials primarily include concerns of the safety of novel vaccines and a lack of trust in those involved in vaccine development. These outcomes aid in identifying issues and setbacks in present registries, providing the VACCELERATE network with feedback on how to potentially increase participation and enrollment in trials across Europe. Development of European health communication strategies among diverse public communities, especially via PAGs, is the key for increasing patients' willingness to participate in clinical studies.

The Challenges of Vaccine Trial Participation among Underserved and Hard-to-Reach Communities: An Internal Expert Consultation of the VACCELERATE Consortium.

Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey), completed an online survey. From 15 eligible groups, those that were more frequently declared underserved/hard-to-reach in vaccine research were ethnic minorities (76.5%), persons experiencing homelessness (70.6%), illegal workers and refugees (64.7%, each). When prioritization for education on vaccine trials was considered, ethnic groups, migrants, and immigrants (5/17, 29.4%) were the groups most frequently identified by the NC as top targets. The most prominent barriers in vaccine trial participation affecting all groups were low levels of health literacy, reluctance to participate in trials due to engagement level, and low levels of trust in vaccines/vaccinations. This study highlighted population groups considered underserved/hard-to-reach in countries contained within the European region, and the respective barriers these groups face when participating in clinical studies. Our findings aid with the design of tailored interventions (within-and across-countries of the European region) and with the development of strategies to overcome major barriers in phase 2 and phase 3 vaccine trial participation.

Enhancing Public Health Communication Regarding Vaccine Trials: Design and Development of the Pan-European VACCELERATE Toolkit.

BACKGROUND: The pan-European VACCELERATE network aims to implement the first transnational harmonized and sustainable vaccine trial Volunteer Registry, being a single entry point for potential volunteers of large-scale vaccine trials across Europe. This work exhibits a set of harmonized vaccine trial-related educational and promotional tools for the general public, designed and disseminated by the pan-European VACCELERATE network. OBJECTIVE: This study primarily aimed to design and develop a standard toolkit to increase positive attitudes and access to trustworthy information for better access and increased recruitment to vaccine trials for the public. More specifically, the produced tools are focused on inclusiveness and equity, and are targeting different population groups, including underserved ones, as potential volunteers for the VACCELERATE Volunteer Registry (older individuals, migrants, children, and adolescents). The promotional and educational material is aligned with the main objectives of the Volunteer Registry to increase public literacy and awareness regarding vaccine-related clinical research or trials and trial participation, including informed consent and legal issues, side effects, and frequently asked questions regarding vaccine trial design. METHODS: Tools were developed per the aims and principles of the VACCELERATE project, focusing on trial inclusiveness and equity, and are adjusted to local country-wise requirements to improve public health communication. The produced tools are selected based on the cognitive theory, inclusiveness, and equity of differently aged and underrepresented groups, and standardized material from several official trustworthy sources (eg, COVID-19 Vaccines Global Access; the European Centre for Disease Prevention and Control; the European Patients' Academy on Therapeutic Innovation; Gavi, the Vaccine Alliance; and the World Health Organization). A team of multidisciplinary specialists (infectious diseases, vaccine research, medicine, and education) edited and reviewed the subtitles and scripts of the educational videos, extended brochures, interactive cards, and puzzles. Graphic designers selected the color palette, audio settings, and dubbing for the video story-tales and implemented QR codes. RESULTS: This study presents the first set of harmonized promotional and educational materials and tools (ie, educational cards, educational and promotional videos, extended brochures, flyers, posters, and puzzles) for vaccine clinical research (eg, COVID-19 vaccines). These tools inform the public about possible benefits and disadvantages of trial participation and build confidence among participants about the safety and efficacy of COVID-19 vaccines and the health care system. This material has been translated into several languages and is intended to be freely and easily accessible to facilitate dissemination among VACCELERATE network participant countries and the European and global scientific, industrial, and public community. CONCLUSIONS: The produced material could help fill knowledge gaps of health care personnel, providing the appropriate future patient education for vaccine trials, and tackling vaccine hesitancy and parents' concerns for potential participation of children in vaccine trials.

Reversible Cerebral Vasoconstriction Syndrome in a Previously Healthy Child: A Case Report.

Objectives: We describe the case of a healthy boy diagnosed with reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES). Methods: He was identified after presenting in the emergency department (ED). A review of the 5 previous cases of RCVS complicated with PRES reported in the literature was performed. Results: A 9-year-old boy was brought to the ED for intense, throbbing headache and vomiting. Physical and neurologic examinations were normal. Brain CT and CSF examination were unremarkable, and he was discharged after symptomatic relief. Five days later, he returned to the ED for generalized tonic-clonic seizures that ceased with levetiracetam. MRI with angiography showed PRES. Systolic hypertension refractory to therapy was documented. New-onset fluctuating right-sided paresis and paresthesia appeared, so MRI was repeated, showing diffuse cerebral vasoconstriction suggesting RCVS. Nimodipine was started with complete resolution of symptoms and normalization of blood pressure. Four weeks after discharge, TD and MRI showed total vasospasm resolution. There was no recurrence in 12-month follow-up. Discussion: This case emphasizes the interconnection between RCVS and PRES, highlighting the need to include both as differential diagnoses for severe headache and the essential role of MR angiography in the investigation.

VACCELERATE Volunteer Registry: A European study participant database to facilitate clinical trial enrolment.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has evidenced the key role of vaccine design, obtention, production and administration to successfully fight against infectious diseases and to provide efficient remedies for the citizens. Although clinical trials were rapidly established during this pandemic, identifying suitable study subjects can be challenging. For this reason, the University Hospital Cologne established a volunteer registry for participation in clinical trials first in Germany, which has now been incorporated into the European VACCELERATE clinical trials network and grew to a European Volunteer Registry. As such, VACCELERATE's Volunteer Registry aims to become a common entry point for potential volunteers in future clinical trials in Europe. METHODS: Interested volunteers who would like to register for clinical trials in the VACCELERATE Volunteer Registry can access the registration questionnaire via http://www.vaccelerate.eu/volunteer-registry. Potential volunteers are requested to provide their current country and area of residence, contact information, including first and last name and e-mail address, age, gender, comorbidities, previous SARS-CoV-2 infection and vaccination status, and maximum distance willing to travel to a clinical trial site. The registry is open to both adults and children, complying with national legal consent requirements. RESULTS: As of May 2022, the questionnaire is available in 12 countries and 14 languages. Up to date, more than 36,000 volunteers have registered, mainly from Germany. Within the first year since its establishment, the VACCELERATE Volunteer Registry has matched more than 15,000 volunteers to clinical trials. The VACCELERATE Volunteer Registry will be launched in further European countries in the coming months. CONCLUSIONS: The VACCELERATE Volunteer Registry is an active single-entry point for European residents interested in COVID-19 clinical trials participation in 12 countries (i.e., Austria, Cyprus, Germany, Greece, Ireland, Lithuania, Norway, Portugal, Spain, Sweden and Turkey). To date, more than 15,000 registered individuals have been connected to clinical trials in Germany alone. The registry is currently in the implementation phase in 5 additional countries (i.e., Belgium, Czech Republic, Hungary, Israel and the Netherlands).

Comprehensive Insight from Phthalates Occurrence: From Health Outcomes to Emerging Analytical Approaches.

Phthalates are a group of chemicals used in a multitude of important industrial products (e.g., medical devices, children's toys, and food packages), mainly as plasticizers to improve mechanical properties such as flexibility, transparency, durability, and longevity of polyvinyl chloride (PVC). The wide occurrence of phthalates in many consumer products, including foods (e.g., bottled water, soft drinks, wine, milk, and meat) brings that most people are exposed to phthalates every day, which raises some concerns. Adverse health outcomes from phthalates exposure have been associated with endocrine disruption, deformities in the human reproductive system, increased risk of preterm birth, carcinogen exposure, among others. Apprehension related to the health risks and ubiquitous incidence of phthalates in foods inspires the development of reliable analytical approaches that allow their detection and quantification at trace levels. The purpose of the current review is to provide information related to the presence of phthalates in the food chain, highlighting the health risks associated with their exposure. Moreover, an overview of emerging extraction procedures and high-resolution analytical approaches for a comprehensive quantification of phthalates is presented.

Hyperbaric oxygen therapy for hypoxic-ischemic encephalopathy in non-fatal drowning.

Paroxysmal autonomic instability syndrome with dystonia (PAISD) is a possible complication that worsens the prognosis of hypoxic-ischemic encephalopathy related to non-fatal drowning. There are case reports of hyperbaric oxygen (HBO2) therapy enhancing recovery in such cases. We report a case of a 5-year-old boy admitted to the Pediatric Intensive Care Unit after a non-fatal drowning. He was transferred under mechanical ventilation and sedation, with hemodynamic instability and hypothermia. On admission he had a Glasgow Coma Score of 6. On the fifth day of admission he presented episodes of dystonia with decerebration posture, diaphoresis, tachycardia and hypertension, sometimes with identified triggers, suggesting PAISD. The episodes were difficult to control; multiple drugs were needed. Electroencephalography showed diffuse slow wave activity, and cranioencephalic magnetic resonance imaging showed hypoxia-related lesions, suggesting hypoxic-ischemic encephalopathy. Early after admission the patient started physiotherapy combined with normobaric oxygen therapy. Subsequently he started HBO2 therapy at 2 atmospheres, with a total of 66 sessions. Dystonia progressively subsided, with gradual discontinuation of therapy. He also showed improvement in spasticity, non-verbal communication and cephalic control. This case highlights the diagnostic and therapeutic challenges of PAISD and the potential benefit of HBO2 therapy, even in the subacute phase, in recovery of hypoxic-ischemic encephalopathy.

Men's Intentions to Recommend Professional Help-Seeking to Their Partners in the Postpartum Period: the Direct and Indirect Effects of Gender-Role Conflict.

Women's partners may act as facilitators of professional help-seeking for mental health problems in the postpartum period. This study aimed to examine the sociodemographic and clinical correlates of men's intentions to recommend professional help-seeking to their partners if they display postpartum mood and anxiety disorders and to explore the relationship between gender-role conflict and the intention to recommend help-seeking. A cross-sectional study included 214 adult men in a heterosexual relationship with a partner within the reproductive age. Men presented a high intention to recommend professional help to their partners. All dimensions of gender-role conflict were directly associated with the intention to recommend professional help-seeking (p < 0.05). High levels of gender-role conflict (dimensions success, power and competition, and restricted emotionality) were found to lead to increased levels of stigma and lower levels of intention to seek professional help, which, in turn, translated into lower intention to recommend help-seeking. These results emphasize the importance of developing universal awareness-raising and education campaigns directed at men aiming to reduce levels of gender-role conflict and stigma, and normalize the use of mental health services, to increase men's intentions to recommend professional help-seeking to their partners.

Pseudotumor cerebri as the presentation of Lyme disease in a non-endemic area.

Intracranial hypertension is a rare entity in prepubertal children, and its differential diagnosis includes a number of systemic diseases, drugs, vitamin deficiencies and excesses, and hereditary conditions. Infectious aetiology is rare. The case of a 9-year-old boy with intracranial hypertension secondary to acute neuroborreliosis is described. He presented with daily pulsatile frontotemporal headache, pallor, photophobia and phonophobia. His neurological examination revealed papilledema with no nuchal rigidity. The lumbar puncture showed increased pressure (50 cm H2O) and lymphocytic pleocytosis. Serum and cerebrospinal fluid (CSF) Borrelia burgdorferi antibodies were positive. This kind of infection is rare in Portugal but a trip to an endemic area was identified. A careful history, considering the exposure to rural areas together with the intracranial hypertension and inflammatory CSF, are important clues to the diagnosis, allowing the institution to select appropriate treatment.

Persistent strengthening of the prefrontal cortex - nucleus accumbens pathway during incubation of cocaine-seeking behavior.

High rates of relapse after prolonged abstinence are often triggered by exposure to drug-associated cues that induce drug craving. Incubation of drug craving is a phenomenon that consists of time-dependent increases in cue-induced drug craving during withdrawal. Plasticity mechanisms in the nucleus accumbens (NAc) underlie drug-seeking responses and involve changes in excitatory synaptic transmission's efficacy. In particular, the prefrontal cortex (PFC) glutamatergic input to the NAc core has been well characterized regarding cocaine-evoked plasticity following non-contingent versus contingent exposure to cocaine or alternatively after protracted abstinence. Still, the synaptic strength during the course of withdrawal compared to drug-naïve condition is unknown, since electrophysiological characterizations are mainly performed in brain slices or focus on distinct time points during cocaine-evoked plasticity in vivo. Here we used an incubation paradigm, in which rats had extended accessed to cocaine self-administration, and underwent cue-induced reinstatement at withdrawal day 1 and 30. Longitudinal in vivo field potential recordings in awake rats showed that chronic contingent exposure to cocaine strengthened the prelimbic PFC to NAc core pathway when compared to pre-cocaine condition. This strengthening was associated with decreased paired-pulse ratios (PPR), indicative of presynaptic enhancement of glutamate release, which persisted throughout withdrawal. Moreover, both field potential increase and PPR reduction after chronic cocaine exposure correlated with the number of cocaine infusions received during training. The present results together with previous findings of withdrawal-dependent postsynaptic enhancement of the PFC-NAc core pathway, suggest an additional presynaptic strengthening that is initiated during self-administration and maintained throughout abstinence in drug-seeking rats. These cocaine-driven neuroadaptations may provide a neural substrate for maladaptive processing of cues that can ultimately trigger craving and relapse.

Acute mastoiditis in children: Middle ear cultures may help in reducing use of broad spectrum antibiotics.

BACKGROUND: Acute mastoiditis (AM) is a suppurative infection of the mastoid air cells, representing the most frequent complication of acute otitis media. AM remains an important entity in children due to its potential complications and sequelae. We aim to describe the cases of AM admitted at our department, identify risk factors potentially associated with complications and analyse the changes in clinical approach of AM over time. METHODS: Case review of clinical files of children admitted with acute mastoiditis from June 1996 to May 2013 at a Lisbon metropolitan area hospital. Data was divided into two groups (prior and after May 2005) in order to evaluate changes in AM approach over the years. RESULTS: 135 AM episodes were included. The median age was 3.8 years and 42% children were less than 24 months of age. Symptoms at presentation included fever (69%), ear pain (56%) and otorrhea (40%). Complications occurred in 22% patients and were more common in children under 24 months (33% vs 15%, p ≤ 0.01). Leukocyte count was significantly higher in children with complications (16.7 vs 14.5 × 109/µL, p ≤ 0.05) as was C-Reactive Protein value (13 vs 6.3 mg/dL, p ≤ 0.001). There was a significant association between the development of complications and C-Reactive Protein value at admission (OR 1.892; IC95%: 1.018-2.493, p ≤ 0.01). The optimal cut-off value was 7.21 mg/dL. Over time there was a significant increase in middle ear cultures obtained by tympanocentesis during surgery (2% vs 16%, p ≤ 0,01) and also a decrease in the use of broad spectrum antibiotherapy as initial treatment (52% vs 25%,p ≤ 0,001). CONCLUSIONS: Children under 24 months, with high leukocyte count or with high C-Reactive Protein value should be monitored closely since complications tend to be more frequent. A CRP value of 7.21 mg/dL at admission seems to be a good cut-off to monitor children for potential complications. Throughout the period analysed more cultures were performed allowing identification of the pathogens and implementation of appropriate antibiotic therapy.

[Immigrant children in a pediatric department: what social problems?]. / A criança imigrante num serviçode pediatría: que problemas sociais?

BACKGROUND: Hospital Fernando Fonseca is located in a suburban area that houses a great number of immigrants from developing countries. AIMS: To characterize and compare the immigrant and portuguese pediatric populations which have been admitted and referred to Social Service department. MATERIAL AND METHODS: Prospective study, from November 2004 to March 2005; demographic and socioeconomic data, diagnosis and social problems were analysed. RESULTS: A total of 35 children were observed, 22 (62.8%) immigrants, 42.9% of them less than 12-months old, with a predominance of female (54.5%), African origin (81.8%) and poor social-economical status (72.3%). The majority of parents (72.7%) came from a Portuguese Speaking African Country and 58.3% were illegal in our country. Most had a family doctor assigned (81.3%). Nineteen (87.5%) were admitted for organic disease and the social problem was detected later: poverty (9), negligence (7), physical aggression (3), abandon (2), psychological abuse (1), sexual abuse (1). Children were referred to Child Protection Committee (5) and Court (1); 6 children received economical support and 5 needed social support. When compared to the Portuguese population, social problems are more frequent in immigrant children (20% vs.7.5%; p =0,001), especially in African origin (81.8% vs.15.4%; p=0,00); low economic status (7.3% vs.55.6%; p =0.,423 ), poverty (37.5% vs. 26.6%; p=0.313) and physical aggression (13% vs. 8.3%; p =0.313) were more frequent in the immigrant and negligence being the most frequent social problem in the Portuguese population (33.3% vs. 29%; p =0.313). DISCUSSION: The growing number of immigrants and their social deficiencies raises important questions related to health care and social support for these families, to facilitate their social integration.