The development of nucleic acid and protein drugs for oral delivery has lagged behind their production for conventional nonoral routes. Over the past decade, the evolution of DNA- and RNA-based technologies combined with the innovation of state-of-the-art delivery vehicles for nucleic acids has brought rapid advancements to the biopharmaceutical field. Nucleic acid therapies have the potential to achieve long-lasting effects, or even cures, by inhibiting or editing genes, which is not possible with conventional small-molecule drugs. However, challenges and limitations must be addressed before these therapies can provide cures for chronic conditions and rare diseases, rather than only offering temporary relief. Nucleic acids and proteins face premature degradation in the acidic, enzyme-rich stomach environment and are rapidly cleared by the liver. To overcome these challenges, various delivery vehicles have been developed to transport therapeutic compounds to the intestines, where the active compounds are released and gut microbiota and mucosal immune system also play an important role. This review provides a comprehensive overview of the promises and pitfalls associated with the oral route of administration of biologics, current delivery systems, applications of orally delivered therapeutics, and the challenges and considerations for translation of nucleic acid and protein therapeutics into clinical practice.

Bioinformatics has significantly advanced RNA-based therapeutics, particularly circular RNAs (circRNAs), which outperform mRNA vaccines, by offering superior stability, sustained expression, and enhanced immunogenicity due to their covalently closed structure. This review highlights how bioinformatics and computational biology optimise circRNA vaccine design, elucidates internal ribosome entry sites (IRES) selection, open reading frame (ORF) optimisation, codon usage, RNA secondary structure prediction, and delivery system development. While circRNA vaccines may not always surpass traditional vaccines in stability, their production efficiency and therapeutic efficacy can be enhanced through computational strategies. The discussion also addresses challenges and future prospects, emphasizing the need for innovative solutions to overcome current limitations and advance circRNA vaccine applications.

There are many evidence-based treatments available for pain-relief during subcutaneous vaccine injection in children. However, these methods are commonly labor-intensive and not routinely applied in clinical settings.

To evaluate the safety and pain-relieving effect of local cooling during subcutaneous vaccine injection in young children.

This single-blind, randomized, parallel-group multicenter study was conducted at two pediatric clinics in Hyogo Prefecture, which included preschool children aged 3-6 years scheduled for vaccination against Japanese encephalitis or influenza virus. Participants were randomly assigned to either the cooled group (local cooling applied using a cooling pack before vaccination) or the non-cooled group (provided with a room temperature cooling pack). Randomization was performed using a computer-generated block method. The primary endpoint was infant pain, measured using the FLACC scale (Facial expression, Leg movement, Activity, Crying, Consolability), rated by a third-party reviewing videos of the vaccination process.

A total of 60 children were randomized into the cooling (n = 30) and non-cooling (n = 30) groups, with all participants completing the study. Fifty-four participants received the Japanese encephalitis vaccine, and six received the influenza vaccine. Demographic data, including age, sex, and vaccine type, did not differ significantly between the two groups. The median FLACC score in the cooled group was significantly lower (1 [IQR 0-1.25]) compared to the non-cooled group (2.5 [IQR 1-6]) (P = 0.011). No adverse effects related to cooling were observed.

Local cooling during subcutaneous vaccine administration is a safe and effective method to reduce pain in children aged 3-6 years. This method can be easily implemented in routine vaccinations to improve patient comfort.

Japan Registry of Clinical Trials, jRCTs052200149, Mar 09, 2021, https://jrct.niph.go.jp/en-latest-detail/jRCTs052200149.

To determine the effect of immersive virtual reality (VR) on perceived pain and fear in children during vaccination and parental satisfaction with the procedure.

Virtual reality can reduce the perception of pain by children but only three studies have analysed its use during vaccination to date; these had small sample sizes and imperfect methodological designs.

A randomised controlled clinical trial.

One hundred and sixty participants from the Tres Forques Health Center were randomly assigned to the intervention group (IG) (n = 82) in which distraction with immersive VR was used during the vaccination, while standard distraction techniques were used for the control group (n = 80). The primary outcome was pain (Wong-Baker FACES). Secondary outcomes included (Children's Fear Scale) and parental satisfaction with the vaccination procedure. Chi-squared tests were used for qualitative variables, relationships between quantitative variables were tested with Spearman correlations, and Mann-Whitney U- or Student t-tests were employed to assess the relationship between quantitative and qualitative variables.

Compared to the controls, the children in the IG reported significantly less pain and fear, while parental satisfaction was significantly higher. Reported pain and fear did not differ according to the sex of the patient. Child age was not linked to fear but was related to pain: the younger the patient, the greater the pain they described.

Immersive VR effectively controlled pain and fear in children during vaccination and increased parent satisfaction with the vaccination process. Patient sex did not influence the level of pain and fear but age did.

Improving vaccination experiences can reduce perceived pain and fear in children and increase parent satisfaction, thereby enhancing vaccination schedule adherence and improving group immunity.

The CONSORT Statement for non-pharmacological randomised clinical trials were followed.

Availability of caregiver-administered nasal spray live attenuated influenza vaccine (LAIV) raises the potential for increased influenza vaccine uptake. Direct and indirect benefits (decreased influenza cases and hospitalizations) of increased uptake among school-age children may be realized across the age spectrum. We used an agent-based model to determine the extent to which increased vaccination of children might affect overall influenza epidemiology.

The Framework for Reproducing Epidemiological Dynamics (FRED) uses a population based on the US census and accounts for individual characteristics to estimate the effect of changes in parameters including vaccine uptake, on outcomes. We modeled increases in vaccine uptake among school-age children 5-17 years old on influenza cases and hospitalizations by age group.

Increasing vaccination rates in school-aged children by 5%-15% decreased their symptomatic influenza cases by 3.2%-10.9%, and among all age groups by 3.3%-11.6%, corresponding to an estimated annual reduction in cases of 522,867-1,810,170 among school-age children and of 1,394,687-4,945,952 overall. Annual U.S. hospitalizations could decrease by as much as 49,977, with the greatest impact (23,258) in those ages 65 years and over.

The opportunity to increase vaccination coverage in school-age children using LAIV can have a positive impact across all ages.

This study aimed to evaluate the effectiveness of an intervention that involved interactions within a simulated health care space to reduce medical fear among children in infant classes.

An experimental study involving 86 children divided into an intervention group and a control group with pre- and postintervention measurements was undertaken. The intervention, known as the Health-Friendly Program, consisted of showing children various scenarios that simulated different medical contexts so that they could interact in them, experiment with the materials and ask questions. Medical fear was evaluated using the Spanish version of the revised "Child Medical Fear Scale", which provides a score of the medical fear level ranging between 0 and 34 points. The pretest and posttest levels of medical fear in the intervention and control groups were compared with Student's t test.

The children in the intervention group experienced a significant reduction in fear by 3.21 points (SD: 6.50) compared to the children in the control group. This reduction in fear was shown in all four dimensions of the scale: intrapersonal fears, procedural fears, environmental fears and interpersonal fears.

The Health-Friendly Program provides an innovative intervention to reduce medical fear among children based on information, confrontation strategies and simulation scenarios. This study suggests the potential benefit of incorporating educational interventions in schools in collaboration with university and health care simulation centers.

To evaluate the safety and immunogenicity of adenovirus type 5 vectored COVID-19 vaccine (Ad5-nCoV), by intradermal immunization with a needle-free injector in rats.

This study was divided into two parts. In study A, 105 rats were randomly assigned to seven groups, to receive the low-dose, medium-dose, or high-dose vaccine by needle-free intradermal injections (NFI), or needle-based intramuscular injections (NI), or needle-free intradermal injections with saline solution as a control group. Blood samples were collected on day 0 before vaccination, and day 7, day 14, day 21 and day 28 after vaccination. Binding antibody, pseudovirus neutralizing antibody as well as cellular immune response were measured. The safety endpoints included weight changes and skin reactions. In study B, 32 rats were randomly assigned to four groups to receive low-dose, or medium-dose vaccine by NFI or NI, to observe pathological changes at the injection site following immunization.

No safety concern was noted associated with NFI of Ad5-nCoV. Comparable levels of neutralizing antibodies against various variants induced by NFI compared to NI at the same dosage.

The NFI immunization would be considered as an alternative immunization method to replace the traditional NI for the Ad5-nCoV.

Vaccination represents a critical preventive strategy in the current global healthcare system, serving as an indispensable intervention against diverse pathogenic threats. Although conventional immunization relies predominantly on hypodermic needle-based administration, this method carries substantial limitations, including needle-associated fear, bloodborne pathogen transmission risks, occupational injuries among healthcare workers, waste management issues, and dependence on trained medical personnel. Microneedle technology has emerged as an innovative vaccine delivery system, offering convenient, effective, and minimally invasive administration. These microscale needle devices facilitate targeted antigen delivery to epidermal and dermal tissues, where abundant populations of antigen-presenting cells, specifically Langerhans and dermal dendritic cells, provide robust immunological responses. Multiple research groups have extensively investigated microneedle-based vaccination strategies. This transdermal delivery technique offers several advantages, notably circumventing cold-chain requirements and enabling self-administration. Numerous preclinical investigations and clinical trials have demonstrated the safety profile, immunogenicity, and patient acceptance of microneedle-mediated vaccine delivery across diverse immunization applications. This comprehensive review examines the fundamental aspects of microneedle-based immunization, including vaccination principles, transcutaneous immunization strategies, and microneedle-based transdermal delivery-including classifications, advantages, and barriers. Furthermore, this review addresses critical technical considerations, such as treatment efficacy, application methodologies, wear duration, dimensional optimization, manufacturing processes, regulatory frameworks, and sustainability considerations, followed by an analysis of the future perspective of this technology.

Needle procedures, such as vaccinations, blood draws, and intravenous cannulation, are the most frequent source of childhood pain, causing fear and reducing the uptake of medical procedures. Every child has the right to expect pain relief, and we have evidence-based tools to reduce needle procedure-related pain. Therefore, the lack of analgesic provision for needle pain is not justified. We argue that better informed and motivated healthcare professionals and families can advocate for appropriate pain relief in every child, every time.

Engaging communication campaigns are needed to educate our healthcare professionals. Evidence-based modalities such as topical anaesthesia, sucrose or breastfeeding, comfort positioning, and age-appropriate distractions should be available for every child during needle procedures. However, high-quality information is not enough to change behaviour-healthcare professionals need to be motivated, encouraged, and inspired. Parents and carers should be empowered to advocate for their children and be aware that their child has the right to receive pain relief during these procedures. CONCLUSIONS AND RELEVANCE: This is a call to action-we need collaboration between academics, healthcare professionals, industry and charities, to expedite behavioural change and parental advocacy through high-quality communication strategies. Effective pain management in infants and children can play a crucial role in promoting the uptake of vaccinations and medical procedures and can influence future attitudes to pain.

The user of a pediatric drug includes not only the patient, but also their caregiver and healthcare provider, including nurses, doctors, and pharmacists. Therefore, adopting a patient-centric approach that focuses on all users is critical for the development of pediatric drug products. This article outlines the quality target product profile parameters and a patient-centric approach for the development of pediatric protein-based therapies. The use environment, formulation design, and preparation and in use stability considerations are described. An acceptability profile for the various routes of parenteral administration is described with a focus on pediatric age groups. Furthermore, a risk assessment approach is presented for the selection of excipients to be utilized in pediatric protein-based biopharmaceuticals. Several case studies are included which illustrate the selection of drug product parameters such as formulation, dose volume, and route of administration with the pediatric user in mind.

Bacterial skin diseases are a category of inflammatory skin conditions caused by bacterial infections, which impose a significant global disease burden. However, they have not been well assessed or predicted on a global scale. It is necessary to update the estimates and forecast future trends of the global burden of bacterial skin diseases to evaluate the impact of past healthcare policies and to provide guidance and information for new national and international healthcare strategies. We aimed to describe the burden and trend of bacterial skin diseases and to predict the burden up to 2045. To achieve this, we employed a cross-sectional analysis based on Global Burden of Disease (GBD) data, utilizing advanced statistical models to quantify trends and forecast future burdens. Data on incidence and disability-adjusted life years (DALYs) of bacterial skin diseases were obtained from Global Burden of Disease 2021. We used average annual percent change (AAPC) by Joinpoint Regression to quantify the temporal trends. We conducted decomposition analysis to understand the contribution of aging, epidemiological changes, and population growth. Bayesian Age-Period-Cohort model was used to predict burden up to 2045. Global incidence rate of bacterial skin diseases increased from 8,988.74 per 100,000 in 1990 to 10,823.88 per 100,000, with AAPC of 0.62% (0.61 ~ 0.63%). The highest incidence rate was in low Socio-demographic Index (SDI) region and population aged < 35. The DALYs rate increased from 20.82 per 100,000 in 1990 to 25.45 per 100,000 in 2021, with AAPC of -0.11% (-0.34 ~ 0.13%). The highest increase of DALYs was in high SDI region and population aged > 85. Among the three evaluated factors of decomposition analysis, the major drivers of incident case rise were population growth, followed by epidemiological changes; the major drivers of DALYs case rise were population growth, followed by aging. The number of incidence cases has increased since 1990, reaching nearly 90 million in 2021 and expected to hit 1.2 billion in 2045. The incidence rate has also risen. Meanwhile, DALYs showed an upward trend from 1990 to 2005, peaking at 32/100,000, then a downward trend. Our findings align with our initial objectives, demonstrating a significant increase in the global incidence of bacterial skin diseases and highlighting the need for targeted prevention and treatment strategies. The variation in burden across different regions and age groups underscores the importance of tailored public health interventions. Predictive models suggest a continued rise in incidence rates and incident cases through 2045, emphasizing the urgency for action. This study provides a foundation for future research and policy development aimed at reducing the burden of bacterial skin diseases worldwide.

The use of a rapid, easy-to-use intervention could improve needle-related procedural pain management practices in the context of the Emergency Department (ED). As such, the Buzzy device seems to be a promising alternative to topical anesthetics. The aim of this study was to determine if a cold vibrating device was non-inferior to a topical anesthetic cream for pain management in children undergoing needle-related procedures in the ED. In this randomized controlled non-inferiority trial, we enrolled children between 4 and 17 years presenting to the ED and requiring a needle-related procedure. Participants were randomly assigned to either the cold vibrating device or topical anesthetic (4% liposomal lidocaine; standard of care). The primary outcome was the mean difference (MD) in adjusted procedural pain intensity on the 0-10 Color Analogue Scale (CAS), using a non-inferiority margin of 0.70. A total of 352 participants were randomized (cold vibration device n = 176, topical anesthetic cream n = 176). Adjusted procedural pain scores' MD between groups was 0.56 (95% CI:-0.08-1.20) on the CAS, showing that the cold vibrating device was not considered non-inferior to topical anesthetic. The cold vibrating device was not considered non-inferior to the topical anesthetic cream for pain management in children during a needle-related procedure in the ED. As topical anesthetic creams require an application time of 30 min, cost approximately CAD $40.00 per tube, are underused in the ED setting, the cold vibrating device remains a promising alternative as it is a rapid, easy-to-use, and reusable device.

In late 2022, China became the first country to roll out mucosal COVID-19 vaccines. No prior study has yet compared the immunization stress-related responses (ISRR) among different routes of COVID-19 vaccine delivery. We aimed to compare the immunization-related psychological stress and ISRR between mucosal and intramuscular COVID-19 vaccines.

A cross-sectional questionnaire survey using a biopsychosocial framework design was performed from January 11 to 20, 2023. Adults with COVID-19 vaccination were eligible for the study, and a total of 1073 adults participated with community-based sample. Primary outcomes were the psychological stress levels and prevalence of ISRR. Multivariate regression models were employed to compare these outcomes between the two vaccination groups. The potential mediating effects of stress on vaccination and ISRR were examined using bootstrap sampling method. To further ensure the robustness of our results, sensitivity analysis with propensity score matching was performed.

In the univariate analysis, participants who received mucosal vaccination reported significantly lower stress levels compared to those who received intramuscular vaccination (3.39 ± 3.02 vs. 3.93 ± 3.24, P = .006). The prevalence of overall ISRR was significantly lower in the mucosal group compared to the intramuscular group (38.4% vs. 47.9%, P = .002). Multivariate regression models revealed that participants who received mucosal vaccination had a significantly lower stress level (β = -0.516, 95% CI: -0.852 to -0.180; P = .003) and 38.7% fewer overall ISRR (OR = 0.613, 95% CI: 0.427 to 0.881; P = .008), particularly in terms of neurological symptoms. The immunization-related stress mediated the association between vaccination type and ISRR, with indirect effects estimated at 0.0663 (95% CI: 0.0195 to 0.1346) for overall ISRR.

Mucosal COVID-19 vaccination was associated with reduced psychological stress and physical responses, as compared to intramuscular vaccination, which may contribute to increased trust and compliance with routine or mass vaccination efforts in the future.

To evaluate the effectiveness of Eutectic Mixture of Local Anesthetic (EMLA), a topical anesthetic cream, in office-based invasive andrological procedures such as hydrocelectomy, spermatocelectomy, and others, aimed at minimizing pain perception and enhancing the overall patient experience.

A double-blinded randomized controlled trial was conducted for patients undergoing scrotal andrology surgeries under LA. Power calculation was performed with an estimated sample size of 72. Participants were randomly assigned in a 1:1 ratio to topical EMLA + LA versus LA alone. In the post-operative recovery area, patient will be asked to complete a VAS questionnaire rating pain with LA administration and pain with procedure. Analysis comparing VAS pain scores of both groups was performed using the independent sample t-test method.

Seventy-two patients were included in our analysis, with 36 in the control and 36 in the intervention arm. For patient pain with administration of LA, the control arm reported an average VAS pain score of 4.31, compared to 3.72 in the intervention arm (P = .319). For patient pain with procedure, patients in the control arm reported a median VAS pain score of 3.47 compared to 3.03 (P = .432) in the intervention arm. Overall, 86% (62/72) of patients reported that they would either be "very likely" (4/5) or "highly likely" (5/5) to undergo future procedures under local anesthetic.

While performing scrotal surgeries under LA appears to be well tolerated and a feasible option, the application of EMLA cream does not appear to significantly alter patient-reported outcomes.

Measles and rubella micro-array patches (MR-MAPs) are a promising innovation to address limitations of the current needle and syringe (N&S) presentation due to their single-dose presentation, ease of use, and improved thermostability. To direct and accelerate further research and interventions, an initial full value vaccine assessment (iFVVA) was initiated prior to MR-MAPs entering phase I trials to quantify their value and identify key data gaps and challenges. The iFVVA utilized a mixed-methods approach with rapid assessment of literature, stakeholder interviews and surveys, and quantitative data analyses to (i) assess global need for improved MR vaccines and how MR-MAPs could address MR problem statements; (ii) estimate costs and benefits of MR-MAPs; (iii) identify the best pathway from development to delivery; and (iv) identify outstanding areas of need where stakeholder intervention can be helpful. These analyses found that if MR-MAPs are broadly deployed, they can potentially reach an additional 80 million children compared to the N&S presentation between 2030-2040. MR-MAPs can avert up to 37 million measles cases, 400,000 measles deaths, and 26 million disability-adjusted life years (DALYs). MR-MAPs with the most optimal product characteristics of low price, controlled temperature chain (CTC) properties, and small cold chain volumes were shown to be cost saving for routine immunization (RI) in low- and middle-income countries (LMICs) compared to N&S. Uncertainties about price and future vaccine coverage impact the potential cost-effectiveness of introducing MR-MAPs in LMICs, indicating that it could be cost-effective in 16-81% of LMICs. Furthermore, this iFVVA highlighted the importance of upfront donor investment in manufacturing set-up and clinical studies and the critical influence of an appropriate price to ensure country and manufacturer financial sustainability. To ensure that MR-MAPs achieve the greatest public health benefit, MAP developers, vaccine manufacturers, donors, financiers, and policy- and decision-makers will need close collaboration and open communications.

Routine vaccination procedures, while crucial for public health, can induce pain, fear, and anxiety in children. Distraction techniques such as virtual reality and kaleidoscope have been proposed to alleviate these negative experiences during vaccinations.

This study aimed to compare the effectiveness of virtual reality and kaleidoscope as distraction methods in reducing pain, fear, and anxiety during routine vaccination in children aged 48 months.

This randomized controlled trial allocated children aged 48 months receiving the measles-mumps-rubella vaccine into three groups: virtual reality (n = 42), kaleidoscope (n = 42), and control (n = 42).

The study was conducted in a pediatric clinic.

The study included a total of 126 children aged 48 months.

Pain and fear levels were assessed by both researchers and children before and after the vaccination procedure, while anxiety was evaluated by children after vaccination. Pain was measured using the Wong Baker Faces Pain Rating Scale, fear with the Children's Fear Scale, and anxiety with the Child Anxiety Scale-State Version.

Post-vaccination pain, fear, and anxiety scores were significantly lower in the kaleidoscope group compared to both the virtual reality and control groups (p < .05).

Using kaleidoscope during vaccination in 48-month-old children effectively reduced pain, fear, and anxiety. Integrating kaleidoscope as a distraction method during routine vaccination procedures may enhance the vaccination experience and potentially improve adherence to vaccination schedules.

Clinical trials number is NCT0611XXXX.

(1) Background: Acute pain in hospitalized children remains under-recognized and under-treated. Our objective is to benchmark pain assessment, documentation, treatment, and patient experience in children admitted to a US children's hospital. (2) Methods: A cross-sectional, mixed-method survey of pain for children hospitalized ≥24 h. Charts were reviewed for modalities of pain assessment and treatment for all inpatients. If pain was documented, patients/caregivers were surveyed regarding their experience with pain and its management. (3) Results: Chart review: All 107 patients had ≥1 pain score documented. A total of 47 patients had a pain score ≥0, 35 (74.5%) of whom had ≥1 moderate-severe score. Seventy (65.4%) patients received ≥1 intervention for pain, including medications from ≥1 class (e.g., opioids) (n = 55, 51.4%) and/or integrative/non-pharmacologic intervention(s) (n = 39, 36.4%). There were assessment and documentation gaps. Patient survey: A total of 39 (83.0%) interviews were attempted; 25 (53.2%) were completed. The worst pain was mostly caused by acute illness (n = 13, 52%) and painful procedures (n = 10, 40%). Suggestions for improvement included increasing the use of integrative modalities and optimizing patient-clinician communication. (4) Conclusions: All patients admitted ≥24 h had ≥1 pain score documented; however, gaps in documentation were common. Multimodal treatment and integrative modalities were underutilized. Procedures were a frequent cause of under-treated pain, prompting an institution-wide quality improvement project.

Immunisation is a global health priority, but methods of non-pharmacological pain relief are not widely used in routine clinical practice. In this study, we set out to investigate the effects of maternal singing during the routine vaccination of infants.

We recruited 67 mother-infant pairs at Health Centres in the Aosta Region of Italy. Infants aged 2-4 months were randomly allocated to a singing intervention group or to a control group whose injections were administered following standard practice. Pre- and post-immunisation pain was blindly assessed using the Modified Behavioural Pain Scale, and mother-infant proximity indexes were assigned based on muted video-tracks.

When assessed for pain, the infants in the maternal singing group were assigned significantly lower movement indexes (p = 0.032) and marginally significantly lower cry indexes (p = 0.076). A higher frequency of mother-to-infant gaze (p < 0.005) was observed in the singing group dyads. Finally, the intervention group mothers' self-perceived ease in singing was correlated with their previous singing experience and with lower anxiety following the vaccination procedure (p < 0.05).

Maternal singing during immunisation procedures benefits both mothers and babies. The practice of singing is a biologically rooted and adaptive form of intuitive parental communication that should be encouraged, especially in at-risk populations.

Recent research has explored the effectiveness of interactive virtual experiences in managing pain and anxiety in children during routine medical procedures, compared to conventional care methods. However, the influence of the specific technology used as an interface, 3-dimensions (D) immersive virtual reality (VR) vs. 2D touch screens, during pediatric venipuncture, remains unexamined. This study aimed to determine if immersive VR is more effective than a tablet in reducing pain and anxiety during short procedures.

An interactive game was designed by clinicians and psychologists, expert in pain theory, hypnosis, and procedural pain and anxiety relief, and was tailored for both VR and tablet use. Fifty patients were randomly assigned to either the Tablet or VR group. The primary outcome measures were pain and anxiety levels during the procedure. Secondary outcome measures included the need for physical restraint, duration of the procedure, enjoyment levels, and satisfaction ratings from both parents and nurses.

Participants, in both groups, had low levels of pain and anxiety. Physical restraint was infrequently used, procedures were brief, and high satisfaction levels were reported by patients, parents, and nurses.

This study suggests that the type of technology used as a support for the game has a minimal effect on the child's experience, with both groups reporting low pain and anxiety levels, minimal physical restraint, and high enjoyment. Despite immersive VR's technological advancements, this study underscores the value of traditional tablets with well-designed interactive games in enhancing children's wellbeing during medical procedures.

[ClinicalTrials.gov], identifier [NCT05065307].

Fear of needles is a common phenomenon that can affect the patient's ability to function and to seek medical help. Novel treatment practices are needed to help children cope with this fear. Based on user feedback, immersive virtual reality applications are effective when distracting the patient during a painful procedure. Better understanding of how virtual reality solutions affect the autonomic nervous system should be acquired. We present the case of a 12-year-old boy attending our study examining a novel virtual reality (VR) relaxation method (VirNE). The clinical study aims to determine if pain and anxiety can be relieved by relaxation that has been induced by a virtual natural environment and guided relaxation exercise-mediated autonomic nervous system stimulation. The patient was able to overcome his fear of needles with the help of the guided relaxation and found significant relief from the distress he was experiencing on his monthly visits to the hospital due to his long-term illness requiring repetitious intravenous cannulations.

Many evidence-based tools exist to address pain and distress associated with injections; however, there remains a large gap between the knowledge of these tools and their utilization. Our hospital began a quality improvement (QI) project prior to COVID-19, with the goal of increasing the utilization of Comfort Promise measures during needle procedures. When COVID-19 vaccinations were approved, our mass vaccination clinics provided an opportunity to rapidly increase utilization across the institution. The primary aim was to increase the percentage of comfort measures (CM) offered with COVID-19 vaccinations.

Through this QI project, nurses and other professionals implemented CMs during COVID mass vaccination clinics. Clinics occurred in 3 age-based waves. Waves served as Plan-Do-Study-Act (PDSA) cycles. Families completed post-vaccination surveys to determine what CMs were offered and intention for future use with vaccinations.

Uptake of CMs (PainEase, ShotBlockers, Comfort Positioning, Alternative Focus, Topical Lidocaine, and Breastfeeding/Sucrose) throughout the waves increased and generally remained stable. CMs also seemed to decrease pain/distress with vaccinations (70.5 to 88.7%), and children/caregivers intended to use some combination for future vaccinations (82.5 to 98.5%).

Fast-paced mass vaccination clinics provided an ideal opportunity to significantly increase utilization of CMs. Across age groups CMs yielded high satisfaction and interest in future utilization. Clinic nurses returned to their own sub-specialties and became change agents.

If all healthcare providers can work together to achieve consensus while incorporating comfort measures into daily practice, sustained change with incorporation of these evidence-based tools can be achieved. Future directions are discussed.

The goal of this longitudinal study was to reduce anxiety and pain in children with chronic conditions from the gastrointestinal tract during venipuncture. These children undergo regular venipuncture as part of their medical management and the procedure is often accompanied with anxiety and pain. In addition, children as well as their parents and health care professionals (HCPs) often suffer "compassionate pain" because of emotional interference.

In a realistic clinical setting, different psychological and medical interventions were examined: (1) Psychoeducational brochures and (2) four different medical-technical interventions during venipuncture. In a large hospital in Germany, 169 children, their parents, and HCPs were asked to rate anxiety and pain during venipuncture before and after the intervention.

Children showed a clear preference for some of the medical-technical interventions. Using Linear Mixed Models anxiety and pain rated by the children themselves showed no significant reduction. However, parents and HCPs reported a significant reduction. Age, gender, and status of liver transplantation were associated with a reduction in anxiety and pain in most of the analyses.

Both psychoeducational brochures and medical-technical interventions had a positive impact on anxiety and pain. However, effectivity for the medical-technical interventions was lower than in previous studies utilizing individual interventions. Reasons for this difference as well as possibilities to improve the intervention are discussed. In addition, this study provides practical day-to-day information about the implementation of interventions for the work in pediatric units such as when and how to provide psychoeducational materials.

The use of cancer immunotherapeutics is currently increasing. Cancer vaccines, as a form of immunotherapy, are gaining much attention in the medical community since specific tumor-antigens can activate immune cells to induce an anti-tumor immune response. However, the delivery of cancer vaccines presents many issues for research scientists when designing cancer treatments and requires further investigation. Nanoparticles, synthetic liposomes, bacterial vectors, viral particles, and mammalian exosomes have delivered cancer vaccines. In contrast, the use of many of these nanotechnologies produces many issues of cytotoxicity, immunogenicity, and rapid clearance by the mononuclear phagocyte system (MPS). Plant-exosome-like nanovesicles (PELNVs) can provide solutions for many of these challenges because they are innocuous and nonimmunogenic when delivering nanomedicines. Hence, this review will describe the potential use of PELNVs to deliver cancer vaccines. In this review, different approaches of cancer vaccine delivery will be detailed, the mechanism of oral vaccination for delivering cancer vaccines will be described, and the review will discuss the use of PELNVs as improved drug delivery systems for cancer vaccines via oral administration while also addressing the subsequent challenges for advancing their usage into the clinical setting.

Pain transcends simple physiology, encompassing biological, emotional, psychological, and social facets. Children show pronounced immediate and enduring responses to pain-related procedures. The aim of this meta-analysis is to investigate the efficacy and safety of the Buzzy device for needle-related procedures in children aged twelve years or younger.

PubMed, Web of Science, and Embase were searched from inception to July 2023. Only randomized controlled trials utilizing the Buzzy device for needle-related procedures in children under twelve years old were included. Two reviewers independently conducted study selection, data extraction, and risk of bias assessment. Random-effects models were utilized, and analyses were performed using mean differences or standardized mean differences as well as risk ratios.

A total of 19 studies were included, involving 2846 participants (Buzzy = 1095, Control = 1751). Compared to no intervention, the Buzzy device significantly reduced pain response [self-report SMD = -1.90 (-2.45, -1.36), parental SMD = -3.04 (-4.09, -1.99), observer SMD = -2.88 (-3.75, -2.02)] and anxiety scores [self-report SMD = -1.97 (-3.05, -0.88), parental SMD = -2.01 (-2.93, -1.08), observer SMD = -1.92 (-2.64, -1.19)]. Compared to virtual reality (VR), the Buzzy device reduced self-reported anxiety levels SMD = -0.47 (-0.77, -0.17), and compared to distraction cards, the Buzzy device reduced parental and observer-reported pain [parental SMD = -0.85 (-1.22, -0.48), observer SMD = -0.70 (-1.00, -0.40)] and anxiety [parental SMD = -0.96 (-1.46, -0.47), observer SMD = -0.91 (-1.40, -0.42)]. Subgroup analysis results showed that procedure type, patient age, measurement scales used, and distance of operation were not the reason of heterogeneity. The summarized first puncture attempt success rate did not differ from other interventions. There were no significant adverse events in the included studies.

The Buzzy device reduces pain and anxiety in children during needle procedures, ensuring success and safety. Additionally, the effectiveness of the Buzzy device in reducing pain during venipuncture is superior when compared to its effectiveness during intramuscular injections.

Previous studies have demonstrated that Buzzy® is effective for pain reduction during vaccination. This study aimed to determine if Buzzy® would have an effect on either duration of vaccine administration and/or patient satisfaction. Pediatric patients aged birth to 18 years old receiving a vaccination were randomized to either a control group receiving no intervention, or the experimental group, utilizing Buzzy®. Time of administration was measured by the number of seconds required by nursing to administer vaccines. Patient satisfaction was measured with a survey given to guardians. Time required was reduced by almost 2 min when utilizing Buzzy®, with median time dropping to 190, 95% CI [26.99, 415.92] seconds from 333, 95% CI [51.35, 627.21] seconds. Patient satisfaction surveys showed positive impacts of using the device, with 100% that used the device reporting that it "made a difference in the pain level experienced," but did not demonstrate statistical significance. This study shows that use of Buzzy® increases efficiency of appointments with possible positive effect on patient satisfaction.

Successful oral delivery of liposomes requires formulations designed to withstand harsh gastrointestinal conditions, e.g., by converting to solid-state followed by loading into gastro-resistant delivery devices. The hypothesis was that the use of dextran-trehalose mixtures for spray drying would improve the rehydration kinetics of dried liposomes. The objectives were to determine the protective capacity of trehalose-dextran dehydration precursors and to increase the concentration of liposomes in the dry formulation volume. The study successfully demonstrated that 8.5% dextran combined with 76.5% trehalose protected CAF®04 liposomes during drying, with the liposome content maintained at 15% of the dry powder. Accordingly, the rehydration kinetics were slightly improved in formulations containing up to 8.5% dextran in the dry powder volume. Additionally, a 2.4-fold increase in lipid concentration (3 mM vs 7.245 mM) was achieved for spray dried CAF®04 liposomes. Ultimately, this study demonstrates the significance of trehalose as a primary carrier during spray drying of CAF®04 liposomes and highlights the advantage of incorporating small amounts of dextran to tune rehydration kinetics of spray-dried liposomes.

This qualitative study describes the development and evaluation of a clinical pathway to facilitate the implementation of catch-up vaccinations for children with significant needle fear, particularly in children with developmental disabilities. The Specialist Immunization Team, based at a tertiary level teaching children's hospital, participated in process mapping activities using Motivational Interviewing (MI) techniques and reflective discussions. Team members developed a clinical pathway by incorporating parental feedback from semistructured interviews and clinical expertise from within the team, facilitated by colleagues from the Child Development Unit. A process map was developed that included process strengths and touch points with an action plan that was discussed and agreed upon. A repeat process mapping activity was conducted 16 months later. Reports from parental feedback included: positive, efficient, and successful experiences of having their child undergo catch-up vaccinations. The experience empowered families for further procedures. Team members reported improvements in triaging appropriate children for the pathway, and an increase in confidence to interact and manage behaviors of children with significant anxiety and challenging behaviors. They also reported an increase in successful vaccinations with improved clinical judgment of facilitating the sedation pathway. This study demonstrates that using group facilitation using motivational interviewing in reflective discussions and process mapping utilizing parent and staff feedback in service improvement activities results in efficient and successful service delivery with improved patient outcomes.

Vaccines have saved countless lives by preventing and even irradicating infectious diseases. Commonly used subunit vaccines comprising one or multiple recombinant proteins isolated from a pathogen demonstrate a better safety profile than live or attenuated vaccines. However, the immunogenicity of these vaccines is weak, and therefore, subunit vaccines require a series of doses to achieve sufficient immunity against the pathogen. Here, we show that the biomimetic mineralization of the inert model antigen, ovalbumin (OVA), in zeolitic imidazolate framework-8 (ZIF-8) significantly improves the humoral immune response over three bolus doses of OVA (OVA 3×). Encapsulation of OVA in ZIF-8 (OVA@ZIF) demonstrated higher serum antibody titers against OVA than OVA 3×. OVA@ZIF vaccinated mice displayed higher populations of germinal center (GC) B cells and IgG1+ GC B cells as opposed to OVA 3×, indicative of class-switching recombination. We show that the mechanism of this phenomenon is at least partly owed to the metalloimmunological effects of the zinc metal as well as the sustained release of OVA from the ZIF-8 composite. The system acts as an antigen reservoir for antigen-presenting cells to traffic into the draining lymph node, enhancing the humoral response. Lastly, our model system OVA@ZIF is produced quickly at the gram scale in a laboratory setting, sufficient for up to 20 000 vaccine doses.

Vaccines are essential tools to prevent infection and control transmission of infectious diseases that threaten public health. Most infectious agents enter their hosts across mucosal surfaces, which make up key first lines of host defense against pathogens. Mucosal immune responses play critical roles in host immune defense to provide durable and better recall responses. Substantial attention has been focused on developing effective mucosal vaccines to elicit robust localized and systemic immune responses by administration via mucosal routes. Mucosal vaccines that elicit effective immune responses yield protection superior to parenterally delivered vaccines. Beyond their valuable immunogenicity, mucosal vaccines can be less expensive and easier to administer without a need for injection materials and more highly trained personnel. However, developing effective mucosal vaccines faces many challenges, and much effort has been directed at their development. In this article, we review the history of mucosal vaccine development and present an overview of mucosal compartment biology and the roles that mucosal immunity plays in defending against infection, knowledge that has helped inform mucosal vaccine development. We explore new progress in mucosal vaccine design and optimization and novel approaches created to improve the efficacy and safety of mucosal vaccines.

Studies from multiple countries report that most hospitalized children, especially the youngest and sickest, experience pain that is often severe yet inadequately treated. Evidence suggests this can lead to immediate and lifelong consequences affecting children, families, and communities. Partnership and shared decision-making by children, families, and clinicians is the ideal pediatric healthcare model and can improve care quality and safety, including pain care. A growing evidence base demonstrates that inpatient portals (electronic personal health record applications linked to hospital electronic medical or health records) can improve child and family engagement, outcomes, and satisfaction during hospitalization. This study examined the perspectives of caregivers of hospitalized children and of hospitalized youth about using an inpatient portal to support their engagement in pain care while in hospital. A qualitative descriptive study design was used and 20 participants (15 caregivers and 5 youth) with various painful conditions in one pediatric hospital participated in semistructured interviews. The authors applied a reflexive content analysis to the data and developed 3 broad categories: (1) connecting and sharing knowledge about pain, (2) user-centred designs, and (3) preserving roles. These findings outlined caregiver and youth recommendations for portal configurations that deeply engage and empower children and families in pain care through multidirectional knowledge sharing, supporting caregiver and clinicians' roles without burdening, or replacing human interaction implicit in family-centered pain care. Further research should measure the impact of portals on pain-related outcomes and explore the perspectives of clinicians.

This study investigated the effectiveness of trace image and coloring for kids-book (TICK-B), cough trick, and balloon inflation techniques in reducing pain and fear in children during venipuncture. The current study is a prospective, controlled, and randomized trial (RCT). School-aged children who required venipuncture were involved in the study. Pediatric patients were randomly assigned to four groups: the TICK-B group, the cough trick group, the inflation of balloons, and the control groups. Before and after the procedure, the children and their parents were interviewed. Wong-Baker (FACES) Pain Rating Scale was applied to measure the severity of pain. Children's Fear Scale was applied to measure children's fear. This study involved the 160 children (mean age, 8.39-2.18 years). The severity of pain and fear levels among the children during and after the procedure were significantly different (p = 0.001). Pain and fear were significantly decreased in children in the intervention groups compared with those in the control group (p < 0.05). In the TICK-B group, participants reported significantly less pain and fear during the venipuncture procedure than in the cough trick, balloon inflation, and control groups (P = 0.001, p = 0.001, p = 0.001) and after the procedure (p = 0.001, p = 0.002, p = 0.002). There was a similar significance found in the level of fear during the procedure (p = 0.001, p = 0.002, p = 0.006), and after the procedure (p = 0.001, p = 0.008, p = 0.015).    Conclusion: TICK-B was the most effective method for decreasing the pain and fear of children associated with venipuncture procedures. Furthermore, the distraction technique of coughing and inflating balloons also proved efficacious in decreasing the pain and fear of children during venipuncture.    Trial registration: The study has been registered with ClinicalTrials.org under the number NCT04983303. It was retrospectively registered on July 26, 2021. What is Known: • Venipuncture, one of the most painful and uncomfortable procedures for children, caused great fear and discomfort during the procedure. What is New: • The TICK-B technique, music listening, and cartoon watching techniques are effective, simple, and safe ways to reduce children's fear and pain. These interventions provide a good way for children and their parents to collaborate during painful medical procedures. • No studies have compared the impact of TICK-B during venipuncture.

Seasonal influenza remains a challenge in the United Arab Emirates, and vaccination is an important preventive measure. However, fear of needles may be an obstacle in vaccination efforts.

The purpose of this study was to determine, in a non-clinical sample obtained from the UAE, how much of an impact fear of needles has on the decision to receive the seasonal influenza vaccine.

In the period September-December 2022, 372 participants were surveyed on their willingness to be vaccinated, their level of vaccine knowledge, and their level of fear of needles. Logistic regression models were used to assess the impact of fear of needles and vaccine knowledge on the decision to accept the seasonal influenza vaccine.

Fear of needles and vaccine knowledge are significant predictors in the decision to receive the vaccine. There were no gender or ethnic differences in fear of needles, but there were differences in the decision to receive the vaccines, with women and non-Arabs being more hesitant.

Fear of needles may be an important variable to account for in public policies designed to improve vaccination rates in the UAE. For public health policy in the UAE, this implies that authorities must dedicate efforts to manage fear of needles in the general population. Efforts to address fear of vaccines in the general population must be made with proper training of nurses. Alternatively, authorities may need to seek oral alternatives for the administration of the seasonal influenza vaccine.

An individual with a blood-injection-injury (BII) phobia often avoids exposure to triggers, such as blood tests and clinic appointments, leading to potentially serious health complications. This population-based study examined the prevalence, stability and course of BII phobia in children and adolescents.

The data came from the Trondheim Early Secure Study, conducted from 2007 to 2018. All children born in Trondheim, Norway, in 2003 and 2004 were invited to attend. Clinical interviews were conducted by trained personnel to assess BII phobia in 1042 children (51% female) every 2 years from 4 to 14 years of age. Latent growth curves and logistic regression analyses were used in the data analysis.

Just under 20% of the cohort experienced a BII phobia at least once, with no significant sex differences. The prevalence of BII phobias increased from 3% at 4 years of age and peaked at about 8% at 10 years of age, before levelling off. The two-year stability increased as 12-14 years of age approached.

The prevalence of BII was affected by age, but not sex. Early BII phobias often recede with time, but children may need treatment if they persist from 8 years of age.

Keloids and hypertrophic scars can cause severe pain, pruritus, and psychological distress. Conventional intralesional corticosteroid treatment with needle injections remains challenging, especially in children with needle phobia.

We aimed to evaluate the effectiveness, tolerability, and patient satisfaction of intralesional treatment with triamcinolone acetonide using a needle-free electronic pneumatic jet injector in children with keloids and hypertrophic scars.

A retrospective study was performed in children with keloids and hypertrophic scars who received intralesional triamcinolone acetonide treatments using an electronic pneumatic jet injector. Effectiveness was evaluated using the Patient and Observer Scar Assessment Scale and Global Aesthetic Improvement Score at follow-up versus baseline. Tolerability was assessed with reported adverse effects and injection-related pain using a visual analog scale. Satisfaction questionnaires were used to evaluate treatment-related patient satisfaction.

Six female patients and five male patients aged 5-17 years, with a total of >118 keloids or hypertrophic scars were included. Electronic pneumatic jet injector treatment led to a significant reduction in the total Patient and Observer Scar Assessment Scale observer and patient scores compared with baseline, with a median reduction of 28.9% and 23.8%, respectively (p = 0.005; p = 0.009). Median visual analog scale pain scores for electronic pneumatic jet injector treatment were significantly lower compared with needle injections, 3.0 versus 7.0, respectively (p = 0.027). No severe adverse effects were reported. Overall, 6 patients were 'satisfied' and five patients were 'very satisfied' with the treatment.

Electronic pneumatic jet injector-assisted intralesional triamcinolone acetonide is an effective and well-tolerated treatment for keloids and hypertrophic scars in children. It should be considered as an alternative non-traumatic delivery method, especially in children with needle phobia or severe pain during previous needle injections.

Childhood immunisation is a critically important public health initiative. However, since most vaccines are administered by injection, it is associated with considerable pain and distress. Despite evidence demonstrating the efficacy of various pain management strategies, the frequency with which these are used during routine infant vaccinations in UK practice is unknown.

This study aimed to explore primary care practice nurses' (PNs) use of evidence-based pain management strategies during infant immunisation, as well as barriers to evidence-based practice.

A questionnaire was developed and distributed to nurses throughout the UK via convenience sampling in paper and online formats. Questions assessed the frequency of pain management intervention use during infant immunisation and barriers to their use.

A total of 255 questionnaire responses were received. Over 90% (n = 226) of respondents never used topical anaesthetics or sweet solutions during immunisations, while 41.9% advised breastfeeding occasionally (n = 103). Parent-/caregiver-led distraction was the most frequently used intervention, with most nurses using it occasionally (47.9%, n = 116) or often (30.6%, n = 74). Most practices had no immunisation pain management policy (81.1%, n = 184), and most PNs' previous training had not included pain management (86.9%, n = 186). Barriers to intervention use included lack of time, knowledge and resources. Excluding distraction, pain management strategies were infrequently or never used during infant immunisation. Key barriers to using evidence-based strategies were lack of time, knowledge and resources.

Invasive medical procedures in hospitals are major sources of stress in children, causing pain and fear. Non-pharmacological interventions are indispensable in effective pain and fear management. However, these interventions must be personalized to be effective. This qualitative study aims to gain insight into children's and parents' experiences, needs, and wishes related to supporting children to develop and express their coping preferences for dealing with pain and fear during minor invasive medical procedures in order to decrease pain and fear. A qualitative study using thematic analysis was performed. Data were collected through semi-structured interviews with children and parents who had undergone at least five minor invasive medical procedures in the last year. Nineteen children (8-18 years) and fourteen parents were interviewed individually. The experiences, needs, and wishes expressed in the interviews could be classified into one overarching theme, that of the personal process, and two content-related sub-themes: feeling trust and gaining control. The personal process was divided into two different phases, that of developing and of expressing coping preferences. Children and parents both reported it as a continuous process, different for every child, with their own unique needs. Children and parents expected personalized attention and tailored support from professionals.     Conclusion: Professionals must combine clinical skills with child-tailored care. In the process of searching for and communicating about coping preferences, children's unique needs and personal boundaries will thereby be respected. This gives children and parents increased trust and control during invasive medical procedures. What is Known: • Untreated pain and stress caused by medical procedures can have severe and important short- and long-term consequences for children. Personalized non-pharmacological interventions are an essential element of procedural pain management. What is New: • A personalized coping strategy is important for children when undergoing medical procedures. Each individual child has a personal way of expressing their own coping strategy. Children and their parents need information and the space to develop and express their individual coping preferences. • Children and parents expect to receive child-tailored care from professionals including respect for their own, unique needs and boundaries. Professionals should build trustful relationships and provide appropriately tailored autonomy around medical procedures.

College student populations are considered at greater risk of contracting influenza due to their close living conditions. Despite this increased risk, college students are reluctant to obtain annual vaccination. This pilot study sought to determine perceptions of students on a college campus who received the annual influenza vaccination via an intradermal route. Participants and methods: Forty-nine college students participated in the IRB approved study. After receiving the intradermal influenza vaccination, participants completed a demographic survey and vaccination perceptions questionnaire. Results: Participants were more likely to want to have an intradermal injection in the future and reported less pain with the intradermal injection. Additionally, individuals who reported greater pain with the intramuscular injection in the past were significantly more likely to want to receive an intradermal injection in the future (p < 0.019). Conclusions: Results suggest that intradermal route of vaccination may be more appealing to the college population.

The effects of the COVID-19 pandemic has been felt by all groups in society and people with intellectual disability are especially vulnerable due to underlying conditions/health problems, multi-morbidity, limitations in understanding, frailty and social circumstances. This places people with intellectual disability, their families and carers at increased risk of stress and in need of support.

To update and chart the evidence of the effects of the COVID-19 pandemic on people with intellectual disability, their families and carers reported within the research in 2021.

A scoping review of research published in 2021 across 7 databases.

84 studies met the inclusion criteria, and the findings highlight people with intellectual disability are at a greater risk to COVID-19 health outcomes due to underlying health concerns and access issues. The effects of COVID-19 can be seen from a personal, social and health perspective for people with intellectual disability, their carers and families. However, COVID-19 did have some unanticipated benefits such as: less demand on time, greater opportunity to engage with people of value and building resilience.

COVID-19 presents many challenges but for people with intellectual disability compounding existing obstacles encountered in access issues, service provision and supports available. There is a need to identify and describe the experiences of people with intellectual disability, their families and carers in the medium-long term during COVID-19. Greater supports and evidence of effective interventions to promote health, deliver services and support individual with intellectual disability is needed as there is little evidence of clinical care for people with intellectual disability during COVID-19.

Conventional injectable glucagon (IG) and nasal glucagon (NG), both having similar efficacy, are two options for the emergency treatment of severe hypoglycemia in Spain. This study elicited the effect of changes in key attributes on preferences for NG and IG medication profiles of people with diabetes and caregivers in Spain.

The relative attribute importance (RAI) that participants placed on glucagon preparation, preparation and administration time, delivery method, recovery time, device size, storage temperature, and headache risk was estimated from an online discrete choice experiment. In addition, patients and caregivers were presented with NG and IG profiles that included rates of successful administration; the proportion of participants choosing each profile was summarized.

The analysis included 276 adults with diabetes (65% type 1) and 270 caregivers (49% type 1). Overall mean age was 40 years; 51% were female. The most important attributes were storage temperature (RAI [95% confidence interval] = 27.3% [22.9-32.2]) and delivery method (17.4% [13.1-21.9]). Headache risk (16.2% [11.8-20.7]), time to prepare and administer (14.5% [10.1-18.8]), glucagon preparation (11.4% [6.8-15.8]), recovery time (8.9% [4.3-13.3]), and device size (4.3% [0.3-8.8]) were also relevant. When comparing medication profiles, significantly more participants (78%) preferred NG over IG profiles (P < .001).

Adults with diabetes and caregivers prefer a glucagon treatment with a higher rate of successful administration, wider storage temperature, and nasal delivery method, when efficacy is similar. Participants favored NG over conventional IG as a rescue medication for severe hypoglycemia. This information may help decision-making by payers and treatment discussions between health care professionals and patients.

Children continue to experience harm when undergoing clinical procedures despite increased evidence of the need to improve the provision of child-centred care. The international ISupport collaboration aimed to develop standards to outline and explain good procedural practice and the rights of children within the context of a clinical procedure. The rights-based standards for children undergoing tests, treatments, investigations, examinations and interventions were developed using an iterative, multi-phased, multi-method and multi-stakeholder consensus building approach. This consensus approach used a range of online and face to face methods across three phases to ensure ongoing engagement with multiple stakeholders. The views and perspectives of 203 children and young people, 78 parents and 418 multi-disciplinary professionals gathered over a two year period (2020-2022) informed the development of international rights-based standards for the care of children having tests, treatments, examinations and interventions. The standards are the first to reach international multi-stakeholder consensus on definitions of supportive and restraining holds.    Conclusion: This is the first study of its kind which outlines international rights-based procedural care standards from multi-stakeholder perspectives. The standards offer health professionals and educators clear evidence-based tools to support discussions and practice changes to challenge prevailing assumptions about holding or restraining children and instead encourage a focus on the interests and rights of the child. What is Known: • Children continue to experience short and long-term harm when undergoing clinical procedures despite increased evidence of the need to improve the provision of child-centred care. • Professionals report uncertainty and tensions in applying evidence-based practice to children's procedural care. What is New: • This is the first study of its kind which has developed international rights-based procedural care standards from multi-stakeholder perspectives. • The standards are the first to reach international multi-stakeholder consensus on definitions of supportive and restraining holds.