Selinexor for the treatment of recurrent or metastatic salivary gland tumors: Results from the GEMS-001 clinical trial.

OBJECTIVES: We aimed to evaluate the activity of selinexor, an oral selective inhibitor of nuclear export, in patients with recurrent or metastatic salivary gland tumors (SGT). METHODS: GEMS-001 is an open-label Phase 2 study for patients with recurrent or metastatic SGT with two parts. In Part 1 of the protocol, patients had tumor samples profiled with targeted next generation sequencing as well as immunohistochemistry for androgen receptor, HER-2 and ALK. For Part 2, patients with no targeted therapies available were eligible to receive selinexor 60 mg given twice weekly every 28 days. The primary endpoint was objective response rate. Secondary endpoints included progression-free survival (PFS) and prevalence of druggable alterations across SGT. RESULTS: One hundred patients were enrolled in GEMS-001 and underwent genomic and immunohistochemistry profiling. A total of 21 patients who lacked available matched therapies were treated with selinexor. SGT subtypes (WHO classification) included adenoid cystic carcinoma (n = 10), salivary duct carcinoma (n = 3), acinic cell carcinoma (n = 2), myoepithelial carcinoma (n = 2), carcinoma ex pleomorphic adenoma (n = 2) and other (n = 2). Of 18 evaluable patients, stable disease (SD) was observed in 17 patients (94%) (SD ≥6 months in 7 patients (39%)). However, no objective responses were observed. The median PFS was 4.9 months (95% confidence interval, 3.4-10). The most common treatment-related Grade 1-2 adverse events were nausea [17 patients (81%)], fatigue [16 patients (76%)], and dysgeusia [12 patients (57%)]. Most common treatment-related Grade 3-4 adverse events were hyponatremia [3 patients (14%)], neutrophil count decrease [3 patients (14%)] and cataracts [2 patients (10%)]. No treatment-related deaths were observed. CONCLUSIONS: Although tumor reduction was observed across participants, single agent selinexor anti-tumor activity was limited.

Design and assessment of amblyopia, strabismus, and myopia treatment and vision training using virtual reality.

Background: Virtual reality is a relatively new intervention that has the potential to be used in the treatment of eye and vision problems. This article reviews the use of virtual reality-related interventions in amblyopia, strabismus, and myopia research. Methods: Sources covered in the review included 48 peer-reviewed research published between January 2000 and January 2023 from five electronic databases (ACM Digital Library, IEEE Xplore, PubMed, ScienceDirect and Web of Science). To prevent any missing relevant articles, the keywords, and terms used in the search included "VR", "virtual reality", "amblyopia", "strabismus," and "myopia". Quality assessment and data extraction were performed independently by two authors to form a narrative synthesis to summarize findings from the included research. Results: Total number of 48 references were reviewed. There were 31 studies published on amblyopia, 18 on strabismus, and 6 on myopia, with 7 studies overlapping amblyopia and strabismus. In terms of technology, smartphone-based virtual reality headset viewers were utilized more often in amblyopia research, but commercial standalone virtual reality headsets were used more frequently in myopia and strabismus-related research. The software and virtual environment were mostly developed based on vision therapy and dichoptic training paradigms. Conclusion: It has been suggested that virtual reality technology offers a potentially effective tool for amblyopia, strabismus, and myopia studies. Nonetheless, a variety of factors, especially the virtual environment and systems employed in the data presented, must be explored before determining whether virtual reality can be effectively applied in clinical settings. This review is significant as the technology in virtual reality software and application design features have been investigated and considered for future reference.

Differential Effects of the COVID-19 Pandemic on Physical Activity Involvements and Exercise Habits in People With and Without Chronic Diseases: A Systematic Review and Meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to summarize evidence regarding differential changes in physical activity (PA) involvements and exercise habits in people with and without chronic diseases during the COVID-19 outbreak. DATA SOURCES: MEDLINE, Embase, SPORTDiscus, Cumulative Index to Nursing and Allied Health, PsycINFO, Cochrane Library, and Physiotherapy Evidence Database were searched from November 2019 to May 2021. STUDY SELECTION: Two reviewers independently screened cross-sectional and longitudinal studies that investigated changes in PA-related outcomes in people with and without chronic diseases during the pandemic. DATA EXTRACTION: PA-related outcomes and sedentary time were extracted from the included studies. Relevant risk of bias were assessed. Meta-analyses were conducted for each PA-related outcome, if applicable. Quality of evidence of each PA-related outcome was evaluated by Grading of Recommendations Assessment, Development, and Evaluation. DATA SYNTHESIS: Of 1226 identified citations, 36 articles (28 with and 8 without chronic diseases) with 800,256 participants were included. Moderate evidence from wearable sensors supported a significant reduction in pooled estimates of step count (standardized mean differences [SMD]=-2.79, P<.01). Very limited to limited evidence substantiated significant decreases in self-reported PA-related outcomes and significant increases in sedentary behaviors among people with and without chronic diseases. Specifically, pooled estimates of metabolic equivalent-minute per week (SMD=-0.16, P=.02) and PA duration (SMD=-0.07, P<.01) were significantly decreased, while sedentary time (SMD=0.09, P=.04) showed significant increases in the general population (small to large effects). Very limited evidence suggested no significant PA changes among people in a country without lockdown. CONCLUSIONS: During the pandemic, objective and self-reported assessments showed significant reductions in PA in people with and without chronic diseases globally. This mainly occurred in countries with lockdowns. Although many countries have adopted the "live with the coronavirus" policy, authorities should implement population-based strategies to revert the potential lockdown-related long-term deleterious effects on people's health.

Utilizing Advanced Technology to Facilitate Diagnosis of Rare Retinal Disorders: A Case of Bietti Crystalline Dystrophy.

SIGNIFICANCE: Optometrists, as primary eye care providers, encounter patients with rare ocular disease such as Bietti crystalline dystrophy from time to time. Using advanced technologies, which are also useful in managing common ocular conditions, to facilitate a prompt diagnosis is highly recommended. PURPOSE: This report describes a patient with clinically diagnosed Bietti crystalline dystrophy with findings on funduscopy, multimodal imaging, and visual electrophysiology. CASE REPORT: A 41-year-old Chinese woman who had subjectively progressing dimmed vision (especially in the left eye) for 9 months was referred to our clinic to test for retinitis pigmentosa. Best-corrected visual acuities were 6/6 and 6/7.6 in the right and left eyes, respectively. Funduscopy revealed multiple crystalline deposits on the posterior pole in both eyes. The 30-2 perimetry displayed bi-inferotemporal scotoma (left > right eye). Scotopic flash electroretinogram (ERG) yielded a normal result, whereas photopic ERG was slightly attenuated. Electro-oculogram showed an abnormal adaptation time course of the retinal pigmented epithelium (RPE). Multifocal ERG revealed a decreased central retinal response, but paracentral responses were relatively better preserved. Optical coherence tomography showed multiple patches of RPE atrophy, with disruption of the left ellipsoid zone. Outer retinal tubulations, hyperreflective dots on RPE-Bruch's membrane interface, and intraretinal bright spots were also identified. CONCLUSIONS: Rare ocular diseases like Bietti crystalline dystrophy can be encountered by optometrists. This case report shows the ophthalmic findings of a rare chorioretinal dystrophy and provides insight on how to better use advanced equipment in an optometric practice to facilitate prompt diagnoses.

Involving stakeholders in informing the development of a Knowledge Translation (KT) intervention to improve the vaccination experience at school.

OBJECTIVE: Pain, fear, and fainting management during school-based vaccinations is suboptimal. The objective was to examine stakeholder perceptions of barriers and facilitators to better practices. Method: Six semi-structured focus groups were conducted in Niagara Region, Ontario: two parent groups (n=7); one grade 7 to 8 student group (n=9); two nurse groups (n=12); and one school staff group (n=6). Participants shared perceptions about school vaccination clinics and the implementation of specific strategies and tools. Focus groups were audio recorded and transcribed. The Consolidated Framework for Implementation Research (CFIR) was used as the framework for analysis. RESULTS: Feedback from stakeholders was categorized into four domains of CFIR: intervention characteristics, inner setting, outer setting, and characteristics of individuals. Intervention characteristics included: vaccine educational materials, vaccination accommodations, distraction techniques, topical anaesthetics, and food. Inner setting factors included: school vaccination procedures, relationships between school staff and nurses, assessment and documentation of student fear, and factors that contribute to a chaotic vaccination clinic. Outer setting factors were: the social environment and addressing parent and student needs. Stakeholder roles were discussed in characteristics of individuals. CONCLUSION: This study identified elements that can facilitate and challenge pain and fear mitigation tools and strategies; these elements should be considered in the development of a Knowledge Translation (KT) intervention to improve the school vaccination experience.

Stakeholder feedback on The CARD™ System to improve the vaccination experience at school.

OBJECTIVE: School-based vaccination programs can be a source of distress for many students due to the pain from the needle injection and related fears. We created a multifaceted Knowledge Translation (KT) intervention to address vaccination and pain, fear, and fainting called The CARD™ System. The objectives were to document acceptability of key tools included in the multifaceted KT intervention and their effectiveness in improving knowledge and attitudes about vaccination pain and fear. METHODS: Quantitative and qualitative methods were used. Students, school staff, public health nurses, and parents participated in separate focus groups whereby they independently completed a knowledge and attitudes survey and provided structured and qualitative feedback on key KT tools of the multifaceted KT intervention. They then repeated the knowledge and attitudes survey. RESULTS: Altogether, 22 students (grade 6 and 7), 16 school staff (principals, grade 7 and 8 teachers, resource teachers, secretaries), 10 nurses (injecting, charge, and school nurses), and 3 parents participated. Knowledge test scores increased post-KT tool review: 8.5 (2.1) versus 7.3 (1.9); P<0.001. Attitudes were more positive about the individual nature of pain and fear experience during vaccination. Student fear scores were lower post-tool review: 5.1 (2.9) versus 4.6 (3.0); P<0.001. The majority of the participants reported they understood all the information, the amount was just right and that the information was useful. DISCUSSION: The KT tools were demonstrated to be acceptable and to improve knowledge. Future research is warranted to determine their impact on student experience during school vaccinations.

Piloting The CARD™ System for education of students about vaccination: Does it improve the vaccination experience at school?

OBJECTIVE: Many students are fearful of vaccine injection-associated pain. In prior research, we created Knowledge Translation (KT) tools to address school vaccinations and associated pain, fear, and fainting. The objectives of this pilot implementation project were to determine the acceptability and impact of these KT tools on student knowledge, attitudes, and perceptions of their vaccination experience. METHODS: Pre-post mixed methods design. Students in an independent school in the Greater Toronto Area, Ontario, participated in two separate focus groups before and after school vaccinations. In both sessions, they independently completed a knowledge and attitudes survey, reviewed three KT tools (two videos and one pamphlet) and then repeated the knowledge and attitudes survey. They provided structured and qualitative feedback about the KT tools and described the impact of the education on the vaccination experience. RESULTS: Altogether, 11 grade 7 students participated. Knowledge scores were higher post-tool review compared to baseline in the first focus group. There was no significant difference in fear scores and attitudes about getting vaccinated. Qualitative feedback was categorized into two themes: intervention characteristics and characteristics of the school environment. Students reported the KT tools helped them to prepare for vaccination. They used the information on vaccination day to reduce their own fear and pain and to assist peers. They believed all students should view the KT tools. Students reported that teachers and nurses did not do enough to make vaccinations a positive experience. For example, they did not provide a private setting as an option for vaccination and prevented them from using some coping strategies recommended in the KT tools. DISCUSSION: This study provides preliminary evidence of the acceptability and positive impact of the KT tools on students' vaccination experiences. Future research is recommended that involves inclusion of all students and adults in the KT intervention.

The CARD™ System for improving the vaccination experience at school: Results of a small-scale implementation project on student symptoms.

BACKGROUND: Many students are afraid of receiving vaccinations at school. We implemented a novel, multifaceted knowledge translation intervention incorporating evidence-based vaccination coping strategies-The CARD™ System (C-Comfort, A-Ask, R-Relax, D-Distract)-and evaluated impact on student attitudes, knowledge, coping strategies used, and symptoms during school-based vaccinations. METHODS: Mixed methods. Ten schools participated in a controlled clinical trial: five experimental and five control. Experimental School (ES) students completed a knowledge and attitudes survey during an in-class CARD™ educational session prior to school vaccinations and selected coping strategies for upcoming vaccinations. Control School (CS) students received the usual vaccine education lesson, which did not include information about or selection of coping strategies. At all schools and during both vaccination clinic visits (fall and spring), injecting nurses recorded specific coping strategies used, and students independently rated their fear, pain, and dizziness during vaccinations. Focus groups were conducted at five schools after all clinics were completed (three ES, two CS). RESULTS: ES students had higher knowledge (P<0.001), less fear (P=0.03), and greater willingness to be vaccinated (P=0.001) after the in-class education session. Students rated the education as understandable, sufficient, useful, and that it prepared them for vaccinations. During school vaccination clinics, ES students selected more coping interventions than CS students. There were fewer students with high levels of fear (P=0.008) and dizziness (P=0.04) in the ES group. In round 2, fewer students (P=0.02) in the ES group returned to the clinic postvaccination because they were feeling unwell. ES students participating in focus groups scored higher on their knowledge test (P<0.001) compared with CS students and reported learning and benefitting from CARD™. DISCUSSION: This small-scale implementation study provides preliminary evidence of the effectiveness of CARD™ in improving vaccination experiences for students at school. Future research is recommended that examines CARD™ in different settings to confirm these results.

Effect of alcohol skin cleansing on vaccination-associated infections and local skin reactions: a randomized controlled trial.

OBJECTIVES: Recommendations regarding the need to use alcohol prior to vaccine injections are inconsistent and based on low-level evidence. The objective was to assess the effectiveness of alcohol in reducing local skin reactions and infection post-vaccination. METHODS: Randomized controlled trial in a pediatric clinic. A research assistant cleansed the skin with alcohol at (swab group) or adjacent to (control group) the pre-defined injection site(s). Clinicians, parents and children were blinded to group allocation. Parents reported local skin reactions using paper diaries for 15 days post-vaccination (Day 0-14). Telephone interviews were conducted Day 1, 5, and 14. The Brighton Collaboration criteria were used to diagnose cellulitis and infectious abscess Day 5 and afterward. RESULTS: 170 children participated (May-November 2017). Baseline characteristics did not differ (p > 0.05) between groups. Children received 1-4 separate injections. There were no differences between swab and control groups in the incidence of any local skin reactions (58% vs. 54%), and specifically, pain (45% vs. 40%), redness (26% vs. 21%), swelling (20% vs. 13%), warmth (19% vs. 27%), and spontaneous drainage of pus (0% in both groups) over the post-vaccination follow-up period. Day 5 data was available for 99% of participants from diaries and telephone surveys; there were no cases of cellulitis or infectious abscess. CONCLUSION: These findings are the first direct evidence for vaccine injections demonstrating that cleansing the skin with alcohol may not be needed. Our study is underpowered; however, to detect a difference in incidence of skin infection, future research is recommended.

Effectiveness of a hospital-based postnatal parent education intervention about pain management during infant vaccination: a randomized controlled trial.

BACKGROUND: Parents have reported that they want to learn how to reduce pain in infants during vaccinations. Our objective was to compare different levels of intensity of postnatal education about pain mitigation on parental self-reported use of interventions at future infant vaccinations. METHODS: We conducted a longitudinal, 3-group parallel, add-on, randomized controlled trial on the postnatal ward of a hospital. New mothers, unaware of the hypothesis, were randomly assigned to 1 of 3 intervention groups and 3 follow-up groups (i.e., 9 groups, 3 × 3). The 3 intervention groups were control (general immunization information), pain pamphlet (pain mitigation information), and pain pamphlet and pain video (pain mitigation information). Both pain mitigation education groups also received general immunization information. The 3 follow-up groups were 2-, 4- and 6-month infant vaccinations. Mothers reported use of breastfeeding, sucrose and topical anesthetics during infant vaccinations in a telephone survey. RESULTS: Of 3420 participants, follow-up was available for 2549 (75%): 36.1%, 34.2% and 29.7% reported on pain mitigation practices at 2-, 4- and 6-month vaccinations, respectively (p = 0.9). Maternal characteristics did not differ (p > 0.05): mean age, 33.6 years; 58% were primipara. Utilization of any intervention (breastfeeding, sucrose or topical anesthetics) was 53.2%, 61.4% and 63.0% for control, pain pamphlet, and pain pamphlet and pain video groups, respectively (p < 0.001); both pain education groups had higher utilization than the control group, but did not differ from one another. Uptake differed among intervention groups at 2 and 4 months but not at 6 months. INTERPRETATION: Hospital-based postnatal education increased parental use of pain interventions at infant vaccinations and can be added to existing education. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01937143.

To look or not to look during vaccination: A pilot randomized trial.

BACKGROUND: Clinicians commonly advise patients to look away from the needle during vaccinations; however, this recommendation is not evidence based. AIM: The aim of this study was to determine whether looking at the needle versus looking away affects pain and fear during vaccinations in adults. METHODS: This was a pilot randomized two-group parallel trial with university students receiving influenza vaccinations. Participants were stratified according to their initial needle-looking preference and randomly assigned to either look at versus away from the needle. Participants self-reported their pain and fear during vaccination. RESULTS: Of the 184 subjects who agreed to participate, 160 were enrolled; 66% were female. A three-way analysis of variance (ANOVA; Looking allocation assignment × Looking preference × Sex) revealed a significant main effect of looking allocation assignment on fear (P = 0.025); those who were randomized to look had higher fear scores than those who were randomized to look away. There was also a significant main effect of looking preference on fear (P < 0.001); those who preferred to look away had higher fear scores than those who preferred to look. There was no evidence of an effect of looking allocation assignment or looking preference on pain. There was a significant main effect of sex on fear and pain, with females reporting higher pain and fear scores than males (P = 0.017 and P = 0.001, respectively). There were no significant interactions. CONCLUSION: These preliminary findings suggest that advising individuals to look away from the needle reduces fear. A larger trial including more individuals and a different population is recommended to confirm the results.

Contexte: Les cliniciens conseillent habituellement aux patients de ne pas regarder l'aiguille pendant la vaccination; toutefois, cette recommandation ne s'appuie pas sur des données probantes.But: Déterminer si le fait de regarder l'aiguille ou de ne pas la regarder influence la douleur et la peur pendant la vaccination chez les adultes.Méthodes: Un essai pilote randomisé avec deux groupes parallèles a été mené auprès d'étudiants universitaires devant recevoir un vaccin contre l'influenza. Les participants ont été stratifiés selon leur préférence initiale pour regarder l'aiguille ou ne pas la regarder. Ils ont ensuite été répartis de façon aléatoire entre un groupe assigné à regarder l'aiguille et un groupe assigné à ne pas la regarder. Les participants ont autodéclaré leur douleur et leur peur pendant la vaccination.Résultats: Parmi les 184 sujets ayant accepté de participer à l'étude, 160 y ont été inscrits, dont 66 % de femmes. Une ANOVA à trois critères (ne pas regarder l'aiguille x préférence pour regarder ou ne pas regarder l'aiguille x sexe) a révélé un effet significatif de l'assignation à  regarder l'aiguille sur la peur (p = 0,025); ceux qui ont été randomisés pour regarder l'aiguille ont obtenu un score plus élevé en ce qui concerne la peur que ceux qui ont été randomisés pour ne pas la regarder. Un effet significatif de la préférence pour regarder sur la peur également été observé (p < 0,001) : ceux qui préféraient ne pas regarder l'aiguille ont obtenu un score plus élevé en ce qui concerne la peur que ceux qui préféraient regarder. Aucune preuve d'un effet de l'assignation à regarder ou de la préférence pour regarder sur la douleur n'a été relevée. Un effet significatif du sexe sur la peur et sur la douleur a été observé, les femmes ayant déclaré des niveaux de douleur et de peur plus élevés que les hommes (p = 0,017 et p = 0,001, respectivement). Aucune interaction significative n'a été observée.Conclusion: Ces résultats préliminaires suggèrent que le fait de conseiller aux personnes de ne pas regarder l'aiguille réduit la peur. Un essai plus vaste mené auprès d'un plus grand nombre d'individus et d'une population différente est recommandé afin de confirmer les résultats.Trial Registration No. NCT02937428.

A Longitudinal Randomized Trial of the Effect of Consistent Pain Management for Infant Vaccinations on Future Vaccination Distress.

The objective was to determine if consistent pain management during vaccine injections has a beneficial effect on future infant pain reactivity. This was a multicenter, longitudinal, double-blind, double-dummy, add-on, randomized controlled trial. Healthy infants were randomized to 1 of 4 add-on pain management regimens for all vaccinations in the first year of life: 1) placebo control (standard care), 2) parent video education about infant soothing (video), 3) video and oral sucrose solution (sucrose), 4) video and sucrose and topical liposomal lidocaine (lidocaine). At 15-month vaccinations, all active pain interventions were administered (video and sucrose and lidocaine); however, individuals remained blinded to the original treatments given. Pain at 15 months was evaluated during 3 procedure phases (baseline, needle injection, and recovery) by a researcher unaware of group allocation using a validated measure, the Modified Behavioural Pain Scale (range, 0-10). Altogether, 352 infants participated; characteristics did not differ among groups (P > .05). Pain scores did not differ among groups during baseline (P = .642), needle injection (P = .739), or recovery (P = .750) phases. In conclusion, there was no evidence of a long-term benefit of consistent use of pain interventions in the first year of life on future infant pain responsivity at 15-month vaccinations. PERSPECTIVE: This randomized controlled trial did not find a long-term benefit of consistent pain management during infant vaccinations on future infant pain responsivity at 15 months. The results are relevant to clinicians and researchers studying and evaluating pain interventions in children undergoing medical procedures.

Relative effectiveness of additive pain interventions during vaccination in infants.

BACKGROUND: Vaccine injections can cause acute pain and distress in infants, which can contribute to dissatisfaction with the vaccination experience and vaccine hesitancy. We sought to compare the effectiveness of additive pain interventions administered consistently during vaccine injections in the first year of life. METHODS: We conducted a multicentre, longitudinal, double-blind, add-on, randomized controlled trial. Healthy infants were randomly assigned to 1 of 4 levels of pain management for all vaccine injections at 2, 4, 6 and 12 months: (i) placebo control; (ii) parent-directed video education about infant soothing; (iii) the video plus sucrose administered orally or (iv) the video plus sucrose plus liposomal lidocaine applied topically. All infants benefit from injection techniques that minimize pain. We used a double-dummy design; hence all parents watched a video (active psychological intervention or placebo) and all infants received oral solution (sucrose or placebo) and topical cream (lidocaine or placebo). We assessed infant distress during 3 phases - preinjection (baseline), vaccine injection (needle), and 1 minute postinjection (recovery) - using the Modified Behavioural Pain Scale (range 0-10). We compared scores between groups and across infant ages using a mixed-model repeated-measures analysis. RESULTS: A total of 352 infants participated in the study, from Jan. 17, 2012, to Feb. 2, 2016. Demographics did not differ among intervention groups (p > 0.05). Baseline pain scores did not differ among intervention groups (p = 0.4), but did differ across ages (p < 0.001). Needle pain scores differed among groups (p = 0.003) and across ages (p < 0.001). The mean (± standard deviation) needle score was 6.3 (± 0.8) in the video-sucrose-lidocaine group compared with 6.7 (± 0.8) in each of the other groups. There were no other between-group differences. Recovery scores did not differ among groups (p = 0.98), but did differ across ages (p < 0.001). INTERPRETATION: Only liposomal lidocaine provided consistent analgesia within an additive pain intervention regimen during vaccinations in infants. Trial registration: ClinicalTrials.gov, no. NCT01503060.

A randomized trial of the effect of vaccine injection speed on acute pain in infants.

OBJECTIVE: This study compared the pain caused from fast vs. slow vaccine injections. METHODS: Infants aged 2-6months receiving primary immunizations were randomized to fast (2-4mL/s) or slow (5-10mL/s) injections during routine 0.5mL Diphtheria, Tetanus, acellular Pertussis, Inactivated Polio Virus, Haemophilus influenzae type b vaccine (DTaP-IPV-Hib) injections. Those aged 2 and 4months additionally received 0.5mL Pneumococcal Conjugate Vaccine (PCV) injections. A research assistant and parent unaware of treatment allocation and hypothesis assessed pain using validated and recommended tools, including; the Modified Behavioural Pain Scale (MBPS, range 0-10), cry duration, and Numerical Rating Scale (NRS, range 0-10). The primary outcome was infant pain score using the MBPS. RESULTS: Altogether, 120 were recruited; 61 were randomized to fast injections and 59 to slow injections. One hundred and ninteen infants participated. There were no differences in characteristics, including; age (p=0.994) and sex (p=0.540). The mean MPBS score (standard deviation) during DTaP-IPV-Hib injection was lower in the fast injection group: 6.4 (2.7) vs. 7.4 (2.5), respectively; p=0.046. Regression analysis demonstrated a positive correlation between injection speed and pain. There were no other differences between groups. CONCLUSION: Fast injection reduced injection-induced pain in infants receiving DTaP-IPV-Hib but not PCV vaccine. Fast injections are recommended when administering vaccines because of the potential for a reduction in pain, feasibility and practicality. TRIAL REGISTRATION: NCT02504398.

Protective effects of ferulic acid and related polyphenols against glyoxal- or methylglyoxal-induced cytotoxicity and oxidative stress in isolated rat hepatocytes.

Glyoxal (GO) and methylglyoxal (MGO) cause protein and nucleic acid carbonylation and oxidative stress by forming reactive oxygen and carbonyl species which have been associated with toxic effects that may contribute to cardiovascular disease, complications associated with diabetes mellitus, Alzheimer's and Parkinson's disease. GO and MGO can be formed through oxidation of commonly used reducing sugars e.g., fructose under chronic hyperglycemic conditions. GO and MGO form advanced glycation end products which lead to an increased potential for developing inflammatory diseases. In the current study, we have investigated the protective effects of ferulic acid and related polyphenols e.g., caffeic acid, p-coumaric acid, methyl ferulate, ethyl ferulate, and ferulaldehyde on GO- or MGO-induced cytotoxicity and oxidative stress (ROS formation, protein carbonylation and mitochondrial membrane potential maintenance) in freshly isolated rat hepatocytes. To investigate and compare the protective effects of ferulic acid and related polyphenols against GO- or MGO-induced toxicity, five hepatocyte models were used: (a) control hepatocytes, (b) GSH-depleted hepatocytes, (c) catalase-inhibited hepatocytes, (d) aldehyde dehydrogenase (ALDH2)-inhibited hepatocytes, and (e) hepatocyte inflammation system (a non-toxic H2O2-generating system). All of the polyphenols tested significantly decreased GO- or MGO-induced cytotoxicity, ROS formation and improved mitochondrial membrane potential in these models. The rank order of their effectiveness was caffeic acid∼ferulaldehyde>ferulic acid>ethyl ferulate>methyl ferulate>p-coumaric acid. Ferulic acid was found to decrease protein carbonylation in GSH-depleted hepatocytes. This study suggests that ferulic acid and related polyphenols can be used therapeutically to inhibit or decrease GO- or MGO-induced hepatotoxicity.