Immunogenicity, Efficacy, and Safety of Biosimilar Insulin Glargine (Gan & Lee Glargine) Compared With Originator Insulin Glargine (Lantus) in Patients With Type 1 Diabetes After 26 Weeks Treatment.

OBJECTIVE: To compare the immunogenicity, safety, and efficacy of Gan & Lee insulin glargine (GL Glargine) with that of the originator insulin glargine (Lantus) in patients with type 1 diabetes mellitus (T1DM). METHODS: This was a phase 3, multicenter, randomized, open-label, equivalence study. Five hundred seventy-six subjects with T1DM were randomized 1:1 to receive either GL Glargine or Lantus treatment for 26 weeks. The primary end point was the percentage of subjects in each treatment group who developed treatment-induced anti-insulin antibody after baseline and up to visit week 26, which was evaluated using a country-adjusted logistic regression model. The study also compared the changes in glycated hemoglobin, and adverse events including hypoglycemia. RESULTS: The percentage of subjects positive for treatment-induced anti-insulin antibody by Week 26 was 25.8% in the GL Glargine treatment group and 25.3% in the Lantus treatment group, with a 90% confidence interval (-5.4, 6.5) of the difference in proportions that fell completely between the similarity margins (-11.3, 11.3). The least squares mean difference between treatment groups for changes in glycated hemoglobin was -0.08 (90% confidence interval: -0.23, 0.06), and the other immunogenicity and safety profiles were comparable. CONCLUSION: GL Glargine demonstrated similar immunogenicity, efficacy, and safety compared to Lantus over 26 weeks in patients with T1DM.

Immunogenicity, efficacy, and safety of biosimilar insulin glargine (Gan & Lee glargine) compared with originator insulin glargine (Lantus®) in patients with type 2 diabetes after 26 weeks' treatment: A randomized open label study.

AIM: To evaluate the equivalence of immunogenicity, safety and efficacy of Gan & Lee (GL) Glargine (Basalin®; Gan & Lee Pharmaceutical) with that of the reference product (Lantus®) in adult participants with type 2 diabetes mellitus. METHODS: This was a phase 3, multicenter, open-label, equivalence trial conducted across 57 sites. In total, 567 participants with type 2 diabetes mellitus were randomized in a 1:1 ratio to undergo treatment with either GL Glargine or Lantus® for 26 weeks. The primary endpoint was the proportion of participants in each treatment arm who manifested treatment-induced anti-insulin antibodies (AIA). Secondary endpoints included efficacy and safety metrics, changes in glycated haemoglobin levels, and a comparative assessment of adverse events. Results were analysed using an equivalence test comparing the limits of the 90% confidence interval (CI) for treatment-induced AIA development to the prespecified margins. RESULTS: The percentages of participants positive for treatment-induced glycated haemoglobin by week 26 were similar between the GL Glargine (19.2%) and Lantus® (21.3%) treatment groups, with a treatment difference of -2.1 percentage points and a 90% CI (-7.6%, 3.5%) (predefined similarity margins: -10.7%, 10.7%). The difference in glycated haemoglobin was -0.08% (90% CI, -0.23, 0.06). The overall percentage of participants with any treatment-emergent adverse events was similar between the GL Glargine (80.1%) and Lantus® (81.6%) treatment groups. CONCLUSIONS: GL Glargine was similar to Lantus® in terms of immunogenicity, efficacy, and safety, based on the current study.

Where to start? The Irish Emergency Department Antimicrobial Discharge (EDAD) study: a multicentre, prospective cohort analysis.

Objectives: To determine the percentage of patients across Ireland who are discharged from the Emergency Department (ED) with an antimicrobial prescription, the indication, classification of infections, and guideline compliance. To identify potential areas for antimicrobial stewardship (AMS) interventions in the ED. Patients and methods: A multicentre, prospective cohort analysis study in EDs across eight hospitals in Ireland. At each site, patients aged 1 month and older who presented to the ED and were discharged directly from the ED were included. A random selection of records of patients discharged from the ED were reviewed until a minimum of 30 records with an infection diagnosis resulting in an antibiotic prescription were obtained per hospital. The number of patient discharges with no antibiotic prescriptions were included to calculate the denominator. The indication, infection classification and guideline compliance data were collected on the 30 prescriptions in the participating hospitals. Results: A total of 2619 patient records were reviewed. Of these, 249 (9.5%) patients were discharged with antimicrobial prescriptions from the ED. Most (158; 63%) were classified as probable bacterial infection, 21 (8%) as probable viral, and 18 (7%) had no documented evidence of infection. Three indications accounted for 73% of antimicrobial prescriptions: skin/soft tissue infection; ear, nose and throat infection; and urinary tract infection. Overall guideline compliance was 64%. Conclusions: Several areas for AMS interventions to optimize antimicrobial prescribing in the ED were identified, including targeted local and national guideline reviews, delayed prescribing, improved point-of-care testing and prescriber and patient education.

Increased rates of invasive bacterial disease in late 2022.

Invasive bacterial disease is associated with significant morbidity and mortality. In winter 2022, there was an apparent increased rate of invasive bacterial disease compared to preceding years. Cross-site retrospective analysis of the three Children's Health Ireland (CHI) hospitals looking at children admitted between 1st October 2022-31st December 2022 (Q4) with community-acquired invasive bacterial disease, defined as an abscess in a normally sterile site in the head, neck and chest or isolation or PCR detection of Streptococcus pneumoniae, Neisseria meningitidis, Streptococcus pyogenes (Group A streptococcus) or Haemophilus influenzae from a normally sterile site. Case numbers were compared to Q4 in each of 2018-2021. Eighty-two children met the case definition in Q4 2022 vs 97 (Q4 2018-2021). In 2022, 42/82 (51%) were female, median age 3.75 years (1.5-8.25 years). Only 2 (2%) were immunosuppressed and 2 others (2%) had underlying neurodisability. Fifty (61%) were admitted on second or subsequent presentation to a healthcare setting. Fifty-six (68%) had an abscess in a sterile site. Bloodstream infection (positive blood culture or PCR: 24 (29%)) was the most common site of infection, followed by neck 22 (27%) and intracranial 12 (15%). Group A streptococcus (GAS) 27 (33%) was the most common organism isolated. Seven cases (9%) died in 2022 compared to 2 patients (2%) from 2018 to 2021 (p < 0.05). More children had Paediatric Overall Performance Category (POPC) scores > 1 in 2022 than 2018-2021 (p = 0.003).  Conclusion: Invasive bacterial diseases increased in Q4 2022 with higher morbidity and mortality than in the preceding 4 years. Group A streptococcal infection was the most significant organism in 2022. What is known: • Invasive bacterial disease is the leading cause of childhood mortality globally. • There was an increase in cases of invasive Group A streptococcus infections reported in many countries (including Ireland) during the winter of 2022/23. What is new: • Head, neck and chest abscesses increased in Q4 of 2022 compared to the previous 4 years combined. • Invasive bacterial infections in Q4 of 2022 were associated with higher rates of mortality (9%), paediatric intensive care unit (PICU) admission (24%) and requirement for surgical drainage or intervention (67%) than in the preceding years.

Improving health literacy using the power of digital communications to achieve better health outcomes for patients and practitioners.

Digital communication tools have demonstrated significant potential to improve health literacy which ultimately leads to better health outcomes. In this article, we examine the power of digital communication tools such as mobile health apps, telemedicine and online health information resources to promote health and digital literacy. We outline evidence that digital tools facilitate patient education, self-management and empowerment possibilities. In addition, digital technology is optimising the potential for improved clinical decision-making, treatment options and communication among providers. We also explore the challenges and limitations associated with digital health literacy, including issues related to access, reliability and privacy. We propose leveraging digital communication tools is key to optimising engagement to enhance health literacy across demographics leading to transformation of healthcare delivery and driving better outcomes for all.

Randomized trial to evaluate the safety, tolerability, and immunogenicity of a booster (third dose) of BNT162b2 COVID-19 vaccine coadministered with 20-valent pneumococcal conjugate vaccine in adults ≥65 years old.

BACKGROUND: Older adults are at increased risk of adverse outcomes from pneumococcal disease and COVID-19. Vaccination is an established strategy for preventing both illnesses. This study evaluated the safety and immunogenicity of coadministration of the 20-valent pneumococcal conjugate vaccine (PCV20) and a booster (third dose) of BNT162b2 COVID-19 vaccine. METHODS: This phase 3, randomized, double-blind, multicentre study included 570 participants aged ≥65 years randomized 1:1:1 to PCV20 and BNT162b2 coadministered, or PCV20 or BNT162b2 only (administered with saline for blinding). Primary safety endpoints included local reactions, systemic events, adverse events (AEs) and serious AEs (SAEs). Secondary objectives were immunogenicity of PCV20 and BNT162b2 when administered together or separately. RESULTS: Coadministration of PCV20 and BNT162b2 was well tolerated. Local reactions and systemic events were generally mild-moderate; injection-site pain and fatigue were the most frequent local and systemic events, respectively. AE and SAE rates were low and similar across groups. No AEs led to discontinuation; no SAEs were considered vaccination-related. Robust immune responses were observed, with opsonophagocytic activity geometric mean fold rises (GMFRs; from baseline to 1 month) of 2.5-24.5 and 2.3-30.6 across PCV20 serotypes in Coadministration and PCV20-only groups, respectively. GMFRs for full-length S-binding IgG of 35.5 and 39.0, and for neutralizing titres against SARS-CoV-2-wild type virus of 58.8 and 65.4, were observed in the Coadministration and BNT162b2-only groups, respectively. CONCLUSIONS: Safety and immunogenicity of coadministered PCV20 and BNT162b2 were similar to those of PCV20 or BNT162b2 administered alone, suggesting that the 2 vaccines may be coadministered. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04887948.

Staff competence in caring for LGBTQ+ patients in the paediatric emergency department.

OBJECTIVE: This study aimed to assess the competency of paediatric emergency department (PED) multidisciplinary staff in caring for LGBTQ+ (lesbian, gay, bisexual, transgender, queer/questioning, + inclusive of all identities) adolescents. DESIGN: This was an observational study within which participants were required to complete the LGBT-Development of Clinical Skills Scale self-assessment tool of clinical competence. SETTING: It was conducted across three PEDs and one urgent care centre pertaining to the Children's Health Ireland healthcare group. PARTICIPANTS: Doctors, nurses and healthcare workers were eligible to participate. EXCLUSION CRITERIA: non-front facing staff; prior completion of an eLearning module intended to serve as a future educational intervention. MAIN OUTCOME MEASURES: Participants were assessed on: (1) attitudinal awareness towards LGBTQ+ individuals; (2) knowledge of LGBTQ+ health issues and (3) clinical preparedness in caring for LGBTQ+ patients. Each domain is scored out of a maximum of 7 points. RESULTS: 71 eligible participants completed the study. 40/71 (56%) were doctors, and 31/71 (44%) were nurses. The mean score for attitudinal awareness was 6.54/7 (SD 0.59), indicating overall positive attitudes. The mean score for knowledge was lower (5.34/7, SD 1.03) and lowest for clinical preparedness (3.39/7, SD 0.94). Participants were less confident in caring for transgender than LGB patients and scored very low when asked if they had received adequate training in caring for transgender young people (2.11/7). CONCLUSIONS: This study demonstrates positive attitudes towards LGBTQ+ patients among PED staff. However, there was a gap in knowledge and clinical preparedness. Increased training in caring for LGBTQ+ young people is necessary.

Bivalent Omicron BA.1-Adapted BNT162b2 Booster in Adults Older than 55 Years.

BACKGROUND: The emergence of immune-escape variants of severe acute respiratory syndrome coronavirus 2 warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019. METHODS: In an ongoing phase 3 trial, adults older than 55 years who had previously received three 30-µg doses of the BNT162b2 vaccine were randomly assigned to receive 30 µg or 60 µg of BNT162b2, 30 µg or 60 µg of monovalent B.1.1.529 (omicron) BA.1-adapted BNT162b2 (monovalent BA.1), or 30 µg (15 µg of BNT162b2 + 15 µg of monovalent BA.1) or 60 µg (30 µg of BNT162b2 + 30 µg of monovalent BA.1) of BA.1-adapted BNT162b2 (bivalent BA.1). Primary objectives were to determine superiority (with respect to 50% neutralizing titer [NT50] against BA.1) and noninferiority (with respect to seroresponse) of the BA.1-adapted vaccines to BNT162b2 (30 µg). A secondary objective was to determine noninferiority of bivalent BA.1 to BNT162b2 (30 µg) with respect to neutralizing activity against the ancestral strain. Exploratory analyses assessed immune responses against omicron BA.4, BA.5, and BA.2.75 subvariants. RESULTS: A total of 1846 participants underwent randomization. At 1 month after vaccination, bivalent BA.1 (30 µg and 60 µg) and monovalent BA.1 (60 µg) showed neutralizing activity against BA.1 superior to that of BNT162b2 (30 µg), with NT50 geometric mean ratios (GMRs) of 1.56 (95% confidence interval [CI], 1.17 to 2.08), 1.97 (95% CI, 1.45 to 2.68), and 3.15 (95% CI, 2.38 to 4.16), respectively. Bivalent BA.1 (both doses) and monovalent BA.1 (60 µg) were also noninferior to BNT162b2 (30 µg) with respect to seroresponse against BA.1; between-group differences ranged from 10.9 to 29.1 percentage points. Bivalent BA.1 (either dose) was noninferior to BNT162b2 (30 µg) with respect to neutralizing activity against the ancestral strain, with NT50 GMRs of 0.99 (95% CI, 0.82 to 1.20) and 1.30 (95% CI, 1.07 to 1.58), respectively. BA.4-BA.5 and BA.2.75 neutralizing titers were numerically higher with 30-µg bivalent BA.1 than with 30-µg BNT162b2. The safety profile of either dose of monovalent or bivalent BA.1 was similar to that of BNT162b2 (30 µg). Adverse events were more common in the 30-µg monovalent-BA.1 (8.5%) and 60-µg bivalent-BA.1 (10.4%) groups than in the other groups (3.6 to 6.6%). CONCLUSIONS: The candidate monovalent or bivalent omicron BA.1-adapted vaccines had a safety profile similar to that of BNT162b2 (30 µg), induced substantial neutralizing responses against ancestral and omicron BA.1 strains, and, to a lesser extent, neutralized BA.4, BA.5, and BA.2.75 strains. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04955626.).

Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system.

BACKGROUND: Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries. METHODS: We conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling. RESULTS: In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI -100- -54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from -97% (95% CI -100- -47%; p=0.0005) to -36% (95% CI -79-7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14-0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20-0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25-0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31-0.97); p=0.038) were independently associated with reducing bronchiolitis. CONCLUSIONS: Several NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.

Stroke Telemedicine for Arizona Rural Residents, the Legacy Telestroke Study.

Background: Efficacy of telemedicine for stroke was first established by the Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC) trials in California and Arizona. Following these randomized controlled trials, the Stroke Telemedicine for Arizona Rural Residents (STARR) network was the first telestroke network to be established in Arizona. It consisted of a 7 spoke 1 hub telestroke system, and it was designed to serve rural, remote, or neurologically underserved communities. Objective: The objective of STARR was to establish a multicenter state-wide telestroke research network to determine the feasibility of prospective collection, recording, and regularly analysis of telestroke patient consultations and care data for the purposes of establishing quality measures, improvement, and benchmarking against other national and international telestroke programs. Methods: The STARR trial was open to enrollment for 29 months from 2008 to 2011. Mayo Clinic Hospital, Phoenix, Arizona served as the hub primary stroke center and its vascular neurologists provided emergency telestroke consultations to seven participating rural, remote, or underserved spoke community hospitals in Arizona. Eligibility criteria for activation of a telestroke alert and study enrollment were established. Consecutive patients exhibiting symptoms and signs of acute stroke within a 12 h window were enrolled, assessed, and treated by telemedicine. The state government sponsor, Arizona Department of Health Services' research grant covered the cost of acquisition, maintenance, and service of the selected telemedicine equipment as well as the professional telestroke services provided. The study deployed multiple telemedicine video cart systems, picture archive and communications systems software, and call management solutions. The STARR protocol was reviewed and approved by Mayo Clinic IRB, which served as the central IRB of record for all the participating hospitals, and the trial was registered at ClinicalTrials.gov. Results: The telestroke hotline was activated 537 times, and ultimately 443 subjects met criteria and consented to participate. The STARR successfully established a multicenter state-wide telestroke research network. The STARR developed a feasible and pragmatic approach to the prospective collection, storage, and analysis of telestroke patient consultations and care data for the purposes of establishing quality measures and tracking improvement. STARR benchmarked well against other national and international telestroke programs. STARR helped set the foundation for multiple regional and state telestroke networks and ultimately evolved into a national telestroke network. Conclusions: Multiple small and rurally located community hospitals and health systems can successfully collaborate with a more centrally located larger hospital center through telemedicine technologies to develop a coordinated approach to the assessment, diagnosis, and emergency treatment of patients manifesting symptoms and signs of an acute stroke syndrome. This model may serve well the needs of patients presenting with other time-sensitive medical emergencies.Clinical Trial Registration number: NCT00829361.

Safety and Efficacy of a Third Dose of BNT162b2 Covid-19 Vaccine.

BACKGROUND: Active immunization with the BNT162b2 vaccine (Pfizer-BioNTech) has been a critical mitigation tool against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the coronavirus disease 2019 (Covid-19) pandemic. In light of reports of waning protection occurring 6 months after the primary two-dose vaccine series, data are needed on the safety and efficacy of offering a third (booster) dose in persons 16 years of age or older. METHODS: In this ongoing, placebo-controlled, randomized, phase 3 trial, we assigned participants who had received two 30-µg doses of the BNT162b2 vaccine at least 6 months earlier to be injected with a third dose of the BNT162b2 vaccine or with placebo. We assessed vaccine safety and efficacy against Covid-19 starting 7 days after the third dose. RESULTS: A total of 5081 participants received a third BNT162b2 dose and 5044 received placebo. The median interval between dose 2 and dose 3 was 10.8 months in the vaccine group and 10.7 months in the placebo group; the median follow-up was 2.5 months. Local and systemic reactogenicity events from the third dose were generally of low grade. No new safety signals were identified, and no cases of myocarditis or pericarditis were reported. Among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated, Covid-19 with onset at least 7 days after dose 3 was observed in 6 participants in the vaccine group and in 123 participants in the placebo group, which corresponded to a relative vaccine efficacy of 95.3% (95% confidence interval, 89.5 to 98.3). CONCLUSIONS: A third dose of the BNT162b2 vaccine administered a median of 10.8 months after the second dose provided 95.3% efficacy against Covid-19 as compared with two doses of the BNT162b2 vaccine during a median follow-up of 2.5 months. (Funded by BioNTech and Pfizer; C4591031 ClinicalTrials.gov number, NCT04955626.).

VO2peak prior to transplant differentiates survival post kidney transplant.

The OPTN/UNOS utilizes the calculated estimated posttransplant survival (EPTS) score as the measure of post-kidney transplant survival to guide allocation of deceased donor kidney transplantation. This score does not include any metric of functional capacity. Peak oxygen uptake (VO2peak ), is an established predictor of survival among both the general and diseased populations. We assessed the association and discriminative capacity of VO2peak and that of EPTS score and all-cause mortality post-kidney transplant. Additionally, we assessed the "mortality risk" lower VO2peak conferred on those patients with low EPTS score. Among a cohort of 293 transplant recipients with at least 3-years post-transplant follow-up, the median VO2peak was 15.0 ml/Kg/min. Lower pre-transplant VO2peak and higher EPTS score conferred higher risk of post-transplant mortality. Among the cohort of "low-risk" patients (patients with EPTS score < 50) those with lower VO2peak had significantly higher risk of mortality (log rank p = 0.045). In fact, the mortality risk among those with low-EPTS (< 50) and low VO2peak  < 12 ml/Kg/min was equivalent to those with high EPTS (> 80) score. We concluded functional capacity as defined by VO2peak is an important reflection of post-transplant survival. VO2peak is able to identify those with low EPTS who have similar survival to that of high EPTS phenotype.

Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F Vaccine When Coadministered With a Tetanus, Diphtheria, and Acellular Pertussis Vaccine.

BACKGROUND: Prevention of respiratory syncytial virus (RSV) disease in infants is an unmet vaccine need, and maternal immunization is a potential strategy to address this need. This study evaluated concomitant administration of RSV stabilized prefusion F subunit vaccine (RSVpreF) and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (Tdap) in healthy, nonpregnant women 18‒49 years of age. METHODS: In this phase 2b, multicenter, placebo-controlled, observer-blind, noninferiority study, participants were randomized to receive RSVpreF in a range of doses and formulations with Tdap or alone, or Tdap alone. Safety and immunogenicity were assessed. RESULTS: Local reactions and systemic events were generally similar across vaccine groups. Noninferiority of anti-RSV-A and anti-RSV-B immune responses induced by RSVpreF with Tdap was demonstrated compared to RSVpreF alone. Noninferiority of anti-diphtheria toxoid and anti-tetanus toxoid immune responses after administration of RSVpreF with Tdap was demonstrated compared to Tdap alone; noninferiority was not met for anti-pertussis component responses. CONCLUSIONS: RSVpreF was safe and well tolerated when administered with Tdap or alone in nonpregnant women 18‒49 years of age. Immune responses induced by Tdap administered with RSVpreF were noninferior for the tetanus and diphtheria components of Tdap, but not for pertussis. CLINICAL TRIALS REGISTRATION: NCT04071158.

A randomized phase 1 study of the safety and immunogenicity of 2 novel pneumococcal conjugate vaccines in healthy Japanese adults in the United States.

Expanding serotype coverage of pneumococcal conjugate vaccines (PCVs) to target prevailing disease-causing serotypes could further reduce disease burden. To address this need, 2 different PCVs have been investigated: a 20-valent PCV (PCV20; includes the 13 serotypes in the 13-valent PCV [PCV13] plus 7 additional serotypes [8, 10A, 11A, 12F, 15B, 22F, 33F]) and a complementary 7-valent PCV (cPCV7; contains only the 7 additional serotypes). This phase 1b, randomized, controlled, double-blind study evaluated PCV20 and cPCV7 safety and immunogenicity in healthy Japanese adults 18-49 years of age residing in the United States for ≤5 years. Participants (n = 104) were randomized equally to receive a single dose of PCV20, cPCV7, or PCV13. Immunogenicity was assessed at baseline and 1 month after vaccination using serotype-specific opsonophagocytic activity (OPA) titers and serotype-specific immunoglobulin G (IgG) concentrations. Prompted local reactions and systemic events; adverse events (AEs); and serious AEs and newly diagnosed chronic disease were assessed 14 days, through 1 month, and upto 6 months following vaccination, respectively. OPA immune responses were robust for all 20 serotypes in the PCV20 group and for the 7 serotypes in the cPCV7 group 1 month after vaccination. IgG immune response showed similar trends. Injection site pain and muscle pain were the most common local reaction and systemic event; the majority were mild or moderate in severity. Few AEs and no severe AEs, serious AEs, or safety-related withdrawals were reported. Taken together, administration of PCV20 or cPCV7 in Japanese adults was well tolerated and induced robust serotype-specific functional immune responses. NCT03642847.

Use of anti-reflux medications in infants under 1 year of age: a retrospective drug utilization study using national prescription reimbursement data.

Non-specific symptoms such as irritability, vomiting, and back arching during the infant period are often attributed to gastroesophageal reflux. While numerous studies have shown no significant benefit to the use of acid suppressant medications in this population, these medications are frequently prescribed in response to these symptoms. Our goals were to understand how often children were being prescribed this medication. To do this, data was extracted from a national database for reimbursement of prescribed medications through the General Medical Services scheme (GMS). Infants aged less than 1 year and eligible for reimbursement under GMS were included for analysis. A total of 450 infants per 10,000 eligible population received an anti-reflux preparation from the following drug classes (H2 antagonists, proton pump inhibitors, or alginate preparations) in 2018. This is compared with that in 2009 where only 137 per 10,000 eligible infants received these medications. This increase was predominantly attributable to an increase in ranitidine prescriptions.Conclusion: Despite a change in clinical guidelines, anti-reflux preparations are increasingly being prescribed to infants aged less than 1 year. The reasons behind the increase in prescriptions containing these medications cannot be ascertained from this data. This may suggest a proportion of these prescriptions may be unwarranted in this population. What is Known: • The prescription of PPIs in infants has increased in a number of countries. • Use of anti-reflux medications has a very poor evidence base in infancy. What is New: • This data focuses only on an infant age group in a "well" cohort. • Ranitidine may contribute to increased acid-suppressant use in infancy.

User experiences with second-generation 32-gauge × 4 mm vs. thinner comparator pen needles: prospective randomized trial.

OBJECTIVE: Two similarly designed studies compared user experiences with a second-generation extra-thin-wall, 5-bevel 32 G × 4 mm pen needle (PN) with redesigned hub versus four thinner commercially available PNs. METHODS: Adults (18-75 years old) with type 1 or type 2 diabetes and ≥3 months of experience with pen injectors qualified for single-visit, single-blinded randomized studies. The investigational 32 G PN was compared with three 33-34 G × 3.5-4 mm PNs in Study 1 and one 34 G × 4 mm PN in Study 2. Participants completed 12 abdominal injections of 0.3 mL sterile saline using insulin pens in 6 pairs, each comprising one investigational 32 G PN and one comparator PN in random order. After each injection pair, participants compared injection pain via relative 150 mm visual analog scale (VAS) and perceived dose delivery force via relative 5 point Likert scale. Adjusted models tested injection pain scores (primary endpoint) for noninferiority and, if met, then for superiority. ClinicalTrials.gov identifiers: NCT03878758 and NCT03878745. RESULTS: The investigational 32 G PN met noninferiority as well as superiority criteria for less injection pain vs. each comparator (p < .01), with adjusted mean relative VAS scores 9.1-17.6 in Study 1 (n = 154) and 7.3 in Study 2 (n = 55). The investigational 32 G PN was also superior vs. each comparator PN in requiring less relative perceived force to deliver the dose (p < .01). CONCLUSIONS: The investigational 32 G PN was associated with less participant-reported injection pain and less perceived dose delivery force compared with four thinner PNs, suggesting no additional pain reduction or force reduction benefit conferred by the thinner PNs.

National rotavirus vaccination programme implementation and gastroenteritis presentations: the paediatric emergency medicine perspective.

BACKGROUND: Throughout the developed world, the introduction of rotavirus vaccination has led to reductions in the incidence and severity of acute gastroenteritis (AGE) in young children and consequently to reductions in paediatric emergency department (PED) attendances with AGE. Rotavirus vaccination was added to the Irish National Immunisation Schedule in November 2016. AIMS: To assess the impact of vaccine introduction on citywide PED attendances and hospital admissions with all-cause AGE during rotavirus season. METHODS: In an observational study, a retrospective search was performed of electronic records in three independent PEDs in Dublin. Weekly presentations and admissions with AGE in the first 30 weeks (gastroenteritis season) of the years 2012-2018 were counted and stratified by age. RESULTS: Median weekly presentations in 2017-2018, 126 (interquartile range (IQR) 103-165) were significantly lower than in 2012-2016, 160 (IQR 128-214) (p < 0.001). A reduction in presentations was seen across the three hospitals and in those aged less than 5 years. In one PED, median admissions in 2017-2018 were 10 (IQR 7-13) in comparison with nine (IQR 7-13) in 2012-2016, (p = 0.463). The emergency department AGE presentations to hospital ward admission rate was 6.7:1. CONCLUSION: A reduction in PED presentations with AGE is demonstrated post-rotavirus vaccine introduction into the Irish National Immunisation Schedule. No significant change in paediatric hospital admissions was demonstrated.

Safety and efficacy of verinurad, a selective URAT1 inhibitor, for the treatment of patients with gout and/or asymptomatic hyperuricemia in the United States and Japan: Findings from two phase II trials.

Objective: Evaluate efficacy/safety of verinurad monotherapy in patients with gout (Japan/US) or asymptomatic hyperuricemia (Japan).Methods: Two randomized, placebo-controlled, phase II studies were conducted (NCT01927198/NCT02078219). Patients were randomized to once-daily doses of placebo or escalating doses of verinurad (study 1: 5-12.5 mg; study 2: 2.5-15 mg). Primary endpoint was percentage change from baseline in serum urate (sUA) at week 12 (study 1)/week 16 (study 2). Safety was also assessed.Results: Most patients in study 1 (n = 171) were white (74.9%); all patients were Japanese in study 2 (n = 204). Least squares means (±SE) estimate of percentage change in sUA levels from baseline in study 1 was 1.2 ± 2.9 for placebo, and -17.5 ± 2.8, -29.1 ± 2.8, -34.4 ± 2.9 for verinurad 5, 10, 12.5 mg, respectively. In study 2, results were -2.4 ± 2.5 and -31.7 ± 2.5, -51.7 ± 2.6,-55.8 ± 2.5, respectively. Difference from placebo was significant for each verinurad dose (p<.0001). The proportion of patients with treatment-emergent adverse events (TEAEs) was similar across all groups. Renal-related TEAEs were more common with verinurad than placebo.Conclusion: Verinurad monotherapy resulted in sustained reductions in sUA in Japanese/US patients but renal AEs occurred, so verinurad alone is not recommended for treatment of hyperuricemia or gout. The renal consequences of excessive uric acid excretion deserve study.