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Background. Solid organ transplant recipients have a high risk of severe outcomes from SARS-CoV-2 infection. A comprehensive understanding of the impact of the COVID-19 pandemic across multiple waves in the solid organ transplant population and how this compares to the general population is limited. We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada to answer this question. Methods. We included 15 306 solid organ transplant recipients and 12 160 904 individuals from the general population. Our primary outcome was the rate (per 100 person-years) of severe COVID-19 (ie, hospitalization or death with a positive SARS-CoV-2 test) occurring between January 25, 2020, and November 30, 2022. Results. Compared with the general population, solid organ transplant recipients had almost a 6 times higher rate of severe COVID-19 (20.39 versus 3.44 per 100 person-years), with almost 5.5 times as high a rate of death alone (4.19 versus 0.77 per 100 person-years). Transplant recipients with severe COVID-19 were substantially younger (60.1 versus 66.5 y) and had more comorbidities. The rate of severe COVID-19 declined over time in the solid organ transplant population, with an incidence rate of 41.25 per 100 person-years in the first wave (January 25, 2020, to August 31, 2020) and 18.41 in the seventh wave (June 19, 2022, to November 30, 2022, Omicron era). Conclusions. Solid organ transplant recipients remain at high risk of severe outcomes when they are infected with SARS-CoV-2. Resources and strategies to mitigate the impact of SARS-CoV-2 exposure are needed in this vulnerable patient population.

Background. Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia–reperfusion injury to improve transplant outcomes. Methods. We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively. Results. Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47). Conclusions. Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application.

Background: Routinely used cardiac medications, based on pharmacokinetics, are hypothesized to increase drug levels of direct oral anticoagulants (DOACs), with the potential to increase the risk of hemorrhage. We set out to compare the risk for hemorrhage following initiation of amiodarone, verapamil, or diltiazem (moderate cytochrome P450 3A4 and/or P-glycoprotein activity) vs metoprolol or amlodipine (weak or no activity), among older adults prescribed DOACs. Methods: We conducted a population-based, retrospective cohort study of all adults (aged ≥ 66 years) on a DOAC (dabigatran, apixaban, rivaroxaban; n = 295,038) who were newly prescribed amiodarone (n = 4872), verapamil (n = 1284), or diltiazem (n = 14,638), compared with metoprolol or amlodipine, from Ontario, Canada (2009-2016). The outcome was hospital admission or emergency room visit with a major hemorrhage (upper or lower gastrointestinal tract, intracranial), examined using weighted models. Results: A total of 1737 hemorrhage events occurred (amiodarone, 80 [1.6%] vs metoprolol 503 [2.3%]; verapamil, 32 [2.5%] vs amlodipine, 406 [1.6%]; diltiazem, 312 [2.1%] vs amlodipine, 404 [1.5%]). The weighted risk of major hemorrhage was not elevated with amiodarone, verapamil, or diltiazem initiation in DOAC users, compared to metoprolol or amlodipine, during the full follow-up period (hazard ratio [HR; 95% confidence interval]: amiodarone HR 0.77 [0.61-0.97]; verapamil HR 1.32 [0.88-1.98]; diltiazem HR 0.99 [0.85-1.15]). This finding was consistent with a broader definition of bleeding, adjusting for kidney function, by DOAC type or dosage. Conclusions: Hemorrhage risk with amiodarone, verapamil, and diltiazem was similar to that with comparators, among DOAC users aged > 66 years. Résumé: Contexte: Les médicaments cardiaques couramment utilisés, selon la pharmacocinétique, devraient théoriquement augmenter les taux d’anticoagulants oraux directs (AOD), ce qui s'accompagne d'un risque accru d’hémorragie. Nous avons entrepris de comparer le risque d’hémorragie après l’instauration de l’amiodarone, du vérapamil ou du diltiazem (activité modérée du cytochrome P450 3A4 ou de la P-glycoprotéine) par rapport au métoprolol ou à l’amlodipine (activité faible ou nulle), chez des personnes âgées à qui l’on avait prescrit des AOD. Méthodologie: Nous avons mené une étude de cohortes rétrospective en population auprès de tous les adultes (âgés de 66 ans et plus) prenant un AOD (dabigatran, apixaban, rivaroxaban; n = 295 038) à qui l’on venait de prescrire de l’amiodarone (n = 4872), du vérapamil (n = 1284) ou du diltiazem (n = 14 638), comparativement au métoprolol ou à l’amlodipine, en Ontario, au Canada (2009-2016). Le critère d’évaluation était une admission à l’hôpital ou une consultation à l’urgence pour une hémorragie grave (voie gastro-intestinale supérieure ou inférieure, intracrânienne), examiné à l’aide de mo-dèles pondérés. Résultats: Au total, 1 737 événements hémorragiques sont survenus (amiodarone, 80 [1,6 %] contre métoprolol, 503 [2,3 %]; vérapamil, 32 [2,5 %] contre amlodipine, 406 [1,6 %]; diltiazem, 312 [2,1 %] contre amlodipine, 404 [1,5 %]). Le risque pondéré d’hémorragie grave ne s’est pas accru avec l’instauration de l’amiodarone, du vérapamil ou du diltiazem chez les utilisateurs d’AOD, comparativement au métoprolol ou à l’amlodipine, pendant toute la période de suivi (rapport des risques instantanés [RRI; intervalle de confiance à 95 %] : amiodarone : RRI 0,77 [0,61-0,97]; vérapamil : RRI 1,32 [0,88-1,98]; diltiazem : RRI 0,99 [0,85-1,15]). Ce résultat concorde avec une définition plus large du saignement, après ajustement pour la fonction rénale, par type ou posologie d’AOD. Conclusions: Le risque d’hémorragie associé à l’amiodarone, au vérapamil et au diltiazem était semblable à celui des médicaments de comparaison chez les utilisateurs d’AOD âgés de plus de 66 ans.

Otolaryngology surgical education continues to evolve where trainees increasingly use videos to learn technical skills. Trainees commonly use YouTube, but no study to date has evaluated the educational quality (EQ) of otologic surgical videos on YouTube. We aim to assess the EQ of cholesteatoma surgical videos. Cholesteatoma surgical videos were queried using YouTube search terms, assessed using LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS), a validated assessment tool for publication, and categorized into low (0-6), medium (7-12), and high (13-18) EQ groups. In total, 74 videos were identified (mean LAP-VEGaS score = 9.6 ± 4.0) and 44.6% had medium EQ. Videos commonly lacked graphic aids to highlight anatomy (71.6%) and postprocedural outcomes (68.9%). LAP-VEGaS scores were greater in videos originating from US surgeons compared to non-US surgeons (12.4 ± 3.4 vs 8.0 ± 3.5; P < .001). Our study highlights that otolaryngology trainees may experience difficulty finding high-EQ cholesteatoma surgery videos on YouTube. Areas for improved EQ content are discussed. Level of evidence : IV

Background: Patients with obstructive sleep apnea (OSA) have increased sympathetic activity and frequently also have resistant hypertension (HTN). Treatment of OSA with continuous positive airway pressure (CPAP) decreases awake and sleep blood pressure (BP) and sympathetic activity. This study was designed to assess the effect of treatment of OSA with CPAP on sympathetic activity and BP in patients with diabetes mellitus (DM), chronic kidney disease (CKD), and resistant HTN. Methods: This was a randomized, double-blind, sham-controlled trial. Patients with DM, CKD, and resistant HTN were randomized to treatment with a therapeutic or subtherapeutic CPAP for 6 weeks. They underwent 24-hour ambulatory BP monitoring and assessment of muscle sympathetic nerve activity before and after 6 weeks on treatment. Results: Treatment with therapeutic CPAP caused significant decreases in awake systolic and diastolic BP from 144 to 136 mm Hg (P = 0.004) and from 79 to 74 mm Hg (P = 0.004) and in sleep BP from 135 to 119 mm Hg (P = 0.045) and from 75 to 65 mm Hg (P = 0.015) compared with treatment with subtherapeutic CPAP. In contrast, treatment with therapeutic CPAP did not decrease sympathetic activity as assessed from muscle sympathetic nerve activity. Conclusions: Decrease in BP by treatment with CPAP in patients with DM, CKD, and OSA indicates the contribution of OSA to severity of HTN in this clinical scenario. Decrease in BP in the absence of changes in sympathetic activity is suggestive that other mechanisms induced by OSA play a larger role in the maintenance of HTN in these patients. Résumé: Contexte: Les patients atteints d’apnée obstructive du sommeil (AOS) présentent une activité sympathique accrue qui est souvent accompagnée d’hypertension artérielle (HTA) réfractaire. Le traitement de l’AOS par ventilation en pression positive continue (CPAP, pour Continuous Positive Airway Pressure) diminue la pression artérielle (PA) à l’état de veille et durant le sommeil ainsi que l’activité sympathique. Cette étude était conçue pour évaluer l’effet du traitement de l’AOS par CPAP sur l’activité sympathique et la PA chez des patients atteints de diabète sucré (DS), d’insuffisance rénale chronique (IRC) et d’HTA réfractaire. Méthodologie: Il s’agissait d’une étude à double insu et à répartition aléatoire contrôlée par simulation. Les patients atteints de DS, d’IRC et d’HTA réfractaire ont été répartis de façon aléatoire pour recevoir un traitement par CPAP thérapeutique ou subthérapeutique pendant 6 semaines. Une surveillance ambulatoire de la PA et une évaluation de l’activité nerveuse sympathique musculaire sur 24 h ont été effectuées chez les patients avant et après 6 semaines de traitement. Résultats: Comparativement à la CPAP subthérapeutique, la CPAP thérapeutique a entraîné une diminution significative de la PA systolique et de la PA diastolique à l’état de veille, qui sont passées respectivement de 144 à 136 mmHg (p = 0,004) et de 79 à 74 mmHg (p = 0,004). La même observation a été faite à l’égard de la PA systolique et de la PA diastolique durant le sommeil, qui sont passées respectivement de 135 à 119 mmHg (p = 0,045) et de 75 à 65 mmHg (p = 0,015). En revanche, l’évaluation de l’activité nerveuse sympathique musculaire n’a révélé aucune diminution de l’activité sympathique associée au traitement par CPAP thérapeutique. Conclusions: La diminution de la PA associée au traitement par CPAP chez les patients atteints de DS, d’IRC et d’AOS indique que l’AOS contribue à l’intensité de l’HTA dans ce scénario clinique. La diminution de la PA en l’absence de modification de l’activité sympathique laisse supposer que d’autres mécanismes induits par l’AOS jouent un rôle plus important dans le maintien de l’HTA chez ces patients.

Summary: Background: Glaucoma is a major cause of sight loss worldwide, with the highest regional prevalence and incidence reported in Africa. The most common low-cost treatment used to control glaucoma is long-term timolol eye drops. However, low adherence is a major challenge. We aimed to investigate whether selective laser trabeculoplasty (SLT) was superior to timolol eye drops for controlling intraocular pressure (IOP) in patients with open-angle glaucoma. Methods: We did a two-arm, parallel-group, single-masked randomised controlled trial at the Eye Department of Kilimanjaro Christian Medical Centre, Moshi, Tanzania. Eligible participants (aged ≥18 years) had open-angle glaucoma and an IOP above 21 mm Hg, and did not have asthma or a history of glaucoma surgery or laser. Participants were randomly assigned (1:1) to receive 0·5% timolol eye drops to administer twice daily or to receive SLT. The primary outcome was the proportion of eyes from both groups with treatment success, defined as an IOP below or equal to target pressure according to glaucoma severity, at 12 months following randomisation. Re-explanation of eye drop application or a repeat SLT was permitted once. The primary analysis was by modified intention-to-treat, excluding participants lost to follow-up, using logistic regression; generalised estimating equations were used to adjust for the correlation between eyes. This trial was registered with the Pan African Clinical Trials Registry, number PACTR201508001235339. Findings: 840 patients were screened for eligibility, of whom 201 (24%) participants (382 eligible eyes) were enrolled between Aug 31, 2015, and May 12, 2017. 100 (50%) participants (191 eyes) were randomly assigned to the timolol group and 101 (50%; 191 eyes) to the SLT group. After 1 year, 339 (89%) of 382 eyes were analysed. Treatment was successful in 55 (31%) of 176 eyes in the timolol group (16 [29%] of 55 eyes required repeat administration counselling) and in 99 (61%) of 163 eyes in the SLT group (33 [33%] of 99 eyes required repeat SLT; odds ratio 3·37 [95% CI 1·96–5·80]; p

The proportion of female trainees in radiation oncology has generally declined despite increasing numbers of female medical students; as a result, radiation oncology is among the bottom 5 specialties in terms of the percentage of female applicants. Recently, social media has been harnessed as a tool to bring recognition to underrepresented groups within medicine and other fields. Inspired by the wide-reaching social media campaign of #ILookLikeASurgeon to promote female physicians, members of the Society for Women in Radiation Oncology penned a new hashtag and launched the #WomenWhoCurie social media campaign on Marie Curie's birthday November 7th, as part of their strategy to raise public awareness. From November 6, 2018 until November 10, 2018, the #WomenWhoCurie hashtag delivered 1,135,000 impressions, including 408 photos from all over the world including United States, Spain, Canada, France, Australia, Ireland, the United Kingdom, Mexico, Japan, the Netherlands, India, Ecuador, Panama, Brazil, and Nigeria. Alongside continued gender disparity research, social media should continue to be used as a tool to engage the community and spur conversations to formulate solutions for gender inequity.

Purpose: Resident physicians use social media (SM) for many reasons. We sought to characterize current SM use by radiation oncology (RO) trainees for education and professional development. Methods and Materials: An anonymous 40-question survey was sent by e-mail to RO residents in the 2018 to 2019 academic year. SM platform use, time spent on SM, professional use, and opinions regarding SM use were assessed. Descriptive statistics and a univariate logistic regression analysis were performed to identify factors associated with perceptions of SM and spending >25% of SM time for academic or professional purposes. Results: Of the 615 residents surveyed, 149 responded (24% response rate). Facebook (73%), theMednet (62%), Instagram (59%), Twitter (57%), and Doximity (50%) were the top SM platforms used. Most respondents (53%) reported 60 minutes per day over the past week. Residents with an RO mentor on SM (n = 35; 24%; odds ratio [OR]: 2.79; 95% confidence interval [CI], 1.29-6.08; P = .010), those participating in RO discussions on SM (n = 71; 48%; OR: 2.85; 95% CI, 1.42-5.72; P = .003), and those interacting with professional societies (n = 69; 46%; OR: 7.11; 95% CI, 3.32-15.24; P < .001) were more likely to spend >25% of their SM time on professional/academic purposes. The vast majority of respondents agreed that SM exposed them to novel educational content (82%) and was helpful for career development (65%). In addition, 69% agreed that SM can improve clinical skills and knowledge. A substantial minority agreed that SM distracts them from studying (38%) or they felt pressure to have a SM presence (29%). Conclusions: Most RO residents reported that SM provides novel educational content and can help with career development. Potential disadvantages of SM for trainees may include distraction and pressure to maintain a SM presence. SM use by RO trainees merits further research to optimize its potential for education and professional development.

This article describes a simple surgical skin preparation technique for total knee arthroplasty that permits the application of skin prep agent with the knee in maximal flexion. While most surgeons prep the knee in extension, it is believed that prep of the knee in flexion will provide superior coverage of the skin surface and reduce the potential for surgical-site infection, particularly in obese patients with large soft-tissue layers anterior to the knee.

Objective: There are no randomized data to support the use of postoperative radiation for salivary gland malignancies. This study uses the National Cancer Database (NCDB) to describe the epidemiology of salivary gland cancer patients and to investigate whether treatment with adjuvant radiation improves overall survival. Methods and materials: A total of 8243 patients diagnosed with a major salivary gland cancer were identified from the NCDB. All patients received primary surgical resection of their malignancy. Patients were risk-stratified by adverse features, and overall survival rates were determined. Patients were considered high risk if they had extracapsular extension and/or positive margin after resection. Patients were considered intermediate risk if they did not meet the criteria for high risk but had pT3-T4 disease, pN+ disease, lymphovascular space invasion, adenoid cystic histology, or grade 2-3 disease. Patients who did not meet criteria for high or intermediate risk were considered low risk. Overall patient demographics, disease characteristics, treatment factors, and outcomes were summarized with descriptive statistics and analyzed with STATA. Results: Median follow-up in this cohort was 42.4 months, with the median age of 58 years. Patients in the high-risk group had greater survival (hazard ratio [HR], 0.76; P = .002; 95% confidence interval [CI], 0.64-0.91) if they received adjuvant radiation therapy. In contrast, patients in the intermediate- (HR, 1.01; P = .904; 95% CI, 0.85-1.20) and low-risk groups (HR, 0.85; P = .427; 95% CI, 0.57-1.26) did not experience a survival benefit with adjuvant radiation therapy. Conclusions: This large analysis compared survival outcomes between observation and adjuvant radiation alone in risk-stratified patients after resection of major salivary glands using a national database. The use of adjuvant radiation for high-risk major salivary gland cancers appears to offer a survival benefit. Although an overall survival benefit was not seen in low- and intermediate-risk salivary gland cancers, this study could not address impact on local control because of the limitations of the NCDB.

Background. Nephrology trials assessing the impact of interventions on “standard” outcomes, such as doubling of creatinine, end-stage renal disease (ESRD), and/or death, are difficult to conduct given the time required for endpoints to accrue. The objective of this study was to determine if using lesser declines in kidney function would alter the interpretation of a previous randomized controlled trial. Methods. This study was a secondary analysis of a kidney transplant trial comparing the use of a 40% or greater, 30% or greater, or 20% or greater decline in estimated glomerular filtration rate (eGFR) as a substitute for doubling of serum creatinine. Declines in eGFR were determined relative to baseline. This trial enrolled 212 kidney transplant patients with proteinuria and assessed the clinical impact of ramipril versus placebo on a primary outcome of doubling of serum creatinine, ESRD, or death. In this analysis, the declines in eGFR replaced doubling of creatinine in the composite endpoint. Results. Mean trial follow-up was 41 months. A time-to-event composite of death, ESRD, or a 40% or greater, 30% or greater, or 20% or greater eGFR decline occurred in 45 (26 placebo vs 19 ramipril), 68 (35 vs 33), and 99 (50 vs 49) patients, respectively. Substituting these eGFR declines for doubling of serum creatinine resulted in an increase of 12, 35, and 66 endpoints compared with the original trial. In all 3 eGFR declines, ramipril treatment was not associated with any statistically significant differences despite the increase in events. Conclusions. Substituting doubling of serum creatinine for lesser eGFR percentage decline thresholds did not alter trial interpretation but did increase the number of events.

Background. There is currently no agreement as to what constitutes quality transplant care, and there is a lack of consistency in the approach to assessing transplantation quality. We aimed to ascertain the views of patients, clinicians, and program administrators about quality care for kidney transplant patients. Methods. Semistructured qualitative interviews were conducted with 20 patients, 17 physicians, and 11 program administrators. Transcripts were analyzed using inductive thematic analysis. Results. We identified 8 themes: access to treatment (standardized transplant referral, lengthy transplant evaluation process, lengthy living donor evaluation); accessibility of services (alternative access options, flexible appointment availability, appropriate amount of follow-up, barriers for accessing care); program resources (comprehensive multidisciplinary care, knowledgeable staff, peer support groups, educational resources, patient navigators/ advocates); communication of information (taking time to answer questions, clear communication about treatment, communication tailored to patients, health promotion and illness prevention); attitude of care providers (positive and supportive attitude, patient centered care); health outcomes (freedom from dialysis, Long-term health, short-term health, fear of infections); patient satisfaction (returning to normal life, patient satisfaction with care); and safety (reducing infection risk, quick response to complications, patient health status on the waitlist). Conclusions. There is a need to move beyond basic clinical outcomes and focus on increasing ease of access, the patient-provider relationship, and outcomes that are most important to the patients.

Background. A shortage of transplantable organs is a global problem. The purpose of this study was to explore frontline intensive care unit professionals' and organ donor coordinators' perceptions and beliefs around the process of, and the barriers and enablers to, donation after circulatory determination death (DCDD). Methods. This qualitative descriptive study used a semistructured interview guide informed by the Theoretical Domains Framework to interview 55 key informants (physicians, nurses, and organ donation coordinators) in intensive care units (hospitals) and organ donation organizations across Canada. Results. Interviews were analyzed using a 6-step systematic approach: coding, generation of specific beliefs, identification of themes, aggregation of themes into categories, assignment of barrier or enabler and analysis for shared and unique discipline barriers and enablers. Seven broad categories encompassing 29 themes of barriers (n = 21) and enablers (n = 4) to DCDD use were identified; n = 4 (14%) themes were conflicting, acting as barriers and enablers. Most themes (n = 26) were shared across the 3 key informant groups while n = 3 themes were unique to physicians. The top 3 shared barriers were: (1) DCDD education is needed for healthcare professionals, (2) a standardized and systematic screening process to identify potential DCDD donors is needed, and (3) practice variation across regions with respect to communication about DCDD with families. A limited number of differences were found by region. Conclusions. Multiple barriers and enablers to DCDD use were identified. These beliefs identify potential individual, team, organization, and system targets for behavior change interventions to increase DCDD rates which, in turn, should lead to more transplantation, reducing patient morbidity and mortality at a population level.

Background. Patients, families, and caregivers have a unique understanding of the diseases they live with and provide care for every day. Their experience and expertise are important and should be taken into consideration when determining research priorities. The aim of this study was to gather the perspectives of Canadian patients, families, caregivers, researchers, and healthcare professionals on what research priorities were important to them in the field of organ and hematopoietic cell transplantation (HCT) and donation within the Canadian National Transplant Research Program (CNTRP). Methods. The CNTRP developed a national consultation process, which included a Web-based survey and in-person workshop, to ascertain and validate the viewpoints of the Canadian donation and transplant community. The Web-based survey identified 3 principal research priorities (increasing donation, developing better antirejection drugs and developing tolerance), which were further refined and prioritized during the one-and-a-half day national workshop held in Toronto in November 2015. Results. A total of 505 participants answered the Web-based survey, and 46 participants (28 patients, 12 researchers and 6 healthcare professionals) participated in the in-person workshop. Workshop participants ranked the following 2 priorities as the most important in the fields of donation, HCT, and solid organ transplantation: methods for developing a culture of donation (within healthcare organizations and throughout society); and methods for improving graft survival and antirejection therapy. Conclusion. The CNTRP will use these results to prioritize future research projects and studies in donation, HCT, and solid organ transplantation in the years to come.

Introduction: Collagenase Clostridium histolyticum (CCH) intralesional injection was efficacious for the management of Peyronie's disease (PD) in the double-blinded, randomized, placebo-controlled Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies I and II (IMPRESS I and II). Little is known about the consequences of PD or treatment on the sexual partners of affected men. Aim: To assess the safety and efficacy of CCH treatment in men who received placebo in the IMPRESS I or II study and to evaluate the men's PD symptoms and partner bother as reported by female sexual partners. Methods: In this phase 3, open-label study (NCT01685437), men (n = 189) received up to eight injections of CCH (0.58 mg/injection). Female sexual partners who provided informed consent at screening (n = 30) participated in the study. Main Outcome Measures: Co-primary end points were change or percentage of change in penile curvature deformity and change in PD symptom bother domain score of the Peyronie's Disease Questionnaire (PDQ) from baseline to week 36. Participating women completed the PDQ for female sexual partners (PDQ-FSP) and the Female Sexual Function Index (FSFI). Results: Statistically significant mean improvements were observed in penile curvature deformity (36.3% decrease; 95% CI = −41.6 to −30.9) and PDQ symptom bother score (2.4-point decrease; 95% CI = −3.0 to −1.8) from baseline to week 36. Most treatment-emergent adverse events were mild or moderate. After CCH treatment of their male partners, female sexual partners reported improvement (using the PDQ-FSP) in their male partner's PD symptoms and female bother regarding their partner's PD. The percentage of female sexual partners with sexual dysfunction (FSFI total score ≤ 26.55) also decreased after male partner treatment, from 75.0% at baseline to 33.3%. Conclusions: These results support the safety and efficacy of CCH in the management of appropriate patients with PD and the potential benefits for patients' partners. Goldstein I, Knoll LD, Lipshultz LI, et al. Changes in the Effects of Peyronie's Disease After Treatment With Collagenase Clostridium histolyticum: Male Partners and Their Female Partners. Sex Med 2017;5:e124–e130.

The SARS-COV2 pandemic caused significant disruptions in immunization delivery. Baseline deficit gaps in immunization completion exacerbated ongoing disparities in immunization coverage in low- and middle-income. Emerging reports focused on global strategies for return to routine immunization schedules. Currently, there are no studies that examined the dual challenge of returning to normal immunization in a conflict-recovery setting, such as the ISIS (Islamic State of Iraq and Syria) occupation of Iraq post-COVID-19 pandemic. The objective of this study was to estimate the number of children in Hadeetha, Iraq from 12 to 24 months of age who continued to be lost to the routine immunization schedule due to the COVID-19 pandemic shutdowns. Random sampling occurred from a compiled district health facility registrar of all children in the target birth cohort who had a 12-month immunization scheduled during the 2020 lockdown and were lost to the immunization schedule. A total of 171 households from the sampling frame were included in the final sample. In this cross-sectional study, survey data was collected on the head of the household, the caregiver and the child. Additional questions assessed vaccine hesitancy, vaccine information trusted sources and COVID-19 impact on healthcare access. A risk factor analysis was applied to assess using Chi-square (Χ 2 ) for predictors of lack of DTP3 (Diphtheria, Tetanus and Polio) third dose completion. Of children in the study, 67.3 % did not complete the 6-antigen series at 12-months of age and 46.2 % were missing DTP3 for vaccines to be completed during the pandemic shutdown. Specific risk factors for lack of immunization for the DTP3 vaccine included area of residence, age and caregiver knowledge of vaccines. Respondents indicated a dependence on mass vaccination campaigns but also indicated a willingness to receive phone reminders and television campaigns about vaccination schedules., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sara Al-Dahir reports a relationship with Pfizer Inc. that includes: funding grants. Sara Al-Dahir reports a relationship with Genentech Inc. that includes: funding grants. Kawsar Talaat reports a relationship with Pfizer that includes: funding grants. Kawsar Talaat reports a relationship with AstraZeneca Pharmaceuticals LP that includes: funding grants. Kawsar Talaat reports a relationship with Moderna Inc. that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: High priority efforts are underway to support the development of novel mucosal COVID-19 vaccines, such as the US Government's Project NextGen and the Center for Epidemic Preparedness Innovations' goal to respond to the next pandemic with a new vaccine in 100 days. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how to evaluate immunogenicity of mucosal vaccines. This study investigated the role of oral mucosal antibody responses in viral clearance and COVID-19 symptom duration., Methods: Participants with PCR-confirmed SARS-CoV-2 infection provided oral fluid for testing with SARS-CoV-2 antibody multiplex assays, nasal swabs for RT-PCR and symptom information at up to eight follow-ups from April 2020 to February 2022., Results: High and moderate oral fluid anti-spike (S) secretory IgA (SIgA) post infection was associated with significantly faster viral clearance and symptom resolution across age groups with effect sizes equivalent to having COVID-19 vaccine immunity at the time of infection. Those with high and moderate anti-S SIgA cleared the virus 14 days (95% CI: 10-18) and recovered 9-10 days (95% CI: 6-14) earlier. Delayed and higher anti-S IgG was associated with significantly longer time to clearance and recovery. Experiencing symptoms longer than four weeks was associated with lower anti-RBD SIgA 15-30 days after infection onset (p<0.001)., Conclusion: Robust mucosal SIgA early post infection appears to support faster clearance of SARS-CoV-2 and recovery from COVID-19 symptoms. This research underscores the importance of harmonizing mucosal immune response assays to evaluate new mucosal vaccines., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: Evidence of COVID-19 vaccine safety relied upon the global vaccine monitoring infrastructure due to shortened clinical development timelines and emergency use licensure. Differences in AVSS capacity between high-income countries (HICs) versus low- and middle-income countries (LMICs) were known prior to the pandemic., Objective: To assess the global landscape of COVID-19 vaccine AVSS activities to identify gaps in safety evidence generation across vaccine products and populations with a focus on LMICs., Methods: A cross-sectional survey was conducted in January 2022 on AVSS activities evaluating adverse events following immunization (AEFI). Data collected included country, targeted population, COVID-19 vaccine product(s), design of surveillance/monitoring activities or study, and AEFIs to be monitored.To supplement these findings, we conducted a literature review of COVID-19 vaccine safety activities published in PubMed through January 2023. Observational activities assessing AEFI, specifically adverse events of special interest (AESI), following routine use of COVID-19 vaccines in medical practice were included; systematic reviews, benefit/risk assessments, clinical trials, and case reports/series were excluded., Results: The survey, completed by 34 respondents and compiled with reviews of 7 publicly available Risk Management Plans from five vaccine manufacturers, identified 79 monitoring activities in HICs, 24 in LMICs, and 9 in multiple regions. Most activities in LMICs were planned cohort event monitoring (CEM) studies (n = 18); two multi-national hospital-based sentinel surveillance studies for AESI were ongoing. Activities in LMICs evaluated multiple COVID-19 vaccine products simultaneously and were sponsored by health authorities. The literature review identified 1245 unique citations, of which 379 met inclusion criteria. The majority evaluated vaccines primarily used in high-income countries: Pfizer BioNTech (Comirnaty; n = 303), Moderna (mRNA-1273; n = 164), AstraZeneca (AZD1222; n = 126), and Janssen (Ad26.COV2.S); n = 62); 14 citations assessed vaccines used exclusively in LMICs: Sinovac (CoronaVac), Beijing CNBG (BBIBP-Corv), Bharat (Covaxin), SII (Covashield), and Gamaleya (Gam-Covid-Vac) vaccines., Conclusions: Robust safety evidence for input into benefit/risk assessments is likely unavailable for most COVID-19 vaccines used primarily in LMICs due to emphasis on cohort event monitoring methods. Goals for equitable vaccine access should be coupled with investment and support for building infrastructure and capacity for safety evidence generation to inform policy and regulatory decisions at local levels., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Parisa ShamaeiZadeh reports financial support was provided by Coalition for Epidemic Preparedness Innovations. Parisa ShamaeiZadeh reports a relationship with Coalition for Epidemic Preparedness Innovations that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

Introduction: In 2012, the World Health Organization revised treatment guidelines for childhood pneumonia with lower chest wall indrawing (LCWI) but no 'danger signs', to recommend home-based treatment. We analysed data from children hospitalized with LCWI pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) study to identify sub-groups with high odds of mortality, who might continue to benefit from hospital management but may not be admitted by staff implementing the 2012 guidelines. We compare the proportion of deaths identified using the criteria in the 2012 guidelines, and the proportion of deaths identified using an alternative set of criteria from our model., Methods: PERCH enrolled a cohort of 2189 HIV-negative children aged 2-59 months who were admitted to hospital with LCWI pneumonia (without obvious cyanosis, inability to feed, vomiting, convulsions, lethargy or head nodding) between 2011-2014 in Kenya, Zambia, South Africa, Mali, The Gambia, Bangladesh, and Thailand. We analysed risk factors for mortality among these cases using predictive logistic regression. Malnutrition was defined as mid-upper-arm circumference <125mm or weight-for-age z-score <-2., Results: Among 2189 cases, 76 (3·6%) died. Mortality was associated with oxygen saturation <92% (aOR 3·33, 1·99-5·99), HIV negative but exposed status (4·59, 1·81-11·7), moderate or severe malnutrition (6·85, 3·22-14·6) and younger age (infants compared to children 12-59 months old, OR 2·03, 95%CI 1·05-3·93). At least one of three risk factors: hypoxaemia, HIV exposure, or malnutrition identified 807 children in this population, 40% of LCWI pneumonia cases and identified 86% of the children who died in hospital (65/76). Risk factors identified using the 2012 WHO treatment guidelines identified 66% of the children who died in hospital (n = 50/76)., Conclusions: Although it focuses on treatment failure in hospital, this study supports the proposal for better risk stratification of children with LCWI pneumonia. Those who have hypoxaemia, any malnutrition or those who were born to HIV positive mothers, experience poorer outcomes than other children with LCWI pneumonia. Consistent identification of these risk factors should be prioritised and children with at least one of these risk factors should not be managed in the community., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: During the coronavirus disease 2019 (COVID-19) pandemic, human parainfluenza type 3 (HPIV-3) and respiratory syncytial virus (RSV) circulation increased as nonpharmaceutical interventions were relaxed. Using data from 175 households (n = 690 members) followed between November 2020 and October 2021, we characterized HPIV-3 and RSV epidemiology in children aged 0-4 years and their households., Methods: Households with ≥1 child aged 0-4 years were enrolled; members collected weekly nasal swabs (NS) and additional NS with respiratory illnesses (RI). We tested NS from RI episodes in children aged 0-4 years for HPIV-3, RSV, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse-transcriptase polymerase chain reaction (RT-PCR). Among children with HPIV-3 or RSV infection, we tested contemporaneous NS from household members. We compared incidence rates (IRs) of RI with each virus during epidemic periods and identified household primary cases (the earliest detected household infection), and associated community exposures., Results: 41 of 175 (23.4%) households had individuals with HPIV-3 (n = 45) or RSV (n = 46) infections. Among children aged 0-4 years, RI IRs /1000 person-weeks were 8.7 [6.0, 12.2] for HPIV-3, 7.6 [4.8, 11.4] for RSV, and 1.9 [1.0, 3.5] for SARS-CoV-2. Children aged 0-4 years accounted for 35 of 36 primary HPIV-3 or RSV cases. Children attending childcare or preschool had higher odds of primary infection (odds ratio, 10.81; 95% confidence interval, 3.14-37.23)., Conclusions: Among children aged 0-4 years, RI IRs for HPIV-3 and RSV infection were 4-fold higher than for SARS-CoV-2 during epidemic periods. HPIV-3 and RSV were almost exclusively introduced into households by young children., Competing Interests: Potential conflicts of interest. M. K. H. and M. D. K. report grant support from the CDC during this study and from Pfizer that is unrelated to this work. J. O. and K. W. report grant support from the CDC and the National Institutes of Health (NIH) during this study. M. L. is an employee of Merck & Co, Inc, with responsibilities related to device development. R. A. K. reports grant support from the CDC and support from the NIH, Sanofi Pasteur, and the Bill and Melinda Gates Foundation for research pertaining to respiratory syncytial virus vaccines. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although 13-valent pneumococcal conjugate vaccine (PCV13) is available in China's private market, it has yet to be introduced into the National Immunization Programme (NIP) and is therefore not available to large parts of the population. This study aimed to estimate the cost-effectiveness of including PCV13 in China's NIP at national and provincial levels., Methods: We adopted a decision-tree Markov model to estimate the cost-effectiveness of adding 3-dose PCV13 in the NIP compared to the status quo in the private market from a societal perspective. The model hypothesized a birth cohort for five years after vaccine introduction. Treatment costs and vaccine program costs were calculated from Chinese Center for Disease Control and Prevention (CDC) and national insurance databases. Disease burden data, incidence rate ratios, and other parameters were derived from published and grey literature. Cases and deaths averted, quality-adjusted life years (QALYs) gained, and incremental cost-effectiveness ratios (ICERs) were estimated at the provincial, regional, and national levels. One-way, scenario and probabilistic sensitivity analyses were conducted to explore model uncertainty., Findings: At the national level, introducing PCV13 in the NIP was predicted to prevent approximately 4807 pneumococcal deaths (66% reduction) and 1,057,650 pneumococcal cases (17% reduction) in the first five years of the 2019 birth cohort. Under the assumed base case price of US$ 25 per dose in the NIP, PCV13 in the NIP was cost-effective nationally with ICER of US$ 5.222 per QALY gained, and was cost-effective in 17 and cost-saving in 4 of the 31 provinces compared to the status quo . One-way and scenario sensitivity analyses indicated robust results when varying all model parameters, and probabilistic sensitivity analysis showed a 98% probability of cost-effectiveness nationally., Interpretation: Our findings highlight the cost-effectiveness of introducing PCV13 in China's NIP. Provincial results supported subnational introduction of PCV13, and priority should be given to less socioeconomically developed provinces. Since vaccination cost is the most influential model parameter, efforts to improve PCV affordability after pooled procurement will benefit public health in a cost-effective manner., Funding: The Bill & Melinda Gates Foundation., Competing Interests: HF reports grants from the 10.13039/100000865Bill & Melinda Gates Foundation and 10.13039/100014588Sanofi Pasteur. BW reports grants from the 10.13039/100000865Bill & Melinda Gates Foundation. MDK reports grants from the 10.13039/100000865Bill & Melinda Gates Foundation, the 10.13039/100004423World Health Organization, 10.13039/100004334Merck, 10.13039/100004319Pfizer and Gavi Alliance, and personal fees from Merck. CG reports grants from the 10.13039/100000865Bill & Melinda Gates Foundation and 10.13039/100004319Pfizer, and personal fees from 10.13039/100004334Merck. All other authors declare no competing interests., (© 2022 The Authors.)

Background: The emergence of the Omicron variant (B.1.1.529), which correlated with dramatic losses in cross-neutralization capacity of post-vaccination sera, raised concerns about the effectiveness of COVID-19 vaccines against infection and disease. Several clinically relevant sub-variants subsequently emerged rapidly., Methods: We evaluated published and pre-print studies reporting sub-variant specific reductions in cross-neutralization compared to the prototype strain of SARS-CoV-2 and between sub-variants. Median fold-reduction across studies was calculated by sub-variant and vaccine platform., Results: Among 178 studies with post-vaccination data, after primary vaccination the sub-variant specific fold-reduction in neutralization capacity compared to the prototype antigen varied widely, from median 4.2-fold for BA.3 to 40.1-fold for BA.2.75; in boosted participants fold-reduction was similar for most sub-variants (5.3-fold to 7.0-fold); however, a more pronounced fold-change was observed for sub-variants related to BA.4 and BA.5 (10.4-fold to 14.2-fold). Relative to BA.1, the other Omicron sub-variants had similar neutralization capacity post-primary vaccination (range median 0.8-fold to 1.1-fold) and post-booster (0.9-fold to 1.4-fold) except for BA.4/5-related sub-variants which was higher (2.1-fold to 2.7-fold). Omicron sub-variant-specific responder rates were low post-primary vaccination (range median 28.0% to 65.9%) compared to the prototype (median 100%) but improved post-booster (range median 73.3% to 100%)., Conclusions: Fold-reductions in neutralization titers were comparable post-booster except for sub-variants related to BA.4 and BA.5, which had higher fold-reduction. Assessment after primary vaccination was not possible because of overall poor neutralization responses causing extreme heterogeneity. Considering large fold-decreases in neutralization titers relative to the parental strain for all Omicron sub-variants, vaccine effectiveness is very likely to be reduced against all Omicron sub-variants, and probably more so against variants related to BA.4 or BA.5.

Background: In Nepal, Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial pneumonia in children, and is a major health concern. There are few data on the effect of vaccination on the disease or colonisation with pneumococci in the nasopharynx of children in this setting. The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine infant immunisation schedule in Nepal in 2015. We aimed to investigate the effect of the introduction of PCV10 on pneumococcal carriage and disease in children in Nepal., Methods: We did an observational cohort study in children in Nepal. The hospital surveillance study took place in Patan Hospital, Kathmandu, and community studies in healthy children took place in Kathmandu and Okhaldhunga district. For the surveillance study, all children admitted to Patan Hospital between March 20, 2014, and Dec 31, 2019, aged between 2 months and 14 years with clinician-suspected pneumonia, were eligible for enrolment. For the community study, healthy children aged 0-8 weeks, 6-23 months, and 24-59 months were recruited from Kathmandu, and healthy children aged 6-23 months were recruited from Okhaldhunga. We assessed the programmatic effect of PCV10 introduction using surveillance for nasopharyngeal colonisation, pneumonia, and invasive bacterial disease from 1·5 years before vaccine introduction and 4·5 years after vaccine introduction. For the surveillance study, nasopharyngeal swabs, blood cultures, and chest radiographs were obtained from children admitted to Patan Hospital with suspected pneumonia or invasive bacterial disease. For the community study, nasopharyngeal swabs were obtained from healthy children in the urban and rural settings. Pneumonia outcomes were analysed using log-binomial models and adjusted prevalence ratios (aPR) comparing each calendar year after the introduction of the vaccine into the national programme with the pre-vaccine period (2014-15), adjusted for calendar month, age, and sex., Findings: Between March 20, 2014, and Dec 31, 2019, we enrolled 2051 children with suspected pneumonia, and 11 354 healthy children (8483 children aged 6-23 months, 761 aged 24-59 months, and 2110 aged 0-8 weeks) to assess nasopharyngeal colonisation. Among clinical pneumonia cases younger than 2 years, vaccine serotype carriage declined 82% (aPR 0·18 [95% CI 0·07-0·50]) by 2019. There was no decrease in vaccine serotype carriage in cases among older unvaccinated age groups. Carriage of the additional serotypes in PCV13 was 2·2 times higher by 2019 (aPR 2·17 [95% CI 1·16-4·05]), due to increases in serotypes 19A and 3. Vaccine serotype carriage in healthy children declined by 75% in those aged 6-23 months (aPR 0·25 [95% CI 0·19-0·33]) but not in those aged 24-59 months (aPR 0·59 [0·29-1·19]). A decrease in overall vaccine serotype carriage of 61% by 2019 (aPR 0·39 [95% CI 0·18-0·85]) was also observed in children younger than 8 weeks who were not yet immunised. Carriage of the additional PCV13 serotypes in children aged 6-23 months increased after PCV10 introduction for serotype 3 and 19A, but not for serotype 6A. The proportion of clinical pneumonia cases with endpoint consolidation on chest radiographs declined from 41% in the pre-vaccine period to 25% by 2018, but rose again in 2019 to 36%., Interpretation: The introduction of the PCV10 vaccine into the routine immunisation programme in Nepal has reduced vaccine serotype carriage in both healthy children and children younger than 2 years with pneumonia. Increases in serotypes 19A and 3 highlight the importance of continued surveillance to monitor the effect of vaccine programmes. This analysis demonstrates a robust approach to assessing vaccine effect in situations in which pneumococcal disease endpoint effectiveness studies are not possible., Funding: Gavi, the Vaccine Alliance and the World Health Organization., Competing Interests: Declaration of interests AJP is Chair of the UK Department of Health and Social Care's Joint Committee on Vaccination and Immunisation and was a member of WHO's SAGE until 2022. KLO'B was a member of WHO's SAGE and is now Director of Immunisation at WHO. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Estimates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in young children and risk factors for seropositivity are scarce. Using data from a prospective cohort study of households during the pre-coronavirus disease 2019 (COVID-19) vaccine period, we estimated SARS-CoV-2 seroprevalence by age and evaluated risk factors for SARS-CoV-2 seropositivity., Methods: The SARS-CoV-2 Epidemiology and Response in Children (SEARCh) study enrolled 175 Maryland households (690 participants) with ≥1 child aged 0-4 years during November 2020-March 2021; individuals vaccinated against COVID-19 were ineligible. At enrollment, participants completed questionnaires about sociodemographic and health status and work, school, and daycare attendance. Participants were tested for SARS-CoV-2 antibodies in sera. Logistic regression models with generalized estimating equations (GEE) to account for correlation within households assessed predictors of individual- and household-level SARS-CoV-2 seropositivity., Results: Of 681 (98.7%) participants with enrollment serology results, 55 (8.1%; 95% confidence interval [CI], 6.3%-10.4%) participants from 21 (12.0%) households were seropositive for SARS-CoV-2. Among seropositive participants, fewer children than adults reported being tested for SARS-CoV-2 infection before enrollment (odds ratio [OR] = 0.23; 95% CI, .06-.73). Seropositivity was similar by age (GEE OR vs 0-4 years: 1.19 for 5-17 years, 1.36 for adults; P = .16) and was significantly higher among adults working outside the home (GEE adjusted OR = 2.2; 95% CI, 1.1-4.4) but not among children attending daycare or school., Conclusions: Before study enrollment, children and adults in this cohort had similar rates of SARS-CoV-2 infection as measured by serology. An adult household member working outside the home increased a household's odds of SARS-CoV-2 infection, whereas a child attending daycare or school in person did not., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Few studies have prospectively assessed SARS-CoV-2 community infection in children aged 0 to 4 years. Information about SARS-CoV-2 incidence and clinical and virological features in young children could help guide prevention and mitigation strategies., Objective: To assess SARS-CoV-2 incidence, clinical and virological features, and symptoms in a prospective household cohort and to compare viral load by age group, symptoms, and SARS-CoV-2 lineage in young children, older children, and adults., Design, Setting, and Participants: This prospective cohort study enrolled 690 participants from 175 Maryland households with 1 or more children aged 0 to 4 years between November 24, 2020, and October 15, 2021. For 8 months after enrollment, participants completed weekly symptom questionnaires and submitted self-collected nasal swabs for SARS-CoV-2 qualitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing, quantitative RT-PCR testing, and viral lineage determination. For the analyses, SARS-CoV-2 Alpha and Delta lineages were considered variants of interest or concern. Sera collected at enrollment and at approximately 4 months and 8 months after enrollment were assayed for SARS-CoV-2 spike and nucleocapsid protein antibodies., Main Outcomes and Measures: Incidence, clinical and virological characteristics, and symptoms of SARS-CoV-2 infection by age group and correlations between (1) highest detected viral load and symptom frequency and (2) highest detected viral load and SARS-CoV-2 lineage., Results: Among 690 participants (355 [51.4%] female and 335 [48.6%] male), 256 individuals (37.1%) were children aged 0 to 4 years, 100 (14.5%) were children aged 5 to 17 years, and 334 (48.4%) were adults aged 18 to 74 years. A total of 15 participants (2.2%) were Asian, 24 (3.5%) were Black, 603 (87.4%) were White, 43 (6.2%) were multiracial, and 5 (0.7%) were of other races; 33 participants (4.8%) were Hispanic, and 657 (95.2%) were non-Hispanic. Overall, 54 participants (7.8%) had SARS-CoV-2 infection during the surveillance period, including 22 of 256 children (8.6%) aged 0 to 4 years, 11 of 100 children (11.0%) aged 5 to 17 years, and 21 of 334 adults (6.3%). Incidence rates per 1000 person-weeks were 2.25 (95% CI, 1.28-3.65) infections among children aged 0 to 4 years, 3.48 (95% CI, 1.59-6.61) infections among children aged 5 to 17 years, and 1.08 (95% CI, 0.52-1.98) infections among adults. Children aged 0 to 17 years with SARS-CoV-2 infection were more frequently asymptomatic (11 of 30 individuals [36.7%]) compared with adults (3 of 21 individuals [14.3%]), with children aged 0 to 4 years most frequently asymptomatic (7 of 19 individuals [36.8%]). The highest detected viral load did not differ between asymptomatic vs symptomatic individuals overall (median [IQR], 2.8 [1.5-3.3] log10 copies/mL vs 2.8 [1.8-4.4] log10 copies/mL) or by age group (median [IQR] for ages 0-4 years, 2.7 [2.4-4.4] log10 copies/mL; ages 5-17 years: 2.4 [1.1-4.0] log10 copies/mL; ages 18-74 years: 2.9 [1.9-4.6] log10 copies/mL). The number of symptoms was significantly correlated with viral load among adults (R = 0.69; P < .001) but not children (ages 0-4 years: R = 0.02; P = .91; ages 5-17 years: R = 0.18; P = .58). The highest detected viral load was greater among those with Delta variant infections (median [IQR], 4.4 [3.9-5.1] log10 copies/mL) than those with infections from variants not of interest or concern (median [IQR], 1.9 [1.1-3.6] log10 copies/mL; P = .009) or those with Alpha variant infections (median [IQR], 2.6 [2.3-3.4] log10 copies/mL; P = .006)., Conclusions and Relevance: In this study, SARS-CoV-2 infections were frequently asymptomatic among children aged 0 to 4 years; the presence and number of symptoms did not correlate with viral load. These findings suggest that symptom screening may be insufficient to prevent outbreaks involving young children.

Assessing COVID-19 vaccine effectiveness against emerging SARS-CoV-2 variants is crucial for determining future vaccination strategies and other public health strategies. When clinical effectiveness data are unavailable, a common method of assessing vaccine performance is to utilize neutralization assays using post-vaccination sera. Neutralization studies are typically performed across a wide array of settings, populations and vaccination strategies, and using different methodologies. For any comparison and meta-analysis to be meaningful, the design and methodology of the studies used must at minimum address aspects that confer a certain degree of reliability and comparability. We identified and characterized three important categories in which studies differ (cohort details, assay details and data reporting details) and that can affect the overall reliability and/or usefulness of neutralization assay results. We define reliability as a measure of methodological accuracy, proper study setting concerning subjects, samples and viruses, and reporting quality. Each category comprises a set of several relevant key parameters. To each parameter, we assigned a possible impact (ranging from low to high) on overall study reliability depending on its potential to influence the results. We then developed a reliability assessment tool that assesses the aggregate reliability of a study across all parameters. The reliability assessment tool provides explicit selection criteria for inclusion of comparable studies in meta-analyses of neutralization activity of SARS-CoV-2 variants in post-vaccination sera and can also both guide the design of future neutralization studies and serve as a checklist for including important details on key parameters in publications.

Background: Vaccination against Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib) is not included in China's national immunization programme. To inform China's immunization polices, we estimated annual national, regional, and provincial childhood mortality and morbidity attributable to pneumococcus and Hib in 2010-17., Methods: We estimated proportions of pneumonia and meningitis deaths and cases attributable to pneumococcus and Hib using evidence from vaccine clinical trials and surveillance studies of bacterial meningitis and pathogen-specific case fatality ratios (CFR). Then we applied the proportions to model provincial-level pneumonia cases and deaths, meningitis deaths and meningitis CFR in children aged 1-59 months, accounting for vaccine coverage. Non-pneumonia, non-meningitis (NPNM) invasive disease cases were derived by applying NPNM meningitis ratios to meningitis estimates., Findings: In 2010-17, annual pneumococcal deaths fell by 49% from 15 600 (uncertainty range: 10 800-17 300) to 8 000 (5 500-8 900), and Hib deaths fell by 56% from 6 500 (4 500-8 800) to 2 900 (2 000-3 900). Severe pneumococcal and Hib cases decreased by 16% to 218 200 (161 500-252 200) in 2017 and 29% to 49 900 (29 000-99 100). Estimated 2017 national three-dose coverage in private market was 1·3% for PCV and 33·4% for Hib vaccine among children aged 1-59 months. Provinces in the west region had the highest disease burden., Interpretation: Childhood mortality and morbidity attributable to pneumococcal and Hib has decreased in China, but still substantially varied by region and province. Higher vaccine coverage could further reduce disease burden., Funding: Bill & Melinda Gates Foundation., Competing Interests: HF reports grants from the Bill & Melinda Gates Foundation and Sanofi Pasteur. BW reports grants from the Bill & Melinda Gates Foundation. MDK reports grants from the Bill & Melinda Gates Foundation, Pfizer and Gavi Alliance, and personal fees from Merck. CG reports grants from the Bill & Melinda Gates Foundation and Pfizer, and personal fees from Merck. All other authors declare no competing interests., (© 2022 The Author(s).)

Background: Globally, Haemophilus influenzae type b (Hib) vaccine has substantially reduced the burden of Hib invasive disease. However, China remains the only country not to include Hib vaccine into its national immunization program (NIP), although it accounts for 11% of global Hib deaths. We aimed to assess the cost-effectiveness of including Hib vaccine in China's NIP at the national and provincial levels., Methods: Using a decision-tree Markov state transition model, we estimated the cost-effectiveness of Hib vaccine in the NIP compared to the status quo of Hib vaccine in the private market for the 2017 birth cohort. Treatment costs and vaccine program costs were calculated from Chinese Center for Disease Control and Prevention (CDC) and national insurance databases. Epidemiological data and other model parameters were obtained from published literature. Cases and deaths averted, quality-adjusted life years (QALYs) gained, and incremental cost-effectiveness ratios (ICER) were predicted by province. Deterministic and probabilistic sensitivity analyses were performed to explore model uncertainty., Results: Including Hib vaccine in the NIP was projected to prevent approximately 2700 deaths (93% reduction) and 235,700 cases of Hib disease (92% reduction) for the 2017 birth cohort at the national level. Hib vaccine was cost-effective nationally (US$ 8001 per QALY gained) compared to the GDP per capita and cost-effective in 15 of 31 provinces. One-way and scenario sensitivity analyses indicated results were robust when varying model parameters, and in probabilistic sensitivity analysis, Hib vaccine had a 64% probability of being cost-effective nationally., Conclusion: Introducing Hib vaccine in China's NIP is cost-effective nationally and in many provinces. Less socioeconomically developed provinces with high Hib disease burden and low access to Hib vaccine in the current private market, such as those in the west region, would benefit the most from adding Hib vaccine to the NIP. In the absence of a national policy decision on Hib vaccine, this analysis provides evidence for provincial governments to include Hib vaccine into local immunization programs to substantially reduce disease burden and treatment costs., (© 2021. The Author(s).)

Competing Interests: Conflicts of Interest:No potential conflicts of interest was reported by the authors.

Rhinovirus (RV) is commonly detected in asymptomatic children; hence, its pathogenicity during childhood pneumonia remains controversial. We evaluated RV epidemiology in HIV-uninfected children hospitalized with clinical pneumonia and among community controls. PERCH was a case-control study that enrolled children (1-59 months) hospitalized with severe and very severe pneumonia per World Health Organization clinical criteria and age-frequency-matched community controls in seven countries. Nasopharyngeal/oropharyngeal swabs were collected for all participants, combined, and tested for RV and 18 other respiratory viruses using the Fast Track multiplex real-time PCR assay. RV detection was more common among cases (24%) than controls (21%) (aOR = 1.5, 95%CI:1.3-1.6). This association was driven by the children aged 12-59 months, where 28% of cases vs. 18% of controls were RV-positive (aOR = 2.1, 95%CI:1.8-2.5). Wheezing was 1.8-fold (aOR 95%CI:1.4-2.2) more prevalent among pneumonia cases who were RV-positive vs. RV-negative. Of the RV-positive cases, 13% had a higher probability (>75%) that RV was the cause of their pneumonia based on the PERCH integrated etiology analysis; 99% of these cases occurred in children over 12 months in Bangladesh. RV was commonly identified in both cases and controls and was significantly associated with severe pneumonia status among children over 12 months of age, particularly those in Bangladesh. RV-positive pneumonia was associated with wheezing.

Background: The World Health Organization (WHO)-defined radiological pneumonia is a preferred endpoint in pneumococcal vaccine efficacy and effectiveness studies in children. Automating the WHO methodology may support more widespread application of this endpoint., Methods: We trained a deep learning model to classify pneumonia CXRs in children using the World Health Organization (WHO)'s standardized methodology. The model was pretrained on CheXpert, a dataset containing 224,316 adult CXRs, and fine-tuned on PERCH, a pediatric dataset containing 4,172 CXRs. The model was then tested on two pediatric CXR datasets released by WHO. We also compared the model's performance to that of radiologists and pediatricians., Results: The average area under the receiver operating characteristic curve (AUC) for primary endpoint pneumonia (PEP) across 10-fold validation of PERCH images was 0.928; average AUC after testing on WHO images was 0.977. The model's classification performance was better on test images with high inter-observer agreement; however, the model still outperformed human assessments in AUC and precision-recall spaces on low agreement images., Conclusion: A deep learning model can classify pneumonia CXR images in children at a performance comparable to human readers. Our method lays a strong foundation for the potential inclusion of computer-aided readings of pediatric CXRs in vaccine trials and epidemiology studies., Competing Interests: Yiyun Chen, Tanaz Petigara, Wanmei Ou, Craig S. Robert, Gregory V. Goldmacher were employees of Merck & Co., Inc. during the conduct of the study. Maria Deloria Knoll received grant from Merck & Co. to cover expenses related to preparing the PERCH dataset shared for use in the study, and for consulting on the manuscripts. The commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials.

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites ( N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites ( N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.

Background: The COVID-19 pandemic has caused significant diseases and economic burdens in the world. Vaccines are often considered as a cost-effective way to prevent and control infectious diseases, and the research and development of COVID-19 vaccines have been progressing unprecedently. It is needed to understand individuals' willingness to pay (WTP) among general population, which provides information about social demand, access and financing for future COVID-19 vaccination., Objective: To investigate individuals' WTP and financing mechanism preference for COVID-19 vaccination during the pandemic period in China., Methods: During March 1-18, 2020, we conducted a network stratified random sampling survey with 2058 respondents in China. The survey questionnaires included out-of-pocket WTP, financing mechanism preference as well as basic characteristics of the respondents; risk perception and impact of the COVID-19 pandemic; attitude for future COVID-19 vaccination. Multivariable Tobit regression was used to determine impact factors for respondents' out-of-pocket WTP., Results: The individuals' mean WTP for full COVID-19 vaccination was CNY 254 (USD 36.8) with median of CNY 100 (USD 14.5). Most respondents believed that governments (90.9%) and health insurance (78.0%) needed to pay for some or full portions of COVID-19 vaccination, although 84.3% stated that individuals needed to pay. Annual family income, employee size in the workplace, and whether considering the COVID-19 pandemic in China in a declining trend affected respondents' WTP significantly., Conclusion: The findings demonstrated the individuals' WTP for COVID-19 vaccination in China and their preferences for financing sources from individuals, governments and health insurance. And to suggest an effective and optimal financing strategy, the public health perspective with equal access to COVID-19 vaccination should be prioritized to ensure a high vaccination rate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

By 2050, the number of adults over 65 years of age will be double the under-5 population, and heavily concentrated in low- and middle-income countries. Population growth and increasing life expectancies call for effective healthy aging strategies inclusive of immunization to reduce the burden of vaccine-preventable diseases, improve quality of life, and mitigate antimicrobial resistance. Based on a review of available literature on the pneumococcal disease, influenza, and herpes zoster epidemiology and economic burden, and the health systems and policy barriers for adult immunization, we identified evidence gaps and considerations for prioritizing adult immunization. The body of evidence for adult immunization and the health and economic burden of adult disease is heavily concentrated in high-income countries. The few countries reporting adult immunization policies generally focus on high-risk groups. Despite robust child immunization programs in most countries, adult immunization programs and policies lag far behind and there is a general lack of appropriate delivery platforms. Global adult disease burden and economic costs are substantial but evidence from low- and middle-income countries is limited. There is a need for a strengthened evidence base and political commitment to drive a comprehensive, global technical consensus on adult immunization., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Lois Privor-Dumm has previously received funding from drug companies for investigator driven policy research (Pfizer, GSK and Merck). This does not alter our adherence to Vaccine policies on sharing data and materials. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The World Health Organization (WHO) has developed a global roadmap to defeat meningitis by 2030. To advocate for and track progress of the roadmap, the burden of meningitis as a syndrome and by pathogen must be accurately defined. Three major global health models estimating meningitis mortality as a syndrome and/or by causative pathogen were identified and compared for the baseline year 2015. Two models, (1) the WHO and the Johns Hopkins Bloomberg School of Public Health's Maternal and Child Epidemiology Estimation (MCEE) group's Child Mortality Estimation (WHO-MCEE) and (2) the Institute for Health Metrics and Evaluation (IHME) Global Burden of Disease Study (GBD 2017), identified meningitis, encephalitis and neonatal sepsis, collectively, to be the second and third largest infectious killers of children under five years, respectively. Global meningitis/encephalitis and neonatal sepsis mortality estimates differed more substantially between models than mortality estimates for selected infectious causes of death and all causes of death combined. Estimates at national level and by pathogen also differed markedly between models. Aligning modelled estimates with additional data sources, such as national or sentinel surveillance, could more accurately define the global burden of meningitis and help track progress against the WHO roadmap.

Background: Whether digitally recorded lung sounds are associated with radiographic pneumonia or clinical outcomes among children in low-income and middle-income countries is unknown. We sought to address these knowledge gaps., Methods: We enrolled 1 to 59monthold children hospitalized with pneumonia at eight African and Asian Pneumonia Etiology Research for Child Health sites in six countries, recorded digital stethoscope lung sounds, obtained chest radiographs, and collected clinical outcomes. Recordings were processed and classified into binary categories positive or negative for adventitial lung sounds. Listening and reading panels classified recordings and radiographs. Recording classification associations with chest radiographs with World Health Organization (WHO)-defined primary endpoint pneumonia (radiographic pneumonia) or mortality were evaluated. We also examined case fatality among risk strata., Results: Among children without WHO danger signs, wheezing (without crackles) had a lower adjusted odds ratio (aOR) for radiographic pneumonia (0.35, 95% confidence interval (CI): 0.15, 0.82), compared to children with normal recordings. Neither crackle only (no wheeze) (aOR: 2.13, 95% CI: 0.91, 4.96) or any wheeze (with or without crackle) (aOR: 0.63, 95% CI: 0.34, 1.15) were associated with radiographic pneumonia. Among children with WHO danger signs no lung recording classification was independently associated with radiographic pneumonia, although trends toward greater odds of radiographic pneumonia were observed among children classified with crackle only (no wheeze) or any wheeze (with or without crackle). Among children without WHO danger signs, those with recorded wheezing had a lower case fatality than those without wheezing (3.8% vs. 9.1%, p = .03)., Conclusions: Among lower risk children without WHO danger signs digitally recorded wheezing is associated with a lower odds for radiographic pneumonia and with lower mortality. Although further research is needed, these data indicate that with further development digital auscultation may eventually contribute to child pneumonia care., (© 2020 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: The absolute number of pneumonia deaths in India has declined substantially since 2000. However, pneumonia remains a major cause of morbidity in children in the country. We used a risk factor-based model to estimate pneumonia and severe pneumonia morbidity in Indian states in 2000 and 2015., Methods: In this modelling study, we estimated the burden of pneumonia and severe pneumonia in children younger than 5 years using a risk factor-based model. We did a systematic literature review to identify published data on the incidence of pneumonia from community-based longitudinal studies and calculated summary estimates. We estimated state-specific incidence rates for WHO-defined clinical pneumonia between 2000 and 2015 using Poisson regression and the prevalence of risk factors in each state was obtained from National Family Health Surveys. From clinical pneumonia studies, we identified studies reporting the proportion of clinical pneumonia cases with lower chest wall indrawing to estimate WHO-defined severe pneumonia cases. We used the estimate of the proportion of cases with lower chest wall indrawing to estimate WHO-defined severe pneumonia cases for each state., Findings: Between 2000 and 2015, the estimated number of pneumonia cases in Indian HIV-uninfected children younger than 5 years decreased from 83·8 million cases (95% uncertainty interval [UI] 14·0-300·8) to 49·8 million cases (9·1-174·2), representing a 41% reduction in pneumonia cases. The incidence of pneumonia in children younger than 5 years in India was 657 cases per 1000 children (95% UI 110-2357) in 2000 and 403 cases per 1000 children (74-1408) in 2015. The estimated national pneumonia case fatality rate in 2015 was 0·38% (95% UI 0·11-2·10). In 2015, the estimated number of severe pneumonia cases was 8·4 million (95% UI 1·2-31·7), with an incidence of 68 cases per 1000 children (9-257) and a case fatality ratio of 2·26% (0·60-16·30). In 2015, the estimated number of pneumonia cases in HIV-uninfected children was highest in Uttar Pradesh (12·4 million [95% UI 2·1-45·0]), Bihar (7·3 million [1·3-26·1]), and Madhya Pradesh (4·6 million [0·7-17·0]). Between 2000 and 2015, the greatest reduction in pneumonia cases was observed in Kerala (82% reduction). In 2015, pneumonia incidence was greater than 500 cases per 1000 children in two states: Uttar Pradesh (565 cases per 1000 children [95% UI 94-2047]) and Madhya Pradesh (563 cases per 1000 children [88-2084])., Interpretation: The estimated number of pneumonia and severe pneumonia cases among children younger than 5 years in India decreased between 2000 and 2015. Improvements in socioeconomic indicators and specific government initiatives are likely to have contributed to declines in the prevalence of pneumonia risk factors in many states. However, pneumonia incidence in many states remains high. The introduction of new vaccines that target pneumonia pathogens and reduce risk factors will help further reduce the burden of pneumonia in the country., Funding: Bill & Melinda Gates Foundation., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Faced with the coronavirus disease 2019 (COVID-19) pandemic, the development of COVID-19 vaccines has been progressing at an unprecedented rate. This study aimed to evaluate the acceptance of COVID-19 vaccination in China and give suggestions for vaccination strategies and immunization programs accordingly., Methods: In March 2020, an anonymous cross-sectional survey was conducted online among Chinese adults. The questionnaire collected socio-demographic characteristics, risk perception, the impact of COVID-19, attitudes, acceptance and attribute preferences of vaccines against COVID-19 during the pandemic. Multivariate logistic regression was performed to identify the influencing factors of vaccination acceptance., Results: Of the 2058 participants surveyed, 1879 (91.3%) stated that they would accept COVID-19 vaccination after the vaccine becomes available, among whom 980 (52.2%) wanted to get vaccinated as soon as possible, while others (47.8%) would delay the vaccination until the vaccine's safety was confirmed. Participants preferred a routine immunization schedule (49.4%) to emergency vaccination (9.0%) or either of them (41.6%). Logistic regression showed that being male, being married, perceiving a high risk of infection, being vaccinated against influenza in the past season, believing in the efficacy of COVID-19 vaccination or valuing doctor's recommendations could increase the probability of accepting COVID-19 vaccination as soon as possible, while having confirmed or suspected cases in local areas, valuing vaccination convenience or vaccine price in decision-making could hinder participants from immediate vaccination., Conclusion: During the pandemic period, a strong demand for and high acceptance of COVID-19 vaccination has been shown among the Chinese population, while concerns about vaccine safety may hinder the promotion of vaccine uptake. To expand vaccination coverage, immunization programs should be designed to remove barriers in terms of vaccine price and vaccination convenience, and health education and communication from authoritative sources are important ways to alleviate public concerns about vaccine safety.

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.