•After 10 years of post-marketing use, safety of zoster vaccine live remains favorable.•93% of reports of adverse experiences were non-serious.•Injection-site reactions were the most commonly ...reported adverse experience.•Vaccine-strain varicella-zoster virus was identified by PCR in 14 specimens.•Disseminated herpes zoster was reported very rarely.
Zoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed.
All post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed.
A total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination.
The safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies.
Abstract
Background
The VARIVAX® Pregnancy Registry was established in 1995 to monitor pregnancy outcomes of women who received varicella vaccine (ie, VARIVAX) inadvertently while pregnant.
Methods
...Health care providers and consumers sent voluntary reports about women who received VARIVAX 3 months before or during pregnancy. Follow-up occurred to evaluate pregnancy outcomes for birth defects. Outcomes from prospectively reported pregnancy exposures (ie, reports received before the outcome of the pregnancy was known) among varicella-zoster virus (VZV)-seronegative women were used to calculate rates and 95% confidence intervals (CIs).
Results
From 17 March 1995 through 16 October 2013, 1601 women were enrolled—966 prospectively—among whom there were 819 live births. Among 164 infants born to women who were VZV seronegative at the time of vaccination, no cases of congenital varicella syndrome (CVS) were identified (rate, 0 per 100, 95% CI, 0.0–2.2) and the birth prevalence of major birth defects was 4.3 per 100 liveborn infants (95% CI 1.7–8.6) with no pattern suggestive of CVS. No defects consistent with CVS were identified in any registry reports.
Conclusions
Data collected through the VARIVAX pregnancy registry do not support a relationship between the occurrence of CVS or major birth defects and varicella vaccine exposure during pregnancy, although the small numbers of exposures cannot rule out a low risk. VARIVAX remains contraindicated during pregnancy.
ZOSTAVAX (ZVL; Zoster Virus Live), is a single dose, live, attenuated vaccine licensed for the prevention of herpes zoster (HZ) and post herpetic neuralgia (PHN) in adults ≥50 years of age. Injection ...site adverse events (AEs) of erythema, swelling and pain were solicited within 5 days post vaccination in the 2 pivotal studies of ZVL; ZEST (ZOSTAVAX Efficacy and Safety Trial) and SPS (Shingles Prevention Study). Protocol specified criteria were used to report the frequency and intensity of injection site AEs in ZEST and SPS studies. Subsequently, the FDA Toxicity Grading Scale provided guidance for uniform assessment of AEs across all adult vaccine clinical trials. The objective of this post-hoc analysis was to categorize the previously reported injection site AEs in two pivotal trials of ZVL according to the current FDA Toxicity Grading Scale.
The current FDA Toxicity Grading Scale provides a measure for classifying injection site AEs by four grades Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe) and Grade 4 (life threatening). Injection site erythema, swelling, and pain intensity gradings were assigned to the respective FDA Toxicity Grade based on this appropriation. A descriptive analysis of the proportion and risk difference (within 95% confidence intervals) of injection site AEs per the FDA Toxicity Grading Scale is provided.
The frequency of injection site AEs (erythema, swelling, pain) after subcutaneous vaccination with ZVL were higher in recipients of ZVL compared with placebo. Majority of the injection site AEs observed were Grade 1 (mild) or Grade 2 (moderate) in intensity. Additionally, Grade 3 (severe) injection site AEs were observed infrequently.
Application of the FDA Toxicity Grading Scale provides a uniform AE assessment tool across different adult vaccines. This post hoc summary of injection site AEs using FDA Toxicity Grading Scale provides further evidence of low frequency of severe injection site AEs post ZVL vaccination.
Vaccines that contain live attenuated varicella-zoster virus (VZV) (Varivax, ProQuad, and Zostavax all products of Merck & Co., Inc.) are contraindicated during pregnancy. To monitor the pregnancy ...outcomes of women inadvertently vaccinated with VZV-containing vaccines immediately before or during pregnancy, Merck and CDC established the Merck/CDC Pregnancy Registry for VZV-Containing Vaccines in 1995. This report updates previously published summaries of registry data, provides the rationale for the closure of the registry, and describes plans for continued monitoring of the safety of these vaccines when inadvertently administered to pregnant women or immediately before pregnancy. From inception of the registry in 1995 through March 2012, no cases of congenital varicella syndrome and no increased prevalence of other birth defects have been detected among women vaccinated within 3 months before or during pregnancy. Although a small risk for congenital varicella syndrome cannot be ruled out, the number of exposures being registered each year (approximately two varicella-susceptible women exposed during the high-risk period for congenital varicella syndrome) is now too low to improve on the current estimate of the risk.
Background: ZOSTAVAX (ZVL; Zoster Virus Live), is a single dose, live, attenuated vaccine licensed for the prevention of herpes zoster (HZ) and post herpetic neuralgia (PHN) in adults ≥50 years of ...age. Injection site adverse events (AEs) of erythema, swelling and pain were solicited within 5 days post vaccination in the 2 pivotal studies of ZVL; ZEST (
Z
OSTAVAX
E
fficacy and
S
afety
T
rial) and SPS (
S
hingles
P
revention
S
tudy). Protocol specified criteria were used to report the frequency and intensity of injection site AEs in ZEST and SPS studies. Subsequently, the FDA Toxicity Grading Scale provided guidance for uniform assessment of AEs across all adult vaccine clinical trials. The objective of this post-hoc analysis was to categorize the previously reported injection site AEs in two pivotal trials of ZVL according to the current FDA Toxicity Grading Scale.
Methods: The current FDA Toxicity Grading Scale provides a measure for classifying injection site AEs by four grades Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe) and Grade 4 (life threatening). Injection site erythema, swelling, and pain intensity gradings were assigned to the respective FDA Toxicity Grade based on this appropriation. A descriptive analysis of the proportion and risk difference (within 95% confidence intervals) of injection site AEs per the FDA Toxicity Grading Scale is provided.
Results: The frequency of injection site AEs (erythema, swelling, pain) after subcutaneous vaccination with ZVL were higher in recipients of ZVL compared with placebo. Majority of the injection site AEs observed were Grade 1 (mild) or Grade 2 (moderate) in intensity. Additionally, Grade 3 (severe) injection site AEs were observed infrequently.
Conclusions: Application of the FDA Toxicity Grading Scale provides a uniform AE assessment tool across different adult vaccines. This post hoc summary of injection site AEs using FDA Toxicity Grading Scale provides further evidence of low frequency of severe injection site AEs post ZVL vaccination.
We used Bayes' theorem to evaluate the probability of vaginal foreign bodies in girls with genital complaints. The prevalence of vaginal foreign bodies in outpatient girls under 13 years of age with ...gynecologic disorders was found to be 4%. Review of the charts of 17 pre-menarcheal girls who had foreign bodies on 19 occasions and of 28 girls with infectious or nonspecific vaginitis demonstrated that patients with foreign bodies reported vaginal bleeding more frequently than discharge (14 and two of 15 symptomatic cases, respectively), while in contrast, patients with infectious or nonspecific vaginitis reported vaginal discharge more often than bleeding (23 and five of 28 symptomatic controls, respectively). Bayes' theorem indicates that, in populations resembling the one we studied, approximately 18% of preteenage girls with vaginal bleeding with or without discharge and 50% of those with bleeding and no discharge will prove to have vaginal foreign bodies.
This open access book focuses on the public health crisis of youth suicide and provides a review of current research and prevention practices. It addresses important topics, including suicide ...epidemiology, suicide risk detection in school and medical settings, critical cultural considerations, and approaches to lethal means safety. This book offers cutting-edge research on emerging discoveries in the neurobiology of suicide, psychopharmacology, and machine learning. It focuses on upstream suicide prevention research methods and details how cost-effective approaches can mitigate youth suicide risk when implemented at a universal level. Chapters discuss critical areas for future research, including how to evaluate the effectiveness of suicide prevention and intervention efforts, increase access to mental health care, and overcome systemic barriers that undermine generalizability of prevention strategies. Finally, this book highlights what is currently working well in youth suicide prevention and, just as important, which areas require more attention and support. Key topics include: The neurobiology of suicide in at-risk children and adolescents. The role of machine learning in youth suicide prevention. Suicide prevention, intervention, and postvention in schools. Suicide risk screening and assessment in medical settings. Culturally informed risk assessment and suicide prevention efforts with minority youth. School mental health partnerships and telehealth models of care in rural communities. Suicide and self-harm prevention and interventions for LGBTQ+ youth. Risk factors associated with suicidal behavior in Black youth. Preventing suicide in youth with autism spectrum disorder (ASD) and intellectual disability (ID). Youth Suicide Prevention and Intervention is a must-have resource for policy makers and related professionals, graduate students, and researchers in child and school psychology, family studies, public health, social work, law/criminal justice, sociology, and all related disciplines.
A case of salicylate hepatitis in a seven-week-old boy with Kawasaki's disease, mucocutaneous lymph node syndrome, is reported. The infant was admitted to the hospital with fever and a diffuse ...maculopapular petechial rash. He was treated with antibiotics for 72 hours for presumed septicemia. His condition deteriorated and he developed mucous membrane lesions and edema in his hands and feet. When the cultures of spinal fluid, blood, and urine were found to be negative, the antimicrobial therapy was discontinued; however, the cyanosis of his extremities progressed and gangrenous regions developed in his toe and finger pads. Oral aspirin therapy was started at a dosage of 100 mg/kg/day, every six hours. After five days, the rash, membrane lesions, and swelling in his hands and feet resolved. The cyanosis regressed. Liver enzyme tests revealed mild elevations of SGOT and LDH, and on the 12th hospital day these values peaked to a level consistent with salicylate hepatitis. The aspirin therapy was discontinued and within four days the liver function test results were normal. Aspirin therapy was reinstituted at a single daily dose of 30 mg/kg with no recurrence of hepatitis. The careful monitoring of liver function tests is recommended for children with Kawasaki's disease receiving aspirin therapy to avoid salicylate-induced hepatitis.
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