Patient and carer experiences of living with multiple myeloma and myelodysplastic syndrome.

OBJECTIVE: Multiple myeloma (MM) and myelodysplastic syndrome (MDS) are treatable but incurable conditions that can substantially impact the daily lives of people living with these conditions and their carers. We sought to understand the experience of people living with and carers affected by these conditions in Tasmania, a regional area of Australia. METHODS: Exploratory qualitative study. People living with MM or MDS or their carers in Southern Tasmania were recruited by a haematology nurse and invited to participate in focus groups. Data collection was by groups held online and face-to-face in 2022. Thematic analysis was used. RESULTS: Ten groups were held with 48 participants (n = 23 with MM, n = 9 with MDS, n = 16 carers). Key themes arising from focus groups with people living with MM/MDS were (1) Relationships and Support; (2) Positive Attitude; (3) Perception of Condition; and (4) Symptoms and Comorbidities. Some people with MM/MDS had to take on a caring role for their carer due to carer illness. Key themes arising from carer focus groups included (1) Supportive Relationships; (2) Accommodating Change; and (3) Own Needs. Not all carers viewed their caring role as burdensome. CONCLUSION: Future work should consider what supports are required for patients acting as carers, and carer burden should not be assumed.

Reports of Injection Site Necrosis After 23-Valent Pneumococcal Vaccine Use.

This case series uses postmarketing data to evaluate the incidence of injection site necrosis after 23-valent pneumococcal vaccine use in the global market.

Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively. These common variant analyses were supported by exome sequence analysis of ~220,000 women, identifying several genes, including rare loss of function variants in ZNF483 which abolished the impact of polygenic risk. Next, we implicated 660 genes in pubertal development using a combination of in silico variant-to-gene mapping approaches and integration with dynamic gene expression data from mouse embryonic GnRH neurons. This included an uncharacterized G-protein coupled receptor GPR83, which we demonstrate amplifies signaling of MC3R, a key sensor of nutritional status. Finally, we identified several genes, including ovary-expressed genes involved in DNA damage response that co-localize with signals associated with menopause timing, leading us to hypothesize that the ovarian reserve might signal centrally to trigger puberty. Collectively these findings extend our understanding of the biological complexity of puberty timing and highlight body size dependent and independent mechanisms that potentially link reproductive timing to later life disease.

COVID-19 Vaccine Safety First Year Findings in Adolescents.

BACKGROUND AND OBJECTIVES: The Food and Drug Administration expanded Emergency Use Authorization for use of Pfizer-BioNTech (BNT-162b2) coronavirus disease 2019 vaccine to include people ages 12 years and older on May 10, 2021. We describe adverse events observed during the first full year of the US coronavirus disease 2019 vaccination program for adolescents ages 12 to 17 years. METHODS: We conducted descriptive analyses using data from 2 complementary US vaccine safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health impacts, and the Vaccine Adverse Event Reporting System (VAERS), the national spontaneous reporting system. We reviewed reports and calculated adverse event reporting rates using vaccine administration data. RESULTS: Among 172 032 adolescents ages 12 to 17 years enrolled in v-safe, most reported reactions following BNT-162b2 were mild to moderate, most frequently reported on the day after vaccination, and more common after dose 2. VAERS received 20 240 adverse event reports; 91.5% were nonserious. Among adverse events of interest, we verified 40 cases of multisystem inflammation syndrome in children (1.2 cases per million vaccinations), 34 (85%) of which had evidence of prior severe acute respiratory syndrome coronavirus 2 infection; and 570 cases of myocarditis (17.7 cases per million vaccinations), most of whom (77%) reported symptom resolution at the time of report. CONCLUSIONS: During the first year BNT-162b2 was administered to adolescents ages 12 to 17 years, most reported adverse events were mild and appeared self-limited. Rates of myocarditis were lower than earlier reports. No new serious safety concerns were identified.

Development of a Peer-Based Intervention Educating Teenagers about Long-Acting Reversible Contraception.

OBJECTIVE: Despite a decrease in teenage pregnancy rates in the United States in the past decades, teen pregnancy continues to be a considerable health issue. In this paper, we outline the development of our novel peer-based intervention, Get It?, that aims to increase awareness of and self-efficacy to use long-active reversible contraceptives (LARCs) among teenagers. METHODS: Peer narrative videos were created from audio recording semi-structured, one-on-one interviews with teenage LARC users. Focus groups of young women 19 years old and younger were conducted to choose the most audience-appropriate videos to be included in the final intervention. Using a thematic content analysis approach, transcripts of the audio recorded focus groups were reviewed and manually coded. RESULTS: The final layout of Get It? included 4 videos that were chosen by participants of the focus groups, as well as supplemental activities that included a basic description of the LARC devices, the ability to anonymously post personal stories about LARCs that can be shared with others, and the opportunity to email the primary investigator questions about LARCs. Thematic analysis of the focus group discussions revealed that when it came to narrative videos, participants desired (1) an authentic narrator, (2) more information on the narrator, and (3) narrators displaying ample emotions. CONCLUSION: Peer narratives play a vital role in influencing a teenager's perspective on their health status; therefore, understanding what constitutes reliable narration from an online format was critical in the development of a peer-based electronic intervention that informs teenagers of the most effective contraceptive available to them.

Reports of Guillain-Barré Syndrome After COVID-19 Vaccination in the United States.

Importance: Because of historical associations between vaccines and Guillain-Barré syndrome (GBS), the condition was a prespecified adverse event of special interest for COVID-19 vaccine monitoring. Objective: To evaluate GBS reports to the Vaccine Adverse Event Reporting System (VAERS) and compare reporting patterns within 21 and 42 days after vaccination with Ad26.COV2.S (Janssen), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) COVID-19 vaccines. Design, Setting, and Participants: This retrospective cohort study was conducted using US VAERS reports submitted during December 2020 to January 2022. GBS case reports verified as meeting the Brighton Collaboration case definition for GBS in US adults after COVID-19 vaccination were included. Exposures: Receipt of the Ad26.COV2.S, BNT162b2, or mRNA-1273 COVID-19 vaccine. Main Outcomes and Measures: Descriptive analyses of GBS case were conducted. GBS reporting rates within 21 and 42 days after Ad26.COV2.S, BNT162b2, or mRNA-1273 vaccination based on doses administered were calculated. Reporting rate ratios (RRRs) after receipt of Ad26.COV2.S vs BNT162b2 or mRNA-1273 within 21- and 42-day postvaccination intervals were calculated. Observed-to-expected (OE) ratios were estimated using published GBS background rates. Results: Among 487 651 785 COVID-19 vaccine doses, 17 944 515 doses (3.7%) were Ad26.COV2.S, 266 859 784 doses (54.7%) were BNT162b2, and 202 847 486 doses (41.6%) were mRNA-1273. Of 295 verified reports of individuals with GBS identified after COVID-19 vaccination (12 Asian [4.1%], 18 Black [6.1%], and 193 White [65.4%]; 17 Hispanic [5.8%]; 169 males [57.3%]; median [IQR] age, 59.0 [46.0-68.0] years), 275 reports (93.2%) documented hospitalization. There were 209 and 253 reports of GBS that occurred within 21 days and 42 days of vaccination, respectively. Within 21 days of vaccination, GBS reporting rates per 1 000 000 doses were 3.29 for Ad26.COV.2, 0.29 for BNT162b2, and 0.35 for mRNA-1273 administered; within 42 days of vaccination, they were 4.07 for Ad26.COV.2, 0.34 for BNT162b2, and 0.44 for mRNA-1273. GBS was more frequently reported within 21 days after Ad26.COV2.S than after BNT162b2 (RRR = 11.40; 95% CI, 8.11-15.99) or mRNA-1273 (RRR = 9.26; 95% CI, 6.57-13.07) vaccination; similar findings were observed within 42 days after vaccination (BNT162b2: RRR = 12.06; 95% CI, 8.86-16.43; mRNA-1273: RRR = 9.27; 95% CI, 6.80-12.63). OE ratios were 3.79 (95% CI, 2.88-4.88) for 21-day and 2.34 (95% CI, 1.83-2.94) for 42-day intervals after Ad26.COV2.S vaccination and less than 1 (not significant) after BNT162b2 and mRNA-1273 vaccination within both postvaccination periods. Conclusions and Relevance: This study found disproportionate reporting and imbalances after Ad26.COV2.S vaccination, suggesting that Ad26.COV2.S vaccination was associated with increased risk for GBS. No associations between mRNA COVID-19 vaccines and risk of GBS were observed.

Reporting rates for VAERS death reports following COVID-19 vaccination, December 14, 2020-November 17, 2021.

PURPOSE: Despite widely available safety information for the COVID-19 vaccines, vaccine hesitancy remains a challenge. In some cases, vaccine hesitancy may be related to concerns about the number of reports of death to the Vaccine Adverse Event Reporting System (VAERS). We aimed to provide information and context about reports of death to VAERS following COVID-19 vaccination. METHODS: This is a descriptive study evaluating reporting rates for VAERS death reports for COVID-19 vaccine recipients in the United States between December 14, 2020, and November 17, 2021. Reporting rates were calculated as death events per million persons vaccinated and compared to expected all-cause (background) death rates. RESULTS: 9201 death events were reported for COVID-19 vaccine recipients aged 5 years and older (or age unknown). Reporting rates for death events increased with increasing age, and males generally had higher reporting rates than females. For death events within 7 days and 42 days of vaccination, respectively, observed reporting rates were lower than the expected all-cause death rates. Reporting rates for Ad26.COV2.S vaccine were generally higher than for mRNA COVID-19 vaccines, but still lower than the expected all-cause death rates. Limitations of VAERS data include potential reporting bias, missing or inaccurate information, lack of a control group, and reported diagnoses, including deaths, are not causally verified diagnoses. CONCLUSIONS: Reporting rates for death events were lower than the all-cause death rates expected in the general population. Trends in reporting rates reflected known trends in background death rates. These findings do not suggest an association between vaccination and overall increased mortality.

Surveillance for Multisystem Inflammatory Syndrome in US Children Aged 5-11 Years Who Received Pfizer-BioNTech COVID-19 Vaccine, November 2021 through March 2022.

Multisystem inflammatory syndrome in children (MIS-C) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; in the United States, reporting of MIS-C after coronavirus disease 2019 (COVID-19) vaccination is required for vaccine safety monitoring. Pfizer-BioNTech COVID-19 vaccine was authorized for children aged 5-11 years on 29 October 2021. Covering a period when approximately 7 million children received vaccine, surveillance for MIS-C ≤ 90 days postvaccination using passive systems identified 58 children with MIS-C and laboratory evidence of past/recent SARS-CoV-2 infection, and 4 without evidence. During a period with extensive SARS-CoV-2 circulation, MIS-C illness in children after COVID-19 vaccination who lacked evidence of SARS-CoV-2 infection was rare (<1 per million vaccinated children).

Safety Monitoring of Bivalent COVID-19 mRNA Vaccine Booster Doses Among Children Aged 5-11 Years - United States, October 12-January 1, 2023.

On October 12, 2022, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for bivalent (mRNA encoding the spike protein from the SARS-CoV-2 ancestral strain and BA.4/BA.5 Omicron variants) formulations of Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines for use as a single booster dose ≥2 months after completion of primary series or monovalent booster vaccination for children aged 5-11 years (Pfizer-BioNTech) and 6-17 years (Moderna); on December 8, 2022, FDA amended the EUAs to include children aged ≥6 months (1,2). The Advisory Committee on Immunization Practices (ACIP) recommends that all persons aged ≥6 months receive an age-appropriate bivalent mRNA booster dose (3). The safety of bivalent mRNA booster doses among persons aged ≥12 years has previously been described (4). To characterize the safety of bivalent mRNA booster doses among children aged 5-11 years after receipt of bivalent Pfizer-BioNTech and Moderna booster doses, CDC reviewed adverse events and health impacts reported to v-safe,* a voluntary, smartphone-based U.S. safety surveillance system established by CDC to monitor adverse events after COVID-19 vaccination, and to the Vaccine Adverse Event Reporting System (VAERS), a U.S. passive vaccine safety surveillance system co-managed by CDC and FDA† (5). During October 12-January 1, 2023, a total of 861,251 children aged 5-11 years received a bivalent Pfizer-BioNTech booster, and 92,108 children aged 6-11 years received a bivalent Moderna booster.§ Among 3,259 children aged 5-11 years registered in v-safe who received a bivalent booster dose, local (68.7%) and systemic reactions (49.5%) were commonly reported in the week after vaccination. Approximately 99.8% of reports to VAERS for children aged 5-11 years after bivalent booster vaccination were nonserious. There were no reports of myocarditis or death after bivalent booster vaccination. Eighty-four percent of VAERS reports were related to vaccination errors, 90.5% of which did not list an adverse health event. Local and systemic reactions reported after receipt of a bivalent booster dose are consistent with those reported after a monovalent booster dose; serious adverse events are rare. Vaccine providers should provide this information when counseling parents or guardians about bivalent booster vaccination. Preliminary safety findings from the first 11 weeks of bivalent booster vaccination among children aged 5-11 years are reassuring. Compared with the low risk of serious health effects after mRNA COVID-19 vaccination, the health effects of SARS-CoV-2 infection include death and serious long-term sequalae (6). ACIP recommends that all persons aged ≥6 months receive an age-appropriate bivalent mRNA booster dose ≥2 months after completion of a COVID-19 primary series or receipt of a monovalent booster dose.¶.

Background rates of adverse events of special interest for COVID-19 vaccine safety monitoring in the United States, 2019-2020.

BACKGROUND: The U.S. Food and Drug Administration (FDA) Biologics Effectiveness and Safety (BEST) Initiative conducts active surveillance of adverse events of special interest (AESI) after COVID-19 vaccination. Historical incidence rates (IRs) of AESI are comparators to evaluate safety. METHODS: We estimated IRs of 17 AESI in six administrative claims databases from January 1, 2019, to December 11, 2020: Medicare claims for adults ≥ 65 years and commercial claims (Blue Health Intelligence®, CVS Health, HealthCore Integrated Research Database, IBM® MarketScan® Commercial Database, Optum pre-adjudicated claims) for adults < 65 years. IRs were estimated by sex, age, race/ethnicity (Medicare), and nursing home residency (Medicare) in 2019 and for specific periods in 2020. RESULTS: The study included >100 million enrollees annually. In 2019, rates of most AESI increased with age. However, compared with commercially insured adults, Medicare enrollees had lower IRs of anaphylaxis (11 vs 12-19 per 100,000 person-years), appendicitis (80 vs 117-155), and narcolepsy (38 vs 41-53). Rates were higher in males than females for most AESI across databases and varied by race/ethnicity and nursing home status (Medicare). Acute myocardial infarction (Medicare) and anaphylaxis (all databases) IRs varied by season. IRs of most AESI were lower during March-May 2020 compared with March-May 2019 but returned to pre-pandemic levels after May 2020. However, rates of Bell's palsy, Guillain-Barré syndrome, narcolepsy, and hemorrhagic/non-hemorrhagic stroke remained lower in multiple databases after May 2020, whereas some AESI (e.g., disseminated intravascular coagulation) exhibited higher rates after May 2020 compared with 2019. CONCLUSION: AESI background rates varied by database and demographics and fluctuated in March-December 2020, but most returned to pre-pandemic levels after May 2020. It is critical to standardize demographics and consider seasonal and other trends when comparing historical rates with post-vaccination AESI rates in the same database to evaluate COVID-19 vaccine safety.

Surveillance of COVID-19 vaccine safety among elderly persons aged 65 years and older.

BACKGROUND: Monitoring safety outcomes following COVID-19 vaccination is critical for understanding vaccine safety especially when used in key populations such as elderly persons age 65 years and older who can benefit greatly from vaccination. We present new findings from a nationally representative early warning system that may expand the safety knowledge base to further public trust and inform decision making on vaccine safety by government agencies, healthcare providers, interested stakeholders, and the public. METHODS: We evaluated 14 outcomes of interest following COVID-19 vaccination using the US Centers for Medicare & Medicaid Services (CMS) data covering 30,712,101 elderly persons. The CMS data from December 11, 2020 through Jan 15, 2022 included 17,411,342 COVID-19 vaccinees who received a total of 34,639,937 doses. We conducted weekly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination. FINDINGS: Four outcomes met the threshold for a statistical signal following BNT162b2 vaccination including pulmonary embolism (PE; RR = 1.54), acute myocardial infarction (AMI; RR = 1.42), disseminated intravascular coagulation (DIC; RR = 1.91), and immune thrombocytopenia (ITP; RR = 1.44). After further evaluation, only the RR for PE still met the statistical threshold for a signal; however, the RRs for AMI, DIC, and ITP no longer did. No statistical signals were identified following vaccination with either the mRNA-1273 or Ad26 COV2.S vaccines. INTERPRETATION: This early warning system is the first to identify temporal associations for PE, AMI, DIC, and ITP following BNT162b2 vaccination in the elderly. Because an early warning system does not prove that the vaccines cause these outcomes, more robust epidemiologic studies with adjustment for confounding, including age and nursing home residency, are underway to further evaluate these signals. FDA strongly believes the potential benefits of COVID-19 vaccination outweigh the potential risks of COVID-19 infection.

Isolation in a Sea of "Experts": Identifying the Parental Struggles Caring for Children With Early-Onset Obesity.

Background: Severe early-onset childhood obesity is diagnosed by having a BMI >120% of the 95th percentile before age 5 years. Treatment for early-onset obesity is frequently unsuccessful. Prior studies have shown parents of children with obesity often face stigmatization and those who experience weight bias also experience poorer medical care. Home environment influences many risk factors, and parents are crucial for intervention. Research on the parental perspective of care is lacking and greater understanding could increase the effectiveness of treatment. We sought to understand the common stressors and obstacles parents encounter caring for a child with early-onset severe obesity. Methods: Parents of children with early-onset severe obesity participated in semistructured interviews. Interviews were digitally recorded, transcribed verbatim, coded, and analyzed using hybrid thematic analysis. Results: We identified a global theme of "Isolation in a sea of 'experts'," supported by three organizing themes: (i) Facing barriers at every turn; (ii) Carrying all the burdens; and (iii) Struggling to get their child seen as an individual. Within each organizing theme, subthemes emerged that highlighted the struggles that parents encountered. These included significant conflict with others when attempting to implement dietary changes (e.g., spouses, other children, and extended family), protecting their child's self-esteem, perceived weight bias from medical staff, lack of experienced obesity clinicians, lack of access to weight management services, and judgment from others (e.g., family, friends, and strangers). Conclusions: This study highlighted that many parents of children with early-onset severe obesity felt significant struggles, both internal and external. Understanding the barriers parents face when caring for their children is critical to improving relationships and medical care.

Developing frailty friendly hospitals: the Specialised Clinical Frailty Network.

Introduction: The aim of the Specialised Clinical Frailty Network (SCFN) was to develop frailty-attuned pathways in specialised services in England. Methods: We developed a breakthrough series collaborative involving a range of specialised services, using quality improvement methods (including experience-based design) to implement improvements designed to enhance the experience and outcomes of older people living with frailty who have specialised healthcare needs. Results: Specialised teams responded positively to the SCFN, many implementing process changes aligned to the needs of older people living with frailty. Some were able to demonstrate improvements in service and/or patient outcomes, including greater identification of frailty, more holistic care and increased use of shared decision making. Discussion: The network has successfully demonstrated how frailty can be assessed both at individual, as well as population level, to support both local teams and systems to best manage the health of their patients.

Staff Experience in the NHS: A National Study-An Experience-Based Design Approach.

Introduction: A positive patient experience is a key component of good quality of care. Post-pandemic healthcare systems face the challenge of addressing burnout among healthcare staff, who are directly involved in the delivery of healthcare, which has implications for the patient experience. There is an established association between staff and patient experience; exploring the experience of staff may give insights into factors that negatively impact the patient experience. Experience-based design (EBD) is a quality improvement approach that uses the experience of service users to derive improvements. The purpose of this study is to design, validate, and test an EBD tool that may be used to capture the staff experience. Methods: A focus group of clinical and nonclinical staff (identified through the NHS Elect networks) and the development team coproduced an EBD survey based on nine "touch-points" of a typical working day. Once the survey questionnaire was tested and agreed with it was distributed to 1300 members of NHS networks. Results: A total of 377 NHS staff responded to the questionnaire. Analysis revealed effective teamwork had a positive psychological impact on staff. However, increased workload, missed meal breaks, and an increased administrative/IT burden were associated with the greatest negative responses by clinical and nonclinical staff. Conclusion: Overall, factors impacting staff well-being are multifaceted and varied between trusts. However, leaders in healthcare can use EBD to identify targeted improvements for the day-to-day experiences of staff.

Safety Monitoring of Bivalent COVID-19 mRNA Vaccine Booster Doses Among Persons Aged ≥12 Years - United States, August 31-October 23, 2022.

On August 31, 2022, the Food and Drug Administration (FDA) authorized bivalent formulations of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines; these vaccines include mRNA encoding the spike protein from the original (ancestral) strain of SARS-CoV-2 (the virus that causes COVID-19) and from the B.1.1.529 (Omicron) variants BA.4 and BA.5 (BA.4/BA.5). These bivalent mRNA vaccines were authorized for use as a single booster dose ≥2 months after completion of primary series or monovalent booster vaccination; Pfizer-BioNTech bivalent booster was authorized for persons aged ≥12 years and Moderna for adults aged ≥18 years.*,† On September 1, 2022, the Advisory Committee on Immunization Practices (ACIP) recommended that all persons aged ≥12 years receive an age-appropriate bivalent mRNA booster dose.§ To characterize the safety of bivalent mRNA booster doses, CDC reviewed adverse events and health impacts reported after receipt of bivalent Pfizer-BioNTech and Moderna booster doses during August 31-October 23, 2022, to v-safe,¶ a voluntary smartphone-based U.S. safety surveillance system established by CDC to monitor adverse events after COVID-19 vaccination, and the Vaccine Adverse Event Reporting System (VAERS),** a U.S. passive vaccine safety surveillance system managed by CDC and FDA (1). During August 31-October 23, 2022, approximately 14.4 million persons aged ≥12 years received a bivalent Pfizer-BioNTech booster dose, and 8.2 million adults aged ≥18 years received a bivalent Moderna booster dose.†† Among the 211,959 registrants aged ≥12 years who reported receiving a bivalent booster dose to v-safe, injection site and systemic reactions were frequently reported in the week after vaccination (60.8% and 54.8%, respectively); fewer than 1% of v-safe registrants reported receiving medical care. VAERS received 5,542 reports of adverse events after bivalent booster vaccination among persons aged ≥12 years; 95.5% of reports were nonserious and 4.5% were serious events. Health care providers and patients can be reassured that adverse events reported after a bivalent booster dose are consistent with those reported after monovalent doses. Health impacts after COVID-19 vaccination are less frequent and less severe than those associated with COVID-19 illness (2).

Safety Monitoring of Pfizer-BioNTech COVID-19 Vaccine Booster Doses Among Children Aged 5-11 Years - United States, May 17-July 31, 2022.

On May 17, 2022, the Food and Drug Administration (FDA) amended the Emergency Use Authorization (EUA) for BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine to authorize a homologous* booster dose for children aged 5-11 years ≥5 months after receipt of the second primary series dose† (1) based on findings from a clinical trial conducted among 401 children aged 5-11 years (2). To further characterize the safety of booster vaccination in this age group, CDC reviewed adverse events and health impact assessments after receipt of a Pfizer-BioNTech third dose reported to v-safe, a voluntary smartphone-based safety surveillance system for adverse events occurring after COVID-19 vaccination, and adverse events reported to the Vaccine Adverse Event Reporting System (VAERS), a passive vaccine safety surveillance system comanaged by CDC and FDA. During May 17-July 31, 2022, approximately 657,302 U.S. children aged 5-11 years received a third Pfizer-BioNTech dose (either a third primary series dose administered to immunocompromised children or a booster dose administered to immunocompetent children)§; 3,249 Pfizer-BioNTech third doses were reported to v-safe for children in this age group. Local and systemic reactions were reported to v-safe after a second dose and a third dose with similar frequency; some reactions (e.g., pain) were reported to be moderate or severe more frequently after a third dose. VAERS received 581 reports of adverse events after receipt of a Pfizer-BioNTech third dose by children aged 5-11 years; 578 (99.5%) reports were considered nonserious, and the most common events reported were vaccine administration errors. Three (0.5%) reports were considered serious; no reports of myocarditis or death were received. Local and systemic reactions were common among children after Pfizer-BioNTech third dose vaccination, but reports of serious adverse events were rare. Initial safety findings are consistent with those of the clinical trial (2).

Safety Monitoring of COVID-19 mRNA Vaccine First Booster Doses Among Persons Aged ≥12 Years with Presumed Immunocompromise Status - United States, January 12, 2022-March 28, 2022.

Persons with moderate to severe immunocompromising conditions are at risk for severe COVID-19, and their immune response to COVID-19 vaccination might not be as robust as the response in persons who are not immunocompromised* (1). The Advisory Committee on Immunization Practices (ACIP) recommends that immunocompromised persons aged ≥12 years complete a 3-dose primary mRNA COVID-19 vaccination series followed by a first booster dose (dose 4) ≥3 months after dose 3 and a second booster dose (dose 5) ≥4 months after dose 4.† To characterize the safety of first booster doses among immunocompromised persons aged ≥12 years during January 12, 2022-March 28, 2022, CDC reviewed adverse events and health impact assessments reported to v-safe and the Vaccine Adverse Event Reporting System (VAERS) during the week after receipt of an mRNA COVID-19 first booster dose. V-safe is a voluntary smartphone-based safety surveillance system for adverse events after COVID-19 vaccination. VAERS is a passive surveillance system for all vaccine-associated adverse events co-managed by CDC and the Food and Drug Administration (FDA). A fourth mRNA dose reported to v-safe or VAERS during January 12, 2022-March 28, 2022, was presumed to be an mRNA COVID-19 vaccine booster dose administered to an immunocompromised person because no other population was authorized to receive a fourth dose during that period (2,3). In the United States, during January 12, 2022-March 28, 2022, approximately 518,113 persons aged ≥12 years received a fourth dose. Among 4,015 v-safe registrants who received a fourth dose, local and systemic reactions were less frequently reported than were those following dose 3 of their primary series. VAERS received 145 reports after fourth doses; 128 (88.3%) were nonserious and 17 (11.7%) were serious. Health care providers, immunocompromised persons, and parents of immunocompromised children should be aware that local and systemic reactions are expected after a first booster mRNA COVID-19 vaccine dose, serious adverse events are rare, and safety findings were consistent with those previously described among nonimmunocompromised persons (4,5).

Development and evaluation of polygenic risk scores for prediction of endometrial cancer risk in European women.

PURPOSE: Single-nucleotide variations (SNVs) (formerly single-nucleotide polymorphism [SNV]) influence genetic predisposition to endometrial cancer. We hypothesized that a polygenic risk score (PRS) comprising multiple SNVs may improve endometrial cancer risk prediction for targeted screening and prevention. METHODS: We developed PRSs from SNVs identified from a systematic review of published studies and suggestive SNVs from the Endometrial Cancer Association Consortium. These were tested in an independent study of 555 surgically-confirmed endometrial cancer cases and 1202 geographically-matched controls from Manchester, United Kingdom and validated in 1676 cases and 116,960 controls from the UK Biobank (UKBB). RESULTS: Age and body mass index predicted endometrial cancer in both data sets (Manchester: area under the receiver operator curve [AUC] = 0.77, 95% CI = 0.74-0.80; UKBB: AUC = 0.74, 95% CI = 0.73-0.75). The AUC for PRS19, PRS24, and PRS72 were 0.58, 0.55, and 0.57 in the Manchester study and 0.56, 0.54, and 0.54 in UKBB, respectively. For PRS19, women in the third tertile had a 2.1-fold increased risk of endometrial cancer compared with those in the first tertile of the Manchester study (odds ratio = 2.08, 95% CI = 1.61-2.68, Ptrend = 5.75E-9). Combining PRS19 with age and body mass index improved discriminatory power (Manchester study: AUC = 0.79, 95% CI = 0.76-0.82; UKBB: AUC =0.75, 95% CI = 0.73-0.76). CONCLUSION: An endometrial cancer risk prediction model incorporating a PRS derived from multiple SNVs may help stratify women for screening and prevention strategies.