Trust, influence, and community: Why pharmacists and pharmacies are central for addressing vaccine hesitancy.

In 2019, the World Health Organization listed vaccine hesitancy, defined as the reluctance or refusal to vaccinate against preventable infectious diseases, as one of the top ten threats to global health. To address hesitancy, we must focus our attention on building vaccine confidence, trust in the vaccine itself, in providers who administer vaccines, and in the process that leads to vaccine licensure and the recommended vaccination schedule. Building vaccine confidence, particularly in communities that have higher levels of distrust of vaccines and low vaccination coverage rates, is a critical public health priority, particularly in the current climate as the United States and the global public health community grapple with the coronavirus disease 2019 pandemic. In this commentary, we focus on the central role that pharmacists play in promoting the health and wellness of the local communities in which they are embedded, how they are one of the most trusted sources for their communities when it comes to health information and care, and their unique position in making a profound contribution to building vaccine confidence. We propose to arm all health professionals with a tool, the ASPIRE framework, which serves as a series of actionable steps to facilitate conversations with communities. This framework is intended to assist pharmacists in communicating with community members who may have concerns about vaccines by sharing trustworthy health information about vaccines to increase vaccine adoption. We conclude that it is insufficient to merely relay accurate health information about vaccines to the public and expect dramatic increases to vaccination rates. Accurate health information needs to be conveyed by trusted sources. Open engagement and dialogue layered on top of fundamental facts and messages are central to building confidence. Pharmacists and other providers can use tools such as ASPIRE to guide their conversations with community members to increase vaccine adoption.

Vaccine Coverage Across the Life Course in Michigan During the COVID-19 Pandemic: January‒September 2020.

Objectives. To assess the impact of the COVID-19 pandemic on immunization services across the life course. Methods. In this retrospective study, we used Michigan immunization registry data from 2018 through September 2020 to assess the number of vaccine doses administered, number of sites providing immunization services to the Vaccines for Children population, provider location types that administer adult vaccines, and vaccination coverage for children. Results. Of 12 004 384 individual vaccine doses assessed, 48.6%, 15.6%, and 35.8% were administered to children (aged 0-8 years), adolescents (aged 9-18 years), and adults (aged 19‒105 years), respectively. Doses administered overall decreased beginning in February 2020, with peak declines observed in April 2020 (63.3%). Overall decreases in adult doses were observed in all settings except obstetrics and gynecology provider offices and pharmacies. Local health departments reported a 66.4% decrease in doses reported. For children, the total number of sites administering pediatric vaccines decreased while childhood vaccination coverage decreased 4.4% overall and 5.8% in Medicaid-enrolled children. Conclusions. The critical challenge is to return to prepandemic levels of vaccine doses administered as well as to catch up individuals for vaccinations missed. (Am J Public Health. 2021;111(11):2027-2035. https://doi.org/10.2105/AJPH.2021.306474).

Decline in Child Vaccination Coverage During the COVID-19 Pandemic - Michigan Care Improvement Registry, May 2016-May 2020.

On March 13, 2020, the United States declared a national state of emergency to control the pandemic spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). Public health response measures to mitigate the pandemic have centered on social distancing and quarantine policies, including shelter-in-place and stay-at-home orders. Michigan implemented a stay-at-home order on March 23, 2020, to facilitate social distancing (2). Such strategies might result in decreased accessibility to routine immunization services, leaving children at risk for vaccine-preventable diseases and their complications (3). To evaluate whether vaccination coverage has changed during the pandemic, data from the Michigan Care Improvement Registry (the state's immunization information system) (MCIR) were analyzed. Changes in vaccine doses administered to children and the effects of those changes on up-to-date status were examined for vaccinations recommended at milestone ages corresponding to the end of an Advisory Committee on Immunization Practices (ACIP) recommendation period for one or more vaccines (4).

Exogenous attention facilitates perceptual learning in visual acuity to untrained stimulus locations and features.

Visual perceptual learning (VPL) refers to the improvement in performance on a visual task due to practice. A hallmark of VPL is specificity, as improvements are often confined to the trained retinal locations or stimulus features. We have previously found that exogenous (involuntary, stimulus-driven) and endogenous (voluntary, goal-driven) spatial attention can facilitate the transfer of VPL across locations in orientation discrimination tasks mediated by contrast sensitivity. Here, we investigated whether exogenous spatial attention can facilitate such transfer in acuity tasks that have been associated with higher specificity. We trained observers for 3 days (days 2-4) in a Landolt acuity task (Experiment 1) or a Vernier hyperacuity task (Experiment 2), with either exogenous precues (attention group) or neutral precues (neutral group). Importantly, during pre-tests (day 1) and post-tests (day 5), all observers were tested with neutral precues; thus, groups differed only in their attentional allocation during training. For the Landolt acuity task, we found evidence of location transfer in both the neutral and attention groups, suggesting weak location specificity of VPL. For the Vernier hyperacuity task, we found evidence of location and feature specificity in the neutral group, and learning transfer in the attention group-similar improvement at trained and untrained locations and features. Our results reveal that, when there is specificity in a perceptual acuity task, exogenous spatial attention can overcome that specificity and facilitate learning transfer to both untrained locations and features simultaneously with the same training. Thus, in addition to improving performance, exogenous attention generalizes perceptual learning across locations and features.

Chemical Sympathectomy, but not Adrenergic Blockade, Improves Stroke Outcome.

BACKGROUND: A robust adrenergic response following stroke impairs lymphocyte function, which may prevent the development of autoimmune responses to brain antigens. We tested whether inhibition of the sympathetic response after stroke would increase the propensity for developing autoimmune responses to brain antigens. METHODS: Male Lewis rats were treated with 6-hydroxydopamine (OHDA) prior to middle cerebral artery occlusion (MCAO), labetalol after MCAO, or appropriate controls. Behavior was assessed weekly and animals survived to 1 month at which time ELISPOT assays were done on lymphocytes from spleen and brain to determine the Th1 and Th17 responses to myelin basic protein (MBP), ovalbumin (OVA), and concanavalin A. A subset of animals was sacrificed 72 hours after MCAO for evaluation of infarct volume and lymphocyte responsiveness. Plasma C-reactive protein (CRP) was measured as a biomarker of systemic inflammation. RESULTS: Despite similar initial stroke severity and infarct volumes, 6-OHDA-treated animals lost less weight and experienced less hyperthermia after stroke. 6-OHDA-treated animals also had decreased CRP in circulation early after stroke and experienced better neurological outcomes at 1 month. The Th1 and Th17 responses to MBP did not differ among treatment groups at 1 month, but the Th1 response to OVA in spleen was more robust in labetalol and less robust in 6-OHDA-treated animals. CONCLUSIONS: Chemical sympathectomy with 6-OHDA, but not treatment with labetalol, decreased systemic markers of inflammation early after stroke and improved long-term outcome. An increase in Th1 and Th17 responses to MBP was not seen with inhibition of the sympathetic response.

Splenectomy Does Not Improve Long-Term Outcome After Stroke.

BACKGROUND AND PURPOSE: Immune responses to brain antigens after stroke contribute to poor outcome. We hypothesized that splenectomy would lessen the development of such responses and improve outcome. METHODS: Male Lewis rats (275-350 g) underwent 2-hour middle cerebral artery occlusion immediately after splenectomy or sham splenectomy. Animals were survived to 4 weeks (672 hrs), and immune responses to myelin basic protein determined at euthanasia. Infarct volume was determined in a subset of animals euthanized at 72 hours. Behavioral outcomes were assessed to 672 hours. RESULTS: Splenectomy was associated with worse neurological scores early after stroke, but infarct size at 72 hours was similar in both groups. Behavioral outcomes and immune responses to myelin basic protein were also similar among splenectomized and sham-operated animals 672 hours after middle cerebral artery occlusion. CONCLUSIONS: Splenectomy did not alter the immune responses to brain antigens or improve outcome after stroke. Differences between this study and other studies of splenectomy and stroke are examined.

Chimeric antigen receptor T cells for sustained remissions in leukemia.

BACKGROUND: Relapsed acute lymphoblastic leukemia (ALL) is difficult to treat despite the availability of aggressive therapies. Chimeric antigen receptor-modified T cells targeting CD19 may overcome many limitations of conventional therapies and induce remission in patients with refractory disease. METHODS: We infused autologous T cells transduced with a CD19-directed chimeric antigen receptor (CTL019) lentiviral vector in patients with relapsed or refractory ALL at doses of 0.76×10(6) to 20.6×10(6) CTL019 cells per kilogram of body weight. Patients were monitored for a response, toxic effects, and the expansion and persistence of circulating CTL019 T cells. RESULTS: A total of 30 children and adults received CTL019. Complete remission was achieved in 27 patients (90%), including 2 patients with blinatumomab-refractory disease and 15 who had undergone stem-cell transplantation. CTL019 cells proliferated in vivo and were detectable in the blood, bone marrow, and cerebrospinal fluid of patients who had a response. Sustained remission was achieved with a 6-month event-free survival rate of 67% (95% confidence interval [CI], 51 to 88) and an overall survival rate of 78% (95% CI, 65 to 95). At 6 months, the probability that a patient would have persistence of CTL019 was 68% (95% CI, 50 to 92) and the probability that a patient would have relapse-free B-cell aplasia was 73% (95% CI, 57 to 94). All the patients had the cytokine-release syndrome. Severe cytokine-release syndrome, which developed in 27% of the patients, was associated with a higher disease burden before infusion and was effectively treated with the anti-interleukin-6 receptor antibody tocilizumab. CONCLUSIONS: Chimeric antigen receptor-modified T-cell therapy against CD19 was effective in treating relapsed and refractory ALL. CTL019 was associated with a high remission rate, even among patients for whom stem-cell transplantation had failed, and durable remissions up to 24 months were observed. (Funded by Novartis and others; CART19 ClinicalTrials.gov numbers, NCT01626495 and NCT01029366.).

A first-in-human phase I study to evaluate the MEK1/2 inhibitor, cobimetinib, administered daily in patients with advanced solid tumors.

Objective Cobimetinib, a MEK1/2 inhibitor, was administered to patients with advanced solid tumors to assess safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity. Methods For dose-escalation, a 3 + 3 design was used. Oral cobimetinib was administered once daily on a 21-day on/7-day off (21/7) or a 14-day on/14-day off (14/14) schedule. Serial plasma samples were collected for pharmacokinetic (PK) analysis on Day 1 and at steady state. In expansion stages, patients with RAS or RAF mutant tumors were treated at the maximum tolerated dose (MTD) of the 21/7 or 14/14 schedule. Results Ninety-seven patients received cobimetinib. In the 21/7 dose escalation, 36 patients enrolled in 8 cohorts (0.05 mg/kg-80 mg). Dose-limiting toxicities (DLTs) were Grade 4 hepatic encephalopathy, Grade 3 diarrhea, and Grade 3 rash. In the 14/14 dose escalation, 20 patients enrolled in 4 cohorts (60-125 mg). DLTs were Grade 3 rash and Grade 3 blurred vision associated with presence of reversible subretinal fluid. The MTD was 60 mg on 21/7 schedule and 100 mg on 14/14 schedule. Cobimetinib PK showed dose-proportional increases in exposure. The most frequent adverse events attributed to cobimetinib were diarrhea, rash, fatigue, edema, nausea, and vomiting. In patients treated at the 60-mg (21/7) or 100-mg (14/14) dose, one unconfirmed complete response and 6 confirmed partial responses were observed. All responses occurred in melanoma patients; 6 harbored the BRAF(V600E) mutation. Conclusions Cobimetinib is generally well tolerated and durable responses were observed in BRAF(V600E) mutant melanoma patients. Evaluation of cobimetinib in combination with other therapies is ongoing.

Trusted messengers and trusted messages: The role for community-based organizations in promoting COVID-19 and routine immunizations.

We sought to explore the trust and influence community-based organizations have within the communities they serve to inform public health strategies in tailoring vaccine and other health messages. A qualitative study was conducted between March 15 - April 12, 2021 of key informants in community-based organizations serving communities in and around Philadelphia, Pennsylvania. These organizations serve communities with high Social Vulnerability Index scores. We explored four key questions including: (1) What was and continues to be the impact of COVID-19 on communities; (2) How have trust and influence been cultivated in the community; (3) Who are trusted sources of information and health messengers; and (4) What are the community's perceptions about vaccines, vaccinations, and intent to vaccinate in the context of the COVID-19 pandemic. Fifteen key informants from nine community-based organizations who serve vulnerable populations (e.g., mental health, homeless, substance use, medically complex, food insecurity) were interviewed. Five key findings include: (1) The pandemic has exacerbated disparities in existing social determinants of health for individuals and families and have created new concerns for these communities; (2) components of how to build the trust and influence (e.g., demonstrate empathy, create a safe space, deliver on results)resonated with key informants; (3) regardless of the source, presenting health information in a respectful and understandable manner is key to effective delivery; (4) trust and influence can be transferred by association to a secondary messenger connected to or introduced by the primary trusted source; and (5) increased awareness about vaccines and vaccinations offers opportunities to think differently, changing previously held beliefs or attitudes, as many individuals are now more cognizant of risks associated with vaccine-preventable diseases and the importance of vaccines. Community-based organizations offer unique opportunities to address population-level health disparities as trusted vaccine messengers to deliver public health messages.

Persuading the "Movable Middle": Characteristics of effective messages to promote routine and COVID-19 vaccinations for adults and children - The impact of COVID-19 on beliefs and attitudes.

PURPOSE: We sought to 1) explore trusted sources for vaccine information, 2) describe persuasive characteristics of trusted messages promoting routine and COVID-19 vaccines for children and adults and 3) explore how the pandemic has impacted attitudes and beliefs about routine vaccinations. We conducted a mixed method cross-sectional study between May 3-June 14, 2021 including a survey and six focus groups among a sub-set of survey respondents. A total of 1,553 survey respondents (from which n = 33 participated in the focus groups) including adults without children under age nineteen years (n = 582) and parents with children under age nineteen years (n = 971). RESULTS: Primary care providers, family, and credible sources, characterized as known and well-established entities, were top sources of vaccine information. Neutrality, honesty, and having a trusted source to rely on in sorting through volumes of sometimes conflicting information were highly valued. Trustworthy qualities about sources included: 1) expertise, 2) fact-based, 3) unbiased, and 4) having an established process for sharing information. Because of the evolving nature of the pandemic, attitudes and beliefs about COVID-19 vaccine and sources of COVID-19 information differed from typical views about routine vaccines. Of 1,327 (85.4 %) survey respondents, 12.7 % and 9.4 % of adults and parents cited that the pandemic impacted their attitudes and beliefs. Among these respondents, 8 % of adults and 3 % of parents cited more favorable attitudes and beliefs about getting vaccinated with routine vaccines because of the pandemic. CONCLUSION: Vaccine attitudes and beliefs which inform intent to vaccinate can change and differ among different vaccines. Messaging should be tailored to resonate with parents and adults to improve vaccine uptake.

Phase 1 study of CART-ddBCMA for the treatment of subjects with relapsed and refractory multiple myeloma.

Relapsed and refractory multiple myeloma (RRMM) is a plasma cell neoplasm defined by progressively refractory disease necessitating chronic and increasingly intensive therapy. Despite recent advances, limited treatment options exist for RRMM. This single-arm, open label phase 1 study aimed to evaluate the safety of novel B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T construct that leverages a completely synthetic antigen-binding domain (CART-ddBCMA), which was specifically engineered to reduce immunogenicity and improve CAR cell surface stability. Thirteen patients ≥18 years with RRMM who received at least 3 prior regimens of systemic therapy were enrolled in the study. Patients received a single dose of 100 × 106 CART-ddBCMA (DL1) or 300 × 106 CART-ddBCMA (DL2) following standard lymphodepleting chemotherapy. The primary endpoints of the study were to evaluate the incidence of treatment emergent adverse events, including dose-limiting toxicities, and establish a recommended phase 2 dose. Results showed that CART-ddBCMA was well tolerated and demonstrated a favorable toxicity profile. Only 1 case of grade ≥3 cytokine release syndrome and 1 case of immune effector cell-associated neurotoxicity were reported; both were at DL2 and were manageable with standard treatment. No atypical neurological toxicities and Parkinson disease-like movement disorders were observed. The maximum tolerated dose was not reached. All infused patients responded to CART-ddBCMA, and 9/12 (75%) patients achieved complete response/stringent complete response. Responses deepened over time, and at the time of last data-cut (median follow-up 56 weeks), 8/9 (89%) evaluable patients achieved minimal residual disease negativity. In conclusion, the findings demonstrate the safety of CART-ddBCMA cells and document durable responses to CART-ddBCMA in patients with RRMM. This trial was registered at www.clinicaltrials.gov as #NCT04155749.

Primary cutaneous infection by Mycobacterium avium: a case report and literature review.

Nontuberculous mycobacteria (NTM) are becoming increasingly important cutaneous pathogens as the number of susceptible patients increases. Nevertheless, primary cutaneous infection by one particular species, Mycobacterium avium complex (MAC), remains relatively unusual, particularly in immunocompetent patients. We review the English-language literature on primary cutaneous MAC in patients who were neither immunocompromised nor pharmacologically immunosuppressed. We offer an additional report of a healthy patient who presented to our clinic with primary cutaneous MAC following seemingly innocuous trauma to the leg.

Trends in Vaccine Refusal and Acceptance Using Electronic Health Records from a Large Pediatric Hospital Network, 2013-2020: Strategies for Change.

Understanding trends in vaccine refusal is critical to monitor as small declines in vaccination coverage can lead to outbreaks of vaccine-preventable diseases. Using electronic heath record (EHR) data from the Children's Hospital of Philadelphia's 31 outpatient primary care sites, we created a cohort of 403,448 children less than age 20 years who received at least one visit from 1 January 2013 through 31 December 2020. The sample represented 1,449,061 annualized patient and 181,131 annualized preventive vaccination visits per year. We characterized trends in vaccine refusal and acceptance using a repeated cross-sectional observational analysis of electronic health records (EHR) data using a single annual merged observation measure for patients seen multiple times for preventive healthcare within a calendar year. Refusals were identified for 212,900 annualized patient-visit year observations, which represented 14.6% of annualized patient-visit year observations and 25.1% of annualized vaccine patient-year observations. The odds of having a refusal marker were significantly increased in patients seen in suburban practices (aOR [CI]: 2.35 [2.30−2.40, p < 0.001]), in patients with increased age 11−17 years (aOR [CI]: 3.85 [3.79−3.91], p < 0.001), and those eligible for the VFC program (aOR [CI]: 1.10 [1.08−1.11]. Parental refusal (61.0%) and provider decisions (32.0%) were the most common documented in progress notes for not administering vaccines, whereas contraindications (2.5%) and supply issues (1.8%) were the least common. When offered, vaccine acceptance increased for human papillomavirus, hepatitis B, measles-mumps-rubella-containing and varicella-containing vaccines and decreased for hepatitis A and meningococcal vaccines. Repeated offering of vaccines was central to increasing acceptance, in part due to increased opportunities to address specific concerns.

How ready was the US vaccination infrastructure and network of immunization information systems for COVID-19 vaccination campaigns: Recommendations to strengthen the routine vaccination program and prepare for the next pandemic.

Coronavirus disease 2019 (COVID-19) pandemic vaccination campaigns globally have been unlike any effort in history. In the United States, the success of these efforts, in part, has hinged on the timely capture and reporting of an unprecedented amount of data from a significantly greater number of administering providers than for routine vaccinations. The pandemic response has highlighted the need to explore the status and value of vaccination data as the critical glue that connects all aspects of the upstream US vaccine development and downstream vaccination delivery system. In this review, we examine immunization information systems and the role that data and staffing play in pandemic responses. We offer three strategic recommendations-regarding funding, expanded provider enrollment, and data reporting-informed by a literature review, a survey and focus group from a convenience sample of 22 immunization jurisdictions, and the vision for enhanced data flow to improve future pandemic responses and routine vaccination.

Coronavirus disease 2019 (COVID-19) vaccine hesitancy among physicians, physician assistants, nurse practitioners, and nurses in two academic hospitals in Philadelphia.

OBJECTIVE: To evaluate coronavirus disease 2019 (COVID-19) vaccine hesitancy among healthcare personnel (HCP) with significant clinical exposure to COVID-19 at 2 large, academic hospitals in Philadelphia, Pennsylvania. DESIGN, SETTING, AND PARTICIPANTS: HCP were surveyed in November-December 2020 about their intention to receive the COVID-19 vaccine. METHODS: The survey measured the intent among HCP to receive a COVID-19 vaccine, timing of vaccination, and reasons for or against vaccination. Among patient-facing HCP, multivariate regression evaluated the associations between healthcare positions (medical doctor, nurse practitioner or physician assistant, and registered nurse) and vaccine hesitancy (intending to decline, delay, or were unsure about vaccination), adjusting for demographic characteristics, reasons why or why not to receive the vaccine, and prior receipt of routine vaccines. RESULTS: Among 5,929 HCP (2,253 medical doctors [MDs] and doctors of osteopathy [DOs], 582 nurse practitioners [NPs], 158 physician assistants [PAs], and 2,936 nurses), a higher proportion of nurses (47.3%) were COVID-vaccine hesitant compared with 30.0% of PAs and NPs and 13.1% of MDs and DOs. The most common reasons for vaccine hesitancy included concerns about side effects, the newness of the vaccines, and lack of vaccine knowledge. Regardless of position, Black HCP were more hesitant than White HCP (odds ratio [OR], ∼5) and females were more hesitant than males (OR, ∼2). CONCLUSIONS: Although most clinical HCP intended to receive a COVID-19 vaccine, intention varied by healthcare position. Consistent with other studies, hesitancy was also significantly associated with race or ethnicity across all positions. These results highlight the importance of understanding and effectively addressing reasons for hesitancy, especially among frontline HCP who are at increased risk of COVID exposure and play a critical role in recommending vaccines to patients.

Factors Influencing Parental and Individual COVID-19 Vaccine Decision Making in a Pediatric Network.

Aspects of the COVID-19 vaccination campaign differed from routine vaccines, including emergency use authorizations, the prioritization of access, and the politicization of messaging. Subsequently, many parents reported lower vaccine confidence relative to routine vaccines, and vaccination coverage stalled below targets. This study aimed to understand parental vaccine decision making and compare COVID-19 versus routine vaccine decision making. We conducted nine virtual focus groups between 25 February 2022-11 March 2022 with parents (n = 41) of the Children's Hospital of Philadelphia's patients, recruited via email and stratified by vaccine hesitancy status (non-hesitant vs. hesitant). Transcripts were analyzed using the vaccine hesitancy matrix domains. Of 41 total participants, 25 (61.0%) were non-hesitant, 16 (39.0%) were hesitant or their children were not up-to-date on adolescent vaccines, and most self-identified as female (95.1%) and White/Caucasian (61.0%). Most participants (87.5%) were fully vaccinated against COVID-19 and many of their first children (n = 26, 63.4%) were vaccinated against influenza. Several themes emerged regarding decision making: individual influences, group influences, vaccine and vaccine program influences, and contextual influences. While some influences were similar for routine and COVID-19 vaccine decision making (e.g., needing evidence-based information), other factors were vaccine- or situation-specific. Building trust requires a multi-faceted concerted effort that involves addressing the complex vaccine decision-making process.