Immune to addiction: the ethical dimensions of vaccines against substance abuse.

Promising advances have been made in recent years for a unique class of immunotherapies that use vaccination to combat substance-use disorders. Although such vaccines are potentially useful for addictions, they raise a variety of ethical and social questions.

Understanding the Factors Influencing Health Care Provider Recommendations about Adolescent Vaccines: A Proposed Framework.

Health care provider recommendations are among the most important factors influencing parents' decisions to vaccinate their adolescents. However, delivery of high-quality health care provider recommendations for vaccination is not universal. There is wide variation in the strength, timeliness and consistency of the delivery of recommendations for all adolescent vaccines. The factors that influence health care providers' recommendations are multi-level and can be conceptualized in much the same way as vaccine acceptance among parents. Health care providers are influenced by their own attitudes and beliefs about a vaccine and also by the patient they are treating and by the community in which they practice as well as state and national level vaccine policy. We propose a multi-level framework for understanding the factors that influence health care providers' recommendations at the individual, interpersonal and community level to both develop and adapt interventions to improve providers' recommendations.

Promoting COVID-19 vaccine acceptance: recommendations from the Lancet Commission on Vaccine Refusal, Acceptance, and Demand in the USA.

Since the first case of COVID-19 was identified in the USA in January, 2020, over 46 million people in the country have tested positive for SARS-CoV-2 infection. Several COVID-19 vaccines have received emergency use authorisations from the US Food and Drug Administration, with the Pfizer-BioNTech vaccine receiving full approval on Aug 23, 2021. When paired with masking, physical distancing, and ventilation, COVID-19 vaccines are the best intervention to sustainably control the pandemic. However, surveys have consistently found that a sizeable minority of US residents do not plan to get a COVID-19 vaccine. The most severe consequence of an inadequate uptake of COVID-19 vaccines has been sustained community transmission (including of the delta [B.1.617.2] variant, a surge of which began in July, 2021). Exacerbating the direct impact of the virus, a low uptake of COVID-19 vaccines will prolong the social and economic repercussions of the pandemic on families and communities, especially low-income and minority ethnic groups, into 2022, or even longer. The scale and challenges of the COVID-19 vaccination campaign are unprecedented. Therefore, through a series of recommendations, we present a coordinated, evidence-based education, communication, and behavioural intervention strategy that is likely to improve the success of COVID-19 vaccine programmes across the USA.

COVID-19 vaccine perceptions in the initial phases of US vaccine roll-out: an observational study on reddit.

BACKGROUND: Open online forums like Reddit provide an opportunity to quantitatively examine COVID-19 vaccine perceptions early in the vaccine timeline. We examine COVID-19 misinformation on Reddit following vaccine scientific announcements, in the initial phases of the vaccine timeline. METHODS: We collected all posts on Reddit (reddit.com) from January 1 2020 - December 14 2020 (n=266,840) that contained both COVID-19 and vaccine-related keywords. We used topic modeling to understand changes in word prevalence within topics after the release of vaccine trial data. Social network analysis was also conducted to determine the relationship between Reddit communities (subreddits) that shared COVID-19 vaccine posts, and the movement of posts between subreddits. RESULTS: There was an association between a Pfizer press release reporting 90% efficacy and increased discussion on vaccine misinformation. We observed an association between Johnson and Johnson temporarily halting its vaccine trials and reduced misinformation. We found that information skeptical of vaccination was first posted in a subreddit (r/Coronavirus) which favored accurate information and then reposted in subreddits associated with antivaccine beliefs and conspiracy theories (e.g. conspiracy, NoNewNormal). CONCLUSIONS: Our findings can inform the development of interventions where individuals determine the accuracy of vaccine information, and communications campaigns to improve COVID-19 vaccine perceptions, early in the vaccine timeline. Such efforts can increase individual- and population-level awareness of accurate and scientifically sound information regarding vaccines and thereby improve attitudes about vaccines, especially in the early phases of vaccine roll-out. Further research is needed to understand how social media can contribute to COVID-19 vaccination services.

Assessing COVID-19 Prevention Strategies to Permit the Safe Opening of Residential Colleges in Fall 2021.

BACKGROUND: Effective vaccines, improved testing technologies, and decreases in COVID-19 incidence prompt an examination of the choices available to residential college administrators seeking to safely resume in-person campus activities in fall 2021. OBJECTIVE: To help college administrators design and evaluate customized COVID-19 safety plans. DESIGN: Decision analysis using a compartmental epidemic model to optimize vaccination, testing, and other nonpharmaceutical interventions depending on decision makers' preferences, choices, and assumptions about epidemic severity and vaccine effectiveness against infection, transmission, and disease progression. SETTING: U.S. residential colleges. PARTICIPANTS: Hypothetical cohort of 5000 persons (students, faculty, and staff) living and working in close proximity on campus. MEASUREMENTS: Cumulative infections over a 120-day semester. RESULTS: Under base-case assumptions, if 90% coverage can be attained with a vaccine that is 85% protective against infection and 25% protective against asymptomatic transmission, the model finds that campus activities can be resumed while holding cumulative cases below 5% of the population without the need for routine, asymptomatic testing. With 50% population coverage using such a vaccine, a similar cap on cumulative cases would require either daily asymptomatic testing of unvaccinated persons or a combination of less frequent testing and resumption of aggressive distancing and other nonpharmaceutical prevention policies. Colleges returning to pre-COVID-19 campus activities without either broad vaccination coverage or high-frequency testing put their campus population at risk for widespread viral transmission. LIMITATION: Uncertainty in data, particularly vaccine effectiveness (preventive and transmission); no distinguishing between students and employees; and assumes limited community intermixing. CONCLUSION: Vaccination coverage is the most powerful tool available to residential college administrators seeking to achieve a safe return to prepandemic operations this fall. Given the breadth of potential outcomes in the face of uncontrollable and uncertain factors, even colleges with high vaccination rates should be prepared to reinstitute or expand testing and distancing policies on short notice. PRIMARY FUNDING SOURCE: National Institute on Drug Abuse.

Outcomes of Hematopoietic Cell Transplantation in Patients with Germline SAMD9/SAMD9L Mutations.

Germline mutations in SAMD9 and SAMD9L genes cause MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) (OMIM: *610456) and ataxia-pancytopenia (OMIM: *611170) syndromes, respectively, and are associated with chromosome 7 deletions, myelodysplastic syndrome (MDS), and bone marrow failure. In this retrospective series, we report outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with hematologic disorders associated with SAMD9/SAMD9L mutations. Twelve patients underwent allogeneic HCT for MDS (n = 10), congenital amegakaryocytic thrombocytopenia (n = 1), and dyskeratosis congenita (n = 1). Exome sequencing revealed heterozygous mutations in SAMD9 (n = 6) or SAMD9L (n = 6) genes. Four SAMD9 patients had features of MIRAGE syndrome. Median age at HCT was 2.8 years (range, 1.2 to 12.8 years). Conditioning was myeloablative in 9 cases and reduced intensity in 3 cases. Syndrome-related comorbidities (diarrhea, infections, adrenal insufficiency, malnutrition, and electrolyte imbalance) were present in MIRAGE syndrome cases. One patient with a familial SAMD9L mutation, MDS, and morbid obesity failed to engraft and died of refractory acute myeloid leukemia. The other 11 patients achieved neutrophil engraftment. Acute post-transplant course was complicated by syndrome-related comorbidities in MIRAGE cases. A patient with SAMD9L-associated MDS died of diffuse alveolar hemorrhage. The other 10 patients had resolution of hematologic disorder and sustained peripheral blood donor chimerism. Ten of 12 patients were alive with a median follow-up of 3.1 years (range, 0.1 to 14.7 years). More data are needed to refine transplant approaches in SAMD9/SAMD9L patients with significant comorbidities and to develop guidelines for their long-term follow-up.

Comparison of the effects of standard vs low-dose prolonged-release tacrolimus with or without ACEi/ARB on the histology and function of renal allografts.

Targeting the renin-angiotensin system and optimizing tacrolimus exposure are both postulated to improve outcomes in renal transplant recipients (RTRs) by preventing interstitial fibrosis/tubular atrophy (IF/TA). In this multicenter, prospective, open-label controlled trial, adult de novo RTRs were randomized in a 2 × 2 design to low- vs standard-dose (LOW vs STD) prolonged-release tacrolimus and to angiotensin-converting enzyme inhibitors/angiotensin II receptor 1 blockers (ACEi/ARBs) vs other antihypertensive therapy (OAHT). There were 2 coprimary endpoints: the prevalence of IF/TA at month 6 and at month 24. IF/TA prevalence was similar for LOW vs STD tacrolimus at month 6 (36.8% vs 39.5%; P = .80) and ACEi/ARBs vs OAHT at month 24 (54.8% vs 58.2%; P = .33). IF/TA progression decreased significantly with LOW vs STD tacrolimus at month 24 (mean [SD] change, +0.42 [1.477] vs +1.10 [1.577]; P = .0039). Across the 4 treatment groups, LOW + ACEi/ARB patients exhibited the lowest mean IF/TA change and, compared with LOW + OAHT patients, experienced significantly delayed time to first T cell-mediated rejection. Renal function was stable from month 1 to month 24 in all treatment groups. No unexpected safety findings were detected. Coupled with LOW tacrolimus dosing, ACEi/ARBs appear to reduce IF/TA progression and delay rejection relative to reduced tacrolimus exposure without renin-angiotensin system blockade. ClinicalTrials.gov identifier: NCT00933231.

Association Between Food and Drug Administration Advisory Committee Recommendations and Agency Actions, 2008-2015.

Policy Points Food and Drug Administration (FDA) advisory committee recommendations and the agency's final actions exhibit high rates of agreement, with cases of disagreement tending to reflect the proposed action type and degree of advisory committee consensus. In the case of disagreements, the FDA tended to be less likely than its advisory committees to approve new products, approve new supplemental indications, or enact new safety changes. These findings raise important issues regarding the factors that differentially shape decision making by advisory committees and the FDA as an agency, including institutional or reputational concerns. CONTEXT: The Food and Drug Administration (FDA) convenes advisory committees to provide external scientific counsel on potential agency actions and to inform regulatory decision making. The degree to which advisory committees and their respective agency divisions disagree on recommendations has not been well characterized across product and action types. METHODS: We examined public documents from FDA advisory committee meetings and medical product databases for all FDA advisory committee meetings from 2008 through 2015. We classified the 376 voting meetings in that period by medical product, regulatory, and advisory committee meeting characteristics. We used multivariable logistic regression to determine the associations between these characteristics and discordance between the advisory committee's recommendations and the FDA's final actions. FINDINGS: Twenty-two percent of the FDA's final actions were discordant with the advisory committee's recommendations. Of these, 75% resulted in the FDA making more restrictive decisions after favorable committee recommendations, and 25% resulted in the agency making less restrictive decisions after unfavorable committee recommendations. Discordance was associated with lower degrees of advisory committee consensus and was more likely for agency actions focused on medical product safety than for novel approvals or supplemental indications. Statements by public speakers, advisory committee conflicts of interest, and media coverage were not associated with discordance between the committee and the agency. CONCLUSIONS: The FDA disagrees with the recommendation of its advisory committees a minority of the time, and in these cases it tends to be less likely to approve new products or supplemental indications and take safety actions. Deviations from recommendations thus offer an opportunity to understand the factors influencing decisions made by both the agency and its expert advisory groups.

The Spanish Flu, Epidemics, and the Turn to Biomedical Responses.

A century ago, nonpharmaceutical interventions such as school closings, restrictions on large gatherings, and isolation and quarantine were the centerpiece of the response to the Spanish Flu. Yet, even though its cause was unknown and the science of vaccine development was in its infancy, considerable enthusiasm also existed for using vaccines to prevent its spread. This desire far exceeded the scientific knowledge and technological capabilities of the time. Beginning in the early 1930s, however, advances in virology and influenza vaccine development reshaped the relative priority given to biomedical approaches in epidemic response over traditional public health activities. Today, the large-scale implementation of nonpharmaceutical interventions akin to the response to the Spanish Flu would face enormous legal, ethical, and political challenges, but the enthusiasm for vaccines and other biomedical interventions that was emerging in 1918 has flourished. The Spanish Flu functioned as an inflection point in the history of epidemic responses, a critical moment in the long transition from approaches dominated by traditional public health activities to those in which biomedical interventions are viewed as the most potent and promising tools in the epidemic response arsenal.

The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation.

BACKGROUND: CMV infection (CMV-I) remains an important complication of hematopoietic stem cell transplantation (HSCT). METHODS: This was a retrospective, single-center cohort study in HSCT recipients. Primary outcomes were adjusted cost and all-cause mortality. Secondary analyses investigated CMV risk factors and the effect of serostatus. RESULTS: Overall, 690 transplant episodes were included (allogeneic [n = 310]; autologous [n = 380]). All received preemptive CMV antiviral therapy at first detectable DNAemia. CMV-I occurred in 34.8% of allogeneic and 2.1% of autologous transplants; median time to onset was 45 days. In allogeneic HSCT recipients, the primary risk factor for CMV-I was CMV donor/recipient (D/R) serostatus. In a Markov multi-state model for allogeneic HSCT recipients, the hazard ratio for CMV-I and relapse was 1.5 (95% CI 0.8-2.8) and for CMV-I and mortality 2.4 (95% CI 0.9-6.5). In a multivariable model for all patients, CMV-I was associated with increased total cost (coefficient = 0.21, estimated incremental daily cost USD $500; P = 0.02). Cost was attenuated in allogeneic HSCT recipients (coefficient = 0.13, USD $699 vs $613, or $24 892 per transplant episode; P = 0.23). CMV disease (CMV-D) complicated 29.6% of CMV-I events in allogeneic HSCT recipients, but was not associated with an incrementally increased adjusted risk of mortality compared with CMV-I alone. CMV-I (56.4%) and CMV-D (19.8%) were significantly overrepresented in D-/R+ serostatus HSCT recipients, and mortality was higher in R+ HSCT recipients. CONCLUSIONS: Despite early preemptive antiviral treatment, CMV-I impacts clinical outcomes and cost after HSCT, but the impact on cost is less pronounced in allogeneic HSCT recipients compared with autologous HSCT recipients.

Kindergarten Vaccination Status in California After Changes to Medical Exemption Policy.

This study evaluates changes in medical exemptions and geographic distribution of kindergarteners in California not up to date on vaccination after changes to state legislation.

State-Level Voting Patterns and Adolescent Vaccination Coverage in the United States, 2014.

OBJECTIVES: To examine state-level associations between voting patterns and adolescent coverage for at least 1 dose of human papillomavirus (HPV), tetanus-containing (Tdap), and meningococcal (MCV4) vaccination. METHODS: We classified states as "blue" (Democratic affiliation) or "red" (Republican affiliation) based on the Presidential election results in 2012. We used multivariable models to adjust for potential confounding by sociodemographic and health care access characteristics and vaccination policies. For HPV, separate models were fitted for boys and girls. RESULTS: Adolescent vaccination coverage was significantly higher in blue states than red states for each vaccine (P < .05). The adjusted percent differences between blue and red states were 10.2% for HPV among girls, 24.9% for HPV among boys, 6.2% for tetanus-containing vaccine, and 14.1% for MCV4. CONCLUSIONS: State-level voting patterns are independently and significantly associated with coverage for routinely recommended adolescent vaccines. These differences may reflect population-level differences in cultural norms and social values. PUBLIC HEALTH IMPLICATIONS: Strategies to increase coverage at the individual, community, or structural level should consider local political settings that may facilitate or hinder effectiveness.