A Comparative Case Study Analysis: Applying the HIPE Framework to Combat Harmful Health Information and Drive COVID-19 Vaccine Adoption in Underserved Communities.

This descriptive, observational paper utilizes the comparative case study approach to analyze the application of the HIPE™ Framework to two health campaigns addressing vaccine hesitancy in underserved communities. Exposure to inaccurate/misleading health information impacts vaccination adoption, especially for individuals with low health/digital literacy. Underserved groups-like minority, racial/ethnic, or rural populations-typically have lower literacy and higher rates of vaccine hesitancy. Grounded in persuasion and behavioral change theory, the Health Information Persuasion Exploration (HIPE™) Framework was applied to the Black/Haitian community in Miami-Dade, Florida and the Migrant Agricultural Worker Community in Central Valley, California. The campaigns addressed each community's unique characteristics via Detect, Analyze, Design, and Evaluate phases of the HIPE framework. Both campaigns achieved their respective vaccine uptake goals. For Miami-Dade, over 850 vaccinations were administered (the goal was 800 vaccinations), and vaccination rates increased by 25.22%. In Central Valley, vaccination rates for 5-11-year-old children in Merced and Stanislaus counties increased about 20% and 14%, respectively, and overall vaccination rates increased compared to surrounding counties. Discussion of the results and recommendations for future research highlight the potential efficacy of applying the HIPE™ Framework for developing health campaigns and response strategies to improve health outcomes.

Effects of conditioning regimens and T cell depletion in hematopoietic cell transplantation for primary immune deficiency.

This study analyzes the hematopoietic cell transplantation experience in patients with immune deficiency at a single institution. The objective is to comprehensively evaluate the short-term and long-term outcomes with various preparative regimens, donor grafts, and ex vivo manipulations to identify transplantation approaches that most likely favor early donor immune competency without generating excessive toxicity. Clinical outcomes were evaluated in 52 consecutive patients with immune deficiencies. Thirty-seven of the 52 patients (71%) survived with attenuation of their underlying disease. The use of a melphalan-based reduced-intensity conditioning preparative regimen and immunomagnetic CD3(+) T cell depletion techniques (when T cell depletion was indicated) were associated with improved event-free survival. Survivors who received a preparative regimen other than a melphalan-based reduced-intensity regimen suffered from therapy-related morbidities or chronic/recurrent infections. Our findings indicate that melphalan-based reduced-intensity conditioning regimens and immunomagnetic CD3(+) T cell depletion limit therapy-related toxicity, and demonstrate promising results for the early establishment of donor immune competency.

Primary B cell immunodeficiencies: comparisons and contrasts.

Sophisticated genetic tools have made possible the identification of the genes responsible for most well-described immunodeficiencies in the past 15 years. Mutations in Btk, components of the pre-B cell and B cell receptor (lambda5, Igalpha, Igbeta), or the scaffold protein BLNK account for approximately 90% of patients with defects in early B cell development. Hyper-IgM syndromes result from mutations in CD40 ligand, CD40, AID, or UNG in 70-80% of affected patients. Rare defects in ICOS or CD19 can result in a clinical picture that is consistent with common variable immunodeficiency, and as many as 10% of patients with this disorder have heterozygous amino acid substitutions in TACI. For all these disorders, there is considerable clinical heterogeneity in patients with the same mutation. Identifying the genetic and environmental factors that influence the clinical phenotype may enhance patient care and our understanding of normal B cell development.

Adults with X-linked agammaglobulinemia: impact of disease on daily lives, quality of life, educational and socioeconomic status, knowledge of inheritance, and reproductive attitudes.

Since many children with X-linked agammaglobulinemia (XLA) can now be expected to reach adulthood, knowledge of the status of adults with XLA would be of importance to the patients, their families, and the physicians caring for these patients. We performed the current study in adults with XLA to examine the impact of XLA on their daily lives and quality of life, their educational and socioeconomic status, their knowledge of the inheritance of their disorder, and their reproductive attitudes. Physicians who had entered adult patients with XLA in a national registry were asked to pass on a survey instrument to their patients. The patients then filled out the survey instrument and returned it directly to the investigators. Adults with XLA were hospitalized more frequently and missed more work and/or school than did the general United States population. However, their quality of life was comparable to that of the general United States population. They achieved a higher level of education and had a higher income than did the general United States population. Their knowledge of the inheritance of their disease was excellent. Sixty percent of them would not exercise any reproductive planning options as a result of their disease. The results of the current study suggest that although the disease impacts the daily lives of adults with XLA, they still become productive members of society and excel in many areas.

The health status and quality of life of adults with X-linked agammaglobulinemia.

Forty-one adults (mean age 33) with a definitive diagnosis of X-linked agammaglobulinemia (XLA) completed a questionnaire concerning current and past medical problems and quality of life. Thirty-six of the 41 were working full time or were full time students; 18 had not missed any work or school due to infection in the previous year. Their quality of life was equivalent to that of the general US male population. Thirteen of the 41 reported that they had chronic lung disease, and 33 indicated that they had one or more episodes of sinusitis in the preceding year. Arthritis, diarrhea and skin infections were common but not debilitating. The 41 study subjects were more likely to have a prior family history of XLA, and they were more likely to have milder mutations in Btk, the gene responsible for XLA. These results indicate that most adults with XLA are moderately healthy and lead productive lives.

Genetic analysis of patients with defects in early B-cell development.

Approximately 85% of patients with defects in early B-cell development have X-linked agammaglobulinemia (XLA), a disorder caused by mutations in the cytoplasmic Bruton's tyrosine kinase (Btk). Although Btk is activated by cross-linking of a variety of cell-surface receptors, the most critical signal transduction pathway is the one initiated by the pre-B cell and B-cell antigen receptor complex. Mutations in Btk are highly diverse, and no single mutation accounts for more than 3% of patients. Although there is no strong genotype/phenotype correlation in XLA, the specific mutation in Btk is one of the factors that influences the severity of disease. Mutations in the components of the pre-B cell and B-cell antigen receptor complex account for an additional 5-7% of patients with defects in early B-cell development. Patients with defects in these proteins are clinically indistinguishable from those with XLA. However, they tend to be younger at the time of diagnosis, and whereas most patients with XLA have a small number of B cells in the peripheral circulation, these cells are not found in patients with defects in micro heavy chain or Igalpha. Polymorphic variants in the components of the pre-B cell and B-cell receptor complex, particularly micro heavy chain and lambda5, may contribute to the severity of XLA.

Stem cell transplants for patients with X-linked agammaglobulinemia.

Six young patients with X-linked agammaglobulinemia and proven mutations in Btk were treated with cord blood or bone marrow transplants from HLA-matched siblings. Complete blood counts, serum chemistries, serum immunoglobulin concentrations, lymphocyte cell surface markers, and physical findings were evaluated at 3- to 5-day intervals for the first 2 weeks after transplant and then every 3 to 6 months. The first three patients were not given any preparative regimen or antirejection drugs and at 24 to 42 months posttransplant these patients have shown no benefit or harm related to the transplants. The second three patients were not given a preparative regimen but were treated with cyclosporine A (70 days) and mycophenolate mophetil (28 days) after transplant. Two of these patients have developed normal sized, nontender cervical lymph nodes 3 to 12 months after transplant but none of the three patients have shown an increase in serum IgM or an increase in the number of peripheral blood B cells. It is likely that successful engraftment will require more aggressive immunosupressive medications.

Clinical findings leading to the diagnosis of X-linked agammaglobulinemia.

To evaluate whether the diagnosis of X-linked agammaglobulinemia (XLA) is being made in a timely fashion, the clinical findings leading to the diagnosis of XLA were determined in 82 patients with proven mutations in Bruton's tyrosine kinase (60 patients with sporadic disease and 22 patients with familial disease). Recurrent otitis was seen in almost all of the patients with sporadic XLA who were older than 12 months at the time of diagnosis. However, fewer than 10% of patients were evaluated for immunodeficiency before they were hospitalized for infection; 38% of patients were hospitalized more than once before diagnosis. We conclude that the majority of patients with XLA were recognized to have immunodeficiency during or shortly after their first hospitalization for infection. Most of the patients had a history of recurrent otitis at the time of diagnosis, which when combined with the physical finding of markedly decreased or absent tonsils and cervical lymph nodes, could have alerted physicians to the diagnosis of XLA.