Surveillance for disease progression of transthyretin amyloidosis after heart transplantation in the era of novel disease modifying therapies.

BACKGROUND: Heart Transplantation (HT) is a rational therapy for advanced transthyretin cardiac amyloidosis (ATTR-CA), but the impact of ongoing amyloid deposition is not well defined. We evaluated a cohort of patients who underwent HT for ATTR-CA to determine the incidence of de novo or progression of post-HT ATTR deposition. METHODS: All patients who were followed post-HT for ATTR-CA at our center were included. Baseline demographics and post-HT manifestations of TTR deposition were collected. All patients completed the Composite Autonomic Symptom Score (COMPASS-31 quantifies autonomic symptoms, with a higher score [0-100] indicating more severe autonomic dysfunction) and Polyneuropathy Disability Score (PND, range from 0 [asymptomatic] to IV [confined to wheelchair/bed]) questionnaires. RESULTS: Twelve patients (5 wild-type, 7 variant [6 p.Val142Ile, 1 p.Thr80Ala]) were included. Mean age at HT was 64.6 (SD: 4.8) years, 83.3% male, and 50% Black. At a median of 4.0 years (IQR 2.4, 5.9) post-HT, 8 patients had symptoms of ATTR deposition (5 with gastrointestinal involvement, 4 orthopedic and 4 neurologic), with 4 patients having ≥2 body systems involved. There were no patients with recurrent cardiac involvement. Median COMPASS-31 score was 17.3 (IQR 11.3, 23.5) at 3.9 years (IQR 2.4, 5.9) post-HT. Four patients had a PND score of stage 1 (sensory disturbance), 1 patient was stage 2 (impaired walking) and 1 patient stage 3b (required a walking aid). CONCLUSIONS: More than 50% of patients had evidence of progressive or de novo ATTR deposition post-HT, impairing quality of life despite a well-functioning cardiac allograft. These observations highlight an unmet need to establish the role of formal surveillance and treatment of TTR using TTR disease-modifying therapies, which may maintain or improve quality of life post-HT for ATTR-CA.

Association Between Human Papillomavirus Vaccination School-Entry Requirements and Vaccination Initiation.

Importance: Human papillomavirus (HPV) vaccination coverage is suboptimal in the US. The association between HPV vaccination requirements for school entry and HPV vaccination coverage remains to be studied. Objective: To examine the association between HPV vaccination school-entry requirements and vaccination initiation in jurisdictions with such vaccination policies (ie, Virginia, the District of Columbia, and Rhode Island) compared with other regions of the US, as determined by the National Center for Chronic Disease Prevention and Health Promotion. Design, Setting, and Participants: In a population-based, cross-sectional study, 2017 data from the National Immunization Survey-Teen database were used to determine HPV vaccination initiation. Data from 2008 to 2017 were then examined to assess the association between HPV vaccination school-entry policies and vaccination initiation. Data were obtained for adolescents aged 13 to 17 years in the US with health care professional-reported HPV vaccination histories (cross-sectional study, n = 4784; pre-post policy comparisons, n = 42 431). This study was conducted from May 1, 2019, to March 31, 2020. Exposures: State-level HPV vaccination school-entry requirements from 2008 to 2017. Main Outcomes and Measures: Health care professional-confirmed HPV vaccination initiation. Results: The 2017 cross-sectional study included 4784 adolescents aged 13 to 17 years (2228 [46.6%] girls; 2556 [53.4%] boys; mean [SD] age, 15.0 [1.4] years; interquartile range, 14-16 years). Compared with nonpolicy jurisdictions within the same region, Rhode Island and the District of Columbia, which have HPV immunization school-entry requirements, had higher levels of HPV vaccination initiation (Rhode Island: adjusted odds ratio [aOR], 4.34; 95% CI, 2.16-10.00; District of Columbia: aOR, 2.35; 95% CI, 1.39-4.19). However, compared with regional nonpolicy states, Virginia's HPV vaccination initiation did not differ significantly (aOR, 1.01; 95% CI, 0.72-1.42). The 2008-2017 pre-post policy comparisons involved 42 431 adolescents aged 13-17 years (22 362 [52.7%] girls; 20 069 [47.3%] boys; mean [SD] age, 15.0 [1.4] years; interquartile range, 14-16 years). Postpolicy levels of HPV vaccination initiation in girls was significantly higher in Rhode Island (aOR, 3.12; 95% CI, 1.92-5.07) than prepolicy values. Similar changes were noted for postpolicy HPV vaccination initiation in boys in the District of Columbia (aOR, 6.36; 95% CI, 4.27-9.46) and Rhode Island (aOR, 5.84; 95% CI, 3.92-8.69) compared with prepolicy measures. With respect to regional nonpolicy states during the same period, both girls and boys in Rhode Island and boys in the District of Columbia experienced larger increases in HPV vaccination initiation. For example, in Rhode Island, boys aged 16 to 17 years had 7.32 (95% CI, 3.56-15.06) times the change in pre-post policy HPV vaccination initiation, while girls aged 16 to 17 years had 1.28 (95% CI, 0.60-2.73) times the change. In the District of Columbia, boys had 6.36 (95% CI, 4.27-9.46) times the change in pre-post policy HPV vaccination initiation. Conclusions and Relevance: The findings of this study suggest that HPV vaccination school-entry requirements are associated with increases in vaccination initiation. Expanding such policies may increase HPV vaccination in the US.

Excess Cancer Cases and Medical Costs Due to Suboptimal Human Papillomavirus Vaccination Coverage in California.

BACKGROUND: Human papillomavirus (HPV) vaccination coverage continues to be at low to moderate levels throughout the United States. HPV infection is linked to multiple types of cancers resulting in high economic and health burden. We aimed to estimate the excess number of cancer cases and associated medical costs due to current HPV vaccination coverage for a 20-year-old birth cohort in California. METHODS: We estimated the lifetime number of cancer cases caused by vaccine-preventable strains of HPV for a cohort of 20 year-olds in California. We then estimated the excess number of cancer cases in that cohort which would occur due to 2017 HPV vaccination coverage compared with an optimal coverage of 99.5%. By multiplying those excess cases by the average cost of treatment, we determined the excess cost due to current HPV vaccination coverage. RESULTS: With current vaccination coverage in California, the 20-year-old cohort is at risk for an excess 1352 cancer cases that could be prevented with a projected optimal vaccination coverage of 99.5%. The excess cost of treatment for those cancer cases would be US $52.2 million. Male oropharyngeal cancer accounts for the greatest projected cost burden US $21.3 million followed by cervical cancer US $16.1 million. CONCLUSIONS: Increased HPV vaccination coverage in California is needed to reduce economic and health burdens associated with cancers caused by HPV infection.

Evaluation of the Bio-Rad Multispot HIV-1/HIV-2 Rapid Test as an alternative to Western blot for confirmation of HIV infection.

BACKGROUND: In the United States, a new HIV diagnostic algorithm has been proposed that uses an HIV-1/HIV-2 antibody differentiation immunoassay instead of Western blot or immunofluoresence for confirmatory testing. OBJECTIVES: To evaluate the Multispot HIV-1/HIV-2 Rapid Test (Multispot) as an alternative to Western blot analysis for confirmation of HIV infection. STUDY DESIGN: A series of 205 serum and plasma specimens positive for HIV-1 or HIV-2 were used to compare the performance of Multispot to a standard HIV-1 Western blot. Positive samples included 63 specimens from patients>18 months of age, 33 proficiency survey specimens, and 109 specimens from nine commercial seroconversion and performance panels. In addition, 63 specimens from 51 HIV-exposed, uninfected children≤18 months of age in various stages of seroreversion and 192 HIV-negative samples were tested. Specimens were initially screened using a 4th generation HIV Ag/Ab Combo assay. RESULTS: Multispot readily discriminated between individuals with HIV-1 or HIV-2 infection and those who were uninfected. Of the 205 samples repeatedly reactive by the 4th generation screening assay, infection status was correctly confirmed by Multispot in 83.9% (172/205) compared to 68.8% (141/205) for Western blot. Multispot detected HIV-1 earlier in 27.6% of low-titer antibody specimens called indeterminate by Western blot, and effectively reduced the number of indeterminate results in seroreverting HIV-1 exposed, uninfected infants and for HIV-2 infections misinterpreted as indeterminate or positive by HIV-1 Western blot. CONCLUSIONS: Multispot offers speed and simplicity over Western blot and has an excellent performance for differentiation and confirmation of antibodies to HIV-1 and HIV-2.