Real-world effectiveness of HPV vaccination against cervical neoplasia among birth cohorts ineligible for routine vaccination

Human papillomavirus (HPV) vaccine effectiveness may differ between settings. Here we present the first real-world effectiveness study of HPV vaccination on high-grade cervical lesions from Norway, among women who received HPV vaccine outside the routine program. We performed an observational study of all Norwegian women born 1975 to 1996 and retrieved individual data from nationwide registries on HPV vaccination status and incidence of histologically verified high-grade cervical neoplasia during 2006 to 2016. We estimated the incidence rate ratio (IRR) and 95% confidence intervals (CI) for vaccination vs no vaccination by Poisson regression stratified by age at vaccination <20 years and ≥20 years. The cohort consisted of 832 732 women, of which 46 381 (5.6%) received at least one dose of HPV vaccine by the end of 2016. The incidence rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) increased with age regardless of vaccination status and was highest at age 25 to 29, at 637/100 000 among unvaccinated women, 487/100 000 among women vaccinated before age 20 and 831/100 000 among women vaccinated at age 20 or older. The adjusted IRR of CIN2+ between vaccinated and unvaccinated women was 0.62 (95% CI: 0.46-0.84) for women vaccinated below age 20, and 1.22 (95% CI: 1.03-1.43) for women vaccinated at age 20 or older. These findings indicate that HPV vaccination among women too old to be eligible for routine HPV vaccination is effective among women who are vaccinated below age 20 but may not have the desired impact among women who are vaccinated at age 20 or older.     

Safety data from the MenB-FHbp clinical development program in healthy individuals aged 10 years and older

BackgroundThe MenB-FHbp vaccine (Trumenba®) is licensed in various countries for the prevention of meningococcal serogroup B disease in individuals ≥ 10 years of age. The clinical development program included 11 completed trials where, in each trial, MenB-FHbp had an acceptable safety profile after a primary vaccination series was administered to individuals 10–65 years of age. However, the detection of potential rare events was limited because of individual clinical trial size. The current safety analysis evaluates pooled reactogenicity and other adverse events (AEs) reported in these trials to identify new safety signals not detectable in individual trials.MethodsEleven trials contributed safety data, of which 10 recorded local and systemic reactogenicity events; 8 of the trials were controlled, and reactogenicity data were pooled for 7 of these 8 trials. Additional AE evaluations included immediate AEs (IAEs), medically attended AEs (MAEs), serious AEs (SAEs), newly diagnosed chronic medical conditions (NDCMCs), and autoimmune or neuroinflammatory conditions.ResultsLocal and systemic reactions were more frequent in the MenB-FHbp group (n = 15,294) compared with controls (n = 5509), although most reactions were transient and mild to moderate in severity. Frequencies of IAEs, SAEs, MAEs, NDCMCs, and autoimmune or neuroinflammatory conditions were similar between the MenB-FHbp and control groups.ConclusionsMenB-FHbp demonstrated a favorable safety and tolerability profile in the clinical development program of > 15,000 vaccine recipients ≥ 10 years of age. No new safety signals were identified in the pooled analysis compared with data from the individual trials. Continued postmarketing safety surveillance is important for the identification of rare events.Clinicaltrials.gov: NCT01299480; NCT000808028; NCT00879814; NCT00780806; NCT01352845; NCT01352793; NCT01461993; NCT01323270; NCT01830855; NCT01461980; NCT01768117.     

Age-related amyloidosis outside the brain: A state-of-the-art review

Inside and outside the brain, accumulation of amyloid fibrils plays key roles in the pathogenesis of fatal age-related diseases such as Alzheimer’s and Parkinson’s diseases and wild-type transthyretin amyloidosis. Although the incidence of all amyloidoses increases with age, for some types of amyloidosis aging is known as the main direct risk factor, and these types are typically diseases of elderly people. More than 10 different precursor proteins are known to cause age-associated amyloidosis; these proteins include amyloid β protein, α-synuclein, transthyretin, islet amyloid polypeptide, atrial natriuretic factor, and the newly discovered epidermal growth factor-containing fibulin-like extracellular matrix protein 1. Except for intracerebral amyloidoses, most age-related amyloidoses have been little studied. Indeed, in view of the increasing life expectancy in our societies, understanding how aging is involved in the process of amyloid fibril accumulation and the effects of amyloid deposits on the aging body is extremely important. In this review, we summarize current knowledge about the nature of amyloid precursor proteins, the prevalence, clinical manifestations, and pathogenesis of amyloidosis, and recent advances in our understanding of age-related amyloidoses outside the brain.     

Vaccination inhibits the human adenoviral transduction in a mouse keratoconjunctivitis model

Adenovirus infections are a major cause of epidemic keratoconjunctivitis (EKC), which can lead to corneal subepithelial infiltrates and multifocal corneal opacity. In the current study, we investigated the use of an E1/E3-deleted adenovirus serotype 5 (Ad5) vector as a vaccine administered intramuscularly (IM) or intranasally (IN) against subsequent challenges with a luciferase-expressing Ad5 (Ad5-Luci) vector via eyedrop. We evaluated the adaptive immune response to Ad5 vector vaccination and confirmed a robust polyfunctional CD8 T cell response in splenic cells. Neutralizing Ad5 antibodies were also measured in the sera of vaccinated mice as well as Ad5 antibody in the eye wash solutions. Upon challenge with Ad5-Luci vector 8 weeks post the primary immunization, transduction was significantly reduced by > 70% in the vaccinated mice, which was slightly better in IM- vs. that in IN-vaccinated animals. Resistance to subsequent challenge was observed 10 months post primary IM vaccination, with sustained reduction up to 60% in the Ad5-Luci vector transduction. Passive immunization of naive mice with antisera from IM to vaccinated mice subsequently challenged with the Ad5-Luci vector resulted in approximately 40% loss in transduction efficiency. Furthermore, the mice that received IM immunization with or without CD8 T cell depletion showed > 40% and 70% reductions, respectively, in Ad8 genomic copies after Ad8 topical challenge. We conclude that Ad-vector vaccination successfully induced an adaptive immune response that prevented subsequent Ad transduction in the cornea and conjunctiva-associated tissues in a mouse model of adenovirus keratoconjunctivitis, and that both cellular and humoral immunity play an important role in preventing Ad transduction.     

中性粒细胞蛋白-1、-2、-3在膀胱癌患者组织中的 表达及与预后的相关性

目的：研究中性粒细胞蛋白（HNP）-1、-2、-3 在膀胱癌患者组织中的表达及与预后的关系。方法：采用 免疫组织化学法检测膀胱癌组织中HNP-1、HNP-2、HNP-3 的表达情况，分析HNP-1、HNP-2、HNP-3 在膀胱癌 组织中的表达与膀胱癌临床病理特征的相关性及预后相关因素的关系。结果：HNP-1、HNP-2、HNP-3 蛋白在膀 胱癌患者组织中的阳性表达率分别为70.51%、72.66%、71.94%，均明显高于癌旁正常组织8.10%、3.23%、6.45%， 差异有统计学意义；HNP1、HNP2、HNP3在膀胱癌患者中的表达水平与肿瘤的病理分级、临床分期、淋巴结转 移及复发等生物学行为相关；生存曲线结果提示这3 种蛋白表达阳性的5 年生存率均显著低于表达阴性的患者。 Cox 比例风险模型分析结果提示HNP-1、HNP-2、HNP-3 的表达是影响膀胱癌预后的关键风险因素。结论：HNP- 1、HNP-2、HNP-3 在膀胱癌组织中高表达且表达程度随肿瘤发展进一步增加；HNP-1、HNP-2、HNP-3 是影响患 者预后的关键危险因素，阳性表达的患者５年生存率显著降低；HNP-1、HNP-2、HNP-3 与膀胱癌病情发展、炎 症程度及预后密切相关。     

Human prostate cancer bone metastases have an actionable immunosuppressive microenvironment

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Higher-risk breast cancer in women aged 80 and older: Exploring the effect of treatment on survival

BackgroundTo understand the association between various treatments and survival for older women with higher-risk breast cancer when controlling for patient and tumor factors.Materials and methodsWe conducted a retrospective, population-based study. Women aged 80 years or older and diagnosed between 2004 and 2017 with non-metastatic, higher-risk breast cancer were identified form the provincial cancer registry in Alberta, Canada. Higher-risk was defined as any of following: T3/4, node positive, human epidermal factor receptor-2 (Her2) positive or triple negative disease. Treatments were surgery, radiotherapy and systemic therapy (hormonal therapy, and/or chemotherapy and/or trastuzumab) or a combination of the previous. Cox regression models were used to examine the association between treatments and breast cancer specific survival (BCSS) and overall survival (OS).Results1369 patients were included. The median age was 84 years. 332 (24%) of women had T3-T4 tumors, 792 (58%) had nodal involvement, 130 (10%) had Her2 positive tumors, 124 (9%) had triple negative tumors. After a median follow-up of 35 months, 29.5% of patients died of breast cancer whereas 34.2% died from other causes. Patients had a lower adjusted hazard for BCSS if they had surgery (hazard ratio [HR] = 0.37 95% confidence interval [CI]: 0.27, 0.51), or systemic therapy (HR = 0.75, 95%CI: 0.58, 0.98). Patients had an increased probability of breast cancer death in the first 5 years after diagnosis compared to death from other causes.ConclusionsSurgery and systemic therapy were associated with longer BCSS and OS. This suggests that maximizing treatments might benefit higher-risk patients.     

Patients Are Knowledge Workers in the Clinical Information Space

Background  Limited research exists on patient knowledge/cognition or “getting inside patients'' heads.” Because patients possess unique and privileged knowledge, clinicians need this information to make patient-centered and coordinated treatment planning decisions. To achieve patient-centered care, we characterize patient knowledge and contributions to the clinical information space. Methods and Objectives  In a theoretical overview, we explore the relevance of patient knowledge to care provision, apply historical perspectives of knowledge acquisition to patient knowledge, propose a representation of patient knowledge types across the continuum of care, and include illustrative vignettes about Mr. Jones. We highlight how the field of human factors (a core competency of health informatics) provides a perspective and methods for eliciting and characterizing patient knowledge. Conclusion  Patients play a vital role in the clinical information space by possessing and sharing unique knowledge relevant to the clinical picture. Without a patient''s contributions, the clinical picture of the patient is incomplete. A human factors perspective informs patient-centered care and health information technology solutions to support clinical information sharing.