Proposal for the revision of guidelines for clinical trials of vaccines to prevent infectious diseases in Japan.

The development of vaccines against infectious diseases requires a different approach from that of therapeutics, because vaccines are inoculated into healthy individuals and have a preventive effect by activating the immunity of the inoculated human. In Japan, "The Guideline for Clinical Trials of Vaccines for the Prevention of Infectious Diseases" was published in 2010 before changes occurred in the vaccine development environment in Japan, such as the introductions of foreign vaccines and simultaneous global development. This study aimed to identify current challenges in vaccine development through a questionnaire-based survey of pharmaceutical companies in Japan and by comparing the domestic and international guidelines and surveying review reports of 35 vaccines approved in Japan between April 2010 and December 2020. Identified challenges included the requirement for protective efficacy trials, efficacy evaluation of combination vaccines, development of multiregional and foreign clinical trials, and immunization of older adults and immunocompromised patients. We propose that new vaccines against infectious diseases should be evaluated for the protective efficacy, preferably through multiregional clinical trials. Additionally, differences in the incidence of infectious diseases or in epidemic virus strains between regions may affect the trials, when multiregional clinical trials are conducted, but immunogenicity-based studies can be conducted if a correlation between protective efficacy and immunogenicity has been established. We suggest that licensed combination vaccines can be used as comparators when an antigen is added to a licensed combination vaccine. We also proposed that the efficacy of a vaccine in non-major subjects, such as older adults or immunocompromised patients could be evaluated by comparing immunogenicity in major subjects with the confirmed protective effects of the vaccine. It is expected that these revisions will lead to the rapid advancement of vaccine development, which should contribute to the improvement of public health.

Exploration for reliable radiographic assessment method for hinge-like hypermobility at atlanto-occipital joint.

PURPOSE: Hinge-like hyper-mobility is occasionally observed at the atlanto-occipital (O-C1) joint. However, it has not been clear if this kind of hinge-like hyper-mobility at the O-C1 joint should be regarded as "pathologic", or referred to as "instability". To solve this issue, we aimed to establish a reliable radiographic assessment method for this specific type of O-C1 instability and figure out the "standard value" for the range of motion (ROM) of the O-C1 joint. METHODS: To figure out the standard range of the O-C1 angle, we acquired magnetic resonance imaging (MRI) sagittal views of the cervical spine for 157 healthy volunteers [average: 37.4 year-old (yo)] without spine diseases, at neutral, maximum flexion and maximum extension positions. RESULTS: The average value (AVE) for ROM of O-C1 angle was 9.91°. The standard value for ROM of O-C1 angle was calculated as 0°-21°. There was no statistically significant gender difference. We also found that the older population (≧ 40 yo) significantly had a larger ROM of O-C1 angle (AVE: 11.72°) compared to the younger population (< 40 yo) (AVE: 8.99°). CONCLUSIONS: We consider that hinge-like instability at O-C1 joint, which cannot be assessed by measuring Powers ratio, can be assessed by measuring the range of O-C1 angles using dynamic-MRI. Evaluation of O-C1 instability is important especially when we perform surgical treatment for diseases with upper cervical instability (such as retro-odontoid pseudotumor). We consider that the current study provides important information in such a case.

Improved Diagnosis and Care for Rare Diseases through Implementation of Precision Public Health Framework.

Public health relies on technologies to produce and analyse data, as well as effectively develop and implement policies and practices. An example is the public health practice of epidemiology, which relies on computational technology to monitor the health status of populations, identify disadvantaged or at risk population groups and thereby inform health policy and priority setting. Critical to achieving health improvements for the underserved population of people living with rare diseases is early diagnosis and best care. In the rare diseases field, the vast majority of diseases are caused by destructive but previously difficult to identify protein-coding gene mutations. The reduction in cost of genetic testing and advances in the clinical use of genome sequencing, data science and imaging are converging to provide more precise understandings of the 'person-time-place' triad. That is: who is affected (people); when the disease is occurring (time); and where the disease is occurring (place). Consequently we are witnessing a paradigm shift in public health policy and practice towards 'precision public health'.Patient and stakeholder engagement has informed the need for a national public health policy framework for rare diseases. The engagement approach in different countries has produced highly comparable outcomes and objectives. Knowledge and experience sharing across the international rare diseases networks and partnerships has informed the development of the Western Australian Rare Diseases Strategic Framework 2015-2018 (RD Framework) and Australian government health briefings on the need for a National plan.The RD Framework is guiding the translation of genomic and other technologies into the Western Australian health system, leading to greater precision in diagnostic pathways and care, and is an example of how a precision public health framework can improve health outcomes for the rare diseases population.Five vignettes are used to illustrate how policy decisions provide the scaffolding for translation of new genomics knowledge, and catalyze transformative change in delivery of clinical services. The vignettes presented here are from an Australian perspective and are not intended to be comprehensive, but rather to provide insights into how a new and emerging 'precision public health' paradigm can improve the experiences of patients living with rare diseases, their caregivers and families.The conclusion is that genomic public health is informed by the individual and family needs, and the population health imperatives of an early and accurate diagnosis; which is the portal to best practice care. Knowledge sharing is critical for public health policy development and improving the lives of people living with rare diseases.