It is often very difficult and time–consuming to care dementia patients who have short term memory loss or trouble in understanding medical treatment. In our hospital, when nurses have difficulty in caring dementia patients, Dementia&Delirium Support Team (D2ST) provides advices or support for caring these patients. D2ST is based on the concept of person–centered care and help nurses to give best care to dementia patients. D2ST members include doctors and nurses who are specialized in treating elderly people or dementia patients.

One of the most important things to do when you care dementia patients is to communicate with them. Many medical staffs consider that it is impossible to have communications with dementia patients. However, with the implimentation of Humanitude, it becomes possible to have a good relationship with dementia patients. Humanitude is a comprehensive care methodology that emphasizes importance of eye contact, touch, verbal communication, and assist of upright position to care dementia patients. The most important thing in practicing Humanitude is to convey your respect for the patients as a human being with communication skills mentioned above and to provide every care in one sequence contains 5 elements. Humanitude has made possible for medical staffs to have better communications with dementia patients.

It is possible to have good relationships with dementia patients if you have the right skills for communication. Having the good communication skills, we will be able to practice person centered care to give better cares for dementia patients.

The medical history proves that clinical research has been a powerful weapon for disease control even when the etiology of the disease is unknown, as John Snow found the causal relationship between drinking water and cholera infection, and Kanehiro Takagi between nourishment and beriberi.

Medical science progresses along with the development of new medical technology such as new drugs and medical devices. In the history of hypertension, a great cohort study in Framingham in the USA has enhanced enormous scientific knowledge about the causal relationship between hypertension and cardiovascular diseases. The new sphygmomanometers and a lot of antihypertensive agents contributed to validation of the hypothesis generated from the Framingham study and development of hypertension practice guidelines. The modern data analyzing techniques like multivariable analysis were also produced in the struggle of the statisticians working for that study.

Every research method has strengths and weaknesses, even a randomized controlled trial is no exception. The important point is to use a method well suited to answer a question, whether it is randomized or not. Clinical research methods have been developed for solving several medical issues and will be developed with advances in medical science in the future. For example, “N–of–1 trial” method has rapidly become popular in these years, and CONSORT extension for reporting N–of–1 trials was published in 2015. We should contribute to development not only of new medical technologies but also of clinical research methods.

In Academia, those selected for the ‘Translational Research Center’ of ‘Coordination, Support and Training Program for Translational Research’ by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) or the ‘Clinical Trial Grant Program’ by Center for Clinical Trials, Japan Medical Association (JMACCT) have implemented investigator–initiated clinical trials and started to show remarkable success. This was brought about by government's healthcare policy, which intends to further develop innovative medicinal products (e.g. pharmaceuticals, medical devices, regenerative medicines) by academia until their application in the medical services.

For approval of a medicinal products, it is needed to submit the document composed of quality, non–clinical and clinical study reports to regulatory authorities. However, most Japanese researchers in academia have less knowledge of development medicinal product especially quality and non–clinical strategy. In general, it is difficult to conduct appropriate non–clinical development for medicinal products based only on medical knowledge, and the presence of those with various expertise (e.g. project management, pharmacology, pharmacokinetics, toxicity, regulatory affairs, intellectual property) is essential. Recently, each ‘Translational and Clinical Research Core Center’ to function as an ‘Academic Research Organization (ARO)’ is capable of overall development of medicinal products. Therefore I recommend that the researchers would collaborate with a one of these Core Center or utilize the PMDA consultation on R&D strategy early.

In this report, I will show the non–clinical strategy for conducting clinical trial of a pharmaceutical based on guidelines published by Japanese authority. For example, obtaining non–clinical study results before initiation of first–in human safety trials should be considered in the ICH M3(R2) guideline (guidance on nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals).

These days, the ethical aspect of biomedical research performed in any country is often highlighted. While biomedical researchers are expected to advance research to improve medical practice, they are also socially pressurized to implement research that is ethically sound. That is why the study of research ethics is being recognized for its importance. This paper outlines current research ethics and important ethical principles, as well as the Japanese Ethical Guidelines for Medical and Health Research Involving Human Subjects.

There are two things that can label a research as unethical : scientific misconduct and problems with the protection of research participants. In a restricted sense, scientific misconduct indicates fabrication, falsification, and plagiarism. In a broader sense, it also includes problems with authorship, conflicts of interest, and indications of harassment.

The protection of research participants is increasingly important these days in biomedical research involving human subjects. The three well–accepted ethical principles are Respect for Persons, Beneficence, and Justice. Biomedical research involving human subjects has to be done in a careful manner to follow these three principles ; otherwise, it could be considered as unethical.

As of 2015, the Japanese Ethical Guidelines for Medical and Health Research Involving Human Subjects is being enforced and covers most of the biomedical research involving human subjects that is performed in Japan. These guidelines reflect many ethical principles, including the three principles cited above, as well as those specified to each setting and method of research. Additionally, the guidelines require ethical education for every biomedical researcher.

Understanding how to verify a hypothesis is a prerequisite for engaging in high–quality clinical research. Unless this is understood, no amount of knowledge regarding experimental design and methods of data analysis by itself will enable the selection of the appropriate types of design and analysis to verify the hypothesis to be tested.

Establishing the appropriate primary endpoint, control group, and sample size is important for proper hypothesis verification in clinical research. A deficiency in any of these makes the interpretation of experimental results problematic and means that the hypothesis cannot be verified. I will outline the basic concepts pertaining to these three matters.

Once these have been determined, the next step is to decide methods for subject enrollment and data collection. For a randomized comparative trial, the method for randomization must be decided. The appropriate method for the study concerned must be chosen in light of the number of subjects and adjustment factors for allocation. In particular, guaranteeing comparability between the experimental groups in a randomized comparative trial is extremely important for guaranteeing the validity of the study results.

In terms of data collection, attention must also be paid to ensuring that data are collected in a manner that is appropriate for the data analysis methods used. In retrospective studies, on the other hand, the analysis population consists of non–randomized patients, and the areas requiring particular care or adjustment are different from those that concern randomized comparative studies. For example, it may be necessary to adjust for confounders and other patient background factors in data analysis. I will explain the different methods used for verifying hypotheses in randomized comparative trials and retrospective studies and describe the data analysis methods appropriate to each.

Given the irregularities seen in some clinical studies in recent years, there is a need to ensure that the quality of clinical research at least meets certain standards, as evidenced by the guidelines on quality assurance for clinical studies (including monitoring and auditing) set out by the Ministry of Health, Labour and Welfare, even before it reaches the stage of a clinical trial. Initiatives to improve the quality of clinical studies are now underway in a variety of fields, including consideration by the Biometric Society of Japan, the professional association for Japanese biostatisticians, of the introduction of a certification system for trial statisticians who take part in general clinical research. Properly guaranteeing the quality of clinical studies will require the cooperation of professionals such as biostatisticians and data managers in addition to that of doctors, pharmacists, nurses, clinical research coordinators, and other medical professionals engaged in research.

Multiple sclerosis (MS) is an immune–mediated inflammatory disease of the central nervous system (CNS), destroying the myelin and the axons to varying degrees. The cause of MS is still unknown, but epidemiological data indicate that both genetic and environmental factors are important for the etiology of MS. It is well known that some major histocompatibility complex haplotypes increase the risk of MS, and environmental factors include Epstein–Barr virus infection, low serum vitamin D level, and smoking. It has been long hypothesized that myelin–reactive T cells access the CNS where they induce an inflammatory cascade that results in demyelination, but this so far remain elusive. Although Th1 cells were previously thought to drive inflammation, Th17 cells are also critically involved in the initiation of disease pathogenesis. Pathological cascade of inflammation correlates with clinical exacerbation ; however, patients gradually develop progressive disease with time, which is characterized by cortical demyelination and neurodegeneration, including neuronal and axonal degeneration. Neuropathological and imaging studies indicate the early and sustained neurodegeneration in MS, indicating both inflammation and neurodegeneration contribute to MS mechanism. However, it is still largely unknown how they interplay over the disease course.

Multiple sclerosis (MS) is determined as a central nervous system (CNS) disease with multiple demyelination that disseminates in time (DIT) and space (DIS). The CNS includes brain, spinal cord, and optic nerves, in which myelin is produced by oligodendrocytes. The term “demyelination” denotes that myelin is selectively destructed. The strict definition of MS therefore requires the histological validation of these features : The definitive diagnosis of MS can only be made with the histological proof as such obtained with brain biopsies.

In reality, however, the clinical diagnosis of MS is made according to the McDonald criteria. The diagnosis criteria is an international consensus for the determination of “CNS demyelination with DIT and DIS” by the use of magnetic resonance imaging (MRI), in order to avoid the invasive biopsy procedure. The most recent McDonald criteria (the 2010 revision) adopted the Swanton MRI criteria, of which sensitivity and specificity for MS reported to be 77% and 92%, respectively, within the European countries. As neuromyelitis optica–spectrum disorder (NMOSD), the major MS–mimic, is relatively more frequent in Japan compared to the European countries, the specificity may be reduced and it may be reasonable to speculate the misdiagnosis rate of MS to be around 10 to 20% in Japan.

How can we reduce the possibility of misdiagnosing MS? Firstly, we must understand the technical limitation of the McDonald criteria upon making MS diagnosis and secondly, we must be aware of major patterns of alternative diagnosis in MS practice. As for the former, for example, “T2-lesions” are considered to be demyelinated lesions in the McDonald criteria, albeit the fact that the T2 signal is not specific to myelin. In order to make more correct speculation that a T2 lesions is likely to be a demyelinated lesion, we may need to focus on the location of such lesion : Accumulating pathological evidence suggested that MS shows a unique pattern of lesion distribution. For the latter, several previous studies provided a list of the major alternative diagnosis in MS practice.

This article reviews and summarizes the practical approach for the differential diagnosis of MS and its mimics.

Two main pathogenetic mechanisms of multiple sclerosis (MS) include ‘inflammation’ and ‘neurodegeneration’. Most of current disease–modifying drugs (DMT) (e.g. interferon–beta [IFNβ], fingolimod, natalizumab and glatiramer acetate) target for inflammatory processes in MS. The pivotal randomized clinical trials (RCT) for clinically isolated syndrome (CIS) with some silent magnetic resonance imaging lesions identified that rate of patients who developed clinically definite MS (CDMS) was reduced by using DMT. A randomized cohort study 21 years after the start of the pivotal IFNβ1b trial provided that early treatment with IFNβ1b is associated with prolonged survival in initially treatment–naïve patients with relapsing–remitting MS. These data support earlier diagnosis and treatment by using DMT in MS. Based on these moves, the McDonald MS diagnostic criteria has been revised in 2010 and the revision allows some patients with a single clinical episode to be diagnosed with MS based on the single scan criterion for dissemination in time and space, reducing the number of patients who will be categorized as CIS. The development of imaging and biological biomarkers is necessary to define the exact clinical courses of MS/CIS due to realize the earlier diagnosis and treatment of MS.

[Background and Objective] It is reported that in patients with tension–type headache (TTH) the severity and frequency of the headache are reduced by real acupuncture in comparison with sham acupuncture. However, we classify TTH into frequent episodic tension–type headache (FTTH) and chronic tension–type headache (CTTH), and have found no report examining the number of sessions and duration of treatment required to attain the desired clinical effect. Therefore the purpose of this study is to clarify the number of acupuncture sessions and the period required for the subjective symptoms of FTTH and CTTH to improve by more than 50%. We also intended to obtain the data necessary to explain these facts to TTH patients at the time of the first medical examination and diagnosis.

[Method] The subjects were 221 ICHD–2 patients diagnosed with TTH who met the selection and exclusion criteria among 355 patients who had been referred to our department by specialists in other areas. There were 82 FTTH patients (28 men, 54 women), average age 52.7+−16.1 years old (mean ± S.D.) and 139 CTTH patients (44 men, 95 women, average age 50.4+−18.3 years old).

[Result] Sixty six (80.1%) FTTH patients and 82 (59.9%) CTTH patients had more than 50% improvement of symptoms showing that FTTH patients responded significantly better to acupuncture treatment. Furthermore, among improved patients, the number of sessions required to attain > 50% improvement of symptoms was significantly lower for FTTH patients and the duration of treatment was significantly shorter compared with CTTH patients [2.8 sessions versus 8.9 (p<0.01) ; 14.9 versus 35.9 days (p<0.01)].

[Conclusion] The significant difference in the required number of sessions and duration of treatment between FTTH and CTTH groups indicates that it is necessary to distinguish between these two types of TTH and explain the differences to the patient at the time of diagnosis.

We report here three patients with encephalopathy developed after administration of Ara–A. All patients were female, in age of 80s or older. Disturbance of consciousness (three patients) or tremor (two patients) occurred following to intravenous infusion of Ara–A for their severe herpes zoster. Cerebrospinal fluid examination revealed no abnormal finding other than mild pleocytosis. All patients showed diffuse slowing of EEG without any abnormality in brain MRI. The patients had several factors which may cause high plasma concentration of Ara–A ; i.e., old age, renal dysfunction in case 1 (eGFR 32.6 ml/min/1.73m²), emaciation in case 2 (BMI 15.9), and renal dysfunction (eGFR 7.4 ml/min/1.73m²) and use of xanthine metabolism inhibitor (allopurinol) in case 3. These factors should be screened thoroughly to prevent Ara–A encephalopathy. One patient who was able to undergo monitoring for plasma concentration of 9–β–d–arabinofuranosyl hypoxanthine (Ara–Hx) showed prolonged elevation of Ara–Hx, which might be useful in prevention of Ara–A encephalopathy.