薬理と治療

Health technology assessment（HTA）organizations have attracted increased global attention for addressing social and economic environment changes in healthcare. Although functions may differ by organization, these organizations mainly engage in validating the cost-effectiveness of healthcare technologies and recommending healthcare based on values. However, further validation is still required to assess the feasibility of proper and efficient allocation of medical resources, while maintaining the overall social system with HTA. Maintenance and improvement of public health, standardization of healthcare costs, and fair assessment of innovations are essential goals for HTA. This review summarizes the current status of HTA in Japan and other countries, as well as the ongoing discussions on HTA.

Since the beginning of the 2020, a new coronavirus has been widely spread worldwide, and results in tens of millions of people infected and millions of death. Several Pharmaceutical companies have been developing vaccines to prevent from spreading. Newly developed vaccines are categorized RNA vaccine which has a new mode of action, therefore, some people are afraid of their potential side reaction. In this article, I tried to summarize the characteristic and the clinical data currently available on SARS-CoV-2 and its disease, COVID-19. Although sequelae is often seen and death rate is high in COVID-19 when compared with seasonable influenza, high preventive effect has been demonstrated in the new RNA vaccines. Then, it is considered better to receive vaccination in spite of their high temporal side reaction rate. Most of the side reactions are mild or moderate and are common for vaccines in general, however, some elderly people with some basic diseases may not tolerate them. Therefore, careful decision should be needed for individual person especially elderly whether vaccination should be received or not taking the merit and demerit into consideration.

Secretory IgA（sIgA）plays an important role in the protection of respiratory, intestinal, and urogenital mucosal epithelia from adhesion of pathogenic microorganisms and harmful antigenic molecules to and invasion into host cells. It is noted that sIgA in saliva functions as a primary defense for preventing development of upper respiratory tract infections（URTIs）and allergic diseases. The magnitude of the beneficial sIgA functions may depend on the amount of sIgA secreted into saliva as represented by salivary sIgA concentration or salivary IgA secretion rate. A large battery of human and animal studies have demonstrated that some daily life-related events, such as excessive physical exercise︱induced stresses and mental stresses, can lower salivary IgA levels, leading to increase sensitivities to infection and allergy. To evade these unfavorable outcomes, a substantial number of nutritional, nutraceutical and biophysical treatments have been investigated as potential candidates for enhancing salivary sIgA secretion, of which some appear promising. This approach will be expected to open up a new way for the prevention and management of URTIs and allergic diseases.

Background　Sucroferric oxyhydroxide is an iron-based phosphate binder that became available for clinical use in November 2015. Objectives　Post-marketing surveillance to evaluate the safety and efficacy of long-term sucroferric oxyhydroxide therapy in patients with hyperphosphatemia undergoing dialysis is currently underway. An interim analysis was performed to examine the adverse events and changes in clinical laboratory values occurring during a 12-month therapy period. Methods　A specific post-marketing surveillance was performed using a prospective central registration system, for an 18-month observation period, to determine patient demographic characteristics, administration status, clinical laboratory values（such as serum phosphorus level and iron-related test values）, and adverse events related to sucroferric oxyhydroxide. Data covering a 12-month therapy period collected up to November 2020 were used. Results　Adverse reactions occurred in 576（25.90％）of the 2224 patients. The major adverse reactions were similar to those observed at the time of marketing approval, and the most frequent adverse reaction was diarrhea（8.68％）. The serum phosphorus levels were within the management target range（3.5︱6.0 mg/dL）during the 12-month period. Conclusions　This interim analysis revealed that a decreased serum phosphorous level was maintained for 12 months, with no new adverse reactions that may cause clinical concerns.

Objectives　In the previous clinical study（jRCTs 031190145）, we evaluated the skin irritation between 2 rivastigmine-containing patches（HP-1040 and the original drug of rivastigmine patch（RIVP））during 9 days administration by the Japanese standard assessment（skin irritation score）. In this study, we further analyzed the skin color from the acquired photographic data at the two drug administration sites and non-administration site by intra-subject comparison of color differences. Methods　For photographic data on 40 volunteers participated in the previous study, the skin colors of the HP-1040 administration site, RIVP administration site and non-administration site were quantificated on L＊a＊b＊ color space using image analysis software Adobe Photoshop（CS4 Version）. Color difference（ΔE）was defined as the Euclidean distance on L＊a＊b＊ color space, and ΔE1 between HP -1040 administration site and non-administration site was compared with ΔE2 between RIVP administration site and non-administration site. Results　The mean ［95％ CI］difference between ΔE1 and ΔE2 at the first administration, the primary endpoint, was －1.5［－2.55 to －0.54］, and the difference was statistically significant （P＝0.0034）. The mean［95％ CI］difference between ΔE1 and ΔE2 from the 4th to the 9th administration was also statistically significant（P＝＜0.001 to 0.015）. Conclusions　Image analysis using photographs of local skin areas is considered to be useful for assessment of skin irritation caused by patch formulations, and may provide additional information to the Japanese standard assessment. In addition, the color difference from non-administration site of HP-1040 was smaller than that of RIVP.

Objectives　The aim of this survey was to investigate potential gaps in perceptions of diabetes treatment between physicians and patients with type 2 diabetes. Methods　We conducted web based survey toward doctors and patients. The age composition ratio of patients was matched to National Health and Nutrition Survey data in 2017. The perceptions of diabetes treatment among doctors and patients were reported by descriptive statistics. Results　We obtained the valid responses from 523 for physicians and 1000 for patients. The overall percentage of patients who answered that they understood their physicianʼs instruction about diabetes, its treatment and HbA1c was higher than the perception of doctors. Physicians answered that the proportion of the patients whom they have not provided guidance on diet and exercise therapy was 11.6％ and 18.5％, respectively, while the proportion of patients who answered“not receiving guidance on diet and exercise therapy form health care professionals” was 27.2％ and 38.3％, respectively. The gaps between doctors and patients who attended internal medicine were numerically greater than those between doctors and patients who attended diabetes or endocrine metabolism. Conclusions　In order to support type 2 diabetes patients to receive appropriate medical care with their maximized outcomes, it is necessary to have assiduous communication on the preposition of the gap in understanding between physicians and patients.

We investigated the immunostimulatory effect of soy resistant protein（SRP）, which is abundant in Kori-tofu. SPR from Kori-tofu was prepared by digestion using digestive enzymes in vitro. SPR significantly induced interferon（IFN）-γ production from mouse spleen cells. This immunomodulatory activity was mediated by the structure composed of SPR. Most of the induction of IFN-γ production by SPR was independent on Toll-like receptor 4 signaling. These findings suggest that SPR and Kori-tofu are a potentially promising immuno-improving material.

Bachground　In vivo studies suggested that heat-killed Lactobacillus helveticus MCC1848 affects anxiety or depression-like symptoms. Objectives　This study examined the effects of heat-killed Lactobacillus helveticus MCC1848 on the quality of life（QOL）of healthy adults. Methods　A single-arm study was conducted involving 13 healthy adult women with slightly higher fatigue. Subjects were supplied with 20 billion heat-killed L. helveticus MCC1848 per day for 5 weeks. Subjective assessment of the QOL, such as mood, fatigue and sleep condition, were evaluated using questionnaires（POMS2 shorted version, VAS, positive mood scale, SF-36v2, Chalder Fatigue Scale, Athens Insomnia Scale and post-test questionnaire）at 0 and 5 weeks of treatment. Results　The POMS2 scores of“Anger-Hostility; AH”,“Fatigue-Inertia; FI”,“ Tension-Anxiety;TA”,“ Vigor-Activity; VA”and“Total Mood Disturbance; TMD”significantly improved at 5 weeks of treatment compared with those at 0 weeks of treatment. The VAS scores of “feeling fatigued”,“ feeling limp”,“feeling good”and“feeling relaxed”also significantly improved at 5 weeks of treatment. The positive mood scale score of “concentration mood”, and the SF-36 scores o“f Vitality”,“ Mental Health”and“Mental Component Summary”significantly increased at 5 weeks of treatment. The scores of the Chalder Fatigue Scale and Athens Insomnia Scale also significantly improved after 5 weeks of treatment. Adverse events due to the consumption of heat-killed Lactobacillus helveticus MCC1848 were not observed. Conclusions　This study suggested that heat-killed Lactobacillus helveticus MCC1848 is a promising agent for improving the QOL such as mood, fatigue and sleep condition. （UMIN000041390）

Background　Human face plays important roles in the identification and communication. Face changes with age, and the wrinkles around eyes are common age-related symptoms. In this study, we examined the effect of a face wash containing placenta extracts, which has anti-inflammatory and whitening effects, on these facial wrinkles. Methods　The study was carried out with 13 healthy female subjects with age ranging between 30 and 59 years. They used Hot Cleansing Whitening Mask, containing placenta extracts（provided by Mʼz Science Corporation, Fukuoka, Japan）, only to one side of their faces twice a day for 4 weeks. Both sides of their faces were taken by the photo, and the wrinkles were evaluated by a single blind method, judged by the special inspectors according to the wrinkle grade established by Japanese Cosmetic Science Society. Skin condition of both side of their faces was also examined by the questionnaire. Results　The wrinkles only on the side of the faces using the face wash containing placenta extracts were significantly improved from the judgement by the special inspectors, while no significant changes were recognized on the other side of the faces. Statistical comparison of the changes in the wrinkle grade between the two sides of the faces also supports the improvement of the wrinkles around eyes by using the face wash. Moreover, result of the questionnaire indicated that almost all the subjects of this experiment realized the improvement effects in the skin condition, such as clarity, moisture, softness, and gloss. Conclusions　Significant effects of a face wash containing placenta extracts on the facial wrinkles around eyes and the improvement in the skin condition were statistically confirmed from the study. We assume that various bioactive substrates contained in placenta extracts are responsible for these antiaging effects on the skin. provement in the skin condition were statistically confirmed from the study. （UMIN000039282）

Background　Efficacy of food ingredients against the common cold incidence were demonstrated in various reports and they often assessed by an index that integrates multiple symptoms of the common cold, such as runny nose and sore throat. Subjects present with a variety of symptoms, many of which are not diagnosed as common cold. We previously reported that the intake of Lactoplantibacillus pentosus strain b240（B240）decreased the incidence rate of the common cold dose-dependently. However, the effects on the individual symptom had not been assessed. Therefore, we investigated the efficacy of B240 on subjective physical symptoms reported by subject. Methods　Additional analyses for the efficacy against subjective physical symptoms were conducted using data obtained from a previously reported randomized, double-blind, placebo-controlled study of 300 healthy elderlies, which suggested the reduction in common cold incidence by the intake of B240. Results　In this study, runny nose was the most common symptom and the intake of both 2 billion B240（P＝0.023）as well as the intake of 20 billion B240（P＝0.028）reduced the average severity of runny nose dose-dependently. In addition, the efficacy against sore throat was also suggested. Conclusions　These findings suggest that B240 which regulates the mucosal immune system improves the subjective physical symptoms by preventing viral or bacterial infection. （UMIN000005398）

Background/Objectives　We aimed to investigate whether co-ingestion of cowʼs milk with highly absorbable calcium absorption and calcium maltobionate with a mineral absorption-promoting function can synergistically promote the absorption of calcium and other minerals in healthy adult men and women. Methods　This study was a combination of an open-label trial and a randomized, double-blind, placebo-controlled, crossover trial. Twenty-three healthy adults（11 men and 12 women） were allocated to two groups that consumed three intervention foods: 0.33 g maltose, 0.67 g calcium carbonate（CaCO3 group）, 0.9 g maltose, 0.1 g calcium carbonate, and 200 mL of milk （milk＋CaCO3 group）, and 1 g Sour-Oligo C（0.63 g calcium maltobionate）and 200 mL of milk（milk＋MBCa group）. Intestinal mineral absorption was assessed by measuring urinary mineral levels during the study period. Results　We conducted intention-to-treat analysis. When milk and maltobionic acid were taken concomitantly, urinary calcium, magnesium, iron, and zinc levels up to 6 h after the start of the intervention were significantly higher than when calcium carbonate and milk were taken alone, indicating a synergistic effect. Maltobionic acid was not digested, but remained in the intestinal tract, where it contributed to the solubilization of minerals in not only breakfast, but also lunch, and was considered to have a sustained（at least 6 h）mineral absorption-enhancing effect. Conclusions　Concurrent intake of milk and calcium maltobionate may synergistically and persistently promote the absorption of calcium and other minerals, contributing to various life-sustaining activities.（UMIN-CTR ID: UMIN000041709）

推測統計学（推計学）を学んだ人なら，Neyman-Pearson 原理，あるいはαエラーとβエラーについて聞いたことがあるでしょう。それに加えて，γエラーの議論された時期がありました。1980 年頃のことですが，今回はこれについてご紹介します。

CONSORT（Consolidated Standards of Reporting Trials: 臨床試験報告に関する統合基準）声明はランダム化比較試験（randomized controlled trial: RCT）の報告を改善するために，世界中で広く用いられている。Kenneth Schulzらは，新たな方法論的エビデンスと蓄積された経験に基づいて改訂した最新版CONSORT 2010を発表した。