薬理と治療

治験に携わるすべての人が品質マネジメントシステムに少なからず関与することは明らかであるが，そのなかで治験事務局業務がどのように治験における品質マネジメントシステム（Clinical QMS）とつながっているかについて説明したい。なお，治験依頼者におけるClinical QMS の経験を基に説明することをあらかじめご了承いただきたい。医療機関の治験関係者を対象に実施された「治験における医療機関の品質マネジメントに関する調査」（モニタリング2.0 Working Group 11，調査期間：2021 年4 月16 日～ 5 月6 日）では，治験業務の一環として，文書等の保管，トレーニング，他部署への連絡・調整，品質管理等が多くの治験実施医療機関で実施されており，Clinical QMS に関連した活動に取り組んでいる治験実施医療機関は少なくないといえる1）。

岡山大学病院（以下，当院）新医療研究開発センター治験推進部（以下，当部）では，おもに文書の保管スペースの削減および業務の効率化を目的として，治験関連文書の電磁化システム（以下，本システム）を導入している。2020 年3 月より本システムによる文書授受・保管の運用を開始し，同年4 月からはIRB においても本システムを利用している。今回， 本システム導入事例とQuality ManagementSystem ( 以下，QMS) とのつながりについて考察する。なお，当院は臨床研究中核病院であり，比較的治験に関する設備やスタッフ等が充実している施設での事例であると考えられるため，この点をふまえ参考としていただきたい。

当社，㈱EP 綜合は，EPS グループのなかでSiteManagement Organization（SMO，治験施設支援機関）事業を展開している会社である。SMO とは，医薬品や医療機器の臨床試験を実施する医療機関の業務を支援する会社であり，具体的には，CRC 業務のほか，Site Management Associate（SMA，治験事務局担当者）業務として書類作成，IRB 運営などの事務局業務を支援している。当社は，全国約6300 の医療機関と提携し，CRC1100 名，SMA は110 名体制の組織である。提携する医療機関とのあいだでGCP 第39 条の2 にもとづいた契約を締結し，その契約のなかで医療機関からSMO への委託業務内容を定めている。また，SMA は院内規定，手順書に従い，各種事務局業務の支援を行っている。当社のIRB 推進部の部員はすべてSMA として治験に関する事務局業務に従事している。IRB 推進部の業務内容は大きく二つに分けられる。一つはセントラルIRB のIRB 事務局支援業務，もう一つはセントラルIRBへ審査依頼している医療機関の治験事務局支援業務である。IRB 事務局支援業務は，IRBSOPの作成/ 更新，IRB 運営に関する業務，IRB 開催日の決定と関係者への連絡，IRB から発行する書類の作成といったところがおもな業務である。治験事務局支援業務としては，治験を実施する医療機関が発行する書類の作成や，依頼者による必須文書閲覧や監査対応などを行っている。当社が支援しているセントラルIRB では，IRB 事務局と治験事務局を同一人物が担当することにより，治験依頼者や実施医療機関の負担軽減や意思疎通のスピードアップとミス削減に取り組んでいる。現在，七つのセントラルIRB を支援している。2020 年4 月以降，すべてのIRB がWeb 会議システムを利用したリモート開催となっており，IRB 委員は勤務先または自宅から，SMA は会社のオフィスからIRB に参加している。各SMA は，複数のIRB の複数の試験を担当しており，試験ごとにメイン，サブの2 名体制を取っている。各試験の実施医療機関の数は1 施設の場合もあれば，10 施設や20 施設など複数になる場合もある。また，当社では2020 年より在宅勤務制度を導入し，SMA は出社と在宅勤務を併用した勤務体制となっている。

治験依頼者による治験関連文書（Trial Master File,TMF）の管理は，治験データの品質管理とともに治験におけるQMS の重要な要素である。顧客の要求事項，すなわち承認申請における規制当局の要求事項を満たし，第三者に対し治験の実施経過の過程が説明可能なように，TMF はつねに最新の状態に保つ必要がある。そのため，治験依頼者での適切なTMF 管理には実施医療機関の協力が不可欠である。実施医療機関での保管文書（Investigators Site File, ISF）もTMFの一部であり，治験依頼者のTMF と同時的に管理する必要がある。治験依頼者と実施医療機関が協働しTMF を構築するための理想的な姿を提案する。

患者自身の健康状態に対する患者の観点の重要性は十分認められており，そのような情報は，治療効果に関する規制上の結論の導出，利益と危険性（ベネフィット・リスク）のバランス評価，または欧州製品概要（Summary of product characteristics: SmPC）5.1 項の特定の効能申請に用いることができる（Secord et al., 2015［医薬品評価における健康関連QOL（HRQL）指標の使用のための規制ガイダンスに関するCHMP リフレクションペーパー］，2005）。特定の効能申請のためには，仮説に導かれた戦略との「適合度（fit）」に基づき，妥当な指標を選択すべきであり，その結果，偏りのないアウトカムが得られる。　がん患者における患者報告アウトカム（PRO）評価の使用に関する本付録は，規制上の観点からこれらのデータの価値に焦点を当てる。したがって，利益と危険性の（ベネフィット・リスク）評価における従来の有効性および安全性データに対するPROデータの許認可の観点からの付加価値の可能性を強調している。がん作業部会はHRQL に関するワークショップを2012 年に開催し，関連する専門家を集め，本付録の内容に対する情報提供を行った（http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/events/2012/04/event_deta il_000558.jsp&mid=WC0b01ac058004d5c3）。本文書作成の目的は，PRO 方法論が発展途上にあることを認識しつつ，科学的なベストプラクティスの広範な原則の概略を述べ，がん治療のための医薬品の開発におけるPRO データの価値に関する指針を提供することである（Calvert et al., 2014, Kyte et al., 2014, Secord et al., 2015）。

Background　D-Allulose（D-psicose）is a rare sugar, containing no calories and exhibiting 70％ relative sweetness compared to sucrose. Recently, several studies have demonstrated the anti-obesity effect of D-allulose, mediated by suppressing lipogenesis and increasing energy expenditure. On the other hand, L-carnitine is necessary for the transfer of long-chain fatty acids from the cytosol to mitochondria for subsequent β-oxidation. L-Carnitine is a nutraceutical that has pleiotropic biologic effects and is recognized to have anti-obesity potential in mammals. Objectives　This study examined the effect of simultaneous intake of diets containing 5％ D- allulose and 0.5％ L-carnitine on body fat accumulation in rats fed a high-fat diet. Methods　Thirty-two 3-week-old male Wistar rats were randomized into the control（C）, L- carnitine（CR）, D-allulose（A）, and L-carnitine＋D-allulose（CRA）groups. The CR and CRA diets contained 0.5％ L-carnitine, and the A and CRA diets contained 5％ D-allulose. Rats were fed on the experimental diets and water ad libitum for eight weeks. Results　D-Allulose noticeably decreased the weight of abdominal and carcass fat with or without dietary L-carnitine, and the slight anti-obesity effect of dietary L-carnitine supplementation. However, no synergistic anti-obesity effect was detected between D-allulose and L-carnitine. Conclusions　The anti-obesity effect of D-allulose was observed with or without dietary L- carnitine, but no interaction was detected between dietary D-allulose and L-carnitine for all indicators of body fat accumulation. These results propound that the usage and conditions of dietary L-carnitine should be considered for synergistic effects between D-allulose and L-carnitine. （Jpn Pharmacol Ther 2022；50：1549‒56）

Objective　The aim of this study was to investigate the effect of oral intake of chocolate contained flavanol on maintenance of arousal level after paperwork load on healthy subjects. Methods　A randomized placebo-controlled, double-blind, cross-over, comparison study was conducted in 20 healthy subjects（40-64 years old men and women）. The subjects were applied the workload of 50 minutes of Uchida-Kraepelin test, and then rest for 20 minutes followed by POMS2 and TDMS surveys and heart rate measurements. They were given either the test product（ 22 g of Morinaga DARS dark chocolate containing 30 mg cacao flavanols）or the control product（containing no flavanol）and 15 minutes of rest followed by POMS2 and TDMS surveys and heart rate measurements. Results　In the comparison between the test products（chocolate containing 30 mg of flavanol） treated group and control product treated group, there were no significant differences in the POMS2, which measures tension and vitality. But in TDMS, which measures arousal and pleasantness╱unpleasantness, the test product treated group showed arousal maintanance. In the heart rate measurement, which measures arousal, an increase in heart rate and a shortening of the R-R interval were observed in the test product treated group. Conclusions　The results suggested that oral intake of 30 mg of cacao flavanols have the function of maintaining arousal level after paper workload. （UMIN000046943）（Jpn Pharmacol Ther 2022；50：1557‒64）

Objective　We examined the effects of uridine 5′-monophosphate disodium salt（5′-UMP）on cognitive functions in healthy middle-aged and older adults who are aware of memory decline. Methods　A randomized, placebo-controlled, double-blind, parallel-group comparison study was conducted for 99 healthy Japanese adults over 40 years old who are aware of memory decline but do not have dementia（Mini-Mental State Examination score＞24）. Subjects were randomized to receive 300 mg or 600 mg of 5′-UMP or placebo daily for 12 weeks. Their cognitive functions were assessed by Cognitrax and self-administered dementia checklist. Results　The 5′-UMP-600 mg group showed a significant improvement in composite memory which is the primary outcome of the trial. Additionally, the 5′-UMP-600 mg group showed an improvement trend in visual memory and verbal memory. In subgroup analyses of subjects with low memory scores on the Cognitrax, both 5′-UMP-300 mg and 5′-UMP-600 mg group showed a significant improvement in composite memory and some other cognitive functions. Consumption of 5′-UMP was safe under the conditions of this study. Conclusion　This study demonstrates that continuous intake of 5′-UMP can improve cognitive function in healthy middle-aged and older adults who are aware of memory decline. （UMIN-CTR ID: UMIN000045507）（Jpn Pharmacol Ther 2022；50：1565‒89）

Objectives　The purpose of this study was to evaluate the effects of continuous gum ingestion on motor function. Methods　Twenty-one healthy subjects participated in a randomized, open, parallel-group comparison trial. Subjects were measured for motor function before and after the four weeks gum consumption intervention. Results　The static balance in the gum intake group was significantly improved compared to the no-gum intake group, but grip strength, dynamic balance, and bite strength showed no change. Conclusions　In conclusion, four weeks of gum consumption suggested improved static balance.（UMIN000047051）（Jpn Pharmacol Ther 2022；50：1591‒6）

Objectives　The purpose of this study was to evaluate the impact of the oral training program “The Exercise of Mouth”on oral function. Methods　A total of 64 elderly subjects were divided into 27 intervention group and 35 control group. The intervention group received the oral training three times a day for four weeks, while the control group received no intervention. Participants were measured for eight types of oral functions before and after the intervention. Results　After the 4-week intervention, the intervention group showed significant improvement in chewing ability using a colour-changeable chewing gum and subjective chewing ability using the food intake questionnaire. Significant improvement in maximum tongue pressure was also observed. Conclusions　The results suggest that implementation of a 4-week oral training program improves oral functions including masticatory ability and tongue motor function in elderly people. （ID: UMIN000045427）（Jpn Pharmacol Ther 2022；50：1597‒603）

Objectives　The purpose of this study was to evaluate the effects of gum chewing on scalp blood flow. Methods　Twenty healthy subjects participated in a randomized, open, cross-over comparison trial. Blood flow in the subjectʼs scalp was measured during gum chewing. Results　Scalp blood flow in the parietal and temporal regions increased significantly during gum chewing compared to the resting state. Conclusions　In conclusion, gum chewing increased scalp blood flow. （UMIN000047877）（Jpn Pharmacol Ther 2022；50：1605‒9）

Objective　This study aimed to evaluate the effects of mekabu（sporophyll of Undaria pinnatifida） ingestion in lowering blood pressure and improving swelling. Methods　A randomized, single-blind, parallel comparison study was conducted on 60 individuals with high blood pressure（systolic blood pressure［SBP］＞160 mmHg and diastolic blood pressure［DBP］＞100 mmHg）. The participants were divided into two groups, a test food group and a control group. The test food group ingested 35 g of raw mekabu once per day in the morning, noon, or evening, prior to meal intake, for a total of four weeks. SBP, DBP, and pulse rate were measured using an automatic blood pressure monitor, and subjective symptoms of swelling were evaluated by a questionnaire. Salt intake was determined by calculating the 24- hour urinary sodium excretion. Results　No significant changes were observed in SBP, DBP, pulse rate, or salt intake before and after the experiment in both groups. In subgroup analysis, a significant reduction in SBP （P＜0.05）was observed in the test food group in those with a pre-experimental SBP of ＜140 mmHg. Subjective symptoms of swelling improved in those with mekabu intake. Conclusion　Regular pre-meal intake of mekabu is an effective means of improving swelling, and lowering blood pressure in participants with SBP＜140 mmHg. （UMIN-ID: UMIN000046597）（Jpn Pharmacol Ther 2022；50：1613‒22）

Background　Studies have reported that eating with another person makes the food more delicious and increases its consumption. They have found that eating with others in person has a psychological effect and is thought to evoke positive changes in oneʼs mood and atmosphere. Meanwhile, the COVID-19 pandemic has restricted eating with friends and encouraged Internet use for such an activity. This study conducted a survey to examine differences in the deliciousness of food under three conditions: solitary eating, video dining, and actual co-eating. Methods　Responses were obtained from 400 university students using Google Forms, of whom 55 had eaten with someone else virtually. The 55 participants were then asked to recall the three meal conditions and rate items on food deliciousness and meal satisfaction. Analysis of variance was performed using R for analysis. Results　Findings demonstrated a significant difference（P＜0.01）between the three conditions in terms of food deliciousness, suggesting that sharing a meal with someone, even virtually, makes food more delicious than eating alone. Conclusion　Online communication, such as conversations, may have a social facilitation effect, influencing food deliciousness. As the COVID-19 pandemic continues, using the Internet to eat together may be useful in solving problems caused by solitary eating and in making meals more delicious.（Jpn Pharmacol Ther 2022；50：1623‒8）

Objectives　The objective of this study was to investigate the safety of medium chain triglycerides diet on elderly type 2 diabetes mellitus. Methods　An assigned was conducted in 25 subjects. They were assigned to fasting blood sugar（FBS）a standard 126 mg╱dL by 2 groups. Medium chain triglycerides containing 6 g the test ingested at 8 weeks. The efficacies were evaluated by analyzing safety. Results　The subject of during intervention period FBS 126 mg╱dL group below and above group of body weight and FBS no changes. There were 2 groups not yet diagnosed diabetic ketoacidosis. There were the 2 groups in any the TG level, and blood insulin levels, ketone bodies, total ketone bodies and acetoacetate ware not significantly. Conclusions　The Medium chain triglycerides intake safety verification of less than 126 ng╱dL groups ware nit the attention points, but 126 mg╱dL more groups is necessary to take them while measuring ketone bodies regularly. The medium chain triglycerides containing diet may intake safety in elderly type 2 diabetes mellitus. （Jpn Pharmacol Ther 2022；50：1629‒38）

Background　Sea buckthorn has been used in medical treatments since ancient time and although the health benefits of this product have been well reported, few studies have disccussed the effect of sea buckthorn on fatigue. Objectives　The aim of this study was to compare a placebo with sea buckthorn juice, which contains significant amount of antioxidant, by assessing its efficacy at combatting fatigue, over 4 weeks period using the Visual Analogue Scale. Methods　We conducted a clinical parallel, double-blind, placebo-controlled trial study to assess the efficacy of sea buckthorn juice on combatting fatigue. 39 healthy women aged 35 to 55 years old were divided by age and body mass index（BMI）at baseline, into the sea buckthorn group, in which the subjects consumed the sea buckthorn juice, and the placebo group, in which the subject consumed placebo. Results　There is a significant difference in changes in the level hunger of pre and post study between the sea buckthorn and placebo groups（P＝0.04）. An decrease in hunger levels was only noted experienced by the participants in the sea buckthorn group（P＜0.05）, whereas these was an increase in hunger level in the placebo group. Conclusions　The study indicated that the intake of sea buckthorn juice decreases hunger through fatigue in the healthy women.（Jpn Pharmacol Ther 2022；50：1639‒44）

Objective　This study focused on whether Coccomyxa sp. KJ changes physical and mental conditions and functional markers of the immune system in healthy Japanese adults. Methods　We conducted a randomized, double-blind, placebo-controlled trial. After the screening stage, we randomly assigned individuals to the placebo group（n＝40）or Coccomyxa sp. KJ group（n＝40）. The participants received the placebo or Coccomyxa sp. KJ tablets for 8 weeks. To clarify the effect of Coccomyxa sp. KJ, we measured health-related quality of life by using a subjective questionnaire（upper respiratory tract, gastrointestinal, and systemic symptoms） for the primary endpoint, and natural killer cell cytotoxicity（NK activity）and cytokine levels in peripheral blood. Results　The Coccomyxa sp. KJ suppressed worsening physical and mental conditions such as nasal symptoms, abdominal discomfort, fatigue, and anxiety. NK activity and TNF-alpha levels were maintained in the Coccomyxa sp. KJ group, however, decreased in the placebo group. In contrast, the Coccomyxa sp. KJ did not affect the IFN-gamma, IL-6, IL-4, and IL-1beta levels. Conclusions　Coccomyxa sp. KJ maintains physical and mental conditions and modulates immune functions in healthy adults. （UMIN-CTR ID: UMIN000044768）（Jpn Pharmacol Ther 2022；50：1645‒55）

Background　The thickness of stratum corneum increases with age which can lead wrinkles, dull and uneven skin. For the treatment of these symptoms, it is desirable to remove the old stratum corneum at the skin surface without causing inflammation. In this study, we examined the effect of a peeling gel containing allantoin, placenta extract, and other natural ingredients on these facial wrinkles. Methods　The study was carried out with 14 healthy female subjects with age ranging between 38 and 59 years. They used Mild Clear Gel provided by Mʼz Science Corporation, Fukuoka, Japan, only to one side of their faces twice a day. After the trial 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 skilled 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　Comparison of the changes in the wrinkle grade judged by the special inspectors between the two sides of the faces suggested the statistically significant improvement of the wrinkles only on the side of the faces using the peeling gel, which was also supported by the result of the questionnaire. Moreover, the result of the questionnaire indicated the improvement effects significantly in the skin condition, smoothness, transparency, makeup adhesion, softness and so on. Conclusions　The peeling gel containing natural ingredients reduced the facial wrinkles around eyes and the skin condition were improved, possibly not only by the removal of the old stratum corneum at the skin surface but also by the various bioactive substrates contained in the natural ingredients.（UMIN ID: UMIN000046711）（Jpn Pharmacol Ther 2022；50：1657‒65）

Objective　The aim of this study was to evaluate the effect of a six non-essential amino acid mixture on the joint conditions in healthy adults with knee joint discomfort. Methods　The study was a randomized, double-blind, placebo-controlled, parallel-group 8 week trial. A total of 50 healthy adults aged 20 and 60 years with joint discomfort but no diagnosed joint disorder were equally assigned to an active group or a placebo. The active group consumed 4.0 g orally（4.0 g once a day）of the non-essential amino acid mixture and the placebo group took equivalent doses of a placebo food for 8 weeks. Primary outcome measures to evaluate the joint condition were the Japanese Knee Osteoarthritis Measure（JKOM）, Japanese Osteoarthritis Association score（JOA）and the range of motion（ROM）of the knee joint. These tests were taken before（week 0）and at 8 weeks（week 8）after the intervention. Results　The JKOM-VAS（Ⅰ: Degree of knee pain）in active group showed significantly lower score than that in placebo group（P＝0.049）at week 8. The results of JOA showed significant improvements in the active group（P＝0.021）. There were no significant differences in JKOM total score and ROM. Conclusion　These results demonstrated that 4.0 g per a day of the non-essential amino acid mixture improved knee joint conditions.（UMIN000044160）（Jpn Pharmacol Ther 2022；50：1667‒76）

Background and Objective　Data analyzed in this study were obtained from a previously reported, randomized, double-blind, placebo controlled study of 26 healthy Japanese adults with mild knee pain but no osteoarthritis by taking chicken leg peptide（CLP）. However, the previous method of analysis obscured the effect of CLP because many people had weak knee pain before starting the test, and a more sensitive method of analysis was needed to more accurately assess the effect of CLP. Methods　In the present study, we examined the gender differences in the degree of knee pain. Further, we decided to extract and reanalyze the subjects with only females in this study and report this result. Results　Compared to the placebo group, 12 weeks after ingestion, the CLP group improved significantly over the placebo group in the total score of Category Ⅱ“knee pain, stiffness”in JKOM. Furthermore, in individual question score of JKOM, the morning initial knee pain significantly improved amongst the subjects. Conclusions　Our result suggest that we can precisely evaluate the effect of CLP on Japanese adults with mild knee pain by subgroup analysis of females.（Jpn Pharmacol Ther 2022；50：1677‒87）

Water soluble dietary fiber, resistant maltodextrin and low methoxy（LM）-pectin which has various physiological functions including reducing postprandial blood glucose levels and inhibiting body weight gain. However, controlling appetite and reducing energy intake are controversial. We investigated the effect of resistant maltodextrin and LM-pectin enriched beverage on appetite and energy intake. The study was conducted as a double-blind randomized crossover design with twenty-five healthy adult men and women. Subjects consumed a breakfast of resistant maltodextrin and LM-pectin enriched shake beverage（TB）or cellulose containing placebo shake beverage（PB）, followed by an ad libitum lunch. Energy intake from the lunch was measured from a self-served plate of food minus leftover waste. Subjectsʼ perception scores on hunger, fullness, prospective food consumption, and satiety were assessed using a visual analogue scale（VAS）before and after the breakfast and lunch. Area under the curve （AUC）between 30 min and 240 min of the VAS scores of hunger after TB breakfast was significantly lower than after PB breakfast. AUCs of the VAS scores of satiety after TB breakfast showed a higher tendency（P＝0.059）. Energy intake at lunch subsequent to TB consumption was significantly lower than PB（P＜0.05）. TB was able to modulate appetite and reduce energy intake. The resistant maltodextrin and LM-pectin enriched shake beverage could play a beneficial role in preventing and treating overweight and obesity.（UMIN000047635）（Jpn Pharmacol Ther 2022；50：1689‒97）

Objectives　We previously reported that Lactobacillus acidophilus L-92 ameliorates subjective local and systemic symptoms by maintaining normal immune functions in healthy adults. The present study aimed to elucidate the effect of L-92 intake not only on subjective symptoms and immune parameters but also on intestinal immunity, including the intestinal microbiota and immunoglobulin A（IgA）levels, in healthy adults. Methods　A randomized, double-blind, placebo-controlled, parallel-group study was conducted on 180 individuals assigned to receive L-92 or placebo tablets for 8 weeks between July 2021 and September 2021. The participants received 21010× L-92 cells per day based on the same composition of the test foods. Results　The L-92 group showed the activation of plasmacytoid dendritic cells and an improvement in local symptoms, such as cough, throat discomfort, and hoarseness and subjective symptoms including fatigue, chill, and lassitude during the intervention period. The intake of L-92 also increased Bacteroides spp. and intestinal IgA. Conclusions　L-92 activates not only intestinal but also systemic immunity and alleviates typical early symptoms of viral infections in the upper respiratory tract and systemic symptoms, including the common cold, suggesting that L-92 might be a beneficial tool to enhance antiviral immunity in humans. Trial registration　https://www.umin.ac.jp/ctr; UMIN ID: UMIN000044138 （Jpn Pharmacol Ther 2022；50：1699‒707）

Objectives　The purpose of this study is to determine the effect of long-term ingestion of tablets containing hotrienol on stress perception, sleep quality, and sleep state. Methods　A randomized, placebo-controlled, double-blind, crossover study was conducted with 42 healthy adult men and women. Subjects ingested the test table（t a daily dose of 0.12 mg hotrienol）, or the placebo tablet for a period of two weeks. Stress perception, subjective sleep satisfaction and sleep quality were evaluated using the SCL30, OSA and Pittsburg Sleep Questionnaires respectively. Sleep variables identified from quantification of movement during sleep were used to evaluate the sleep state. Results　Analysis of the efficacy of long-term ingestion of hotrienol containing tablets in 33 subjects showed significantly higher scores for OSA Factor Ⅱ: sleep onset and sleep maintenance compared to ingestion of the placebo tablet, and significantly lower overall PSQI scores. The sleep variables; sleep onset latency, bed out latency, and wake after sleep oncet significantly decreased and sleep efficiency significantly improved. Conclusions　Long-term ingestion of tablets containing hotrienol, a compound reported to be effective in relieving chronic stress, has resulted in shortened sleep latency, bed out latency, and awakening time during sleep, leading to improved ease of falling asleep, continuity of good sleep, and ease of rising after waking. Subjective analysis too has shown subjects experienced increased satisfaction with the ease of being able to fall asleep and maintain quality sleep; effects which are thought to contribute to their improved quality of sleep.（UMIN ID: UMIN000044060）（Jpn Pharmacol Ther 2022；50：1709‒16）

オミクロン株になってコロナウイルスの感染力がさらに高まり，1 日あたりの感染者は過去最多を更新しています。これだけ感染が拡大しているのに，私の周りに感染者が今のところいません。これはどれだけ珍しいことなのか，少し計算で確かめてみました。もう一つ，いつも不思議に思うことがあります。男性同士で居酒屋へ行くと，私たちのグループだけ喫煙する人がいなかったことです。これもどれだけ珍しいことなのかを計算してみました。