Tanaka Holdings (Japan)

【緒言】「話しにくさ」を主訴として受診し，文レベルの発話時に非流暢性を呈した症例について報告する．症例は，単語レベルの発話は流暢ながらも，文レベルで言いよどみやポーズの挿入による非流暢性が顕著となり，音の連結不良と考えられる症状を呈した．本症例には，「話しにくさ」や発話速度低下の自覚があり，その症状は徐々に進行した．【対象】80歳台前半の右利き男性．初回評価時および15カ月経過時の認知機能検査は正常範囲内であった．SLTAでは文レベルの発話課題で非流暢性を認めたが，その他の項目に異常はみられず，典型的な失語症ではないと考えられた．運動機能障害や口腔顔面失行はみられず，構音障害も否定的であった．発話時に，一貫性のある音の歪みは認められなかった．【評価と経過】クリニックの外来受診時に実施したフォローアップと評価で得られた経時的な言語症状の記録をもとに，本症例の「話しにくさ」に関連する要因を考察した．【結論】原発性進行性発語失行とは，神経変性疾患によって，失語の症状がなく，発語失行のみが進行する症候群を指す．発語失行の特徴として，「全体的な発話速度の低下」，「音節，単語，句などの間隔の長さ」，「発話の長さ，音節や単語の構音の複雑さに伴い生じる困難さ」が挙げられる．本症例がプロソディ型の原発性進行性発語失行を呈している可能性について検討した．

ObjectiveThe controversy persists regarding whether the serum level of γ-glutamyltransferase (GGT), a marker of liver damage, is associated with hypertension irrespective of alcohol intake.MethodsWe investigated the relationship between the GGT level and new-onset hypertension during a 10-year follow-up period in Japanese individuals who underwent annual health examinations (n=28,990). After excluding subjects without systolic blood pressure and GGT data and those with hypertension at baseline, a total of 18,618 subjects (men/women: 11,262/7,356, mean age: 44 years) were enrolled.ResultsDuring the follow-up period, 2,753 men (24.4%) and 837 women (11.4%) developed hypertension. When the subjects were divided by quartiles of GGT at baseline (Q1-Q4), multivariable Cox proportional hazard model analyses after adjustment for age, sex, systolic blood pressure, body mass index, levels of uric acid, estimated glomerular filtration rate, family history of hypertension, habits of current smoking and alcohol drinking, and diagnosis of diabetes mellitus and dyslipidemia showed that hazard ratios (HRs) for the development of hypertension were significantly higher in the Q2, Q3, and Q4 groups than in the Q1 group. A significant interaction was observed between alcohol drinking habits and the GGT level at baseline for the development of hypertension (p=0.022), and adjusted HRs were similarly significant in alcohol infrequent drinkers (≤5 days/week). However, the GGT level was not significantly associated with the development of hypertension in frequent alcohol drinkers (≥6 days/week).ConclusionA high GGT level is an independent predictor of new-onset hypertension in infrequent alcohol drinkers but not in frequent drinkers.

Sodium picosulfate plus magnesium citrate (SP+MC) is a well-tolerated bowel preparation agent. However, Japan currently approves only two methods of taking SP+MC: the day-before and split-dose preparation, without approval of same-day preparations. This study aimed to evaluate the efficacy and safety of same-day SP+MC preparations. This was a multicenter, single-arm, nonrandomized, open-label study. We enrolled 145 Japanese patients between June and December 2023. The patients received two sachets of SP+MC dissolved in 300ml of water and 1200mL or more of clear liquid on the day of colonoscopy. Bowel cleansing efficacy, adverse events (AEs), and patient satisfaction were evaluated. Of the enrolled patients, 137 underwent colonoscopy according to our protocol. Bowel preparation was adequate in 133 patients (97.1%). The mean total Boston Bowel Preparation Score was 8.3±1.2. Five patients experienced AEs (3.6%): two (1.5%), abdominal pain; one (0.73%), ischemic enteritis; one (0.73%), vomiting or nausea; and one (0.73%), headache. All AEs were treated conservatively. None of the patients exhibited abnormal blood test results or clinical symptoms after receiving SP+MC. Regarding patient satisfaction, all patients were able to take SP+MC as directed; 136 (99.2%) expressed a preference for this bowel preparation for future colonoscopies. The same-day SP+MC preparation showed high bowel-cleansing efficacy and satisfaction in Japanese patients without serious AEs.

BackgroundPediatric patients with growth hormone deficiency (GHD) are currently treated with daily injections of recombinant human growth hormone (rhGH) to promote linear growth and enable attainment of normal adult height. One of the main reasons for suboptimal growth during rhGH therapy is non-adherence to treatment. The objective of this systematic literature review was to examine the recent literature on pediatric adherence to injectable treatments for chronic conditions (focusing on rhGH) to characterize levels of adherence and identify the factors/barriers associated with adherence.MethodsThe Embase and MEDLINE databases (January 2015–October 2020) were searched to identify publications describing studies of pediatric patients (aged ≤17 years) with GHD and other chronic conditions requiring daily or weekly injectable treatments; a similar targeted search of Chinese literature was also performed. Adherence data were extracted from the included studies and summarized. Risk of bias was determined using the Cochrane Risk of Bias tool 2 or the Newcastle-Ottawa Scale.ResultsA total of 23 publications were included, with all publications except for one (multiple sclerosis) focused on pediatric GHD studies: there were two clinical trials, 18 observational studies and three survey studies. Study sample sizes ranged from 30 to 13,553 patients (median: 95 patients). The definition of adherence varied between studies and included mean adherence rate, median adherence rate, and the percentage of patients within pre-specified adherence categories. Of the publications assessing adherence to daily rhGH, 11 studies reported 12-month mean adherence rate (range: 73.3%– 95.3%) and eight studies reported median adherence (range: 91%– 99.2%). The barriers to treatment adherence identified included self-administration, increased administration frequency, age (adolescence), longer treatment duration, device design, and insufficient family education, awareness, and/or engagement. Recommendations for increasing adherence included using adherence reminder tools, increasing patient engagement/education, and improving injection device design and drug product.ConclusionsAdherence to rhGH treatment was high (>80%) for many studies, though comparability between studies was limited given the substantial heterogeneity in the way adherence was defined, measured, and reported. To address this heterogeneity, we recommend standardizing how adherence is defined and reported and encourage the use of standardized study designs and outcome measures.

.In Japan, anabolic steroid hormone (ASH) treatment for Turner syndrome (TS) to promote growth had been provided before GH therapy for TS was approved. ASH effectively improved the adult height (AH) of TS patients without spontaneous puberty but decreased the AH of TS patients with spontaneous puberty. Although GH therapy for TS was approved in 1991, the approved dosage remained 0.5 IU/kg/wk for GH-deficient TS patients and improved AH by approximately 7 cm. However, AH did not reach –2 standard deviations in healthy girls. In 1999, the requirement of GH deficiency was removed and a dose of 1.0 IU/kg/wk was approved. Although an increase in AH was expected, no reports showed significant improvements in AH at a high dose of GH. GH + ASH combination therapy was reevaluated and recommended for TS patients with gonadal failure and an extremely short stature or those who respond poorly to GH therapy. Although early estrogen replacement therapy is recommended to improve psychological quality of life and prevent osteoporosis, it lowered AH even at a low dose of ethinyl estradiol (25 ng/kg/d). The initiation of ethynyl estradiol at an extremely low dose (1–5 ng/kg/d) at a relatively young age successfully improved AH.

.The efficacy and safety of recombinant human GH (rhGH) treatment were assessed inJapanese children with small-for-gestational-age short stature. A total of 88 patientswere enrolled in the comparative and extension studies. At the end of the comparativestudy (24 mo), the mean height SD score for chronological age had significantly increasedin the 0.23 mg/kg/wk and 0.47 mg/kg/wk groups with increments of 0.84 ± 0.42 and 1.50 ±0.44 SD, respectively. In the extension study, the dose could be increased based on thepre-defined growth criteria. Increments in height SD scores over the 24 to 36 mo period atdoses of 0.23 mg/kg/wk, 0.23 to 0.47 mg/kg/wk, and 0.47 mg/kg/wk were 0.25 ± 0.28, 0.46 ±0.21, and 0.28 ± 0.16 SD, respectively. The growth effect increased following doseescalation even in the low responders in the initial 2-yr treatment at 0.23 mg/kg/wk,indicating the effectiveness of dose escalation in accordance with the Japaneseguidelines. rhGH at 0.47 mg/kg/wk provided a greater degree of growth promotion after 24mo. The safety profile appeared to be tolerable and was similar in all groups. Consideringthe increased insulin resistance, the recommendations of the regulatory authorities shouldbe followed to minimize the risks of rhGH treatment.

In Japan, treatment of growth hormone deficiency with pituitary-extracted human growth hormone (phGH) was covered by health insurance for the first time in 1975. However, because of the shortage of phGH, the Foundation for Growth Science (FGS) was founded in 1977 to control the use of the product by its registration system and to collect pituitary glands in Japan. In 1986, recombinant human growth hormone was first approved. Since then, the FGS has been involved in the harmonization of growth hormone measurement, assessment for treatment eligibility according to the diagnostic criteria by the research group of the Ministry of Health and Welfare, and database generation and its utilization.