Hypoblast from human pluripotent stem cells regulates epiblast development.

Recently, several studies using cultures of human embryos together with single-cell RNA-seq analyses have revealed differences between humans and mice, necessitating the study of human embryos1-8. Despite the importance of human embryology, ethical and legal restrictions have limited post-implantation-stage studies. Thus, recent efforts have focused on developing in vitro self-organizing models using human stem cells9-17. Here, we report genetic and non-genetic approaches to generate authentic hypoblast cells (naive hPSC-derived hypoblast-like cells (nHyCs))-known to give rise to one of the two extraembryonic tissues essential for embryonic development-from naive human pluripotent stem cells (hPSCs). Our nHyCs spontaneously assemble with naive hPSCs to form a three-dimensional bilaminar structure (bilaminoids) with a pro-amniotic-like cavity. In the presence of additional naive hPSC-derived analogues of the second extraembryonic tissue, the trophectoderm, the efficiency of bilaminoid formation increases from 20% to 40%, and the epiblast within the bilaminoids continues to develop in response to trophectoderm-secreted IL-6. Furthermore, we show that bilaminoids robustly recapitulate the patterning of the anterior-posterior axis and the formation of cells reflecting the pregastrula stage, the emergence of which can be shaped by genetically manipulating the DKK1/OTX2 hypoblast-like domain. We have therefore successfully modelled and identified the mechanisms by which the two extraembryonic tissues efficiently guide the stage-specific growth and progression of the epiblast as it establishes the post-implantation landmarks of human embryogenesis.

Spatial profiling of early primate gastrulation in utero.

Gastrulation controls the emergence of cellular diversity and axis patterning in the early embryo. In mammals, this transformation is orchestrated by dynamic signalling centres at the interface of embryonic and extraembryonic tissues1-3. Elucidating the molecular framework of axis formation in vivo is fundamental for our understanding of human development4-6 and to advance stem-cell-based regenerative approaches7. Here we illuminate early gastrulation of marmoset embryos in utero using spatial transcriptomics and stem-cell-based embryo models. Gaussian process regression-based 3D transcriptomes delineate the emergence of the anterior visceral endoderm, which is hallmarked by conserved (HHEX, LEFTY2, LHX1) and primate-specific (POSTN, SDC4, FZD5) factors. WNT signalling spatially coordinates the formation of the primitive streak in the embryonic disc and is counteracted by SFRP1 and SFRP2 to sustain pluripotency in the anterior domain. Amnion specification occurs at the boundaries of the embryonic disc through ID1, ID2 and ID3 in response to BMP signalling, providing a developmental rationale for amnion differentiation of primate pluripotent stem cells (PSCs). Spatial identity mapping demonstrates that primed marmoset PSCs exhibit the highest similarity to the anterior embryonic disc, whereas naive PSCs resemble the preimplantation epiblast. Our 3D transcriptome models reveal the molecular code of lineage specification in the primate embryo and provide an in vivo reference to decipher human development.

[EPIPEN INSTRUCTIONS FOR ANAPHYLAXIS PATIENTS DURING DISPENSING: FACTORS RELATED TO THE QUALITY OF PHARMACISTS' INSTRUCTIONS].

BACKGROUND AND AIM: We previously reported that pharmacists working in pharmacies don't have enough knowledge and enough experience teaching anaphylaxis (An) and EpiPen use. We administered a questionnaire survey to pharmacists with experience handling EpiPen prescriptions. We investigated the relationship between the questionnaire results and the factors in the pharmacists' background regarding the explanation and guidance to patients. RESULTS: The percentage of pharmacists working in pharmacies who provided guidance using visual information and demonstrations was insufficient. Moreover, this figure decreased after the second guidance session. Objective confirmation of patient understanding was also insufficient. The results indicated that self-examination and participation in drug information sessions were important background factors for pharmacists who provided detailed guidance to patients. DISCUSSION: For appropriate long-term management of their condition, An patients must master the EpiPen technique. Pharmacists' guidance plays a critical role in this regard. A support system should be established for proper instruction of pharmacy patients by improving pharmacists' self-education and other educational opportunities.

Cyclophosphamide exposure via sweat of patients receiving CHOP therapy.

INTRODUCTION: "Secondary exposure to anticancer drugs" refers to exposure to anticancer drugs after chemotherapy via the patient's urine and other excretions. The necessity of countermeasures against secondary exposure to anticancer drugs has been recently highlighted. Although anticancer drugs are also excreted through sweat, few studies have reported exposure to drug residues via this route. We investigated the amount of cyclophosphamide (CPA) excreted in the sweat of patients receiving CHOP therapy (cyclophosphamide, doxorubicin, vincristine, and prednisone). METHODS: The study population included eight patients with malignant lymphoma who received CHOP therapy between May and December 2021. The amount of CPA in their underwear (namely, cotton short-sleeved shirts) worn from the start of the CHOP therapy until 24 h after the end of CPA administration was measured, using liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS: CPA was detected in the underwear of all the patients, with levels ranging between 7.38 and 160.77 ng/cm2. No subjective changes were observed in the sweating status of any patients during the study period. CONCLUSIONS: These results suggested that patients' sweat, as well as urine, is a potential route for exposure to anticancer drugs. Whether visibly contaminated or not, the clothing and linen worn directly by patients should be handled as a source of sweat-mediated exposure to anticancer drugs both in medical facilities and at home.

[SURVEY OF KNOWLEDGE ABOUT ANAPHYLAXIS AND GUIDANCE WHEN DISPENSING EPIPEN FOR PHARMACISTS WORKING IN PHARMACIES].

BACKGROUND/PURPOSE: Anaphylactic shock is a serious and life-threatening condition, and affected patients should be quickly and effectively treated with an EpiPen. Although the correct use of an EpiPen is greatly affected by a user's proficiency level and the instructions accompanying the EpiPen, there has been almost no investigation into the knowledge of the EpiPen and the actual situation of the accompanying instructions for use. Therefore, we conducted this nationwide survey to elucidate these issues. METHODS: A questionnaire survey was conducted among pharmacists registered as members of the system of a research company outside the university and working at pharmacies with experience in handling EpiPen prescriptions. RESULTS: Many of the pharmacists surveyed knew that the EpiPen is the first-line treatment for anaphylactic shock. However, they did not have sufficient knowledge of administration routes and candidates for second-line treatment. Both their occasions and experiences of dealing of EpiPen were found to be low. CONSIDERATION: It is desirable to learn at conferences regarding allergology/clinical allergy and seminars for medical professionals including pharmacists in order to acquire the skills and knowledge to consult with patients with allergic diseases, including action plans presented by doctors in preparation for recurrence of anaphylaxis.

Apparent diffusion coefficient (ADC) values of serous, endometrioid, and clear cell carcinoma of the ovary: pathological correlation.

BACKGROUND: Primary epithelial ovarian cancer is divided into several subtypes. The relationships between apparent diffusion coefficient (ADC) values and their subtypes have not yet been established. PURPOSE: To investigate whether ADC values of epithelial ovarian cancer vary according to histologic tumor cellularity and evaluate the difference of clear cell carcinoma (CCC), high-grade serous carcinoma (HGSC), and endometrioid carcinoma (EC). MATERIAL AND METHODS: This retrospective study included 51 cases of epithelial ovarian cancer (17 CCC, 20 HGSC, and 14 EC) identified by magnetic resonance imaging with pathological confirmation. All patients underwent diffusion-weighted imaging and the ADC values of lesions were measured. We counted the tumor cells in three high-power fields and calculated the average for each case. The Spearman's correlation coefficient test was used to analyze correlation between ADC values and tumor cellularity. The ADC values of HGSC, EC, and CCC were compared using the Steel-Dwass test. RESULTS: The ADC values of all cases were significantly inversely correlated with tumor cellularity (rs = -0.761; P < 0.001). The mean ± SD ADC values (×10-3 mm2/s) of CCC, HGSC, and EC were 1.24 ± 0.17 (range 0.98--1.65), 0.84 ± 0.10 (range 0.67--1.06), and 0.84 ± 0.10 (range 0.67--1.07). The mean ± SD tumor cellularity of CCC, HGSC, and EC was 162.88 ± 63.28 (range 90.33--305.67), 440.60 ± 119.86 (range 204.67--655.67), and 461.02 ± 81.86 (range 333.33--602.33). CONCLUSION: There is a significant inverse correlation between ADC values and tumor cellularity in epithelial ovarian cancer. The mean ADC value of CCC was higher than those of HGSC and EC, seemingly due to the low cellularity of CCC.

Behavioral and neuroanatomical analyses in a genetic mouse model of 2q13 duplication.

Duplications of human chromosome 2q13 have been reported in patients with neurodevelopmental disorder including autism spectrum disorder. Nephronophthisis-1 (NPHP1) was identified as a causative gene in the minimal deletion on chromosome 2q13 for familial juvenile type 1 nephronophthisis and Joubert syndrome, an autosomal recessive neurodevelopmental disorder characterized by a cerebellar and brain stem malformation, hypotonia, developmental delay, ataxia, and sometimes associated with cognitive impairment. NPHP1 encodes a ciliary protein, nephrocystin-1, which is expressed in the brain, yet its function in the brain remains largely unknown. In this study, we generated bacterial artificial chromosome-based transgenic mice, called 2q13 dup, that recapitulate human chromosome 2q13 duplication and contain one extra copy of the Nphp1 transgene. To analyze any behavioral alterations in 2q13 dup mice, we conducted a battery of behavioral tests. Although 2q13 dup mice show no significant differences in social behavior, they show deficits in spontaneous alternation behavior and fear memory. We also carried out magnetic resonance imaging to confirm whether copy number gain in this locus affects the neuroanatomy. There was a trend toward a decrease in the cerebellar paraflocculus of 2q13 dup mice. This is the first report of a genetic mouse model for human 2q13 duplication.

Nuclear inverse polarity papillary lesions lacking myoepithelial cells: A report of two cases.

Here, cases of a 68- (Case 1) and a 44-year-old (Case 2) female are presented. They had an abnormality in the breast, and came to our hospital for further examination and treatment. Radiologically, malignancy could not completely excluded so breast excision was performed. Histologically, both cases revealed papillary neoplastic lesions lined by fibrovascular core and nuclear inverse polarity without atypia. Loss of myoepithelial cells was observed by HE, p63, and calponin. Previous report indicate CK5/6, ER, p63 and MUC3 are important for distinguishing between papillary lesions according to the differential index (based on Allred score) of ([ER total score] + [MUC3 total score])/([CK5/6 total score] + [p63 total score] + 1). Based on this analysis, our two cases had benign lesions. However, based on immunopositivity for cell-cycle marker Cyclin-D1, Case 1 was negative, and Case 2 was about 70% positive. Additionally, the Ki-67 index was <1% in both cases, and no evidence of disease was observed after a maximum 62 months of follow-up in both cases, despite lack of additional treatment. Thus, we propose that lack of myoepithelial cells in papillary lesions do not necessarily indicate malignancy and are thought to be, at the most, uncertain malignant potential.

Endometrial cancer: correlation of apparent diffusion coefficient (ADC) with tumor cellularity and tumor grade.

BACKGROUND: Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) are widely used for detecting uterine endometrial cancer. The relationships between ADC values and pathological features of endometrial cancer have not yet been established. PURPOSE: To investigate whether ADC values of endometrial cancer vary according to histologic tumor cellularity and tumor grade. MATERIAL AND METHODS: We retrospectively reviewed 30 pathologically confirmed endometrial cancers. All patients underwent conventional non-enhanced magnetic resonance imaging (MRI) and DWI procedures, and ADC values were calculated. Tumor cellularity was evaluated by counting cancer cells in three high-power ( × 400) fields. The correlation between ADC values and tumor cellularity was assessed using Pearson's correlation coefficient test for statistical analysis. RESULTS: The mean ± standard deviation (SD) ADC value ( ×10(-3) mm(2)/s) of endometrial cancer was 0.85 ± 0.22 (range, 0.55-1.71). The mean ± SD tumor cellularity was 528.36 ± 16.89 (range, 298.0-763.6). ADC values were significantly inversely correlated with tumor cellularity. No significant relationship was observed between ADC values and tumor grade (mean ADC values: G1, 0.88 ± 0.265 × 10(-3) mm(2)/s; G2, 0.80 ± 0.178 × 10(-3) mm(2)/s; G3, 0.81 ± 0.117 × 10(-3) mm(2)/s). CONCLUSION: There is a significant inverse relationship between ADC values and tumor cellularity in endometrial cancer. No significant differences in average ADC value were observed between G1, G2, and G3 tumors. However, the lower the tumor grade, the wider the SD.

Identifying factors improving the intention to use antibiotics appropriately in children and adults using protection motivation theory.

Objective: This study aimed to employ hypothetical models based on the protection motivation theory (PMT) to identify factors that improve the intention to use antibiotics appropriately (intention) among individuals who take antibiotics or administer them to their children. Methods: Adult Japanese participants, including 600 parents who administer antibiotics to children aged <14 years and 600 adults who take them, completed an online survey. Structural equation modeling (SEM) was conducted on hypothetical models representing intention using 19 questions based on PMT. If the hypothesized model did not fit, SEM was repeated to search for a new model. Results: The hypothesized models did not fit. Two factors were extracted from SEM: "understanding the risk of antimicrobial resistance" and "excessive expectation of antibiotics." In adults, SEM revealed that "excessive expectation of antibiotics" (ß = -0.50, p < 0.001) negatively influenced intention; in children, "excessive expectation of antibiotics" (ß = -0.52, p < 0.001) negatively influenced intention, while "understanding the risk of antimicrobial resistance" (ß = 0.22, p < 0.001) positively influenced intention. Conclusion: Factors influencing intention varied between adult and pediatric antibiotic use. Innovation: Awareness activities for appropriate antibiotic use should be tailored to population characteristics.

Association between Cognitive Impairment Severity and Polypharmacy in Older Patients with Atrial Fibrillation: A Retrospective Study Using Inpatient Data from a Specialised Geriatric Hospital.

This study aimed to investigate the association between cognitive impairment and polypharmacy in patients with atrial fibrillation prone to cognitive decline, and to elucidate if the Dementia Assessment Sheet for Community-based Integrated Care System 21-Items (DASC-21) severity classification indicates drug adjustment. This retrospective cohort study used the DASC-21 and Diagnosis Procedure Combination data at a specialised geriatric hospital with patients hospitalised between April 2019 and March 2022. The association between cognitive severity evaluated using the DASC-21 and polypharmacy was investigated using a multivariate logistic regression model. Data of 1191 inpatients (44.3% aged ≥85 years, 49.0% male) were analysed. Compared with severe cognitive impairment, mild (odds ratio [OR]: 3.33, 95% confidence interval [CI]: 1.29-8.57) and moderate (OR: 2.46, 95% CI: 1.06-5.72) impairments were associated with concurrent use of ≥6 medications. Antithrombotics were related to polypharmacy. The ORs did not change with 6, 8, or 10 medications (2.11 [95% CI: 1.51-2.95, p < 0.001], 2.42 [95% CI: 1.79-3.27, p < 0.001], and 2.01 [95% CI: 1.46-2.77, p < 0.001], respectively). DASC-21 severity was associated with polypharmacy in patients with atrial fibrillation, with a trend toward decreased polypharmacy from moderate to severe. The DASC-21 may serve as an indicator for drug adjustment in clinical practice.

Recognition of Community Pharmacists' Behaviors Related to Information Sharing: A Cross-Sectional Study.

With the recent shift in community pharmacist services toward in-person services and the growing need for centralized and continuous medication management/monitoring, pharmacist-patient information sharing is crucial. This study investigated the pharmacist-patient gap in the recognition of pharmacists' behaviors regarding information sharing and assessed the potential impact of such recognition on patient trust and willingness to self-disclose. This cross-sectional study included 600 patients (aged 21-85 years) using pharmacy services (surveyed online in December 2020) and 591 community pharmacists with ≥1 year of experience (surveyed from September to November 2021). Both groups responded to items on the recognition of pharmacists' behaviors regarding information sharing. There were patient-specific items on trust in community pharmacists and willingness to self-disclose. For all items on the recognition of pharmacists' behaviors, patients' scores were significantly lower (4-5) than pharmacists' own scores (≥5), revealing a notable perception gap. Patients' recognition had a positive, direct effect on trust and willingness, and trust had a positive, direct effect on willingness. Patients' recognition and trust positively influenced their willingness to self-disclose. Pharmacist communication with clear intent is important to bridge the gaps in pharmacist-patient recognition and foster effective patient-pharmacist relationships.

Knowledge of mucin immunostaining status of "nuclear inverse polarity papillary lesions lacking myoepithelial cells" may prevent unnecessary breast surgery: experience of two cases.

We previously reported on two women with breast lesions in whom radiological examination could not exclude malignancy. In both cases, mastectomy was performed, and histological analyses revealed papillary lesions lined by fibrovascular stroma and nuclear inverse polarity. Hematoxylin-eosin, p63, and calponin staining indicated an absence of myoepithelial cells. However, it was concluded that the lesions had been non-malignant. These women have now been under long-term surveillance (74 months for one case and 62 months for the other) and have had no disease recurrence. Mucin (MUC)1, MUC2, MUC4, MUC5AC, MUC5B, and MUC6 immunostaining has also been performed in these women to investigate further whether their tumors were malignant or benign. In both cases, the tumors were only positive for MUC1 in apical luminal apical cells, as in normal breast tissue. MUC5B immunostaining, even when weak, can detect early breast cancer but was completely negative in our two cases. Therefore, both tumors were considered benign. Our findings in these cases suggest that nuclear inverse polarity papillary lesions lacking myoepithelial cells are benign. This knowledge should decrease the number of unnecessary operations performed for this tumor and their negative impact on patients' quality of life.

Creation of the first regional medical resource map for use in a disaster.

Background: Japan is located on the Pacific Ring of Fire and experiences frequent earthquakes. In addition, as the climate is changing due to global warming, heavy rains have caused frequent floods recently. Following the occurrence of disasters, citizens often experience confusion regarding access to healthcare services. Moreover, health professionals often face uncertainty regarding the availability of medical services in their local area. The Tokyo Kita city Pharmacist Association (KPA) independently developed the pharmacist safety confirmation (PSC) and pharmacy status confirmation (PSTC) systems to provide information regarding pharmaceutical resources during a disaster. These systems are very useful; however, they only provide information about pharmacies. Using this system as a base, a regional medical resource (RMR) map was created in cooperation with the Medical Association and Dental Association to provide useful medical resource information for clinicians and citizens during a disaster. Objectives: The study aimed to assess the effectiveness and reliability of the RMR map. Methods: The PSC and PSTC systems were originally invented by the KPA. The systems were employed in the event of actual earthquakes and flood damages and have produced positive results. An RMR map was created as a new resource map system by updating the software and platform of PSC and PSTC, and its reliability and efficacy were verified using drills. Drills were conducted seven times from 2018 to 2021. Results: Out of the 527 member facilities, 450 were registered. The response rate ranged from 49.4% to 73.8% and the system successfully created useful maps. Conclusion: This is the first report on the creation of an effective RMR map that can be used for helping people during disasters in Japan.

Induction of primordial germ cell-like cells from common marmoset embryonic stem cells by inhibition of WNT and retinoic acid signaling.

Reconstitution of the germ cell lineage using pluripotent stem cells provides a unique platform to deepen our understanding of the mechanisms underlying germ cell development and to produce functional gametes for reproduction. This study aimed to establish a culture system that induces a robust number of primordial germ cell-like cells (PGCLCs) from common marmoset (Callithrix jacchus) embryonic stem cells. The robust induction was achieved by not only activation of the conserved PGC-inducing signals, WNT and BMP4, but also temporal inhibitions of WNT and retinoic acid signals, which prevent mesodermal and neural differentiation, respectively, during PGCLC differentiation. Many of the gene expression and differentiation properties of common marmoset PGCLCs were similar to those of human PGCLCs, making this culture system a reliable and useful primate model. Finally, we identified PDPN and KIT as surface marker proteins by which PGCLCs can be isolated from embryonic stem cells without genetic manipulation. This study will expand the opportunities for research on germ cell development and production of functional gametes to the common marmoset.

Changes in chronic disease medications after admission to a Geriatric Health Services Facility: A multi-center prospective cohort study.

Older adults often receive polypharmacy, including some medications for chronic diseases. Nutritional management after admission to a nursing home may enable to deprescribe some chronic disease medications. This study aimed to investigate the status of deprescribing of chronic disease medications among nursing home residents, and to assess the appropriateness based on changes of laboratory test values and nutritional status. A multi-center prospective cohort study was conducted in 6 Geriatric Health Services Facilities, a major type of nursing homes in Japan. Newly admitted residents aged ≥ 65 years who took ≥1 medication for hypertension, diabetes, or dyslipidemia at admission were recruited. Participants who stayed for 3 months were included in the analysis. Medications at admission and 3 months after admission and situations for deprescribing were investigated. Changes in body mass index, blood pressure, laboratory tests (e.g., cholesterol and hemoglobin A1c levels), energy intake, and International Classification of Functioning, Disability and Health staging were evaluated. Sixty-nine participants (68% female, 62% aged ≥ 85 years) were included. At admission, 60 participants had medications for hypertension, 29 for dyslipidemia, and 13 for diabetes. Those receiving lipid-modifying drugs (mainly statins) decreased from 29 to 21 (72%; P = .008), since their cholesterol levels was within the normal range or was low at admission, and they had no history of cardiovascular events. However, there were no statistically significant changes in the frequencies of antihypertensive drugs (60 to 55; 92%; P = .063) or antidiabetic drugs (13 to 12; 92%; P = 1.000). During the 3-month observation, body mass index and diastolic blood pressure decreased, while energy intake and serum albumin level increased. Nutritional management after admission to a ROKEN may facilitate appropriate deprescribing of lipid-modifying drugs, by offseting the effects of discontinuation of these drugs.

Uterine morphology and peristalsis in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with chronic oligo-anovulation and high circulating sex hormone levels. Women with PCOS have an increased risk of developing endometrial cancer. In anovulatory women with PCOS a positive relationship between endometrial thickness and endometrial hyperplasia has been observed. Uterine peristalsis, which has been suggested to be of importance for female fertility, has not previously been studied in PCOS. PURPOSE: To assess whether women with PCOS have altered endometrial thickness, uterine wall morphology, and peristalsis. MATERIAL AND METHODS: In this prospective case-control study 55 women with PCOS (mean age, 29.5 years ± 4.5 SD) and 28 controls (27.6 ± 3.2) were examined using magnetic resonance imaging (MRI), assessing thickness of endometrium, junctional zone (JZ), and myometrium, and evaluating the occurrence, frequency (waves/min), strength (amplitude), pattern, and direction of peristalsis. Uterine morphology was also assessed by transvaginal ultrasonography (TVUS). RESULTS: The endometrium was thinner in PCOS with oligo-amenorrhea compared to controls, also after adjustments for age and BMI (adjusted P = 0.043). There was no difference in thickness of the JZ or the myometrium in cases versus controls. Uterine peristalsis was less commonly observed in women with PCOS than in controls (adjusted P = 0.014). CONCLUSION: There were no differences in myometrial morphology between PCOS and controls, but the endometrium was thinner in PCOS with oligo-amenorrhea. Based on cine MRI, uterine peristalsis was less common in PCOS than in controls.

Relationship between cognitive function affecting motor Functional Independence Measure and hypnotics.

Otsubo H, Kishimoto K, Hirano I, Nakano H, Itaya K, Kumaki R, Osumi H. Relationship between cognitive function affecting motor Functional Independence Measure and hypnotics. Jpn J Compr Rehabil Sci 2022; 13: 4-11. Purpose: The purpose of this study was to examine the relationship between cognitive dysfunction affecting motor Functional Independence Measure (FIM) and hypnotics. Methods: This was a retrospective study involving 509 patients aged ≥ 65 years who were discharged from a convalescent rehabilitation ward. Results: Multiple regression analysis was performed with motor FIM efficiency and motor FIM effectiveness (motor FIM-e) as independent variables and the presence or absence of cognitive dysfunction as the dependent variable. The use of hypnotics in patients with cognitive dysfunction showed a positive relationship with motor FIM efficiency (ß = 0.147, P = 0.019) and motor FIM-e (ß = 0.141, P = 0.026). Multiple regression analyses were performed after further classifying hypnotics by therapeutic class into hypnotics with new mechanisms, non-benzodiazepine (BZ) hypnotics, and BZ hypnotics. Non-BZ hypnotics (ß = 0.141, P = 0.021) showed a positive relationship with motor FIM efficiency. Non-BZ hypnotics (ß = 0.158, P = 0.009) and BZ hypnotics (ß = 0.178, P = 0.003) showed a positive relationship with motor FIM-e, whereas hypnotics with new mechanisms of action did not. In contrast, none of the three combinations of hypnotics showed any significant relationship with either motor FIM efficiency or motor FIM-e in patients without cognitive dysfunction. Conclusion: The results suggested that the use of hypnotics in patients with cognitive dysfunction increases motor FIM efficiency and motor FIM-e.

Identification of factors associated with the efficacy of atomoxetine in adult attention-deficit/hyperactivity disorder.

AIM: Atomoxetine (ATX) is a non-central stimulant and a standard treatment for adult attention-deficit/hyperactivity disorder (ADHD). The long-term efficacy of Atomoxetine is about 40% at 6 months. The variability in efficacy between individuals is thought to be related to patient-specific factors, but no detailed research has been conducted. In this retrospective cohort study, we aimed to identify the factors associated with Atomoxetine efficacy. METHODS: A total of 147 patients with attention-deficit/hyperactivity disorder aged ≥18 years who were using Atomoxetine for the first time were included in this study. The outcome was treatment success (treatment maintained for at least 6 months and improvement in symptoms). Symptom assessment was based on the overall improvement in symptoms judged by an expert physician. RESULTS: Of the patient sample, 103 (70.1%) achieved the outcome. Logistic regression analysis identified "the maximum dose of ATX" and "gambling habit" as factors associated with efficacy ( P  < 0.05). In the process of Atomoxetine titration, the larger the maximum dose, the higher the efficacy was shown to be. Gambling habits may be indicative of impulsivity, which is among the core symptoms of attention-deficit/hyperactivity disorder. Thus, a gambling habit may be considered a surrogate marker for impulsivity. CONCLUSIONS: Knowledge of these factors will help healthcare professionals to predict the likely efficacy of Atomoxetine in a given patient before subscribing it, facilitating individualized pharmacotherapy for adult attention-deficit/hyperactivity disorder.