Efficacy of the unified protocol for transdiagnostic cognitive-behavioral treatment for depressive and anxiety disorders: a randomized controlled trial.

BACKGROUND: The efficacy of the unified protocol of the transdiagnostic treatment for emotional disorders (UP) has been poorly studied in patients with depressive disorders. This study aimed to examine the efficacy of UP for improving depressive symptoms in patients with depressive and/or anxiety-related disorders. METHODS: This assessor-blinded, randomized, 20-week, parallel-group, superiority study compared the efficacy of the UP with treatment-as-usual (UP-TAU) v. wait-list with treatment-as-usual (WL-TAU). Patients diagnosed with depressive and/or anxiety disorders and with depressive symptoms participated. The primary outcome was depressive symptoms assessed by GRID-Hamilton depression rating scale (GRID-HAMD) at 21 weeks. The secondary outcomes included assessor-rated anxiety symptoms, severity and improvement of clinical global impression, responder and remission status, and loss of principal diagnosis. RESULTS: In total, 104 patients participated and were subjected to intention-to-treat analysis [mean age = 37.4, s.d. = 11.5, 63 female (61%), 54 (51.9%) with a principal diagnosis of depressive disorders]. The mean GRID-HAMD scores in the UP-TAU and WL-TAU groups were 16.15 (s.d. = 4.90) and 17.06 (s.d. = 6.46) at baseline and 12.14 (s.d. = 5.47) and 17.34 (s.d. = 5.78) at 21 weeks, with a significant adjusted mean change difference of -3.99 (95% CI -6.10 to -1.87). Patients in the UP-TAU group showed significant superiority in anxiety and clinical global impressions. The improvement in the UP-TAU group was maintained in all outcomes at 43 weeks. No serious adverse events were observed in the UP-TAU group. CONCLUSIONS: The UP is an effective approach for patients with depressive and/or anxiety disorders.

Effect of helicity and hydrophobicity on cell-penetrating ability of arginine-rich peptides.

Arginine (Arg)-rich peptides are one of the typical cell-penetrating peptides (CPPs), which can deliver membrane-impermeable compounds into intracellular compartments. Guanidino groups in Arg-rich peptides are critical for their high cell-penetrating ability, although it remains unclear whether peptide secondary structures contribute to this ability. In the current study, we designed four Arg-rich peptides containing α,α-disubstituted α-amino acids (dAAs), which prefer to adopt a helical structure. The four dAA-containing peptides adopted slightly different peptide secondary structures, from a random structure to a helical structure, with different hydrophobicities. In these peptides, dipropylglycine-containing peptide exhibited the highest helicity and hydrophobicity, and showed the best cell-penetrating ability. These findings suggested that the helicity and hydrophobicity of Arg-rich peptides contributes to their high cell-penetrating ability.

Development of the Parenting Behavior Checklist to Promote Preschoolers' Sleep (PCPP).

OBJECTIVES: To develop the Parenting Behavior Checklist to Promote Preschoolers' sleep (PCPP), quantify sleep-promoting parenting behaviors for children, and examine the scale's reliability and validity. METHODS: The PCPP was developed based on the recommendations of the ABCs of SLEEPING for children's sleep, which is strongly supported by research evidence. Its validity and reliability were evaluated using data from 140 participants. Structural validity was estimated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), and internal consistency was evaluated by Cronbach's α. Hypothesis testing was evaluated by analyzing the correlations between each factor of the Japanese Sleep Questionnaire for Preschoolers (JSQ-P) and the PCPP. RESULTS: Regarding structural validity, EFA was conducted because CFA showed a poor model fit. The PCPP comprised one factor and six items. The JSQ-P subfactors of insomnia or circadian rhythm sleep-wake disorders, undesirable morning symptoms and behaviors, and insufficient sleep were moderately negatively correlated with the PCPP; the subfactor of undesirable daytime behaviors related to sleep problems was weakly negatively correlated with the PCPP. Thus, the sleep-promoting parenting behaviors listed in the PCPP were associated with better sleep in children. CONCLUSIONS: The PCPP showed sufficient reliability and validity. Future studies should use the scale to examine more effective interventions regarding sleep-promoting parental behaviors for children.

Development and validation of the Japanese version of the Hyperarousal Scale.

BACKGROUND: The objectives of this study were to develop a Japanese version of the Hyperarousal Scale (HAS-J) and investigate its factor structure, reliability, and validity, as well as to calculate a cutoff score for the HAS-J and assess different levels of hyperarousal in insomnia patients and community dwellers. METHODS: We recruited 224 outpatients receiving insomnia treatment (56.3% women; mean age 51.7 ± 15.6 years) and 303 community dwellers aged 20 years or older (57.8% women; mean age 43.9 ± 15.2 years). Exploratory and confirmatory factor analysis was performed to examine the factor structure of the HAS-J. Cronbach's α and McDonald's ω were then used to test internal consistency. To examine the scale's validity, we determined correlations between the HAS-J and other indexes and compared HAS-J scores between insomnia patients and community dwellers. We also compared HAS-J scores between two community-dweller groups (normal and poor sleepers) and two insomnia patient groups (with and without alleviation after treatment). RESULTS: Following exploratory and confirmatory factor analysis, a 20-item measure emerged comprising three factors: "Introspectiveness and Reactivity," "Neuroticism," and "Insomnia." Confirmatory factor analysis showed a generally good fit for the model of the three-factor structure suggested by the exploratory factor analysis loadings (χ2 (163) = 327.423, (p <  0.001), CFI = 0.914, GFI = 0.872, AGFI = 0.835, RMSEA = 0.067). In insomnia patients, internal consistency indicated sufficient reliability of the HAS-J. Correlation analysis showed weak to moderate positive correlations of the HAS-J score with other indexes, indicating concurrent validity of the HAS-J. All HAS-J subscale scores were significantly higher in insomnia patients than in community dwellers. Additionally, the total score in patients with alleviation of insomnia was comparable to that in poor sleepers and significantly higher than that in normal sleepers. CONCLUSIONS: This study demonstrated the reliability and validity of the HAS-J, indicating that it is useful as a clinical scale of hyperarousal. The high level of hyperarousal in insomnia patients who were assessed to be in remission by the Insomnia Severity Index suggests a risk of insomnia recurrence in these patients.

Cognitive behavioral therapy for insomnia to treat major depressive disorder with comorbid insomnia: A systematic review and meta-analysis.

OBJECTIVE: Cognitive behavioral therapy for insomnia (CBT-I) has demonstrated efficacy for both insomnia and depression. With a tenfold increase in expected participant numbers, we aimed to update the systematic review and meta-analysis of CBT-I for major depressive disorders (MDD). METHODS: Multiple databases were searched up to March 27th 2024 to include all randomized controlled trials examining CBT-I among adults with MDD. The certainty of evidence was evaluated using GRADE. The primary outcome was depression response at post-treatment. Secondary outcomes included insomnia remission and all-cause dropout at post-treatment. Frequentist random-effects pairwise meta-analyses were performed using odds ratio (OR) for dichotomous outcomes. This study was prospectively registered (https://osf.io/kcndz/). RESULTS: Nineteen trials with 4808 randomized participants were identified (mean age, 33.2 [standardized deviation 15.0] years, 73.2 % women. Mean Insomnia Severity Index 19.2 [5.4], median Patient Health Questionnaire-9 16 [range, 8-21]). CBT-I was more beneficial than control conditions for depression response (OR 2.28 [95 % Confidence Interval (CI), 1.67-3.12; GRADE certainty of evidence: moderate), insomnia remission (OR 3.57 [95%CI, 2.48-5.14]: moderate) but could lead to more dropout (OR 1.69 [95%CI, 0.98-2.89]: low). Depression improvement was seen beyond the sleep domain. With a control condition depression response rate of 17 % at post-treatment (median 8 weeks), CBT-I yielded a 32 % response rate (95 % CI, 26 %-39 %). CONCLUSIONS: This meta-analysis indicates that CBT-I has significant effects on depressive symptoms beyond the sleep domain among people with MDD. Despite higher dropout rates, these findings suggest CBT-I is an effective treatment for depression comorbid with insomnia.

Components and Delivery Formats of Cognitive Behavioral Therapy for Chronic Insomnia in Adults: A Systematic Review and Component Network Meta-Analysis.

Importance: Chronic insomnia disorder is highly prevalent, disabling, and costly. Cognitive behavioral therapy for insomnia (CBT-I), comprising various educational, cognitive, and behavioral strategies delivered in various formats, is the recommended first-line treatment, but the effect of each component and delivery method remains unclear. Objective: To examine the association of each component and delivery format of CBT-I with outcomes. Data Sources: PubMed, Cochrane Central Register of Controlled Trials, PsycInfo, and International Clinical Trials Registry Platform from database inception to July 21, 2023. Study Selection: Published randomized clinical trials comparing any form of CBT-I against another or a control condition for chronic insomnia disorder in adults aged 18 years and older. Insomnia both with and without comorbidities was included. Concomitant treatments were allowed if equally distributed among arms. Data Extraction and Synthesis: Two independent reviewers identified components, extracted data, and assessed trial quality. Random-effects component network meta-analyses were performed. Main Outcomes and Measures: The primary outcome was treatment efficacy (remission defined as reaching a satisfactory state) posttreatment. Secondary outcomes included all-cause dropout, self-reported sleep continuity, and long-term remission. Results: A total of 241 trials were identified including 31 452 participants (mean [SD] age, 45.4 [16.6] years; 21 048 of 31 452 [67%] women). Results suggested that critical components of CBT-I are cognitive restructuring (remission incremental odds ratio [iOR], 1.68; 95% CI, 1.28-2.20) third-wave components (iOR, 1.49; 95% CI, 1.10-2.03), sleep restriction (iOR, 1.49; 95% CI, 1.04-2.13), and stimulus control (iOR, 1.43; 95% CI, 1.00-2.05). Sleep hygiene education was not essential (iOR, 1.01; 95% CI, 0.77-1.32), and relaxation procedures were found to be potentially counterproductive(iOR, 0.81; 95% CI, 0.64-1.02). In-person therapist-led programs were most beneficial (iOR, 1.83; 95% CI, 1.19-2.81). Cognitive restructuring, third-wave components, and in-person delivery were mainly associated with improved subjective sleep quality. Sleep restriction was associated with improved subjective sleep quality, sleep efficiency, and wake after sleep onset, and stimulus control with improved subjective sleep quality, sleep efficiency, and sleep latency. The most efficacious combination-consisting of cognitive restructuring, third wave, sleep restriction, and stimulus control in the in-person format-compared with in-person psychoeducation, was associated with an increase in the remission rate by a risk difference of 0.33 (95% CI, 0.23-0.43) and a number needed to treat of 3.0 (95% CI, 2.3-4.3), given the median observed control event rate of 0.14. Conclusions and Relevance: The findings suggest that beneficial CBT-I packages may include cognitive restructuring, third-wave components, sleep restriction, stimulus control, and in-person delivery but not relaxation. However, potential undetected interactions could undermine the conclusions. Further large-scale, well-designed trials are warranted to confirm the contribution of different treatment components in CBT-I.

Development and validation of the Japanese version of the Athens Insomnia Scale.

AIM: The aim of this study was to develop and validate a Japanese version of the Athens Insomnia Scale (AIS-J). METHODS: The AIS-J was created using a back-translation design. A total of 477 outpatients with chronic insomnia and 163 individuals from the general community were recruited. Participants were asked to complete the AIS-J along with two other insomnia scales - Japanese versions of the Pittsburgh Sleep Quality Index and the Insomnia Severity Index. RESULTS: The AIS-J consisted of a two-factor structure: 'nocturnal sleep problem' (items 1-5) and 'daytime dysfunction' (items 6-8). Internal consistencycoefficients ranged from 0.78 to 0.88. Correlations between the AIS-J and the aforementioned authorized scales were 0.81 and 0.85, respectively. Scores on the AIS-J were significantly higher for the insomnia group than for the control group. The AIS-J cut-off value for identifying pathological insomnia was estimated at 6 points or more, and the AIS-J-nocturnal cut-off value was estimated at 4 points or more. CONCLUSIONS: The AIS-J has sufficient validity and diagnostic utility.

Preliminary assessment of the behavioral activation model in Japanese undergraduate students.

Many studies have reported that behavioral activation is an effective intervention for depression. The behavioral activation model is based on several formulations. For example, depressive mood leads to avoidant behaviors, avoidance negatively affects social contacts, decreased socialization lessens opportunities for positive reinforcement, and a decrease in positive reinforcement results in more depressive mood. The purpose of this study was to examine relationships among avoidant behavior, social contact, frequency of positive reinforcement, and depressive mood by using structural equation modeling to assess support for aspects of this behavioral activation model. Participants were 630 Japanese undergraduate students and vocational school students. Results provided preliminary support for the model. Treating both avoidance and activating behavior might contribute to decreased impairment.

[Association between high altitude and depression in the Himalayas and the Andes].

AIM: Suicide rates in the United States are higher in higher altitude areas, and hypoxia has been cited as a factor in these higher rates. There may be a significant correlation between rates of depression and altitude, but little data exist outside the United States. The purpose of the present study is to conduct a survey of depression among the elderly residing in the Himalayas and the Andes. METHOD: We visited Ladakh (altitude 3,800-4,800 m) in India, Qinghai (3,700 m) in China and Puyca (3,600 m) in Peru between July 2009 and July 2011. We recruited 114 farmers from Domkhar in Ladakh (mean age, 69.2 years; female-male ratio, 58.8%), 206 nomads from Changthang in Ladakh (55.1 years; 43.7%), 173 Tibetan subjects from Qinghai (66.5 years; 61.3%) and 103 indigenous Andean subjects from Puyca (69.0 years; 68.0%). The two-item Patient Health Questionnaire (PHQ-2) was administered to the subjects. A psychiatrist interviewed the residents with single or double positive scores on the PHQ-2. RESULT: The ratio of subjects with one or more positive score in PHQ-2 was significantly higher in Qinghai than in other regions. (Domkhar vs. Changthang vs. Qinghai vs. Puyca = 7.0% vs. 5.3% vs. 36.9% vs. 15.5%, P<0.001). However, prevalence of depression by interview did not change in these regions. (1.8% vs. 1.9% vs. 2.3% vs. 2.9%). CONCLUSION: Despite the high altitude, the prevalence of depression was low in elderly highlanders in the Himalayas and the Andes. These results may relate to being presumed to related to a deep devotion to a religion and tight interpersonal networks.

Set-screw loosening of spinopelvic crab-shaped fixation for a patient with vertically unstable pelvic ring fracture.

Spinopelvic fixation (SPF) is an effective treatment method for vertically unstable pelvic ring fractures with spinopelvic dissociations (Patel et al., 2022). A heavy container fell on a 35-year-old man who was trapped and sustained injuries. His pelvic ring fracture dislocation was identified as AO Classification 61-C2.3 with rotational and vertical unstable pelvic ring; thus, crab-shaped fixation (SPF modification) was performed (Okuda et al., 2019). The pelvic fracture was fused, and the clinical outcome was good with modified Majeed score of 96. However, set-screw loosening was observed during the postoperative course. Reports of implant failures in SPF for unstable pelvic ring fractures commonly occur. However, only a few reports have demonstrated implant failure of crab-shaped fixation. Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Ligament reconstruction using a semitendinosus tendon graft for proximal tibiofibular joint disorder: Case report.

We report our case of ligament reconstruction for treatment of proximal tibiofibular joint disorder using a semitendinosus tendon graft. A 21-year-old male college soccer player with no remarkable history of injury had been suffering from pain at the lateral aspect of the left knee when playing soccer. At another hospital, the patient was diagnosed with a lateral meniscus injury and cartilage injury of the external condyle of the tibia and underwent partial resection of the meniscus and bone drilling. However, his symptoms continued, and he was referred to our institution. Instability of the left proximal tibiofibular joint and pain were noted during weight-bearing dorsiflexion of the ankle. We diagnosed the case as a proximal tibiofibular joint disorder and surgically treated it by dissecting the proximal portion of the semitendinosus tendon, creating one transfibular and two transtibial tunnels, and then reconstructing the proximal tibiofibular ligament using the harvested semitendinosus tendon graft. The patient was allowed to run at postoperative 2 months, with no pain occurring while squatting at postoperative 3 months, subsequently resuming soccer at postoperative 8 months. The proximal tibiofibular joint disorder is a relatively rare pathology, and diagnosis and conservative treatment are often difficult. Although various surgical treatments are known, the clinical outcome of our case has been successful after reconstructing the anterior and posterior proximal tibiofibular ligaments using a semitendinosus tendon graft.

Evaluation of a Japanese brief CBT-I administered by a nurse: a pilot study.

AIM: The aim of this pilot study is to evaluate a Japanese version of brief Cognitive Behavioral Therapy for Insomnia (CBT-I) and contribute to primary care which leads to prevention of a lifestyle-related disease or a psychiatric disorder. METHOD: A single-arm study in nine patients with chronic insomnia who were under the pharmacotherapy was executed. The Insomnia Severity Index (ISI), the Athens Insomnia Scale (AIS), and the European Quality of Life 5 Items (EQ-5D) were assessed at the beginning of intervention, at the end of intervention, and after 12 weeks. FINDINGS: There were no patient dropouts nor adverse events. The average change in ISI score was -7.33 (95% CI: -10.31 to -4.36) at post-treatment and -6.11 (95% CI: -8.20 to -4.03) at the 12-week follow-up point (Cohen's d = 2.25). The AIS score improved as well, and the EQ-5D score improved after 12 weeks. The safety and efficacy of the brief CBT-I were suggested.

Is 4-month-old infants' night waking affected by mothers' responses to them? A cross-sectional survey in Japan.

OBJECTIVE: To investigate the association between night waking frequency in 3- to 4-month-old infants and mothers' response to them. DESIGN: Cross-sectional survey. SAMPLE: We examined 663 mothers of infants aged 3-5 months who attended regular health checks for 4 months at 7 public health centres in Japan between September 2006 and March 2007. MEASUREMENTS: Mother-reported questionnaires were used, measuring the frequency of infants' night waking and four types of responses by mothers. Using multiple regression, the association between number of wakings and each response was evaluated adjusting for covariates, that is mother's (e.g. feelings of worry and bed-sharing) and infant's (e.g. age and sex) demographic variables. RESULTS: The number of wakings was related to "immediately feeding and/or checking diapers" (ß = 0.16, p = .002).This response to infants' night waking may be associated with night waking frequency. CONCLUSION: Modifying caregiver responses to infants' night waking by reducing immediate feeding or diaper checks could improve infants' night waking frequency.

Comparison of three suture-bridge techniques for large or massive rotator cuff tear with delamination.

INTRODUCTION: Rotator cuff tear with delamination is considered a risk factor for postoperative retear. The purpose of this study was to compare clinical outcomes between three repair procedures for large or massive rotator cuff tears with delamination: conventional en masse suture bridge (EMSB), double-layer suture bridge (DLSB), and the combination of DLSB with modified Debyere-Patte (DLSB + DP). METHODS: 53 shoulders of 52 patients who had massive rotator cuff tears with delamination were categorized into three groups: EMSB (18 shoulders), DLSB (24 shoulders), and DLSB + DP (11 shoulders). The mean postoperative follow-up period was 34.6 months. Pre- and postoperative evaluations included a range of motion (ROM), Constant scores, global fatty degeneration (GFDI), and tendon integrity according to Sugaya's classification by magnetic resonance images (MRI). RESULTS: In all groups, ROM significantly improved after the procedures. Mean constant scores significantly improved: from 45.5 to 77.4 after EMSB, from 45.5 to 87.6 after DLSB, and from 46.3 to 88.0 after DLSB + DP. Significant differences were noted in postoperative Constant scores (p = 0.018: DLSB vs. EMSB, and p = 0.045: DLSB + DP vs. EMSB). The Constant pain scores were better for DLSB + DP than for EMSB (p = 0.012). Global fatty degeneration index (GFDI) with DLSB + DP was significantly higher than that for either EMSB or DLSB, indicating significant preoperative fatty degeneration for DLSB + DP. Retear occurred in 27.8% of the EMSB group, 12.5% of the DLSB group, and 9.1% of the DLSB + DP group. DISCUSSION: Comparisons of the three groups demonstrated that DLSB and DLSB + DP achieved better clinical outcomes than EMSB for the repair of large or massive rotator cuff tears. DLSB + DP is useful for massive rotator cuff tears with severe fatty degeneration or for cases where the presence of excessive tension is anticipated when repairing the torn cuff.

Association of mental health help-seeking with mental health-related knowledge and stigma in Japan Rugby Top League players.

BACKGROUND: Globally increasing clinical and research interests are driving a movement to promote understanding and practice of mental health in elite athletes. However, few studies have yet addressed this issue. This study aims to describe the association of the intention to seek help with mental health knowledge and stigma and the severity of depressive symptoms in Japan Rugby Top League players. METHODS: As a target population, we studied 233 Japan Rugby Top League male players (25-29 years = 123 [52.8%]), who were born in Japan, using a cross-sectional design. Surveys were conducted using anonymous, web-based self-administered questionnaires. Structural equation modelling was performed to evaluate the hypothesis of an interrelationship between mental health knowledge, stigma, and severity of depressive symptoms as factors influencing the intention to seek help. RESULTS: Players with more severe depressive symptoms were more reluctant to seek help from others (ß = - 0.20, p = 0.03). Players with greater knowledge about mental health tended to have less stigma toward others with mental health problems (ß = 0.13, p = 0.049), but tended not to seek help with their own mental health problems. CONCLUSIONS: Rugby players in need of mental health support, even with greater knowledge, tend not to seek help from others, while having less stigma toward people with mental health problems. Rugby players might require approaches other than a knowledge-based educational approach to encourage them to seek help.

Recurrent hemarthrosis after total knee arthroplasty in rheumatoid arthritis successfully treated with selective embolization: A case report.

Recurrent hemarthrosis after total knee arthroplasty is a rare complication. This usually occurs in osteoarthritis, but is relatively rare in rheumatoid arthritis. This is a report of recurrent hemarthrosis after total knee arthroplasty in a rheumatoid arthritis patient. An 85-year-old woman with rheumatoid arthritis had received total knee arthroplasty without acute complications. At 6 months after surgery, the first hemarthrosis occurred and an initial conservative treatment failed. Contrast computed tomography showed prominent synovial enhancement in the superior lateral suprapatellar pouch. Selective catheterization revealed an abnormal hyperemic blush supplied from the branches of the superior lateral genicular artery. After embolization with N-butyl-2-cyanoacrylate, abnormal staining of the synovium diminished and knee swelling and pain disappeared without complications. Selective embolization is favorable for successful treatment of recurrent hemarthrosis after total knee arthroplasty in patients with rheumatoid arthritis.

Roles of Trait Mindfulness in Behavioral Activation Mechanism for Patients With Major Depressive Disorder.

Behavioral activation and mindfulness have both been shown to engender improvement of functional impairment in patients with major depressive disorder. In behavioral activation, the practice of engaging with the direct experience of the present moment is central, especially when targeting avoidance. Consequently, mindfulness affects changes of avoidance in behavioral activation. This study was designed to assess exploratory relations among trait mindfulness, avoidance, and functional impairment in behavioral activation mechanism for depression. For 1042 participants with depression only or for depression with anxiety disorders, we used structural equation modeling to examine relations among trait mindfulness, avoidance, and functional impairment. Trait mindfulness non-reactivity, non-judging, and acting with awareness had a direct negative effect on avoidance. Trait mindfulness non-reactivity, trait non-judging, and trait acting with awareness had indirect negative effects on functional impairment. Results show that each trait mindfulness facet exhibited a distinct pattern of relations with avoidance and impairment.

Expressive suppression of emotion is a moderator of anxiety in a unified protocol for transdiagnostic treatment of anxiety and depressive disorders: A secondary analysis.

BACKGROUND: Expressive suppression (ES) of emotion is considered a moderator that reduces the efficacy of cognitive behavioural therapy (CBT); however, whether and how ES moderates the efficacy of the unified protocol for transdiagnostic treatment of emotional disorders (UP), a version of CBT targeting aversive/avoidant responses to emotions, including ES, remain unclear. We investigated whether and how emotion regulation, especially ES, moderates UP efficacy for anxiety symptoms in patients with anxiety and depressive disorders. METHODS: We conducted a secondary analysis of data from a previous trial. Seventeen patients with anxiety and/or depressive disorders were included. Changes (slope estimates) in the Structured Interview Guide for the Hamilton Anxiety Rating Scale from pre-treatment to post-treatment were measured using a latent growth curve model with empirical Bayesian estimation. Pre-treatment ES, cognitive reappraisal, and depressive symptoms were used as slope factor predictors. RESULTS: Only pre-treatment ES significantly predicted the slope in the latent growth curve model (estimate value = 0.45; standard deviation = 0.21; 95% credible interval = 0.03-0.87, one-tailed p-value = 0.004), and an inverse correlation between pre-treatment ES levels and improvement magnitude of anxiety symptoms was demonstrated. LIMITATIONS: Because the data were obtained from a single-arm trial, this study did not have controls, and most participants received pharmacotherapy in addition to UP. Therefore, generalisability of the present findings might be compromised. CONCLUSIONS: Low ES before UP was an effective predictor of greater improvement in anxiety symptoms after UP. The findings suggest that interventions intended to improve ES may improve UP efficacy.

The effect of night shift work on the expression of clock genes in beard hair follicle cells.

OBJECTIVE: Shift work encompasses a broad range of work time arrangements. However, how shift work affects the circadian expression of clock genes remains to be explored. The objective of this study was to evaluate the pattern of clock gene expression in shift workers in the field. METHODS: We examined clock gene expression in Japanese men who work: (1) one night shift followed by a day off (caregivers: nurses and doctors; the one-night group); (2) three or more consecutive night shifts (factory workers; the consecutive-night group); or (3) daytime only (the daytime group), using beard follicle samples. The expression of Period3, Nuclear Receptor Subfamily 1 Group D Member 1 (Nr1d1), and Nuclear Receptor Subfamily 1 Group D Member 2 (Nr1d2) was examined by real-time polymerase chain reaction. RESULTS: Period3 expression in the daytime and one-night groups together with Nr1d2 expression in the one-night group fitted a 24-h-period cosine curve better than in the consecutive-night group (p = 0.004, 0.012, and 0.001, respectively). The level of overall Period3 gene expression, calibrated with that of 18S-rRNA, was decreased in the consecutive-night group compared with that in the daytime group (p = 0.006). The patterns of Period3 and Nr1d2 expression in the daytime and one-night groups were more coherent than those in the consecutive-night group. CONCLUSIONS: These results suggest that night shift work affects the rhythms and levels of circadian Period3 and Nr1d2 expression dependent on the shift schedule or type of the shift; however, there is substantial variation between individuals.

Effectiveness of cognitive behavioral therapy for pharmacotherapy-resistant chronic insomnia: a multi-center randomized controlled trial in Japan.

OBJECTIVES: An insomnia characterized by nighttime symptoms and daytime impairment is common. GABA-A receptor agonist (GABAA-RA) treatment is often used, but long-term use is controversial due to the poor risk-benefit ratio resulting from drug dependence and potential cognitive impairment. This study evaluated the effectiveness of add-on cognitive behavioral therapy for insomnia (CBT-I) and GABAA-RA dose-tapering in patients with primary insomnia resistant to pharmacotherapy. METHODS: This randomized, multicenter, two-arm, parallel-group study compared CBT-I and treatment as usual (TAU) in patients with persistent primary insomnia despite GABAA-RA treatment. Screening was based on sleep diary entries, with ≥31-min sleep latency or wake after sleep onset, occurring ≥3 times in a week and total score of ≥8 on the Insomnia Severity Index (ISI). Primary outcome measures were severity of insomnia and GABAA-RA tapering rate. RESULTS: A total of 51 patients were randomized and 49 patients were analyzed (CBT-I; n = 23, TAU; n = 26). A mixed-effects repeated-measures model revealed significant improvement in insomnia symptoms (ISI score) during the post-intervention (PI) and follow-up (FU) periods in the CBT-I versus the TAU group (PI; 10.91 vs. 14.33, p < 0.05, FU; 10.17 vs. 14.34, p < 0.01). GABAA-RA tapering rate approached 30% during follow-up in the CBT-I group; no significant intergroup difference was observed. CONCLUSION: Add-on CBT-I improved insomnia symptoms that were unresponsive to GABAA-RA therapy. No effect on tapering rate was observed in this study. CBT-I may promote dose reduction by optimizing the protocol and duration of treatment. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000014297.