Quality of life and subjective symptom impact in Japanese patients with myotonic dystrophy type 1.

BACKGROUND: Although functional impairment in patients with myotonic dystrophy is an important determinant of the quality of life (QoL), patients' subjective evaluation of their symptoms may also affect their QoL. The aim of this study was to investigate the association between subjective symptom impact and the QoL of patients with myotonic dystrophy, after controlling for functional impairment. METHODS: Eligible patients with myotonic dystrophy type 1 (DM1) were recruited from four hospitals in Japan. The subjective symptom impact of four symptoms (muscle weakness, fatigue, pain, and myotonia) and overall QoL were evaluated using the Individualized Neuromuscular Quality of Life (INQoL) questionnaire. Functional impairment was assessed using the modified Rankin Scale. RESULTS: Seventy-seven patients with DM1 were included in this study. Overall QoL was significantly associated with subjective symptom impact of muscular weakness, fatigue, pain, myotonia, swallowing difficulty, and droopy eyelids. In the regression models, disease duration (beta = 0.11) and moderate to severe functional impairment (beta = 0.33) explained a significant part of the overall QoL. Furthermore, muscular weakness, fatigue, and myotonia significantly explained additional variance of the overall QoL (beta = 0.17-0.43). CONCLUSIONS: Subjective symptom impact and functional impairment are independent features influencing the QoL of Japanese patients with DM1.

The myotonic dystrophy health index: Japanese adaption and validity testing.

INTRODUCTION: The Myotonic Dystrophy Health Index (MDHI) is a disease-specific, patient-reported outcome measure. The objective of this study was to translate, evaluate, and validate a Japanese version of the MDHI (MDHI-J). METHODS: We utilized forward and backward translations and qualitative interviews with 11 myotonic dystrophy type 1 (DM1) participants. We subsequently tested the internal consistency, test-retest reliability, concurrent validity against muscle strength, and 3 quality-of-life measures, and the known-groups validity of the MDHI-J with 60 adult patients. RESULTS: The MDHI-J was found to be culturally appropriate, comprehensive, and clinically relevant. The MDHI-J and its subscales had high internal consistency (mean Cronbach's α = 0.91), test-retest reliability (intraclass coefficient 0.678-0.915), and concurrent validity (Spearman's ρ - 0.869 to 0.904). MDHI-J scores were strongly associated with employment, duration of symptoms, and modified Rankin Scale. DISCUSSION: The MDHI-J is suitable and valid to measure patient-reported disease burden in adult Japanese patients with DM1. Muscle Nerve 59:577-577, 2019.

Validation of The Individualized Neuromuscular Quality of Life in Japanese patients with myotonic dystrophy.

INTRODUCTION: The Individualized Neuromuscular Quality of Life (INQoL) is used to measure the quality of life (QoL) of patients with neuromuscular disease. We conducted this study to translate and validate the Japanese version of the INQoL in patients with myotonic dystrophy. METHODS: Forward and backward translation, patient testing, and psychometric validation were performed. We used the 36-Item Short Form Health Survey (SF-36) and the modified Rankin scale for concurrent validation. RESULTS: The Japanese INQoL was administered to 90 adult patients. The coefficients for internal consistency and test-retest reliability were adequately high in most domains (Cronbach α 0.88-0.96 and intraclass coefficient 0.64-0.99). INQoL domains were moderately to strongly associated with relevant SF-36 subscales (Spearman's ρ -0.23 to -0.74). Symptom severity, disease duration, employment status, and use of a ventilator influenced overall QoL. DISCUSSION: The INQoL is a reliable and validated measure of QoL for Japanese patients with myotonic dystrophy. Muscle Nerve, 2018.

Cognitive impairment and quality of life in patients with myotonic dystrophy type 1.

INTRODUCTION: This study sought to clarify whether specific cognitive abilities are impaired in patients with myotonic dystrophy type 1 (DM1) as well as to investigate the relationships among quality of life (QoL), cognitive function, and psychological factors. METHODS: Sixty patients with DM1 were evaluated on cognitive functioning (abstract reasoning, attention/working memory, executive function, processing speed, and visuoconstructive ability), apathy, depression, excessive daytime sleepiness, fatigue, and QoL. QoL was assessed by 2 domains of the Muscular Dystrophy Quality of Life Scale (Psychosocial Relationships and Physical Functioning and Health). RESULTS: More than half of the patients exhibited cognitive impairment in attention/working memory, executive function, processing speed, and visuoconstructive ability. The Psychosocial Relationships factor was associated with processing speed, attention/working memory, and apathy, whereas depression and fatigue were associated with 2 QoL domains. DISCUSSION: Our study identified specific cognitive impairments in DM1. Specific cognitive functions and psychological factors may be potential contributors to QoL. Muscle Nerve 57: 742-748, 2018.

Autism spectrum disorders are prevalent among patients with dystrophinopathies.

Recent studies have reported a higher prevalence of autism spectrum disorders among patients with dystrophinopathies. The aim of this study was to investigate the prevalence of autism spectrum disorder (ASD) among those with dystrophinopathies. The possible role of dystrophin isoforms in patients was also explored. Fifty-six patients recruited from Toneyama National Hospital were included in this study (mean age = 12.9 years, SD = 5.2 years). Autistic symptoms were evaluated using the Pervasive Developmental Disorders/Autism Spectrum Disorders Rating Scale (PARS), a clinician rating scale. Eleven patients (19.6%; 95% confidence interval 10.2-32.4) met the criteria for ASD based on their PARS scores. Patients were separated into two groups based on the cumulative loss of dystrophin isoforms predicted from the mutation location. The prevalence of ASD was examined between these groups. Infantile and current autistic symptoms did not differ between the groups, except on one subscale of the PARS. This study revealed that there was a high prevalence of ASD in patients with dystrophinopathies.

Genetic Overlap between General Cognitive Function and Schizophrenia: A Review of Cognitive GWASs.

General cognitive (intelligence) function is substantially heritable, and is a major determinant of economic and health-related life outcomes. Cognitive impairments and intelligence decline are core features of schizophrenia which are evident before the onset of the illness. Genetic overlaps between cognitive impairments and the vulnerability for the illness have been suggested. Here, we review the literature on recent large-scale genome-wide association studies (GWASs) of general cognitive function and correlations between cognitive function and genetic susceptibility to schizophrenia. In the last decade, large-scale GWASs (n > 30,000) of general cognitive function and schizophrenia have demonstrated that substantial proportions of the heritability of the cognitive function and schizophrenia are explained by a polygenic component consisting of many common genetic variants with small effects. To date, GWASs have identified more than 100 loci linked to general cognitive function and 108 loci linked to schizophrenia. These genetic variants are mostly intronic or intergenic. Genes identified around these genetic variants are densely expressed in brain tissues. Schizophrenia-related genetic risks are consistently correlated with lower general cognitive function (rg = -0.20) and higher educational attainment (rg = 0.08). Cognitive functions are associated with many of the socioeconomic and health-related outcomes. Current treatment strategies largely fail to improve cognitive impairments of schizophrenia. Therefore, further study is needed to understand the molecular mechanisms underlying both cognition and schizophrenia.

Estimated cognitive decline in patients with schizophrenia: A multicenter study.

AIM: Studies have reported that cognitive decline occurs after the onset of schizophrenia despite heterogeneity in cognitive function among patients. The aim of this study was to investigate the degree of estimated cognitive decline in patients with schizophrenia by comparing estimated premorbid intellectual functioning and current intellectual functioning. METHODS: A total of 446 patients with schizophrenia (228 male, 218 female), consisting of three sample sets obtained from 11 psychiatric facilities, and 686 healthy controls participated in this study. The Wechsler Adult Intelligence Scale-III (WAIS-III) was used to measure the participants' current full-scale IQ (FSIQ). The premorbid IQ was estimated using the Japanese Adult Reading Test-25. Estimated cognitive decline (difference score) was defined as the difference between the estimated premorbid IQ and the current FSIQ. RESULTS: Patients with schizophrenia showed greater estimated cognitive decline, a lower FSIQ, and a lower premorbid IQ compared with the healthy controls. The mean difference score, FSIQ, and estimated premorbid IQ were -16.3, 84.2, and 100.5, respectively, in patients with schizophrenia. Furthermore, 39.7% of the patients had a difference score of 20 points or greater decline. A discriminant analysis showed that the difference score accurately predicted 81.6% of the patients and healthy controls. CONCLUSION: These results show the distribution of difference score in patients with schizophrenia. These findings may contribute to assessing the severity of estimated cognitive decline and identifying patients with schizophrenia who suffer from cognitive decline.

Whole-exome sequencing and neurite outgrowth analysis in autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex group of clinically heterogeneous neurodevelopmental disorders with unclear etiology and pathogenesis. Genetic studies have identified numerous candidate genetic variants, including de novo mutated ASD-associated genes; however, the function of these de novo mutated genes remains unclear despite extensive bioinformatics resources. Accordingly, it is not easy to assign priorities to numerous candidate ASD-associated genes for further biological analysis. Here we developed a convenient system for identifying an experimental evidence-based annotation of candidate ASD-associated genes. We performed trio-based whole-exome sequencing in 30 sporadic cases of ASD and identified 37 genes with de novo single-nucleotide variations (SNVs). Among them, 5 of those 37 genes, POGZ, PLEKHA4, PCNX, PRKD2 and HERC1, have been previously reported as genes with de novo SNVs in ASD; and consultation with in silico databases showed that only HERC1 might be involved in neural function. To examine whether the identified gene products are involved in neural functions, we performed small hairpin RNA-based assays using neuroblastoma cell lines to assess neurite development. Knockdown of 8 out of the 14 examined genes significantly decreased neurite development (P<0.05, one-way analysis of variance), which was significantly higher than the number expected from gene ontology databases (P=0.010, Fisher's exact test). Our screening system may be valuable for identifying the neural functions of candidate ASD-associated genes for further analysis and a substantial portion of these genes with de novo SNVs might have roles in neuronal systems, although further detailed analysis might eliminate false positive genes from identified candidate ASD genes.

Postural Sway and Clinical Characteristics in Patients with Psychotic Disorders: A Review.

Postural instability is a feature that is frequently observed in patients with psychotic disorders. Previous studies applied rating scales or behavioral test to assess postural instabilities. Recently, a pressure-sensitive platform has been used to study detailed characteristics of postural sway and regulation. However, characteristics of posturography indices in patients with psychotic disorders have not been well documented. To integrate the findings from studies that assessed postural sway using posturography in patients with psychotic disorders, we conducted a systematic review. Following database literature search, we identified nine eligible articles. Assessment conditions and indices of postural stability varied between studies. Postural control was associated with negative and general psychopathology in two studies. Two studies reported associations between posturographic variables and medication dose, whereas four studies reported no associations. This review identified the need to develop standards to assess postural sway in patients with psychiatric disorders. Further studies need to report associations between postural sway and confounding factors.

Performance on the Wechsler Adult Intelligence Scale-III in Japanese patients with schizophrenia.

AIM: Patients with schizophrenia have been reported to perform worse than non-schizophrenic populations on neuropsychological tests, which may be affected by cultural factors. The aim of this study was to examine the performance of a sizable number of patients with schizophrenia on the Japanese version of the Wechsler Adult Intelligence Scale-III (WAIS-III) compared with healthy controls. METHODS: Performance on the WAIS-III was evaluated in 157 Japanese patients with schizophrenia and in 264 healthy control subjects. RESULTS: All IQ scores and four indices from the WAIS-III were impaired for patients with schizophrenia compared with healthy controls. Processing Speed was markedly disturbed, approximately 2 SD below that of the healthy control group. Among the 13 subtests, Comprehension (z = -1.70, d = 1.55), Digit Symbol Coding (z = -1.84, d = 1.88), and Symbol Search (z = -1.85, d = 1.77) were profoundly impaired relative to the healthy controls. CONCLUSION: These results indicate that the pattern and degree of impairment, as evaluated by the WAIS-III, in Japanese patients are similar to those previously reported in English-speaking patients and that the deficits of some neuropsychological domains relevant to functional outcomes are universally characteristic of schizophrenia.

Facioscapulohumeral muscular dystrophy Health Index: Japanese translation and validation study.

PURPOSE: The Facioscapulohumeral Muscular Dystrophy Health Index (FSHD-HI) is a patient-reported outcome measure developed for patients with FSHD. This study aimed to translate the FSHD-HI into Japanese (FSHD-HI-J), evaluate cultural adaptation, and examine its psychometric properties. MATERIALS AND METHODS: We created two forward translations, integrated them into a single Japanese version, and evaluated the back-translated version of the FSHD-HI. After finalizing the translation and cultural adaptation, we conducted a survey of 66 patients with FSHD to examine the reliability and validity of the FSHD-HI-J. For psychometric evaluations, we used Cronbach's alpha to assess internal consistency, the intraclass correlation coefficient (ICC) for test-retest reliability, and assessed validity based on the associations between FSHD-HI-J, clinical variables, and quality of life measures. RESULTS: The FSHD-HI-J was found to be clinically relevant, indicating high internal consistency and test-retest reliability (ICC = 0.92 [95% confidence interval: 0.86-0.95] for the total score), as well as significant associations with clinical variables (D4Z4 repeats and functional impairment) and other quality of life measures (|rho| = 0.25-0.73). CONCLUSIONS: The FSHD-HI-J is a valid and reliable patient-reported outcome measure for Japanese patients with FSHD. This validated, disease-specific patient-reported outcome is essential for future clinical practice and clinical trials.

Facioscapulohumeral muscular dystrophy (FSHD) affects not only a patient's physical abilities but also their social activities, participation, and overall quality of life.The FSHD-Health Index (FSHD-HI) is an instrument developed as a disease-specific patient-reported outcome measure to evaluate the burden experienced by patients.The Japanese version of the FSHD-HI has been established as a reliable and validated measure for Japanese-speaking patients with FSHD.The Japanese version of the FSHD-HI can serve as a useful instrument for evaluating the effectiveness of interventions in future trials.

[Survey for assessing how Duchenne muscular dystrophy is explained to children with the disorder].

OBJECTIVE: There are many difficulties in disclosing Duchenne muscular dystrophy (DMD) to children with the disorder. The purpose of this study was to assess the explanation of DMD given to affected children by child neurologist. METHODS: The questionnaire was mailed to board-certified child neurologists of the Japanese Society of Child Neurology. The questionnaire consisted of questions on how physicians explained the condition to children with DMD (their patterns of explanation) and their attitude towards the children while explaining the disease. RESULTS: We received 311 replies. The contents of physicians' explanations were categorized and correspondence analysis revealed medical support" (explanation about the symptoms, prognosis, medical responses) and "humanistic support" (telling purpose in life, patient group introduction). Parents' understanding of the disease, acceptance, and trust relationships were considered important factors for disease explanation by the physicians. Physicians agreed with the need of clinical psychologist and other psychological professionals when they tell their diagnosis, and agreed with telling the diagnosis to a DMD child reached a certain age. CONCLUSIONS: It was revealed that physicians' explanation were largely categorized into two groups, and the important factors for disease explanation and physicians' attitudes towards disclosure of the diagnosis. This information will help in explaining the disease to children with DMD.

Disinfection behavior for COVID-19 in individuals with Down syndrome and caregivers' distress in Japan: a cross-sectional retrospective study.

The COVID-19 outbreak affected the daily lives of individuals with Down syndrome, who were considered to have a higher risk of severe infection. While several studies have reported mental health issues in children and/or parents in the general population, no study has focused on people with Down syndrome and their caregivers. This study investigated the disinfection behaviors of individuals with Down syndrome and their caregivers' stress. A cross-sectional retrospective survey was conducted in October 2020. Caregivers of children and adults with Down syndrome were administered questionnaires including measures for practiced disinfection behavior in children, caregiver's child-related stress, and psychological distress. About half of the respondents' children practiced hand hygiene and mask-wearing behaviors, while physical distancing was performed less frequently. Habitual practices in physical distancing are affected by intellectual function. Logistic regression showed that caregivers' stress was associated with the irritability of individuals with the disorder (adjusted odds ratio [OR] = 8.44, 95% confidence interval [CI] 1.69-42.09) and the burden of infection-prevention behaviors for people with Down syndrome (adjusted OR = 4.26, 95% CI 1.88-9.65). This study showed the characteristics of disinfection behaviors in individuals with Down syndrome and associated factors for serious caregiver stress.

Dealing with food selectivity and mealtime behaviour in school-children with autism: a qualitative study of special education teachers in Japan.

Food selectivity in children with autism spectrum disorder (ASD) is a serious issue in special needs schools, and special education teachers face various difficulties in their management of the problem. The aim of this study is to investigate the difficulties that special education teachers face in managing food selectivity in children with ASD. Data were obtained from 12 special education teachers in 2018 via semi-structured in-depth interviews. Thematic analysis was used to identify key conceptions of the participants' experiences, while qualitative analysis of the interview data revealed three major themes. Their personal and professional thoughts and hopes regarding eating habits in children, feelings of uncertainty about their practice, and their interactions with the children and their parents were the key factors behind the difficulties they experience as special education teachers. The findings improve our understanding of the challenges experienced by teachers managing food selectivity in children with ASD. A different conceptualisation of the problem may lead to difficulties in collaboration among the people who are tasked with solving the problem.

Evaluating the psychometric properties of the fatigue severity scale using item response theory.

BACKGROUND: Fatigue is a common daily experience and a symptom of various disorders. While scholars have discussed the use of the Fatigue Severity Scale (FSS) using item response theory (IRT), the characteristics of the Japanese version are not yet examined. This study evaluated the psychometric properties of the FSS using IRT and assessed its reliability and concurrent validity with a general sample in Japan. METHODS AND MEASURES: A total of 1,007 Japanese individuals participated in an online survey, with 692 of them providing valid data. Of these, 125 participants partook in a re-test after approximately 18 days and had their longitudinal data analyzed. In addition, the graded response model (GRM) was used to assess the FSS items' characteristics. RESULTS: The GRM's results recommended using seven items and a 6-point scale. The FSS's reliability was acceptable. Furthermore, the validity was adequate from the results of correlation and regression analyses. The synchronous effects models demonstrated that the Multidimensional Fatigue Inventory (MFI) enhanced depression, and depression enhanced FSS. CONCLUSION: This study suggested that the Japanese version of the FSS should be a 7-item scale with a 6-point response scale. Further investigations may reveal the different aspects of fatigue assessed by the analyzed fatigue measures.

Interactions between special education teachers and children with chronic complex conditions: A qualitative study.

Background: The number of children with complex medical conditions has increased in recent decades. In this context, a complex chronic condition is characterized by multiple morbidities that require intensive or continuous health care according to the level of severity. Given their various health conditions, it is challenging to provide special education to these children, but there is still insufficient evidence regarding the practical experiences of educators. The aim of this study was to investigate special education teacher's perceptions, experiences, and challenges while developing interpersonal relationships and communicating with children who have complex chronic conditions. Methods: We recruited and interviewed 21 special education school teachers in Japan. The transcripts of the interviews were analyzed using thematic analysis. Results: Our analysis revealed four themes, including "searching for the meaning," "complex chronic conditions as a difficult reality," "widening experience for the future," and "priority for interacting with children." These themes reflect the perceptions, experiences, and challenges of the special education teachers. Conclusions: In cases where children have severe functional limitations, it is more challenging to understand child-teacher interactions. This highlights the importance of searching for meaning in educational practices used among children with complex chronic conditions. Our findings may provide helpful insight into the experiences and challenges faced by special educators who engage with these children.

Longitudinal Changes in Neuropsychological Functioning in Japanese Patients with Myotonic Dystrophy Type 1: A Five Year Follow-Up Study.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a form of muscular dystrophy that causes various symptoms, including those of the central nervous system. Some studies have reported cognitive decline in patients with DM1, although the available evidence is limited. OBJECTIVE: This study aimed to describe longitudinal differences in neuropsychological function in patients with DM1. METHODS: A total of 66 Japanese adult patients with DM1 were investigated using a neuropsychological battery to assess several cognitive domains, including memory, processing speed, and executive function. The patients underwent neuropsychological evaluation approximately five years after baseline (Times 1 and 2). RESULTS: Thirty-eight patients underwent a second neuropsychological evaluation. The participants in the Time 2 evaluation were younger than those who did not participate in Time 2. Patients showed a decline in the Mini-Mental State Examination, Trail Making Test (TMT), Block Design, and Symbol Digit Modalities Test at Time 2 (P < 0.05). Age at Time 1 was associated with a decline in TMT-A and TMT-B scores (rho = 0.57 and 0.45, respectively). CONCLUSION: These results suggest a cognitive decline in patients with DM1 and warrant further investigation into the possible effects of age-related changes.

Dohsa-hou for unexplained regression in Down syndrome in a 19-year-old man: A case report.

Unexplained regression in Down syndrome (URDS) has become a significant issue in clinical practice and research. This report illustrates the case of a patient with URDS treated with psychological treatment using Dohsa-hou, in addition to medication. Although psychological treatment may be helpful, monitoring potential risks of acute aggression is necessary.

Associations between anger and chronic primary pain: a systematic review and meta-analysis.

OBJECTIVES: Anger is a negative emotion characterized by antagonism toward someone or something, is rooted in an appraisal or attribution of wrongdoing, and is accompanied by an action tendency to undo the wrongdoing. Anger is prevalent in individuals with chronic pain, especially those with chronic primary pain. The associations between anger and pain-related outcomes (e.g., pain intensity, disability) have been examined in previous studies. However, to our knowledge, no systematic review or meta-analysis has summarized the findings of anger-pain associations through a focus on chronic primary pain. Hence, we sought to summarize the findings on the associations of anger-related variables with pain and disability in individuals with chronic primary pain. METHODS: All studies reporting at least one association between anger-related variables and the two pain-related outcomes in individuals with chronic primary pain were eligible. We searched electronic databases using keywords relevant to anger and chronic primary pain. Multiple reviewers independently screened for study eligibility, data extraction, and methodological quality assessment. RESULTS: Thirty-eight studies were included in this systematic review, of which 20 provided data for meta-analyses (2,682 participants with chronic primary pain). Of the included studies, 68.4% had a medium methodological quality. Evidence showed mixed results in the qualitative synthesis. Most anger-related variables had significant positive pooled correlations with small to moderate effect sizes for pain and disability. CONCLUSIONS: Through a comprehensive search, we identified several key anger-related variables associated with pain-related outcomes. In particular, associations with perceived injustice were substantial.

Comparison of the effectiveness of cognitive behavioral therapy for insomnia, cognitive behavioral therapy for pain, and hybrid cognitive behavioral therapy for insomnia and pain in individuals with comorbid insomnia and chronic pain: A systematic review and network meta-analysis.

Considering that insomnia and chronic pain are often comorbid, we aimed to compare the effectiveness of cognitive behavioral therapy for insomnia (CBT-I), cognitive behavioral therapy for pain (CBT-P), and cognitive behavioral therapy for insomnia and pain (CBT-IP) in individuals with comorbid insomnia and chronic pain. We used PubMed, PsycINFO, CENTRAL, and Web of Science for our literature search. The outcomes included sleep, pain, disability, and depression at post-treatment and follow-up (3-12 months). Sixteen randomized controlled trials with 1094 participants were included. In the Bayesian network meta-analysis, CBT-I [standard mean difference (SMD) = -0.99, 95% credible interval (CrI) = -1.50 to -0.54] and CBT-IP (SMD = -0.70, 95% CrI = -1.60 to -0.08) were significantly more effective than the control for sleep at post-treatment. Additionally, CBT-I was significantly more effective than the control for pain, disability, and depression at post-treatment and sleep at follow-up. However, there were no significant differences in effectiveness between CBT-P and the control for any outcomes. Thus, CBT-I might be the most effective treatment option for individuals with comorbid insomnia and chronic pain. However, given the small sample sizes and high risk of bias of the included studies, these results must be interpreted with caution.