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Kabuki syndrome (KS) is a rare neuro-developmental disorder caused by variants in genes of histone modification, including KMT2D and KDM6A . This review assesses our current understanding of KS, which was originally named Niikawa-Kuroki syndrome, and aims to guide surveillance and medical care of affected individuals as well as identify gaps in knowledge and unmet patient needs. Ovid MEDLINE and EMBASE databases were searched from 1981 to 2021 to identify reports related to genotype and systems-based phenotype characterization of KS. A total of 2418 articles were retrieved, and 152 were included in this review, representing a total of 1369 individuals with KS. Genotype, phenotype, and the developmental and behavioral profile of KS are reviewed. There is a continuous clinical phenotype spectrum associated with KS with notable variability between affected individuals and an emerging genotype-phenotype correlation. The observed clinical variability may be attributable to differences in genotypes and/or unknown genetic and epigenetic factors. Clinical management is symptom oriented, fragmented, and lacks established clinical care standards. Additional research should focus on enhancing understanding of the burden of illness, the impact on quality of life, the adult phenotype, life expectancy and development of standard-of-care guidelines.

The current analysis compares changes in pain with changes in function and health status in individuals with painful diabetic peripheral neuropathy (DPN). The post hoc analysis is based on a 12week, multinational, placebo-controlled trial of pregabalin in which 401 patients were randomized to treatment. Study measures included the Brief Pain Inventory short-form (BPI-sf), EQ-5D and other patient-reported outcomes. Cutpoints were derived on the BPI-sf 0-10 average pain numeric rating scale [NRS] to classify pain grades of "mild" (1-3), moderate (4-6) and severe (7-10), adjusting for geographical regions where data were collected. Two different metrics were used to classify the importance of change in pain severity from baseline to 12weeks: changes in pain severity grades (defined by cutpoint categories) and percent reduction in the NRS (categories ranging from 0-9% to 50%). An improvement in one pain grade or a 30% reduction in the NRS served as determinants of a clinically important difference. Patients with a one-grade reduction in pain severity, either from "severe-to-moderate" or "moderate-to-mild," had a 3-point improvement the BPI-sf Pain Interference Index (PII; a composite measure of function); a reduction from "severe-to-mild" pain corresponded to a 6-point improvement in the PII. Similarly, a reduction in the NRS of 30% and 50% corresponded to a 3-point and a 5-point improvement in the PII, respectively. Changes in pain were also associated with changes in health status. Results suggest that patients whose pain is not reduced to a mild level of severity can still experience clinically important changes in function and health status., (Copyright 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Although the construct of "a symptom-free day" has been widely applied in asthma and gastric reflux disease, there is no analogous concept in the field of pain management. This study represents the initial development of a "day of acceptable or manageable pain control," a construct which reflects patients' daily strategic use of pain medication in order to allow the accomplishment of desired activities while minimizing side effects. Focus group methodology was used to extract patient-generated themes of "an acceptable day of pain control." Fifty-three outpatients with persistent moderate to severe average pain intensity due to osteoarthritis (n=18), metastatic cancer (n=15), and low back pain (n=20) participated. Participants preferred the term "manageable" or "tolerable" to "acceptable." Thematic analysis revealed components of a manageable/tolerable day of pain control as including: 1) taking the edge off the pain, 2) performing valued activities; 3) relief from dysphoria and irritability; 4) reduced medication side effects; 5) feeling well enough to socialize. Additional cancer-specific themes included relief from fatigue and ability to have a positive day when one's future days were perceived as being limited. The set of themes is presented and their relevance for developing a measure of "a manageable day of pain control" discussed. Study findings identify a novel construct that can inform development of an outcome for evaluating the effectiveness of different pharmacotherapies for pain management.

Introduction: Kabuki syndrome is a rare congenital condition characterized clinically by unique facial features, abnormalities in the skeleton, finger pad abnormalities, and developmental delays, as well as a range of other health issues. Existing research lacks information on the daily burden of living with Kabuki syndrome.Methods: A survey collected caregiver- and patient-reported data about the experience of living with Kabuki syndrome in order to better understand its presentation and effect on patients and their psychosocial well-being.Results: A total of 68 participants (n = 57 caregivers and n = 11 adolescents) were recruited from the USA and Canada. Caregiver survey participants reported developmental delays and lower IQ in individuals with Kabuki syndrome compared to the general population, as well as difficulty with cognitive-related tasks, need for educational accommodations, and difficulty with particular school subjects and with daily tasks. Additionally, participants reported significant emotional, social, and communication-related impacts of Kabuki syndrome. Adolescent data largely corroborated the information collected from caregivers, with the exception of adolescents reporting the emotional and social impacts as occurring less frequently.Conclusions: Kabuki syndrome is a multidimensional disease which has substantial negative effects on physical, mental, emotional, and social aspects of health-related quality of life. This research adds to the limited existing body of literature on the clinical presentation of Kabuki syndrome and provides a novel perspective into the caregiver and adolescent perception of the burden of Kabuki syndrome. [ABSTRACT FROM AUTHOR]

Background and objective: The Penn Facial Pain Scale (Penn-FPS) was originally developed as a supplemental module to the Brief Pain Inventory Pain Interference Index (BPI-PII) in order to fully assess the impact of trigeminal neuralgia (TN) pain on patients’ health-related quality of life (HRQoL). The current objective is to create and establish the content validity of a new stand-alone version of the measure, the Penn-FPS-Revised (Penn-FPS-R). Methods: Twenty participants (15 USA and 5 UK) with confirmed TN engaged in concept elicitation and cognitive debriefing interviews. These semi-structured interviews allowed participants to spontaneously describe the ways in which TN impacts on HRQoL and report on the extent to which the Penn-FPS and BPI-PII measure concepts are most relevant to them. Participants were also asked to report on the suitability of the instructions, recall period, and response options. Results: Concept elicitation revealed nine themes involving TN restrictions on daily activities and HRQoL, including: “talking,” “self-care,” “eating,” “eating hard foods/chewing foods,” “daily activities,” “activities with temperature change,” “touching,” “mood,” and “relationships.” Cognitive debriefing confirmed that all of the Penn-FPS concepts and some of the BPI-PII concepts (“mood,” “general activities,” and “relations with others”) were relevant, although some items required edits to better capture individuals’ experiences. The impact of temperature and/or weather on activities was also identified as an important concept that is not captured by the Penn-FPS or BPI-PII. Participants confirmed the acceptability of recall period, instructions, and response options. Results from the interviews were applied to create the Penn-FPS-R, a new brief outcome measure that assesses the impacts of TN most important to patients. Conclusion: The Penn-FPS-R is a new 12-item HRQoL outcome measure with content validity that can be used to assess and monitor the impact of TN treatment interventions in both clinical practice and research. [ABSTRACT FROM AUTHOR]

The goal of the current work is to provide a comprehensive review and interpretation of the literature on the human and economic burden of generalized anxiety disorder (GAD) and how it compares with that of other mental disorders. The term “human burden” is used to describe quantified impairments in role functioning and quality of life (QOL). “Economic burden” describes costs related to health care resource utilization and lost work. A review of 34 studies reporting original quantitative data on associations between GAD and role functioning, QOL, and/or economic costs was undertaken. GAD was defined by DMS-III-R, DSM-IV, or ICD-10 DCR. Persons with GAD (both with and without a comorbid mental disorder) described significant impairments due to both physical and emotional problems. Studies typically showed that role and QOL impairments of GAD were at least comparable in magnitude to those of other anxiety disorders, somatoform disorders, and physical conditions, and greater than those of substance use disorders. Large representative studies showed that role impairments of pure GAD were similar in magnitude to those of pure MDD. Studies of DSM-IV disorders showed that QOL impairments of GAD were at least comparable in magnitude to those of MDD; studies of DSM-III-R disorders showed the opposite pattern. GAD was associated with considerable economic costs owing to lost work productivity and high medical resource use. Quality of care initiatives that have been implemented to increase recognition and improve treatment outcomes for persons with MDD should be extended to the effective management of GAD. Depression Anxiety 0:1–19, 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The objective of this study was to adapt the concept of ‘episode-free day’, a metric for measuring symptom relief in daily units, to the clinical outcome literature for persistent pain. The episode-free day metric is widely used in other medical literature, but no analogous measure exists in pain literature. Prior focus groups with this population suggested that a ‘Day of Manageable Pain Control’ was an appropriate name for the metric. In the present study, in order to derive a statistical criterion for ‘Manageable Day’, we used Serlin et al.’s (Pain 61 (1995) 277) cut-point derivation method to derive a single cut-point on a 0–10 scale of average pain that divided groups with significant persistent pain optimally on pain-related functional interference. Participants were 194 patients with moderate-severe low back pain (n=96) or osteoarthritis (n=98). For both patient samples, ‘5’ was the cut-point that optimally distinguished groups on pain-related interference. ‘5–8’ and ‘5–7’ were double cut-point solutions that optimally divided LBP and OA samples into three categories (e.g. lowest, medium and highest average pain), respectively. Derived cut-points were confirmed using a variety of measures of functional disability. Together with research that showed that average pain ratings of approximately 5 and below permit increased function and quality of life in patients with moderate to severe low back pain and osteoarthritis, our findings provide support for the use of 0–5 on a 0–10 numeric average pain severity scale as one possible criterion for a Manageable Day. [Copyright &y& Elsevier]