The paired-pulse TMS paradigm of short intracortical inhibition is mediated by a reduction of repetitive motor neuron discharges.

Transcranial magnetic stimulation (TMS) causes repetitive spinal motoneuron discharges (repMNDs), but the effects of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) on repMNDs remain unknown. Triple stimulation technique (TST) and the extended TST-protocols that include a fourth and fifth stimulation, the Quadruple (QuadS) and Quintuple (QuintS) stimulation, respectively, offer a precise estimate of cortical and spinal motor neuron discharges, including repMNDs. The objective of our study was to explore the effects of SICI and ICF on repMNDs. We explored conventional paired-pulse TMS protocols of SICI and ICF with the TMS, TST, the QuadS, and the QuintS protocols, in a randomized study design in 20 healthy volunteers. We found significantly less repMNDs in the SICI paradigm compared with a single-pulse TMS (SP-TMS). No significant difference was observed in the ICF paradigm. There was a significant inter- and intrasubject variability in both SICI and ICF. We demonstrate a significant reduction of repMNDs in SICI, which may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no increase in repMNDs in ICF suggesting another mechanism underlying facilitation. This study provides the proof that a reduction of repMNDs mediates the inhibition seen in SICI.NEW & NOTEWORTHY Significant reduction of repetitive motor neuron discharges (repMNDs) in short-interval intracortical inhibition (SICI) may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no change in the number of repMNDs in intracortical facilitation (ICF). There was a significant variability in SICI and ICF in healthy subjects.

Allogeneic Hematopoietic Stem Cell Transplantation in Immunodeficiency-Centromeric Instability-Facial Dysmorphism (ICF) Syndrome: an EBMT/ESID Inborn Errors Working Party Study.

Immunodeficiency-Centromeric instability-Facial dysmorphism (ICF) syndrome is an inborn error of immunity characterized by progressive immune dysfunction and multi-organ disease usually treated with antimicrobial prophylaxis and immunoglobulin substitution. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment, but data on outcome are scarce. We provide a detailed description of disease characteristics and HSCT outcome in an international cohort of ICF syndrome patients. Eighteen patients (including all four genotypes) were enrolled. Main HSCT indications were infections (83%), enteropathy/failure to thrive (56%), immune dysregulation (22%) and myelodysplasia/haematological malignancy (17%). Two patients underwent pre-emptive HSCT after early diagnosis. Patients were transplanted between 2003-2021, at median age 4.3 years (range 0.5-19), after myeloablative or reduced-intensity conditioning, from matched sibling or matched family donors, matched unrelated or mismatched donors in 39%, 50% and 12% of cases respectively. Overall survival was 83% (all deaths occurred within the first 5 months post-HSCT; mean follow-up 54 months (range 1-185)). Acute GvHD occurred in 35% of patients, severe (grade III) in two (12%), while none developed chronic GvHD. At latest follow-up (median 2.2 years (range 0.1-14)), complete donor chimerism was achieved in 15/17 surviving patients. All survivors demonstrated normalized T and B cell numbers. Immunoglobulin substitution independence was achieved in all but two patients. All survivors recovered from pre-transplant infections, enteropathy/failure to thrive and immune dysregulation. All three patients transplanted at young age (≤ 3 years), after early diagnosis, survived. The favourable clinical and immunological HSCT outcome in this cohort of patients supports the timely use of this curative treatment in ICF syndrome.

Reliability and construct validity of the ACTIVLIM-Hemo and Haemophilia Activities List (HAL) questionnaires in individuals with haemophilia.

OBJECTIVE: The objective of this study is to assess the reliability and construct validity of ACTIVLIM-Hemo, a newly developed Rasch-built questionnaire designed to evaluate activity limitations in people with haemophilia (PwH), in comparison with the Haemophilia Activities List (HAL), which was developed using Classical Test Theory. METHODS: A total of 130 participants with haemophilia A or B were included. They underwent various assessments, including joint health scoring (HJHS), functional tests (TUG and 2MWT) and completed questionnaires such as the BPI, IPAQ, HAL and ACTIVLIM-Hemo. Reliability indices and the minimum detectable change (MDC95) were determined for ACTIVLIM-Hemo and for HAL. Construct validity was evaluated through correlations and multiple linear regression, considering demographic and clinical factors. RESULTS: Both ACTIVLIM-Hemo (Person Separation Index = 0.92) and HAL (Cronbach's α = 0.98) demonstrated high reliability. The MDC95 for ACTIVLIM-Hemo represented 11.6% of its measurement range, while for HAL, it amounted to 18/100 score points. Activity limitations measured by both instruments were significantly correlated with demographic and clinical factors. Joint health (HJHS), pain severity (BPI) and walking performance (2MWT) emerged as the main predictors of activity limitations, explaining 75% of the variance in ACTIVLIM-Hemo and 60% in HAL. CONCLUSION: ACTIVLIM-Hemo stands as a reliable and valid instrument for assessing activity limitations in PwH. Both instruments exhibited significant correlations with demographic and clinical factors, but ACTIVLIM-Hemo displayed a more homogeneous construct. Given its linear scale and lower MDC95 and better targeting, ACTIVLIM-Hemo shows promise as a patient-centric instrument for assessing responsiveness to treatment during individual follow-up.

Health-related quality of life measures provide information on the contributors, components, and consequences of frailty in HIV: a systematic mapping review.

PURPOSE: Frailty in HIV is extensively explored in epidemiological and clinical studies; it is infrequently assessed as an outcome in routine care. The focus on health-related quality of life (HRQL) measures in HIV presents a unique opportunity to understand frailty at a larger scale. The objective was to identify the extent to which generic and HIV-related HRQL measures capture information relevant to frailty. METHODS: A systematic mapping review using directed and summative content analyses was conducted. An online search in PubMed/Medline identified publications on frailty indices and generic and HIV-related HRQL measures. Directed content analysis involved identifying contributors, components, and consequences of frailty from the frailty indices based on the International Classification of Functioning, Disability, and Health framework. Summative content analysis summarized the results numerically. RESULTS: Electronic and hand search identified 447 review publications for frailty indices; nine reviews that included a total of 135 unique frailty indices. The search for generic and HIV-related HRQL measures identified 2008 records; five reviews that identified 35 HRQL measures (HIV-specific: 17; generic: 18). Of the 135 frailty indices, 88 cover more than one frailty dimension and 47 cover only physical frailty. Contributors to frailty, like sensory symptoms and nutrition, are extensively covered. Components of frailty such as physical capacity, cognitive ability, and mood are also extensively covered. Consequences of frailty namely self-rated health, falls, hospitalization, and health services utilization are incomprehensively covered. HRQL measures are informative for contributing factors, components of frailty, and a consequence of frailty. CONCLUSION: HRQL items and measures show a strong potential to operationalize multidimensional frailty and physical frailty. The study suggests that these measures, connected to evidence-based interventions, could be pivotal in directing resources toward vulnerable populations to mitigate the onset of frailty.

Development of the assessment standards of the International Classification of Functioning, Disability, and Health (ICF) Geriatric Core Set through a modified Delphi method.

BACKGROUND: There is currently a lack of functional assessment tools based on the International Classification of Functioning, Disability, and Health (ICF) theoretical framework that are specific for older adults. OBJECTIVE: The aim of the present study was to develop Chinese assessment standards of the ICF Geriatric Core Set for functional evaluation of older adults. METHODS: A two-stage study process was conducted to develop the assessment standards of the ICF Geriatric Core Set: establishment of candidate assessment standards, and a modified Delphi consensus process including a pilot survey and two-round formal expert survey. Thirty participants in the field of ICF and geriatric rehabilitation were recruited. The suitability of the assessment standards in the questionnaires was rated using a Likert 5-level scoring method. The arithmetic mean, the full mark ratio and the coefficient of variation (CV) were used as screening indicators for the assessment standards, and modification was made for several standards, in line with the Delphi results and the expert panel discussion. RESULTS: Thirty-three candidate assessment standards belonging to 17 categories were generated. A total of 26 and 24 experts in the field of ICF and geriatric rehabilitation participated in the two-round survey, respectively. Five standards belonging to four categories entered into the second-round survey directly, five standards belonged to five categories entered with minor modification, and nine standards belonging to seven categories were redesigned based on the literature and discussion of the expert panel. In the second-round survey,15 assessment standards belonging to 15 categories met the screening requirements and four assessment standards belonged to the two remaining categories that needed a criterion and which the expert panel discussed for the final decision. CONCLUSIONS: Using the modified Delphi method, the assessment standards of the ICF Geriatric Core Set have been developed.Future work should focus on the reliability and validity of the the assessment standards and their application to the health management of older adults.

The first step in developing an International Classification of Functioning, Disability and Health Core Set for Vision Loss: A systematic review.

AIM: As a first step in developing an International Classification of Functioning, Disability and Health (ICF) Core Set for adults with vision loss, this systematic review sought to identify the researchers' perspective by identifying the most often used outcome measures and research topics obtained from studies on adults with vision loss. METHODS: PubMed, Embase, CINAHL, APA PsycINFO and Web of Science were searched for studies on vision loss. Meaningful outcome measures and research topics were linked to the ICF components: environmental factors, body functions, body structures and the Activities and Participation life domains. RESULTS: After deduplication, 7219 records remained, of which 2328 articles were eligible for further review. For feasibility reasons, approximately 20% were randomly chosen from every publication year, resulting in 446 included articles. After full-text reading, 349 articles remained, describing 753 outcome measures based on questionnaires and 2771 additional research topics that could be linked to the ICF. Most were linked to the component Activities and Participation, with a focus on recreation and leisure activities (ICF code d920, 70%), reading (d166, 34%) and driving (d475, 27%). For the component body function, seeing functions (b210, 83%) were most often reported. Outcome measures and research topics were least often linked to the body structure component and environmental factors. CONCLUSION: The broad range of ICF categories identified in this systematic review represents the variety of functioning typical for adults with vision loss. These results reflect the focus of researchers over the past 21 years by using various vision-related outcomes. In our next steps to develop the ICF Core Set for Vision Loss, we will include perspectives of experts and lived experience.

The impact of the Covid-19 pandemic on the effectiveness of psychosomatic rehabilitation in Germany.

BACKGROUND: The aim of the present study is to investigate the impact of the Covid-19 pandemic on the effectiveness of psychosomatic rehabilitation. METHODS: Between April 2019 and March 2022, a total of 18,388 patients from 7 rehabilitation centres could be included in the study. For each patient, score values from the HEALTH-49 and ICF AT-50 Psych questionnaires were calculated at the beginning and at the end of rehabilitation and the effectiveness of the rehabilitation program was determined by comparing the scores at the beginning and at the end of the rehabilitation programme. Using risk adjusted linear mixed models, three time intervals were compared: a pre-pandemic episode (April 2019 to March 2020), the first year of the pandemic (April 2020 to March 2021) and the second year of the pandemic (April 2021 to March 2022). RESULTS: Overall, it can be stated that the pandemic has substantially impaired the effectiveness of psychosomatic rehabilitation measures. This phenomenon can be observed across a wide range of psychosocial markers and even two years after the start of the pandemic there is no end to the limited effectiveness. With regard to 'psychological and somatoform disorders', for example, there was a relative decrease in the effectiveness of the rehabilitation measure by 11.29% in the first year of the pandemic compared to the pre-pandemic episode, p < 0.001. In the second year of the pandemic, the effectiveness of the rehabilitation measure was still decreased by 8.8% compared to the pre-pandemic episode, p < 0.001. In addition, the evaluations show that a division of the pandemic effect into direct effects (on the individual) and indirect effects (via further complication of the occupational problem environment) can be made and that the pandemic-related complication of the occupational problem environment are still prevalent more than two years after the start of the pandemic. DISCUSSION: The Covid-19 pandemic has had a significant impact on the psychosomatic rehabilitation programs reducing the effectiveness of treatment not only for a short period of time but constantly until March 2022. TRIAL REGISTRATION NUMBER: DRKS00029669; Date of registration: 02/08/2022.

Development of a brief core set for knee dysfunction based on the International Classification of Functioning, Disability and Health: assessing construct validity and measurement potential.

BACKGROUND: The comprehensive core set for knee dysfunction was developed to classify the functioning of people with any knee dysfunction. To be used as a clinical instrument to measure the functioning of people with knee dysfunction, the construct validity of the core set still needs to be assessed. The purpose of this study was to analyze the construct validity of the comprehensive core set for knee dysfunction as an instrument to measure functioning. METHODS: A cross-sectional study with 200 participants with knee dysfunction with or without clinical diagnosis of knee pathology, with or without complaint of pain, with or without instability, and/or with or without knee movement restriction of any type. Participants were assessed using the comprehensive core set for knee dysfunction with 25 categories, the subjective form from the International Knee Documentation Committee scale, and measures of self-perceived general health and functioning. The construct validity of the core set was assessed by Rasch analysis, and the external construct validity was assessed by correlation between the score of the brief core set for knee dysfunction with the subjective form from the International Knee Documentation Committee scale, and scores of self-perception of health and functioning. RESULTS: Twelve categories were consistent with a unidimensional construct, with no difference in the response pattern for age, sex, educational level, and time of complaint. These categories were included in the brief core set for knee dysfunction. The mean score of the brief core set was 37 ± 21 points, a value classified as moderate impairment regarding functioning. Correlations with the subjective form from the International Knee Documentation Committee scale and scores of self-perception were adequate (p < 0.01; r > 0.5). CONCLUSION: The brief core set for knee dysfunction, a set with 12 categories, can be used as a clinical instrument to measure and score the functioning of people with knee dysfunction, aged between 18 and 89 years, with adequate construct validity.

Goal setting in people with low back pain attending an education and exercise program (GLA:D Back) and the impact of demographic factors.

BACKGROUND: Individual goal setting is a fundamental element in self-management supportive interventions, serving to guide actions and enhance motivation for engagement. Despite this, little is known about the goals people with back pain have and to what extent these differ across genders, age groups and geographical location. This study aimed to elucidate this by first describing individual goals set by Danish and Canadian participants in a self-management intervention for people with back pain using the ICF framework; then, determining what proportion of these goals met criteria for being specific, measurable, acceptable, and time bound, and finally, by investigating differences between countries, sexes, and age groups. METHODS: In a cross-sectional study conducted August 2018 to June 2020, 394 Danish and 133 Canadian (Alberta Province) participants defined their individual goals of participating in a self-management programme involving patient education and supervised exercises. The goals were linked to the ICF framework. Distribution of goals was compared between countries, sexes, and age groups. RESULTS: Goals most often related to the ICF component of 'Activity and Participation'. The most prevalent goals were "Walking" (DK: 20%; CA: 15%) and "Maintaining a body position" (DK: 17%; CA: 22%). Only few goals differed between populations, age and sex. All elements of SMART goal setting were recorded for 88% of Danish and 94% of Alberta participants. CONCLUSIONS: People with low back pain attending a self-management programme established goals according to the SMART criteria and focused primarily on activity. Goals were similar across countries and showed few differences across sex and age groups. The high number of different goals points to the need for individualised person-centred care.

Validity and Reliability of Dysphagia Outcome Severity Scale (DOSS) When Used to Rate Flexible Endoscopic Evaluations of Swallowing (FEES).

The Dysphagia Outcome and Severity Scale is used both clinically and within dysphagia research, internationally. Although it was developed using videofluoroscopic swallowing studies, it is frequently used to rate Flexible Endoscopic Evaluations of Swallowing. The validity and reliability of DOSS-use with FEES, however, has not previously been evaluated. This study investigated the validity and rater reliability of clinicians using DOSS to rate FEES. Eleven Speech-Language Pathologists (SLPs) with varied dysphagia experience were recruited to review and DOSS-rate 17 soundless FEES (198 bolus swallows) recorded from 11 heterogenic dysphagic patients (2 cases with repeat FEES) and 4 healthy adults. The SLPs DOSS-ratings were compared against the initial comprehensive dysphagia evaluation (including patient diagnosis, interview, cranial nerve and complete FEES assessment) with Functional Oral Intake Scale (FOIS) and DOSS outcome measures. The SLPs were blinded to patient details and comprehensive dysphagia examination. Re-randomised rating of FEES cases occurred two weeks later (intra rater reliability). Criterion validity for DOSS-ratings (compared against comprehensive dysphagia evaluation with FOIS and DOSS) were strong-very strong (rs = 0.858 and 0.936 respectively; p < 0.001). Inter rater reliability demonstrated high agreement (α = 0.891), also intra rater reliability demonstrated almost perfect agreement (Kw = 0.945). This study's results, with strong-very strong criterion validity and high rater reliability by SLPs, adds to the evidence for DOSS-use with FEES. Future validity research comparing DOSS with both FEES and VFSS simultaneously is recommended.

Holistic assessment of cochlear implant outcomes using the international classification of functioning disability and health model: data analysis of a longitudinal prospective multicenter study.

PURPOSE: To study outcome after cochlear implantation using the Cochlear Implant (CI) outcome assessment protocol based on the International Classification of Functioning, Disability and Health (ICF) model (CI-ICF). METHODS: Raw data of a prospective, longitudinal, multicenter study was analyzed. Seventy-two CI candidates were assessed preoperatively and six months postoperatively using the CI-ICF protocol. Following tools were used: (1) Work Rehabilitation Questionnaire (WORQ), (2) Abbreviated Profile of Hearing Aid Benefit (APHAB), (3) Audio Processor Satisfaction Questionnaire (APSQ), (4) Speech, Spatial, and Qualities of Hearing Scale (SSQ12), (5) Hearing Implant Sound Quality Index (HISQUI19), (6) Nijmegen CI Questionnaire (NCIQ) (7) pure tone audiometry, (8) speech audiometry, (9) sound localization. RESULTS: There was a significant improvement of speech discrimination in quiet (p = 0.015; p < 0.001) and in noise (p = 0.041; p < 0.001), sound detection (p < 0.001), tinnitus (p = 0.026), listening (p < 0.001), communicating with-receiving-spoken messages (p < 0.001), conversation (p < 0.001), family relationships (p < 0.001), community life (p = 0.019), NCIQ total score and all subdomain scores (p < 0.001). Subjective sound localization significantly improved (p < 0.001), while psychometric sound localization did not. There was no significant subjective deterioration of vestibular functioning and no substantial change in sound aversiveness. CI users reported a high level of implant satisfaction postoperatively. CONCLUSION: This study highlights the positive impact of cochlear implantation on auditory performance, communication, and subjective well-being. The CI-ICF protocol provides a holistic and comprehensive view of the evolution of CI outcomes.

Activity limitations related to cold hypersensitivity in patients with hand injuries.

BACKGROUND: Knowledge of specific activity limitations due to cold hypersensitivity is sparse. PURPOSE: To explore activity limitations caused by cold hypersensitivity and the associated environmental factors in patients with hand injuries. STUDY DESIGN: Descriptive study. METHODS: Seventy-seven patients with multiple tissue hand injuries described activity limitations related to cold hypersensitivity in questionnaires six and/or 12 months after surgery. To characterize the activity limitations, we performed a quantitative content analysis applying the International classification of functioning and health (ICF). RESULTS: The respondents described on average 3.6 cold related activity limitations in leisure and/or work. The activities were most frequently (n) assigned to the ICF domains d920 Recreation and leisure (95), d440 Fine hand use (77), and d850 Remunerative employment (39). The most common related environmental factors were Products and technology for e140 Culture, recreation and sport (79) and for e135 Employment (71), respectively, and e225 Climate (71). Gloves were both a facilitator and a barrier for activity performance. CONCLUSION: The impact of cold hypersensitivity on activity was related to both the activity and the environment. The results call for clinical interventions and product development, for example of gloves, to help patients solve their cold related activity limitations.

Understanding the implications of hand impairments in light of the International Classification of Function model.

BACKGROUND: Incorporating an occupation-based assessment along with or in place of an assessment of body functions and structures is not performed routinely in hand therapy practice. PURPOSE: (a) Explore correlations between body functions, activities and participation (A&P), and quality of life (QOL); (b) assess the extent to which personal factors and body functions contribute to variations in A&P and QOL; (c) compare the QOL of individuals with and without hand impairment (HI). STUDY DESIGN: Cross-sectional. METHODS: Seventy-seven patients (Mean age=43.70 SD=17.56; 47 males and 30 females) with chronic and acute hand impairment were recruited from two hand clinics and matched with healthy participants. Assessments were administered to participants in their first visit to the hand clinic. QOL was measured with the World Health Organization QOL questionnaire; A&P with the Disabilities of the Arm Shoulder and Hand (DASH) questionnaire; pain with the Patient-Rated Wrist/Hand Evaluation; hand function with The Functional Dexterity Test, Jamar Dynamometer and Pinch Gauge. RESULTS: Significant correlations were found between QOL and A&P, dexterity, and pain, as well as between A&P and hand strength and pain. Personal factors, hand function, and pain collectively explained 28.9% of QOL variance and 61.4% of A&P variance. Pain emerged as the sole significant contributor to QOL variance, while both hand function and pain significantly influenced A&P variance. Comparisons between the study group and controls highlighted significant differences in QOL domains, with the HI group reporting lower perceived QOL in physical, social, and environmental domains. CONCLUSION: The significance of adopting a comprehensive approach in HI intervention was highlighted. A complex interplay of factors across different levels of the International Classification of Functioning, Disability and Health (ICF) framework imply that clinicians should avoid fixating exclusively on isolated factors or specific domains.

Adaptation and Validation of Overall Assessment of the Speaker's Experience of Stuttering for Adults in Kannada (OASES-A-K).

INTRODUCTION: Psychosocial aspects of stuttering may affect the quality of life of a person who stutters (PWS). Further, the social stigma and experiences of PWS may vary globally. The WHO-ICF guidelines recommend quality of life as an essential component in the assessment of individuals who stutter. However, the availability of linguistically and culturally appropriate tools is often a challenge. Thus, the current study adapted and validated the OASES-A for Kannada-speaking adults who stutter. METHOD: The original English version of OASES-A was adapted to Kannada using a standard reverse translation process. The adapted version was administered on 51 Kannada-speaking adults with very mild to very severe stuttering. The data were analyzed for item characteristics, reliability, and validity assessment. RESULTS: The results revealed floor and ceiling effects for six and two items, respectively. The mean overall impact score indicated a moderate impact of stuttering. Further, the impact score for section II was relatively higher when compared to the data from other countries. The reliability and validity analyses showed good internal consistency and test-retest reliability for OASES-A-K. CONCLUSION: The findings of the current research suggest that OASES-A-K is a sensitive and reliable tool to assess the impact of stuttering in Kannada-speaking PWS. The findings also highlight cross-cultural differences and the need for research in this direction.

Examination of Physical Functions, Activity and Participation in Children with Juvenile Idiopathic Arthritis.

AIMS: To examine physical functions, activity, and participation level, and associated factors with participation in children with juvenile idiopathic arthritis (JIA) across the International Classification of Functioning Disability and Health-Children and Youth. METHODS: 49 children (Girl/Boy:28/21) aged between 7 and 18 years (Mean: 13.4 ± 3.3) were included. To evaluate body structure/functioning; pain, fatigue, disease activity, and motor functions were assessed. Childhood Health Assessment Questionnaire and Juvenile Arthritis Biopsychosocial and Clinical Questionnaire were used to determine activity level. Child and Adolescent Scale of Participation was used to assess participation. RESULTS: Mild level of pain (2.0 ± 2.3), disease activity (2.0 ± 2.3), and fatigue (4.1 ± 4.0) were recorded. Decrease in motor functions was determined in 75% of children, while 61% of whom had activity-related disability. There was mild to moderate participation restrictions, and participation was significantly associated with age (r = -0.29), pain severity (r = -0.31), disease activity (r = -0.39), motor functions (r = 0.33), and activity level (r = -0.43), (p Ë‚ 0.05). CONCLUSIONS: Majority of children with JIA have deteriorations in physical functions, activity, and participation. Age, pain, disease activity, motor functions and activity level were associated with participation level. Children with JIA should be regularly evaluated multi-directional and they should be referred to rehabilitation programs to increase functionality and participation.

A novel mutation in DNMT3B gene causing ICF1 syndrome in an infant with refractory thrombocytopenia.

BACKGROUND: ICF syndrome is a rare autosomal recessive condition characterized by immunodeficiency, centromeric instability, and facial abnormalities. It is a clinical condition that depends on the mutation of a few particular genes and is caused by methylation disruption in chromosomes 1, 9, and 16 to varying degrees. CASE PRESENTATION: The 9-months old, female patient was admitted to our clinic for treatment-resistant thrombocytopenia, chronic diarrhea and sepsis. Immunological investigations revealed agammaglobulinemia. In the genetic analysis by NGS of the patient, who had dysmorphic facial findings as well as a history of parental consanguinity, it was determined that she had a novel mutation in the DNMT3B gene, which is one of the responsible genes of ICF, as homozygous. The patient, who was started on regular immunoglobulin replacement therapy and antibiotic therapy, was referred to a center with a stem cell transplant unit to continue her follow-up. CONCLUSIONS: Although autoimmunity has not been commonly reported in previous studies in ICF syndrome, which has a varied clinical presentation, a homozygous mutation in the DNMT3B gene was discovered in a 9-month-old patient with refractory thrombocytopenia and agammaglobulinemia. Examining the literature reveals that this mutation is a novel mutation.

Evaluation of Clinical and Immunological Alterations Associated with ICF Syndrome.

PURPOSE: Immunodeficiency with centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive combined immunodeficiency. The detailed immune responses are not explored widely. We investigated known and novel immune alterations in lymphocyte subpopulations and their association with clinical symptoms in a well-defined ICF cohort. METHODS: We recruited the clinical findings from twelve ICF1 and ICF2 patients. We performed detailed immunological evaluation, including lymphocyte subset analyses, upregulation, and proliferation of T cells. We also determined the frequency of circulating T follicular helper (cTFH) and regulatory T (Treg) cells and their subtypes by flow cytometry. RESULTS: There were ten ICF1 and two ICF2 patients. We identified two novel homozygous missense mutations in the ZBTB24 gene. Respiratory tract infections were the most common recurrent infections among the patients. Gastrointestinal system (GIS) involvements were observed in seven patients. All patients received intravenous immunoglobulin replacement therapy and antibacterial prophylaxis; two died during the follow-up period. Immunologically, CD4+ T-cell counts, percentages of recent thymic emigrant T cells, and naive CD4+ T decreased in two, five, and four patients, respectively. Impaired T-cell proliferation and reduced CD25 upregulation were detected in all patients. These changes were more prominent in CD8+ T cells. GIS involvements negatively correlated with CD3+ T-, CD3+CD4+ T-, CD16+CD56+ NK-cell counts, and CD4+/CD8+ T-cell ratios. Further, we observed expanded cTFH cells and reduced Treg and follicular regulatory T cells with a skewing to a TH2-like phenotype in all tested subpopulations. CONCLUSION: The ICF syndrome encompasses various manifestations affecting multiple end organs. Perturbed T-cell responses with increased cTFH and decreased Treg cells may provide further insight into the immune aberrations observed in ICF syndrome.

ACTIVLIM-Hemo: A new self-reported, unidimensional and linear measure of activity limitations in persons with haemophilia.

INTRODUCTION: To assess activity limitations in people with haemophilia (PwH), the self-reported Haemophilia Activity List (HAL) is widely employed, despite several methodological limitations impacting the interpretation of categorical scores. Modern psychometric approaches avoid these limitations by using a probabilistic model, such as the Rasch model. The ACTIVLIM is a Rasch-built measurement of activity limitations previously validated in several clinical conditions like neuromuscular disorders. AIMS: This study sought to develop the ACTIVLIM-Hemo, meaning an ACTIVLIM scale version specifically adapted to assess daily activity limitations in adult PwH. METHODS: Daily activities were assessed as "impossible," "difficult" or "easy" by 114 PwH (median age of 44 years) with 63 of them reassessed after 12 days. The Rasch Rating Scale model was used to identify activities delineating a unidimensional and linear scale unbiased by demographic and clinical status. Concurrent validity was determined through correlation with the HAL sub-scores and sum score. RESULTS: The ACTIVLIM-Hemo included 22 pertinent activities, with difficulties independent of demographic and clinical conditions, allowing a reliable measure of activity limitations (PSI = .92) expressed on a linear and unidimensional scale in PwH (7%-100 % range, ceiling effect of 1/114) with excellent test-retest reliability (ICC = .978). Spearman rank correlations between ACTIVLIM-Hemo and HAL sub-scores ranged between .623 and .869. CONCLUSIONS: The ACTIVLIM-Hemo is an easy-to-administer, valid and reliable alternative to HAL in assessing activity limitations in PwH. Its invariant scale can be used across conditions and time to compare the functional status of PwH over a wide measurement range.

Activity and participation in haemophiliacs: Item response modelling based on international classification of functioning, disability and health.

BACKGROUND AND OBJECTIVES: There is scant research investigating the user-friendly functional assessment tool conceptualized by the International Classification of Functioning, Disability and Health (ICF) among persons with haemophilia (PWH). This study aims to accomplish two goals: (1) quantifying comprehensive functioning measures of haemophilia through Item Response Theory (IRT); (2) discussing patient-centred care based on the Wright map of personal ability and item difficulty. METHODS: A cross-sectional study was carried out in 70 PWH (mean age, 33.09 ± 11.04) via convenience sampling. All patients completed the 45 ICF categories of haemophilic-specific activity and participation. Psychometric properties of the categories were examined using Mokken scale analysis and parametric item response modelling. RESULTS: We extracted a unidimensional scale with 31 categories, and constructed a Rasch model with good fitness. The Cronbach's α of the scale was .9713, with the Guttman's λ2  = .9730, Molenaar Sijtsma ρ = .9802, and latent class reliability coefficient = .9769, indicating great internal reliability. The estimated individual social competence by the Rasch model was highly related to the index score of the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L) (p < .001, r = .62), and had a moderate correlation (p < .001, r = .54) with the score of Haemophilia Activities List (HAL). CONCLUSIONS: The ICF scale of haemophilic activity and participation with 31 categories (HAPPY-ICF) has good construct validity and internal consistency. The person-item threshold distribution map might be helpful in research and clinical practices for patient-oriented care.

Patient-reported outcome measures for physical function in cancer patients: content comparison of the EORTC CAT Core, EORTC QLQ-C30, SF-36, FACT-G, and PROMIS measures using the International Classification of Functioning, Disability and Health.

BACKGROUND: Patient-reported physical function (PF) is a key endpoint in cancer clinical trials. Using complex statistical methods, common metrics have been developed to compare scores from different patient-reported outcome (PRO) measures, but such methods do not account for possible differences in questionnaire content. Therefore, the aim of our study was a content comparison of frequently used PRO measures for PF in cancer patients. METHODS: Relying on the framework of the International Classification of Functioning, Disability and Health (ICF) we categorized the item content of the physical domains of the following measures: EORTC CAT Core, EORTC QLQ-C30, SF-36, PROMIS Cancer Item Bank for Physical Function, PROMIS Short Form for Physical Function 20a, and the FACT-G. Item content was linked to ICF categories by two independent reviewers. RESULTS: The 118 items investigated were assigned to 3 components ('d - Activities and Participation', 'b - Body Functions', and 'e - Environmental Factors') and 11 first-level ICF categories. All PF items of the EORTC measures but one were assigned to the first-level ICF categories 'd4 - Mobility' and 'd5 - Self-care', all within the component 'd - Activities and Participation'. The SF-36 additionally included item content related to 'd9 - Community, social and civic life' and the PROMIS Short Form for Physical Function 20a also included content related to 'd6 - domestic life'. The PROMIS Cancer Item Bank (v1.1) covered, in addition, two first-level categories within the component 'b - Body Functions'. The FACT-G Physical Well-being scale was found to be the most diverse scale with item content partly not covered by the ICF framework. DISCUSSION: Our results provide information about conceptual differences between common PRO measures for the assessment of PF in cancer patients. Our results complement quantitative information on psychometric characteristics of these measures and provide a better understanding of the possibilities of establishing common metrics.