Development and content validity of the Barth Syndrome Symptom Assessment (BTHS-SA) for adolescents and adults

Abstract Background Barth Syndrome (BTHS) is a rare genetic disorder that presents as a complex of debilitating symptoms and reduced life expectancy. Well-developed, BTHS-specific assessments measuring primary signs and symptoms of BTHS are not currently available, making it difficult to evaluate treatment effects in BTHS clinical studies. The objective of this research was to develop symptom-focused patient-reported outcome (PRO) measures for use in clinical studies with adolescents and adults with BTHS. Methods Concept elicitation interviews (CEIs) with pediatric (n = 18, age < 16 years) and adult (n = 15, age ≥ 16 years) individuals with BTHS and/or their caregivers were conducted to identify signs and symptoms relevant to BTHS and important to individuals with the condition. Based on CEI results, questionnaire construction activities were conducted to create unique adolescent and adult versions of the Barth Syndrome-Symptom Assessment (BTHS-SA). The questionnaires were evaluated in cognitive debriefing interviews (CDIs) with adolescents (n = 12; age 12- < 16 years) and adults (n = 12; age ≥ 16 years) with BTHS to assess relevance and readability of the tools. Results During the CEIs, a total of 48 and 40 signs and symptoms were reported by the pediatric and adult groups, respectively; 31 were reported by both age groups. Fatigue/tiredness and muscle weakness were the symptoms most frequently reported by both pediatric and adult patients with BTHS as important to improve with an effective treatment. The CEI results informed construction of a nine-item version of the BTHS-SA for adolescents and an eight-item version for adults. Developed for daily administration, each version asks respondents to rate symptom severity “at its worst” over the 24 h prior to administration. CDIs with both adolescents and adults with BTHS demonstrated that each BTHS-SA version was reflective of the disease experience and that respondents could interpret the questionnaire as intended and provide responses that accurately reflected their symptom experience. Conclusions The BTHS-SA adolescent and adult versions are content-valid PRO measures that can be used to evaluate severity of disease-specific symptoms in future clinical trials. Given the lack of available and well-developed assessments in this underserved therapeutic area, these tools fulfill a need for clinical researchers developing treatments for individuals with BTHS.

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Development of symptom-focused outcome measures for advanced and indolent systemic mastocytosis: the AdvSM-SAF and ISM-SAF©

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-02035-5 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Fiona Taylor ◽

Cem Akin ◽

Roger E. Lamoureux ◽

Brad Padilla ◽

Tanya Green ◽

...

Keyword(s):

Systemic Mastocytosis ◽

Signs And Symptoms ◽

Symptom Assessment ◽

Patient Reported Outcome ◽

Therapeutic Area ◽

Cognitive Debriefing ◽

Treatment Benefit ◽

Patient Reported ◽

Symptom Level ◽

Indolent Systemic Mastocytosis

Abstract Background Advanced systemic mastocytosis (AdvSM), indolent systemic mastocytosis (ISM), and smoldering systemic mastocytosis (SSM) are rare diseases characterized by neoplastic mast cell infiltration of more than one organ. A content-valid patient-reported outcome (PRO) questionnaire that assesses relevant signs and symptoms that are important and understandable to individuals with a condition is critical for assessing new treatment benefit as well as supporting product labeling claims. Notably, no such PRO questionnaire has been developed in accordance with regulatory and scientific guidelines for use in AdvSM, ISM, and SSM patient populations. To fill that gap, this study documents the development and content validity of instruments evaluating signs and symptoms of systemic mastocytosis. Methods A review of peer-reviewed literature, advice meetings with clinical therapeutic area experts, patient concept elicitation interviews, concept selection and questionnaire construction meetings, and patient cognitive debriefing interviews were conducted, and regulatory feedback was incorporated. Results For AdvSM, 26 sign- and symptom-level concepts were identified in literature, 39 by clinicians, and 33 by patients. For ISM/SSM, 38 sign- and symptom-level concepts were identified in the literature, 39 by clinicians, and 57 by patients. Two patient-reported instruments, the Advanced Systemic Mastocytosis Symptom Assessment Form (AdvSM-SAF) and Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF)(©Blueprint Medicines Corporation), were developed based on consolidated findings. Cognitive debriefing interviews with AdvSM and ISM patients showed the AdvSM-SAF and ISM-SAF were understood and interpreted as intended by the majority of patients. Conclusion The AdvSM-SAF and ISM-SAF are content-valid tools measuring symptoms from AdvSM and ISM patients’ perspective.

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Improvements in skin clearance and patient-reported signs and symptoms of psoriasis with brodalumab: Pooled analysis of phase 3 clinical studies

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2019.06.308 ◽

2019 ◽

Vol 81 (4) ◽

pp. AB78

Keyword(s):

Clinical Studies ◽

Signs And Symptoms ◽

Pooled Analysis ◽

Phase 3 ◽

Patient Reported

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Orthodontic Aspects on the Chronological and Dental Age in Children with Down Syndrome

Revista de Chimie ◽

10.37358/rc.18.1.6075 ◽

2018 ◽

Vol 69 (1) ◽

pp. 208-213

Author(s):

Mariana Pacurar ◽

Bogdan Dragomir ◽

Alina Silvana Szalontay ◽

Cristian Romanec

Keyword(s):

Down Syndrome ◽

Emotional Disorders ◽

Metabolic Diseases ◽

Genetic Disorder ◽

Signs And Symptoms ◽

Deciduous Teeth ◽

Healthy Children ◽

Dental Maturation ◽

Children With Down Syndrome ◽

The Family

Genetics is a key discipline in medicine, but also a clinical discipline with medical and social implications. The interest in reducing the number of genetic disorders and recognizing the risk of them repeating when a family confronts itself with a genetic anomaly becomes more and more important in the hierarchy of prophylactic emergencies. Presenting themselves as metabolic diseases (monogenic mutations) or malformations (polygenic and multifactorial heredity) because of their frequency, these disorders position themselves on an ascendant curve. They become difficult to deal with for the society, for the family and for the interested individual and cause emotional disorders. The Down syndrome is the most frequent type of genetic disorder. It is characterized by a specific set of signs and symptoms. People with Down syndrome require special medical care that, apart from the family, must include a team of doctors of various specializations and also a dentist. They are predisposed to hearing and sight disorders and thyroid problems as well. In 50% of the cases there are also anomalies of the heart, and the risk of leukaemia is 20 times higher. Some of them even develop an Alzheimer type dementia during their life. The people with Down syndrome can have an average IQ up to a moderate form of handicap. In particular, the studies on Down syndrome in dentistry are quite frequent, but they focus more on cavities, periodontal disease and hypodontia. In spite of this, the connection of Down syndrome and dental eruption is less studied. Consequently, the present study is intended to fill this missing part from the specialized literature, focusing on the relation between the Down syndrome and the chronological and dental ages in children. The health of the oral cavity is neglected in these patients, their parents focusing more on the treatment of the other systemic disorders of their children; the lack of interest is reflected in their poor oral hygiene.The trial group included 94 children with mixt dentition, aged between 6 and 12, divided as follows: 36 children with Down syndrome enrolled at the Educational Centre for Inclusive Education no. 1 of Tg. Mures and Alpha Transilvana Foundation. The chronology and the eruption sequences are subjected to certain variations and they are influenced by the presence of cavities, the premature loss or, on the contrary, the prolonged retention of deciduous teeth as well as dental anchylosis. Dental maturation is less subjected to variations, as it is a progressive, continuous and cumulative process. The presence of Down syndrome in children generates a delay in teeth eruption by 1.27 years compared to the data identified in the specialized literature and to the information obtained on the healthy children included in the study.

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Measuring What Matters for Children: A Systematic Review of Frequently Used Pediatric Generic PRO Instruments

Therapeutic Innovation & Regulatory Science ◽

10.1007/s43441-021-00311-x ◽

2021 ◽

Author(s):

Tasneem Arsiwala ◽

Nuzhat Afroz ◽

Kattayoun Kordy ◽

Christel Naujoks ◽

Francesco Patalano

Keyword(s):

Quality Of Life ◽

Child Health ◽

Clinical Studies ◽

Task Force ◽

Emotional Health ◽

Research Practices ◽

European Collaboration ◽

Patient Reported ◽

Good Research

Abstract Objective To provide an assessment of the quality of the most frequently used self-reported, generic patient-reported outcome measures (PROMs) that measure health-related quality of life (HRQoL) in children against the good research practices recommended by ISPOR task force for the pediatric population. Method Literature search was conducted on OvidSP database to identify the generic pediatric PROMs used in published clinical studies. The quality of PROMs used in more than ten clinical studies were descriptively evaluated against the ISPOR task force’s good research practices. Results Six PROMs were evaluated, namely Pediatric Quality-of-Life inventory 4.0 (PedsQL), Child Health Questionnaire (CHQ), KIDSCREEN, KINDL, DISABKIDS and Child Health and Illness Profile (CHIP). All PROMs, except KIDSCREEN, had versions for different age ranges. Domains of physical, social, emotional health and school activities were common across all the instruments, while domains of family activities, parent relations, independence, and self-esteem were not present in all. Children’s input was sought during the development process of PROMs. Likert scales were used in all the instruments, supplemented with faces (smileys) in instruments for children under 8 years. KIDSCREEN and DISABKIDS were developed in a European collaboration project considering the cross-cultural impact during development. Conclusion The comparison of the instruments highlights differences in the versions for different pediatric age groups. None of the PROMs fulfill all the good research practices recommended by the ISPOR task force. Further research is needed to define which age-appropriate domains are important for older children and adolescents.

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Crohn’s disease and ulcerative colitis patient-reported outcomes signs and symptoms for the remote management of inflammatory bowel disease during the COVID-19 pandemic

Journal of Patient-Reported Outcomes ◽

10.1186/s41687-021-00323-z ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Sergio Pinto ◽

Erica Loddo ◽

Salvatore Paba ◽

Agnese Favale ◽

Fabio Chicco ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Bowel Disease ◽

Patient Reported Outcomes ◽

Signs And Symptoms ◽

Patient Reported ◽

Inflammatory Bowel ◽

Active Patients ◽

Active Disease

Abstract Background and aims The COVID-19 pandemic has led to a deep reorganization of hospital services including inflammatory bowel disease (IBD) units. In this situation, conversion of in-person routine follow-up visits into phone consultations might be necessary. Here we explored the feasibility of using the validated Crohn’s Disease (CD) or Ulcerative Colitis (UC) Patient-Reported Outcomes Signs and Symptoms (CD- and UC-PRO/SS) to collect data about abdominal symptoms (abdominal/S) and bowel signs and symptoms (bowel/SS) remotely. Methods CD- and UC-PRO/SS were collected during phone consultations and compared among patients with active and inactive disease. The effectiveness of therapeutic intervention in patients with active disease was assessed by PRO/SS variation. Results Twenty-one CD and 56 UC patients were evaluated by phone. Six (28.6%) CD and 15 (26.8%) UC patients were considered to have active disease. In CD the bowel/SS but not the abdominal/S module was significantly higher in active patients (mean bowel/SS 2.50 [SE ± 0.44] active vs 0.76 [SE ± 0.18] remission, p = 0.008, AUC 0.87; mean abdominal/S 1.11 [SE ± 0.38] active vs 0.24 [SE ± 0.13] remission, p = 0.066). UC-PRO/SS measures were significantly higher in active patients as compared to patients in remission (median bowel/SS 1.63 [SE ± 0.24] active vs 0.33 [SE ± 0.04] remission; p < 0.0001, AUC 0.91; mean abdominal/S 1.03 [SE ± 0.24] vs 0.37 [SE ± 0.12]; p = 0.009, AUC 0.71). Therapy was escalated in 12 patients (3 CD and 9 UC) due to disease relapse. Therapy escalation resulted in the reduction of PRO/SS as evaluated at the subsequent phone consultation. Conclusions PRO/SS might represent a feasible tool to evaluate disease activity and therapy outcome in IBD patients during periods of limited access to outpatient clinics.

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Correction to: Levoketoconazole improves clinical signs and symptoms and patient-reported outcomes in patients with Cushing’s syndrome

Pituitary ◽

10.1007/s11102-020-01116-1 ◽

2020 ◽

Author(s):

Eliza B. Geer ◽

Roberto Salvatori ◽

Atanaska Elenkova ◽

Maria Fleseriu ◽

Rosario Pivonello ◽

...

Keyword(s):

Cushing’S Syndrome ◽

Patient Reported Outcomes ◽

Clinical Signs ◽

Signs And Symptoms ◽

Cushing's Syndrome ◽

Original Version ◽

Patient Reported ◽

Author Group ◽

Clinical Signs And Symptoms

The original version of the article unfortunately contained an error in the first name and the surname of one of the authors in the author group. The last author name was incorrectly published as ‘F. Pecori Giraldi’ and the corrected name is ‘Francesca Pecori Giraldi’ (First name: Francesca; Surname: Pecori Giraldi).

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