A quality-of-life measure for adults with primary ciliary dyskinesia: QOL-PCD

Primary ciliary dyskinesia (PCD) is characterised by chronic suppurative lung disease, rhino-sinusitis, hearing impairment and sub-fertility. We have developed the first multidimensional measure to assess health-related quality of life (HRQoL) in adults with PCD (QOL-PCD). Following a literature review and expert panel meeting, open-ended interviews with patients investigated the impact of PCD on HRQoL in the UK and North America (n=21). Transcripts were content analysed to derive saturation matrices. Items were rated for relevance by patients (n=49). Saturation matrices, relevance scores, literature review, evaluation of existing measures, and expert opinion contributed to development of a preliminary questionnaire. The questionnaire was refined following cognitive interviews (n=18). Open-ended interviews identified a spectrum of issues unique to adults with PCD. Saturation matrices confirmed comprehensive coverage of content. QOL-PCD includes 48 items covering the following seven domains: Physical Functioning, Emotional Functioning, Treatment Burden, Respiratory and Sinus Symptoms, Ears and Hearing, Social Functioning, and Vitality and Health Perceptions. Cognitive testing confirmed that content was comprehensive and the items were well-understood by respondents. Content validity and cognitive testing supported the items and structure. QOL-PCD has been translated into other languages and is awaiting psychometric testing

Primary Ciliary Dyskinesia: First Health-related Quality of Life Measures for Pediatric Patients

Rationale: Primary ciliary dyskinesia (PCD) is a rare disease. There are no available data on disease-specific pediatric patient–reported outcomes

Primary Ciliary Dyskinesia: First Health-related Quality of Life Measures for Pediatric Patients

Rationale: Primary ciliary dyskinesia (PCD) is a rare disease. There are no available data on disease-specific pediatric patient–reported outcomes. Objectives: Our objective was to create developmentally appropriate, health-related quality-of-life questionnaires (QOL-PCD) for children (6–12 yr) and adolescents (13–17 yr) with PCD and a parent proxy measure. Methods: The QOL-PCD was developed using a cross-cultural protocol-driven approach satisfying both North American and European drug regulatory agency guidelines. A conceptual framework was generated by literature review, focus groups (expert clinicians and patients/parents), and open-ended interviews with children, adolescents, and parents of patients with PCD. We recruited participants from international research consortiums, PCD clinics, and patient advocacy groups, aiming for representation of a wide spectrum of disease severity, sociodemographic status, and ethnicity. Qualitative interviews were conducted by trained and experienced research assistants and psychologists. Transcripts were content-analyzed with Atlas.ti/NVivo to assess saturation of content. A self-completed item relevance survey was administered to E.U. participants. Qualitative and quantitative data were used to construct draft instruments. Questionnaires were further refined after cognitive interviews. Measurements and Main Results: Focus groups (n = 62 experts; n = 20 patients/parents) and open-ended interviews with patients/parents (n = 69; 34 males; age at diagnosis, 0–15 yr; FEV(1), 58–118% predicted) revealed a wide spectrum of issues unique to this population. Content analysis of transcripts identified the following domains, depending on age: Respiratory Symptoms, Physical Functioning, Emotional Functioning, Treatment Burden, Ears and Hearing, Sinus Symptoms, Social Functioning, Role Functioning, Vitality, Health Perceptions, School Functioning, and Eating and Weight. Various items were retained in questionnaires, based on age and role of respondent: 37, 43, and 41 items for children, adolescents, and parent proxy, respectively. The item relevance survey (n = 57) yielded results similar to those of open-ended interviews. Cognitive testing (n = 47; 20 males; age at diagnosis, 0–11 yr; FEV(1), 49–124% predicted) confirmed that items and response choices were clear and understood by respondents, and that all relevant items were included. Conclusions: The QOL-PCD measures, developed using rigorous, protocol-driven methods and international collaborations, have demonstrated content validity and cross-cultural equivalence for implementation in English-speaking populations. Psychometric testing is underway to determine their measurement properties for evaluating clinical interventions and informing quality of care

Primary ciliary dyskinesia: first health-related quality of life measures for pediatric patients

Rationale: Primary ciliary dyskinesia (PCD) is a rare disease. There are no available data on disease-specific pediatric patient-reported outcomes. Objectives: Our objective was to create developmentally-appropriate, health-related quality of life questionnaires (QOL-PCD) for children (6-12 years) and adolescents (13-17 years) with PCD and a parent proxy measure. Methods: QOL-PCD was developed using a cross-cultural protocol-driven approach satisfying both North American and European drug regulatory agency guidelines. A conceptual framework was generated by literature review, focus groups (expert clinicians and patients/parents) and open-ended interviews with children, adolescents and parents of PCD patients. We recruited participants from international research consortiums, PCD clinics and patient advocacy groups, aiming for representation of a wide spectrum of disease severity, sociodemographic status and ethnicity. Qualitative interviews were conducted by trained and experienced research assistants and psychologists. Transcripts were content-analyzed with Atlas.ti/Nvivo to assess saturation of content. A self-completed item relevance survey was administered to European Union participants. Qualitative and quantitative data were used to construct draft instruments. Questionnaires were further refined following cognitive interviews. Measurement and Main Results: Focus groups (n=62 experts; n=20 patients/parents) and open-ended interviews with patients/parents (n=69; 34 males; age of diagnosis 0-15 years; forced expiratory volume in one second (FEV1) 58-118% predicted) revealed a wide spectrum of issues unique to this population. Content analysis of transcripts identified the following domains, depending on age: Respiratory Symptoms, Physical Functioning, Emotional Functioning, Treatment Burden, Ears &amp; Hearing, Sinus Symptoms, Social Functioning, Role Functioning, Vitality, Health Perceptions, School Functioning, and Eating &amp; Weight. Different items were retained in questionnaires based on age and role of respondent: 37, 43 and 41 items for children, adolescents, and parent proxy respectively. The item relevance survey (n=57) yielded similar results to open-ended interviews. Cognitive testing (n=47; 20 males; age of diagnosis 0-11 years; FEV 49-124% predicted) confirmed that items and response choices were clear, understood by respondents and that all relevant items were included. Conclusions: QOL-PCD measures developed using rigorous, protocol-driven methods and international collaborations have demonstrated content validity and cross-cultural equivalence for implementation in English-speaking populations. Psychometric testing is underway to determine their measurement properties for evaluating clinical interventions and informing quality of care.<br/

ETS rearrangements and prostate cancer initiation Reply

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62667/1/nature07739.pd

Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer

Recently, we identified recurrent gene fusions involving the 59 untranslated region of the androgen-regulated gene TMPRSS2 and the ETS (E26 transformation-specific) family genes ERG, ETV1 or ETV4 in most prostate cancers(1,2). Whereas TMPRSS2 ERG fusions are predominant, fewer TMPRSS2-ETV1 cases have been identified than expected on the basis of the frequency of high (outlier) expression of ETV1 (refs 3-13). Here we explore the mechanism of ETV1 outlier expression in human prostate tumours and prostate cancer cell lines. We identified previously unknown 59 fusion partners in prostate tumours with ETV1 outlier expression, including untranslated regions from a prostate-specific androgen-induced gene (SLC45A3) and an endogenous retroviral element (HERV-K_22q11.23), a prostate-specific androgen-repressed gene (C15orf21), and a strongly expressed housekeeping gene (HNRPA2B1). To study aberrant activation of ETV1, we identified two prostate cancer cell lines, LNCaP and MDA-PCa 2B, that had ETV1 outlier expression. Through distinct mechanisms, the entire ETV1 locus (7p21) is rearranged to a 1.5-megabase prostate-specific region at 14q13.3-14q21.1 in both LNCaP cells (cryptic insertion) and MDA- PCa 2B cells (balanced translocation). Because the common factor of these rearrangements is aberrant ETV1 overexpression, we recapitulated this event in vitro and in vivo, demonstrating that ETV1 overexpression in benign prostate cells and in the mouse prostate confers neoplastic phenotypes. Identification of distinct classes of ETS gene rearrangements demonstrates that dormant oncogenes can be activated in prostate cancer by juxtaposition to tissue-specific or ubiquitously active genomic loci. Subversion of active genomic regulatory elements may serve as a more generalized mechanism for carcinoma development. Furthermore, the identification of androgen-repressed and insensitive 59 fusion partners may have implications for the anti-androgen treatment of advanced prostate cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62659/1/nature06024.pd