Systematic review of neurotrophic tropomyosin-related kinase inhibition as a tumor-agnostic management strategy.

Aim: To conduct a systematic review and meta-analysis feasibility of clinical, quality of life and economic evidence for neurotrophic tropomyosin-related receptor tyrosine kinases (NTRK) inhibitors in patients with NTRK gene fusion-positive tumors. Materials & methods: Databases were searched for studies on NTRK inhibitors in adult and pediatric patients. Results: 27 publications reported clinical data for seven interventions. Efficacy/safety data were available for two interventions only. Four trials each reported data for larotrectinib and entrectinib with pooled analyses reporting objective response rates of 75% (95% CI: 61-85) and 57.4% (43.2-70.8), respectively. No publications reported economic or quality of life evidence. Conclusion: Preliminary data demonstrate that NTRK inhibitors are well tolerated and show impressive clinical benefit; corroboration of existing studies and real-world data are required.

Global health resource utilization associated with pacemaker complications.

AIM: To estimate health resource utilization (HRU) associated with the management of pacemaker complications in various healthcare systems. METHODS: Electrophysiologists (EPs) from four geographical regions (Western Europe, Australia, Japan, and North America) were invited to participate. Survey questions focused on HRU in the management of three chronic pacemaker complications (i.e. pacemaker infections requiring extraction, lead fractures/insulation breaches requiring replacement, and upper extremity deep venous thrombosis [DVT]). Panelists completed a maximum of two web-based surveys (iterative rounds). Mean, median values, and interquartile ranges were calculated and used to establish consensus. RESULTS: Overall, 32 and 29 panelists participated in the first and second rounds of the Delphi panel, respectively. Consensus was reached on treatment and HRU associated with a typical pacemaker implantation and complications. HRU was similar across regions, except for Japan, where panelists reported the longest duration of hospital stay in all scenarios. Infections were the most resource-intensive complications and were characterized by intravenous antibiotics days of 9.6?13.5 days and 21.3?29.2 days for pocket and lead infections respectively; laboratory and diagnostic tests, and system extraction and replacement procedures. DVT, on the other hand, was the least resource intensive complication. LIMITATIONS: The results of the panel represent the views of the respondents who participated and may not be generalizable outside of this panel. The surveys were limited in scope and, therefore, did not include questions on management of acute complications (e.g. hematoma, pneumothorax). CONCLUSIONS: The Delphi technique provided a reliable and efficient approach to estimating resource utilization associated with chronic pacemaker complications. Estimates from the Delphi panel can be used to generate costs of pacemaker complications in various regions.

An approach to improve the care of mid-life women through the implementation of a Women's Health Assessment Tool/Clinical Decision Support toolkit.

The objectives of this study are to describe the implementation process of the Women's Health Assessment Tool/Clinical Decision Support toolkit and summarize patients' and clinicians' perceptions of the toolkit. The Women's Health Assessment Tool/Clinical Decision Support toolkit was piloted at three clinical sites over a 4-month period in Washington State to evaluate health outcomes among mid-life women. The implementation involved a multistep process and engagement of multiple stakeholders over 18 months. Two-thirds of patients (n = 76/110) and clinicians (n = 8/12) participating in pilot completed feedback surveys; five clinicians participated in qualitative interviews. Most patients felt more prepared for their annual visit (69.7%) and that quality of care improved (68.4%) while clinicians reported streamlined patient visits and improved communication with patients. The Women's Health Assessment Tool/Clinical Decision Support toolkit offers a unique approach to introduce and address some of the key health issues that affect mid-life women.

Outcomes of implementing the women's health assessment tool and clinical decision support toolkit.

AIM: To evaluate outcomes after implementing the women's health assessment tool (WHAT) and clinical decision support toolkit during annual well-women visits. METHODS: An observational project involved women aged 45-64 years attending one of three medical sites in Washington (WA, USA). Responses to the WHAT questionnaire and patients' health resource utilization prepost toolkit implementation were analyzed. RESULTS: A total of 110 women completed the WHAT questionnaire. Majority of women were postmenopausal (77.3%) and experienced depressive mood (63.6%), hot flashes (61.8%) or anxiety (60.9%) in the last 3 months. There was a 72.2% increase in the number of diagnoses made during the annual visit versus the previous 12 months. CONCLUSION: The WHAT/clinical decision support toolkit helped identify conditions relevant to mid-life women.

Insight into Best Variables for COPD Case Identification: A Random Forests Analysis.

RATIONALE: This study is part of a larger, multi-method project to develop a questionnaire for identifying undiagnosed cases of chronic obstructive pulmonary disease (COPD) in primary care settings, with specific interest in the detection of patients with moderate to severe airway obstruction or risk of exacerbation. OBJECTIVES: To examine 3 existing datasets for insight into key features of COPD that could be useful in the identification of undiagnosed COPD. METHODS: Random forests analyses were applied to the following databases: COPD Foundation Peak Flow Study Cohort (N=5761), Burden of Obstructive Lung Disease (BOLD) Kentucky site (N=508), and COPDGene® (N=10,214). Four scenarios were examined to find the best, smallest sets of variables that distinguished cases and controls:(1) moderate to severe COPD (forced expiratory volume in 1 second [FEV1] <50% predicted) versus no COPD; (2) undiagnosed versus diagnosed COPD; (3) COPD with and without exacerbation history; and (4) clinically significant COPD (FEV1<60% predicted or history of acute exacerbation) versus all others. RESULTS: From 4 to 8 variables were able to differentiate cases from controls, with sensitivity ≥73 (range: 73-90) and specificity >68 (range: 68-93). Across scenarios, the best models included age, smoking status or history, symptoms (cough, wheeze, phlegm), general or breathing-related activity limitation, episodes of acute bronchitis, and/or missed work days and non-work activities due to breathing or health. CONCLUSIONS: Results provide insight into variables that should be considered during the development of candidate items for a new questionnaire to identify undiagnosed cases of clinically significant COPD.

A Qualitative Comparison of Symptoms and Impact of Varying Stages of Basal Cell Carcinoma.

INTRODUCTION: Basal cell carcinoma (BCC) is the most common form of skin cancer; however, few data are available relating to patients' perspectives and experiences of this disease. This study explored the spectrum of BCC symptoms and their impact by disease stage to determine how BCC affects the overall health-related quality of life (HRQL) of patients. METHODS: This study comprised a cross-sectional, qualitative approach involving telephone interviews with patients with BCC who had been divided into two groups: group 1 (G1), patients with stage 1, non-advanced BCC (and of superficial or nodular histology); and group 2 (G2), patients with locally advanced or metastatic BCC. Patients were recruited from three clinical sites in the USA based on a separate qualitative interview study (I4J-MC-HHBB [1.3]) over a 10-month period. Techniques in qualitative methodology were used by applying 'open-ended' questions and probing techniques intended to elicit patients' own description of their experiences with BCC. Telephone interviews lasted between 60 and 90 mins. RESULTS: Thirty-four interviews were conducted (G1: N = 13; G2: N = 21). The majority of patients were aged either 55-64 years (32%, N = 11) or 76+ years (32%, N = 11) and were primarily male (82%, N = 28); most (75%, N = 24) patients were actively receiving BCC treatment. Both groups reported similar symptoms, with the most common being red lesions or open sores that failed to heal (41%, N = 14) and cancer-related stress (41%, N = 14). G2 reported more frequent and severe HRQL impact as a result of their cancer condition because most were affected in their daily activities (76%, N = 16) or emotional well-being (71%, N = 15). Cosmetic and functional impacts were relevant and important aspects of HRQL for both patient groups (G1: 31%, N = 4; G2: 48%, N = 10). CONCLUSIONS: Patients with non-advanced or locally advanced and metastatic BCC experience disease-related symptoms that affect their HRQL, activities of daily living, emotional well-being, and social and/or leisure activities. Qualitative descriptions of patient experiences can help healthcare providers and caregivers better understand the impact of BCC from the patient perspective. FUNDING: Eli Lilly and Company.

Evaluating functional outcomes in adolescents with attention-deficit/hyperactivity disorder: development and initial testing of a self-report instrument.

BACKGROUND: Engaging adolescents in decisions about their health may enhance their compliance with treatment and result in better health outcomes. Treatment outcomes in attention-deficit/hyperactivity disorder (ADHD) are rarely evaluated from the adolescents' point of view. There is also concern that adolescents with ADHD may not have insight about the impacts of their disease. This article describes research conducted to understand the experiences of adolescents with ADHD and how the research was used to develop an adolescent self-report instrument. METHODS: This research involved an iterative process to ensure content validity and was conducted in the following stages: concept identification from literature reviews and interviews with teachers and clinicians; concept elicitation interviews with adolescents with ADHD and their caregivers, review of existing instruments; development of a new instrument and cognitive interviews. Experts in instrument development and translation and clinical practitioners in ADHD also participated. RESULTS: A conceptual framework to measure the impact of ADHD on adolescent functioning identified from concept identification research informed concept elicitation interviews with 60 adolescents with ADHD and their primary caregivers. In the interviews, adolescents discussed difficulties with performing activities in various contexts: school, home, leisure activities and social interactions. Caregivers provided additional insights. The instrument review revealed that none of the existing instruments were suitable to collect data on the elicited concepts; therefore, a new instrument was developed. Revisions were made to the format and content of the instrument (a daily diary) based on feedback received from cognitive testing with 15 adolescents. CONCLUSIONS: Our research helped to obtain a comprehensive understanding of the impacts of ADHD on adolescent functioning, to inform the development of a new instrument for measuring outcomes. Adolescents were able to discuss the impact of ADHD on their lives in concept elicitation interviews and report the impacts of ADHD on a self-report instrument. The new instrument developed to reflect the perspective of adolescents with ADHD can be used to supplement outcome assessments in clinic and research settings. Scientific advocacy for the use of such measures can be valuable to measure outcomes meaningful to adolescents with ADHD and the clinical community.

Identifying Patients with Undiagnosed COPD in Primary Care Settings: Insight from Screening Tools and Epidemiologic Studies.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality, yet research suggests this disease is greatly underdiagnosed. This literature review sought to summarize the most common and significant variables associated with case-finding or missed cases of COPD to inform more effective and efficient detection of high-risk COPD patients in primary care. METHODS: PubMed and EMBASE were searched for articles describing case-finding and epidemiologic research to detect or characterize new cases of COPD. International studies in primary and non-primary care settings, published in English from 2002-2014, were eligible for inclusion. Studies related to risk factors for development of COPD were excluded. RESULTS: Of the 33 studies identified and reviewed, 21 were case-finding or screening and 12 were epidemiological, including cross-sectional, longitudinal, and retrospective designs. A range of variables were identified within and across studies. Variables common to both screening and epidemiological studies included age, smoking status, and respiratory symptoms. Seven significant predictors from epidemiologic studies did not appear in screening tools. No studies targeted discovery of higher risk patients such as those with reduced lung function or risks for exacerbations. CONCLUSION: Variables used to identify new cases of COPD or differentiate COPD cases and non-cases are wide- ranging, (from sociodemographic to self-reported health or health history variables), providing insight into important factors for case identification. Further research is underway to develop and test the best, smallest variable set that can be used as a screening tool to identify people with undiagnosed, high-risk COPD in primary care.

Identifying cases of undiagnosed, clinically significant COPD in primary care: qualitative insight from patients in the target population.

BACKGROUND: Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations. AIMS: This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care. METHODS: Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care). Phase I: Eight focus groups and six telephone interviews were conducted to elicit descriptions of risk factors for COPD, recent or historical acute respiratory events, and symptoms to inform the development of candidate items for the new questionnaire. Phase II: A new cohort of subjects participated in cognitive interviews to assess and modify candidate items. Two peak expiratory flow (PEF) devices (electronic, manual) were assessed for use in screening. RESULTS: Of 77 subjects, 50 participated in Phase I and 27 in Phase II. Six themes informed item development: exposure (smoking, second-hand smoke); health history (family history of lung problems, recurrent chest infections); recent history of respiratory events (clinic visits, hospitalisations); symptoms (respiratory, non-respiratory); impact (activity limitations); and attribution (age, obesity). PEF devices were rated easy to use; electronic values were significantly higher than manual (P<0.0001). Revisions were made to the draft items on the basis of cognitive interviews. CONCLUSIONS: Forty-eight candidate items are ready for quantitative testing to select the best, smallest set of questions that, together with PEF, can efficiently identify patients in need of diagnostic evaluation for clinically significant COPD.