Methodological reflections on using pilot data from fracture patients to develop a qualitative study

Background: Qualitative studies are particularly valued for their exploratory nature but, like other research methods, they do require careful planning to ensure rigorous study design. Our objective was to undertake a pilot study to inform the development of a larger qualitative study. Results: We conducted a series of brief interviews with out-patients in a hospital setting. The interviews were designed to elicit superficial information about whether (and how) post-fracture osteoporosis investigation and/or treatment were being initiated among patients receiving treatment or follow-up for a current or recent fracture. We used thematic analysis to identify key themes in the data that related to the broader research questions. We analysed data obtained from 11 out of a total of 12 interviews conducted. Participants were male and female, aged 19-83 years of age (median age 57 years). Participants attended 2-8 medical appointments to seek treatment and follow up for a current or recent fracture. The following four overarching themes emerged from thematic analysis of the data: fracture event, referral pathway, osteoporosis investigation and/or treatment, and communication by health practitioners and staff. Conclusions: This pilot study was necessarily tentative and exploratory in nature, but provided a helpful snapshot of some typical experiences in the public health system following fracture. Several themes emerged for consideration in the design of the main study. Despite its critics, theoretical sampling and saturation continue to provide sustainable methods for ensuring that relevant themes and categories are covered in sufficient depth and breadth, appropriate to the needs of the study

Methodological reflections on using pilot data from fracture patients to develop a qualitative study

Background: Qualitative studies are particularly valued for their exploratory nature but, like other research methods, they do require careful planning to ensure rigorous study design. Our objective was to undertake a pilot study to inform the development of a larger qualitative study.Results: We conducted a series of brief interviews with out-patients in a hospital setting. The interviews were designed to elicit superficial information about whether (and how) post-fracture osteoporosis investigation and/or treatment were being initiated among patients receiving treatment or follow-up for a current or recent fracture. We used thematic analysis to identify key themes in the data that related to the broader research questions. We analysed data obtained from 11 out of a total of 12 interviews conducted. Participants were male and female, aged 19-83 years of age (median age 57 years). Participants attended 2-8 medical appointments to seek treatment and follow up for a current or recent fracture. The following four overarching themes emerged from thematic analysis of the data: fracture event, referral pathway, osteoporosis investigation and/or treatment, and communication by health practitioners and staff.Conclusions: This pilot study was necessarily tentative and exploratory in nature, but provided a helpful snapshot of some typical experiences in the public health system following fracture. Several themes emerged for consideration in the design of the main study. Despite its critics, theoretical sampling and saturation continue to provide sustainable methods for ensuring that relevant themes and categories are covered in sufficient depth and breadth, appropriate to the needs of the study.<br /

Diagnostic and cost utility of whole exome sequencing in peripheral neuropathy.

OBJECTIVE: To explore the diagnostic utility and cost effectiveness of whole exome sequencing (WES) in a cohort of individuals with peripheral neuropathy. METHODS: Singleton WES was performed in individuals recruited though one pediatric and one adult tertiary center between February 2014 and December 2015. Initial analysis was restricted to a virtual panel of 55 genes associated with peripheral neuropathies. Patients with uninformative results underwent expanded analysis of the WES data. Data on the cost of prior investigations and assessments performed for diagnostic purposes in each patient was collected. RESULTS: Fifty patients with a peripheral neuropathy were recruited (median age 18 years; range 2-68 years). The median time from initial presentation to study enrollment was 6 years 9 months (range 2 months-62 years), and the average cost of prior investigations and assessments for diagnostic purposes AU$4013 per patient. Eleven individuals received a diagnosis from the virtual panel. Eight individuals received a diagnosis following expanded analysis of the WES data, increasing the overall diagnostic yield to 38%. Two additional individuals were diagnosed with pathogenic copy number variants through SNP microarray. CONCLUSIONS: This study provides evidence that WES has a high diagnostic utility and is cost effective in patients with a peripheral neuropathy. Expanded analysis of WES data significantly improves the diagnostic yield in patients in whom a diagnosis is not found on the initial targeted analysis. This is primarily due to diagnosis of conditions caused by newly discovered genes and the resolution of complex and atypical phenotypes

Longitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: a genome-wide association study

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an incurable lung disease characterised by progressive scarring leading to alveolar stiffness, reduced lung capacity, and impeded gas transfer. We aimed to identify genetic variants associated with declining lung capacity or declining gas transfer after diagnosis of IPF. METHODS: We did a genome-wide meta-analysis of longitudinal measures of forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) in individuals diagnosed with IPF. Individuals were recruited to three studies between June, 1996, and August, 2017, from across centres in the US, UK, and Spain. Suggestively significant variants were investigated further in an additional independent study (CleanUP-IPF). All four studies diagnosed cases following American Thoracic Society/European Respiratory Society guidelines. Variants were defined as significantly associated if they had a meta-analysis p<5 × 10-8 when meta-analysing across all discovery and follow-up studies, had consistent direction of effects across all four studies, and were nominally significant (p<0·05) in each study. FINDINGS: 1329 individuals with a total of 5216 measures were included in the FVC analysis. 975 individuals with a total of 3361 measures were included in the DLCO analysis. For the discovery genome-wide analyses, 7 611 174 genetic variants were included in the FVC analysis and 7 536 843 in the DLCO analysis. One variant (rs115982800) located in an antisense RNA gene for protein kinase N2 (PKN2) showed a genome-wide significant association with FVC decline (-140 mL/year per risk allele [95% CI -180 to -100]; p=9·14 × 10-12). INTERPRETATION: Our analysis identifies a genetic variant associated with disease progression, which might highlight a new biological mechanism for IPF. We found that PKN2, a Rho and Rac effector protein, is the most likely gene of interest from this analysis. PKN2 inhibitors are currently in development and signify a potential novel therapeutic approach for IPF. FUNDING: Action for Pulmonary Fibrosis, Medical Research Council, Wellcome Trust, and National Institutes of Health National Heart, Lung, and Blood Institute

Rare and common vertebrates span a wide spectrum of population trends

Conservation biologists often assume that rare (or less abundant) species are more likely to be declining under anthropogenic change. Here, the authors synthesise population trend data for ~2000 animal species to show that population trends cover a wide spectrum of change from losses to gains, which are not related to species rarity