Challenges and solutions during analysis in a longitudinal narrative case study.

AIM: To describe the challenges faced by those performing complex qualitative analysis during a narrative study and to offer solutions. BACKGROUND: Qualitative research requires rigorous analysis. However, novice researchers often struggle to identify appropriately robust analytical procedures that will move them from their transcripts to their final findings. The lack of clear and detailed accounts in the literature that consider narrative analysis and how to address some of the common challenges researchers face add to this problem. DATA SOURCES: A longitudinal narrative case study exploring the personal and familial changes reported by uninjured family members during the first year of another family member's traumatic brain injury. Review methods This is a methodological paper. DISCUSSION: The challenges of analysis included: conceptualising analysis; demonstrating the relationship between the different analytical layers and the final research findings; interpreting the data in a way that reflected the priorities of a narrative approach; and managing large quantities of data. The solutions explored were: the mapping of analytic intentions; aligning analysis and interpretation with the conceptual framework; and the use of matrices to store and manage quotes, codes and reflections. CONCLUSION: Working with qualitative data can be daunting for novice researchers. Ensuring rigorous, transparent, and auditable data analysis procedures can further constrain the interpretive aspect of analysis. Implications for research/practice The solutions offered in this paper should help novice researchers to manage and work with their data, assisting them to develop the confidence to be more intuitive and creative in their research

Neurotrauma clinicians' perspectives on the contextual challenges associated with long-term follow-up following traumatic brain injury in low-income and middle-income countries: a qualitative study protocol.

INTRODUCTION: Traumatic brain injury (TBI) is a global public health concern; however, low/middle-income countries (LMICs) face the greatest burden. The WHO recognises the significant differences between patient outcomes following injuries in high-income countries versus those in LMICs. Outcome data are not reliably recorded in LMICs and despite improved injury surveillance data, data on disability and long-term functional outcomes remain poorly recorded. Therefore, the full picture of outcome post-TBI in LMICs is largely unknown. METHODS AND ANALYSIS: This is a cross-sectional pragmatic qualitative study using individual semistructured interviews with clinicians who have experience of neurotrauma in LMICs. The aim of this study is to understand the contextual challenges associated with long-term follow-up of patients following TBI in LMICs. For the purpose of the study, we define 'long-term' as any data collected following discharge from hospital. We aim to conduct individual semistructured interviews with 24-48 neurosurgeons, beginning February 2020. Interviews will be recorded and transcribed verbatim. A reflexive thematic analysis will be conducted supported by NVivo software. ETHICS AND DISSEMINATION: The University of Cambridge Psychology Research Ethics Committee approved this study in February 2020. Ethical issues within this study include consent, confidentiality and anonymity, and data protection. Participants will provide informed consent and their contributions will be kept confidential. Participants will be free to withdraw at any time without penalty; however, their interview data can only be withdrawn up to 1 week after data collection. Findings generated from the study will be shared with relevant stakeholders such as the World Federation of Neurosurgical Societies and disseminated in conference presentations and journal publications

Genetic studies of hypertrophic cardiomyopathy in Singaporeans identify variants in TNNI3 and TNNT2 that are common in Chinese patients

Background - To assess the genetic architecture of hypertrophic cardiomyopathy (HCM) in patients of predominantly Chinese ancestry. Methods - We sequenced HCM disease genes in Singaporean patients (n=224) and Singaporean controls (n=3,634), compared findings with additional populations and Caucasian HCM cohorts (n=6,179) and performed in vitro functional studies. Results - Singaporean HCM patients had significantly fewer confidently interpreted HCM disease variants (Pathogenic (P)/Likely Pathogenic (LP):18%, p<0.0001) but an excess of variants of unknown significance (exVUS: 24%, p<0.0001), as compared to Caucasians (P/LP: 31%, exVUS: 7%). Two missense variants in thin filament encoding genes were commonly seen in Singaporean HCM (TNNI3:p.R79C, disease allele frequency (AF)=0.018; TNNT2:p.R286H, disease AF=0.022) and are enriched in Singaporean HCM when compared with Asian controls (TNNI3:p.R79C, Singaporean controls AF=0.0055, p=0.0057, gnomAD-East Asian (gnomAD-EA) AF=0.0062, p=0.0086; TNNT2:p.R286H, Singaporean controls AF=0.0017, p<0.0001, gnomAD-EA AF=0.0009, p<0.0001). Both these variants have conflicting annotations in ClinVar and are of low penetrance (TNNI3:p.R79C, 0.7%; TNNT2:p.R286H, 2.7%) but are predicted to be deleterious by computational tools. In population controls, TNNI3:p.R79C carriers had significantly thicker left ventricular walls compared to non-carriers while its etiological fraction is limited (0.70, 95% CI: 0.35-0.86) and thus TNNI3:p.R79C is considered a VUS. Mutant TNNT2:p.R286H iPSC-CMs show hypercontractility, increased metabolic requirements and cellular hypertrophy and the etiological fraction (0.93, 95% CI: 0.83-0.97) support the likely pathogenicity of TNNT2:p.R286H. Conclusions - As compared to Caucasians, Chinese HCM patients commonly have low penetrance risk alleles in TNNT2 or TNNI3 but exhibit few clinically actionable HCM variants overall. This highlights the need for greater study of HCM genetics in non-Caucasian populations

Neurosurgeons’ experiences of conducting and disseminating clinical research in low- and middle-income countries: a qualitative study protocol

Low-income and middle-income countries (LMICs) face the greatest burden of neurotrauma. However, most of the research published in scientific journals originates from high-income countries, suggesting those in LMICs are either not engaging in research or are not publishing it. Evidence originating in high-income countries may not be generalisable to LMICs; therefore, it is important to nurture research capacity in LMICs so that a relevant evidence base can be developed. However, little is published about specific challenges or contextual issues relevant to increasing research activity of neurosurgeons in LMICs. Therefore, the aim of this study was to understand neurosurgeons’ experiences of, aspirations for and ability to conduct and disseminate clinical research in LMICs.Methods and analysisThis is a pragmatic qualitative study situated within the naturalistic paradigm using focus groups and interviews with a purposive sample of neurosurgeons from LMICs. First, we will conduct asynchronous online focus groups with 36 neurosurgeons to broadly explore issues relevant to the study aim. Second, we will select 20 participants for follow-up semistructured interviews to explore concepts in more depth and detail than could be achieved in the focus group. Interviews will be audio-recorded and transcribed verbatim. A thematic analysis will be conducted following Braun and Clarke’s six stages and will be supported by NVIVO software.Ethics and disseminationThe University of Cambridge Psychology Research Ethics Committee reviewed this study and provided a favourable opinion in January 2020 (REF PRE.2020.006). Participants will provide informed consent, be able to withdraw at any time and will have their contributions kept confidential. The findings of the study will be shared with relevant stakeholders and disseminated in conference presentations and journal publications.</jats:sec

Qualitative research methods in neurosurgery: an unexplored avenue.

OBJECTIVE: Explore the value and potential of qualitative research to neurosurgery and provide insight and understanding to this underused methodology. BACKGROUND: The definition of qualitative research is critically discussed and the heterogeneity within this field of inquiry explored. The value of qualitative research to the field of neurosurgery is articulated through its contribution to understanding complex clinical problems. DISCUSSION: To resolve some of the misunderstanding of qualitative research, this paper discusses research design choices. We explore approaches that use qualitative techniques but are not, necessarily, situated within a qualitative paradigm in addition to how qualitative research philosophy aids researchers to conduct interpretive inquiry that can reveal more than simply what was said by participants. Common research designs associated with qualitative inquiry are introduced, and how complex analysis may contribute more in-depth insights is explained. Approaches to quality are discussed briefly to support improvements in qualitative methods and qualitative manuscripts. Finally, we consider the future of qualitative research in neurosurgery, and suggest how to move forward in the qualitative neurosurgical evidence base. CONCLUSION: There is enormous potential for qualitative research to contribute to the advancement of person-centred care within neurosurgery. There are signs that more qualitative research is being conducted and that neurosurgical journals are increasingly open to this methodology. While studies that do not engage fully within the qualitative paradigm can make important contributions to the evidence base, due regard should be given to immersive inquiry within qualitative paradigms to allow complex, in-depth, investigations of the human experience

Precision phenotyping of dilated cardiomyopathy using multidimensional data.

BACKGROUND: Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction. OBJECTIVES: The purpose of this study was to identify novel, reproducible subphenotypes of DCM using multiparametric data for improved patient stratification. METHODS: Longitudinal, observational UK-derivation (n = 426; median age 54 years; 67% men) and Dutch-validation (n = 239; median age 56 years; 64% men) cohorts of DCM patients (enrolled 2009-2016) with clinical, genetic, cardiovascular magnetic resonance, and proteomic assessments. Machine learning with profile regression identified novel disease subtypes. Penalized multinomial logistic regression was used for validation. Nested Cox models compared novel groupings to conventional risk measures. Primary composite outcome was cardiovascular death, heart failure, or arrhythmia events (median follow-up 4 years). RESULTS: In total, 3 novel DCM subtypes were identified: profibrotic metabolic, mild nonfibrotic, and biventricular impairment. Prognosis differed between subtypes in both the derivation (P < 0.0001) and validation cohorts. The novel profibrotic metabolic subtype had more diabetes, universal myocardial fibrosis, preserved right ventricular function, and elevated creatinine. For clinical application, 5 variables were sufficient for classification (left and right ventricular end-systolic volumes, left atrial volume, myocardial fibrosis, and creatinine). Adding the novel DCM subtype improved the C-statistic from 0.60 to 0.76. Interleukin-4 receptor-alpha was identified as a novel prognostic biomarker in derivation (HR: 3.6; 95% CI: 1.9-6.5; P = 0.00002) and validation cohorts (HR: 1.94; 95% CI: 1.3-2.8; P = 0.00005). CONCLUSIONS: Three reproducible, mechanistically distinct DCM subtypes were identified using widely available clinical and biological data, adding prognostic value to traditional risk models. They may improve patient selection for novel interventions, thereby enabling precision medicine