Clinical impact of genomic testing in patients with suspected monogenic kidney disease

Purpose: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. Methods: We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Results: ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion: In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design

Meeting the challenges of implementing rapid genomic testing in acute pediatric care

Authors: Stark, Z. Lunke, S. Brett, G. Tan, N. Stapleton, R. Kumble, S. Yeung, A. Phelan, D. Chong, B. Fernandez, M.F. Marum, J.E. Hunter, M. Jarmolowicz, A. Yael Prawer, Y. Riseley, J.R. Regan, M. Elliott, J. Melissa Martyn, M. Best, S. Tan, T. Clara L Gaff, C.L. and White, S.M

Statins and Memory Loss: The Australian Perspective

Background Statins are a first-line drug treatment for hypercholesterolaemia. Recently there has been general public and media interest surrounding uses and side effects of statins, including memory loss. Aims We analysed an Australian experience in statin usage in an attempt to improve understanding of the relationship between statins and memory-related adverse events. Methods Total adverse events (TAE) and adverse events with single suspected medicines (SSM) for memory loss and other memory-related adverse events were searched for statin compounds from January 1992 to May 2013, using the Medicare Australia and Pharmaceutical Benefits Scheme (PBS) websites and Therapeutic Goods Administration (TGA) adverse events data. TAE and SSM were compared to the number of prescriptions by item number searched using the PBS. The process was repeated for non-statin cholesterol-lowering drugs. Results The most common adverse event was amnesia (167 events for statins and six for non-statins). There were 239 TAE (incidence rate=0.88) listed for statins and 10 for non-statins (incidence rate=0.53). There were 217 SSM events listed for the statins (incidence rate = 0.08) and eight for the alternatives (incident rate=0.04). The differences between TAE and SSM incidence rates between statins and non-statins drugs were not significant (both p values >0.05). Conclusion We found that there were no differences in memory-related adverse events between statins and other cholesterol-lowering medications using Australian PBS and TGA adverse events data

Barriers/enablers to genetics in speech-language pathology (Lauretta et al., 2023)

Purpose: Advancements in genetic testing and analysis have allowed improved identification of the genetic basis of childhood apraxia of speech, a rare speech presentation. This study aimed to understand speech-language pathologists’ (SLPs’) consideration of incorporation of genetics in clinical practice using a theory-informed qualitative approach.Method: Semistructured interviews were conducted with 12 pediatric SLPs using a behavior change theory (Theoretical Domains Framework [TDF]) within a case study describing a child with complex co-occurring features, including childhood apraxia of speech. Interviews focused on three stages of the patient journey (prereferral, referral, and postreferral). Interviews were analyzed to identify barriers and enablers to considering incorporation of genetics in current clinical practice. Barriers and enablers were grouped and mapped onto a contextually relevant TDF-coded analysis framework.Results: Barriers were identified across several TDF domains, through all stages of the patient journey. Lack of confidence, relevance, and level of experience were most common prereferral, and connection to and awareness of genetics services and contextual factors were barriers in the referral stage. Perception of professional role, knowledge, and beliefs about effects on families were barriers postreferral. Associated enablers were also identified, including seeing value in genetic diagnosis, support from other health care professionals, supervision, and relationships with genetics services.Conclusions: Results of this qualitative study highlight barriers and enablers to incorporating genetics into speech-language pathology clinical practice. These findings will assist in the development of theory-informed implementation strategies to support SLPs into the future.Supplemental Material S1. Clinical vignette.Supplemental Material S2. Interview guide.Supplemental Material S3. TDF domains in context.Supplemental Material S4. Complete list of barriers and associated enablers.Lauretta, M. L., Jarmolowicz, A., Amor, D. J., Best, S., & Morgan, A. T. (2023). An investigation of barriers and enablers for genetics in speech-language pathology explored through a case study of childhood apraxia of speech. Journal of Speech, Language, and Hearing Research. Advance online publication. https://doi.org/10.1044/2023_JSLHR-22-00714Publisher Note: This article is part of the Special Issue: Selected Papers From the 2022 Apraxia Kids Research Symposium.</p