Using PROGRESS-Plus to identify current approaches to the collection and reporting of equity-relevant data: a scoping review

Objectives: Our objectives were to identify what and how data relating to the social determinants of health are collected and reported in equity-relevant studies and map these data to the PROGRESS-Plus framework. Study Design and Setting: We performed a scoping review. We ran two systematic searches of MEDLINE and Embase for equityrelevant studies published during 2021. We included studies in any language without limitations to participant characteristics. Included studies were required to have collected and reported at least two participant variables relevant to evaluating individual-level social determinants of health. We applied the PROGRESS-Plus framework to identify and organize these data. Results: We extracted data from 200 equity-relevant studies, providing 962 items defined by PROGRESS-Plus. A median of 4 (interquartile range 5 2) PROGRESS-Plus items were reported in the included studies. 92% of studies reported age; 78% reported sex/gender; 65% reported educational attainment; 49% reported socioeconomic status; 45% reported race; 44% reported social capital; 33% reported occupation; 14% reported place and 9% reported religion. Conclusion: Our synthesis demonstrated that researchers currently collect a limited range of equity-relevant data, but usefully provides a range of examples spanning PROGRESS-Plus to inform the development of improved, standardized practices.Emma L. Karrana, Aidan G. Cashina, Trevor Barker, Mark A. Boyd, Alessandro Chiarotto, Omar Dewidar, Vina Mohabir, Jennifer Petkovic Saurab Sharma, Sinan Tejani, Peter Tugwell, G. Lorimer Mosele

A pain science education and walking program to increase physical activity in people with symptomatic knee osteoarthritis: A feasibility study

Introduction: Nine of 10 people with knee osteoarthritis are inactive. Unhelpful pain beliefs may negatively influence physical activity levels. Targeting these unhelpful pain beliefs, through contemporary pain science education (PSE), may provide benefit. Objectives: To evaluate the feasibility of conducting a clinical trial to determine the effect of adding PSE (vs adding sham ultrasound) to an individualised, physiotherapist-led education and walking program in people with painful knee osteoarthritis. Methods: Twenty participants were randomised (1:1) into the PSE group or Control group, each receiving 4 in-person weekly treatments, then 4 weeks of at-home activities (weekly telephone check-in). Clinical outcomes and physical activity (7 days of wristworn accelerometry) were assessed at baseline, 4 (clinical outcomes only), 8, and 26 weeks. A priori feasibility criteria for recruitment, intervention adherence, viability of wrist-based accelerometry, and follow-up retention were set. Perceived intervention credibility, acceptability, and usefulness from participants and clinicians were assessed (ratings, written/verbal feedback). Results: Most feasibility criteria were met. On average, 7 adults/wk were eligible, with 70% recruited. Treatment compliance was high (in-person: 80% PSE; 100% Control; at-home: 78% PSE; 75% Control). Wrist-based accelerometry had .75% valid weartime. Sufficient follow-up rates were not achieved (26 weeks: 65%). Participant and clinician feedback highlighted that PSE was too complex and did not match patient expectations of “physiotherapy”, that sham ultrasound was problematic (clinician), but that both treatments had high credibility, acceptability, and usefulness. Conclusions: Progression to a full trial is warranted. Strategies to increase participant retention, refine the PSE content/delivery, and replace/remove the sham intervention are required.Tasha R. Stanton, Emma L. Karran, David S. Butler, Melissa J. Hull, Sarah N. Schwetlik, Felicity A. Braithwaite, Hannah G. Jones, G. Lorimer Moseley, Catherine L. Hill, Christy Tomkins-Lane, Carol Maher, Kim Bennel

Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes

Deletions of chromosome 8p are a recurrent event in B-cell non-Hodgkin lymphoma (B-NHL), suggesting the presence of a tumor suppressor gene. We have characterized these deletions using comparative genomic hybridization to microarrays, fluorescence in situ hybridization (FISH) mapping, DNA sequencing, and functional studies. A minimal deleted region (MDR) of 600 kb was defined in chromosome 8p21.3, with one mantle cell lymphoma cell line (Z138) exhibiting monoallelic deletion of 650 kb. The MDR extended from bacterial artificial chromosome (BAC) clones RP11-382J24 and RP11-109B10 and included the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene loci. Sequence analysis of the individual expressed genes within the MDR and DNA sequencing of the entire MDR in Z138 did not reveal any mutation. Gene expression analysis and quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) showed down-regulation of TRAIL-R1 and TRAIL-R2 receptor genes as a consistent event in B-NHL with 8p21.3 loss. Epigenetic inactivation was excluded via promoter methylation analysis. In vitro studies showed that TRAIL-induced apoptosis was dependent on TRAIL-R1 and/or -R2 dosage in most tumors. Resistance to apoptosis of cell lines with 8p21.3 deletion was reversed by restoration of TRAIL-R1 or TRAIL-R2 expression by gene transfection. Our data suggest that TRAIL-R1 and TRAIL-R2 act as dosage-dependent tumor suppressor genes whose monoallelic deletion can impair TRAIL-induced apoptosis in B-cell lymphoma

Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas

Integrative genomic and gene-expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene-expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated 20 homozygous deletions at 7 chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them were frequently silenced by epigenetic mechanisms. Notably, the pattern of genetic and epigenetic inactivation differed among B-NHL subtypes. Thus, the P53-inducible PIG7/LITAF was silenced by homozygous deletion in primary mediastinal B-cell lymphoma and by promoter hypermethylation in germinal center lymphoma, the proapoptotic BIM gene presented homozygous deletion in mantle cell lymphoma and promoter hypermethylation in Burkitt lymphoma, the proapoptotic BH3-only NOXA was mutated and preferentially silenced in diffuse large B-cell lymphoma, and INK4c/P18 was silenced by biallelic mutation in mantle-cell lymphoma. Our microarray strategy has identified novel candidate tumor suppressor genes inactivated by genetic and epigenetic mechanisms that substantially vary among the B-NHL subtypes

Back to the drawing board-The relationship between self-report and neuropsychological tests of cognitive flexibility in clinical cohorts: A systematic review and meta-analysis

Published online 7 April 2022Cognitive flexibility has been previously described as the ability to adjust cognitive and behavioral strategies in response to changing contextual demands. Cognitive flexibility is typically assessed via self-report questionnaires and performance on neuropsychological tests in research and clinical practice. A common assumption among researchers and clinicians is that self-report and neuropsychological tests of cognitive flexibility assess the same or similar constructs, but the extent of the relationship between these two assessment approaches in clinical cohorts remains unknown. We undertook a systematic review and meta-analysis to determine the relationship between self-report and neuropsychological tests of cognitive flexibility in clinical samples. We searched 10 databases and relevant gray literature (e.g., other databases and pearling) from inception to October 2020 and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Eleven articles including 405 participants satisfied our eligibility criteria. A multilevel random-effects meta-analysis revealed no relationship between self-report and neuropsychological tests of cognitive flexibility (0.01, 95% CI [-0.16 to 0.18]). Individual random-effects meta-analyses between 12 different tests pairs also found no relationship. Based on our results, it is clear that the two assessment approaches of cognitive flexibility provide independent information-they do not assess the same construct. These findings have important ramifications for future research and clinical practice-there is a need to reconsider what constructs self-report and neuropsychological tests of "cognitive flexibility" actually assess, and avoid the interchangeable use of these assessments in clinical samples.Caitlin A. Howlett, Michael A. Wewege, Carolyn Berryman, Annika Oldach, Elizabeth Jennings, Emily Moore, Emma L. Karran, Kimberley Szeto, Leander Pronk, Stephanie Miles, and G. Lorimer Mosele

Same room - different windows? A systematic review and meta-analysis of the relationship between self-report and neuropsychological tests of cognitive flexibility in healthy adults

Cognitive flexibility can be thought of as the ability to effectively adapt one's cognitive and behavioural strategies in response to changing task or environmental demands. To substantiate the common inference that self-report and neuropsychological tests of cognitive flexibility provide ‘different windows into the same room’, we undertook a systematic review and meta-analysis to determine whether self-report and neuropsychological tests of cognitive flexibility are related in healthy adults. Ten databases and relevant grey literature were searched from inception. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adhered to. Twenty-one articles satisfied our inclusion criteria. A multi-level random-effects meta-analysis revealed no relationship (0.05, 95% CI = −0.00 to 0.10). Random-effects meta-analyses raised the possibility that the Cognitive Flexibility Scale and the Trail Making Test – part B (time) may be related (0.19, 95% CI = 0.06 to 0.31). We conclude that the relationship between self-report and neuropsychological tests of cognitive flexibility is not large enough to be considered convincing evidence for the two assessment approaches sharing construct validity. These results have clear implications for assessing and interpreting cognitive flexibility research and clinical practice.Caitlin A. Howlett, Michael A. Wewege, Carolyn Berryman, Annika Oldach, Elizabeth Jennings, Emily Moore, Emma L. Karran, Kimberley Szeto, Leander Pronk, Stephanie Miles, G. Lorimer Mosele

Key Learning Statements for persistent pain education: an iterative analysis of consumer, clinician and researcher perspectives and development of public messaging

Over the last decade, the content, delivery and media of pain education have been adjusted in line with scientific discovery in pain and educational sciences, and in line with consumer perspectives. This paper describes a decade-long process of exploring consumer perspectives on pain science education concepts to inform clinician-derived educational updates (undertaken by the authors). Data were collected as part of a quality audit via a series of online surveys in which consent (non-specific) was obtained from consumers for their data to be used in published research. Consumers who presented for care for a persistent pain condition and were treated with a pain science education informed approach were invited to provide anonymous feedback about their current health status and pain journey experience 6, 12 or 18 months after initial assessment. Two-hundred eighteen consumers reported improvement in health status at follow-up. Results of the surveys from three cohorts of consumers that reported improvement were used to generate iterative versions of 'Key Learning Statements'. Early iteration of these Key Learning Statements was used to inform the development of Target Concepts and associated community-targeted pain education resources for use in public health and health professional workforce capacity building initiatives. Perspective This paper reflects an explicit interest in the insights of people who have been challenged by persistent pain and then recovered, to improve pain care. Identifying pain science concepts that consumers valued learning provided valuable information to inform resources for clinical interactions and community-targeted pain education campaigns.Hayley B. Leake, Amelia Mardon, Tasha R. Stanton, Daniel S. Harvie, David S. Butler, Emma L. Karran, Dianne Wilson, JohnBooth, Trevor Barker, Pene Wood, Kal Fried, Chris Hayes, Lissanthea Taylor, Melanie Macoun, Amanda Simister, G. Lorimer Moseley, Carolyn Berryma

Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes

Deletions of chromosome 8p are a recurrent event in B-cell non-Hodgkin lymphoma (B-NHL), suggesting the presence of a tumor suppressor gene. We have characterized these deletions using comparative genomic hybridization to microarrays, fluorescence in situ hybridization (FISH) mapping, DNA sequencing, and functional studies. A minimal deleted region (MDR) of 600 kb was defined in chromosome 8p21.3, with one mantle cell lymphoma cell line (Z138) exhibiting monoallelic deletion of 650 kb. The MDR extended from bacterial artificial chromosome (BAC) clones RP11-382J24 and RP11-109B10 and included the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene loci. Sequence analysis of the individual expressed genes within the MDR and DNA sequencing of the entire MDR in Z138 did not reveal any mutation. Gene expression analysis and quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) showed down-regulation of TRAIL-R1 and TRAIL-R2 receptor genes as a consistent event in B-NHL with 8p21.3 loss. Epigenetic inactivation was excluded via promoter methylation analysis. In vitro studies showed that TRAIL-induced apoptosis was dependent on TRAIL-R1 and/or -R2 dosage in most tumors. Resistance to apoptosis of cell lines with 8p21.3 deletion was reversed by restoration of TRAIL-R1 or TRAIL-R2 expression by gene transfection. Our data suggest that TRAIL-R1 and TRAIL-R2 act as dosage-dependent tumor suppressor genes whose monoallelic deletion can impair TRAIL-induced apoptosis in B-cell lymphoma

Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas

Integrative genomic and gene-expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene-expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated 20 homozygous deletions at 7 chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them were frequently silenced by epigenetic mechanisms. Notably, the pattern of genetic and epigenetic inactivation differed among B-NHL subtypes. Thus, the P53-inducible PIG7/LITAF was silenced by homozygous deletion in primary mediastinal B-cell lymphoma and by promoter hypermethylation in germinal center lymphoma, the proapoptotic BIM gene presented homozygous deletion in mantle cell lymphoma and promoter hypermethylation in Burkitt lymphoma, the proapoptotic BH3-only NOXA was mutated and preferentially silenced in diffuse large B-cell lymphoma, and INK4c/P18 was silenced by biallelic mutation in mantle-cell lymphoma. Our microarray strategy has identified novel candidate tumor suppressor genes inactivated by genetic and epigenetic mechanisms that substantially vary among the B-NHL subtypes