Weight loss, insulin resistance, and study design confound results in a meta-analysis of animal models of fatty liver

The classical drug development pipeline necessitates studies using animal models of human disease to gauge future efficacy in humans, however there is a low conversion rate from success in animals to humans. Non-alcoholic fatty liver disease (NAFLD) is a complex chronic disease without any established therapies and a major field of animal research. We performed a meta-analysis with meta-regression of 603 interventional rodent studies (10,364 animals) in NAFLD to assess which variables influenced treatment response. Weight loss and alleviation of insulin resistance were consistently associated with improvement in NAFLD. Multiple drug classes that do not affect weight in humans caused weight loss in animals. Other study design variables, such as age of animals and dietary composition, influenced the magnitude of treatment effect. Publication bias may have increased effect estimates by 37-79%. These findings help to explain the challenge of reproducibility and translation within the field of metabolism

A Systematic Review of Animal Models of NAFLD Finds High‐Fat, High‐Fructose Diets Most Closely Resemble Human NAFLD

Background and Aims: Animal models of human disease are a key component of translational hepatology research, yet there is no consensus on which model is optimal for NAFLD. Approach and Results: We generated a database of 3,920 rodent models of NAFLD. Study designs were highly heterogeneous, and therefore, few models had been cited more than once. Analysis of genetic models supported the current evidence for the role of adipose dysfunction and suggested a role for innate immunity in the progression of NAFLD. We identified that high‐fat, high‐fructose diets most closely recapitulate the human phenotype of NAFLD. There was substantial variability in the nomenclature of animal models: a consensus on terminology of specialist diets is needed. More broadly, this analysis demonstrates the variability in preclinical study design, which has wider implications for the reproducibility of in vivo experiments both in the field of hepatology and beyond. Conclusions: This systematic analysis provides a framework for phenotypic assessment of NAFLD models and highlights the need for increased standardization and replication

A Systematic Review of Animal Models of NAFLD Finds High‐Fat, High‐Fructose Diets Most Closely Resemble Human NAFLD

Background and Aims: Animal models of human disease are a key component of translational hepatology research, yet there is no consensus on which model is optimal for NAFLD. Approach and Results: We generated a database of 3,920 rodent models of NAFLD. Study designs were highly heterogeneous, and therefore, few models had been cited more than once. Analysis of genetic models supported the current evidence for the role of adipose dysfunction and suggested a role for innate immunity in the progression of NAFLD. We identified that high‐fat, high‐fructose diets most closely recapitulate the human phenotype of NAFLD. There was substantial variability in the nomenclature of animal models: a consensus on terminology of specialist diets is needed. More broadly, this analysis demonstrates the variability in preclinical study design, which has wider implications for the reproducibility of in vivo experiments both in the field of hepatology and beyond. Conclusions: This systematic analysis provides a framework for phenotypic assessment of NAFLD models and highlights the need for increased standardization and replication

Conceptualising post-stroke fatigue: a cross-sectional survey of UK-based physiotherapists and occupational therapists.

With survival after stroke improving, more people are discharged into the community with multiple and persistent deficits. Fatigue is a common unmet need for stroke survivors, but there are no evidence-based guidelines for its assessment and management. This study explored how UK-based therapists conceptualise post-stroke fatigue (PSF) in current practice. OBJECTIVE: To describe current understanding of PSF among physiotherapists (PT) and occupational therapists (OT). DESIGN: A cross-sectional online survey using Qualtrics software (a survey creation and analysis programme) was sent to therapists working with stroke survivors in 2019. Responses to the open ended question, 'How would you describe PSF if approached by another healthcare professional?' were analysed thematically by two independent researchers. PARTICIPANTS: 137 survey respondents (71 PT and 66 OT) from a range of clinical settings (25 acute care, 24 sub-acute rehabilitation care, 3 primary care and 85 community care) with 7 months-36 years of experience working with stroke survivors completed the survey. RESULTS: Respondents stated that PSF should be regarded as an important medical condition because it is common and can be associated with severe symptoms. Symptoms were perceived to be highly variable and the syndrome was difficult to define objectively. It was felt to have both physical and cognitive components. A variety of different opinions were expressed with regard to causation, conceptualisation and best management. CONCLUSION: Therapists working with stroke survivors conceptualise and manage PSF in different ways. Clinical practice is hampered by a lack of a widely adopted definition, and a small evidence base. Research into causes and management of PSF is a priority.This study was funded by the Malati Kanbur Studentship fund kindly donated by Ravi Kanbur and Margaret Grieco to Lucy Cavendish College, constituent college of the University of Cambridge. JM is supported by an NIHR Senior Investigator award. Views expressed in this written publication are those of the authors and not necessarily those of the funders

Conceptualising post-stroke fatigue: a cross-sectional survey of UK-based physiotherapists and occupational therapists.

UNLABELLED: With survival after stroke improving, more people are discharged into the community with multiple and persistent deficits. Fatigue is a common unmet need for stroke survivors, but there are no evidence-based guidelines for its assessment and management. This study explored how UK-based therapists conceptualise post-stroke fatigue (PSF) in current practice. OBJECTIVE: To describe current understanding of PSF among physiotherapists (PT) and occupational therapists (OT). DESIGN: A cross-sectional online survey using Qualtrics software (a survey creation and analysis programme) was sent to therapists working with stroke survivors in 2019. Responses to the open ended question, 'How would you describe PSF if approached by another healthcare professional?' were analysed thematically by two independent researchers. PARTICIPANTS: 137 survey respondents (71 PT and 66 OT) from a range of clinical settings (25 acute care, 24 sub-acute rehabilitation care, 3 primary care and 85 community care) with 7 months-36 years of experience working with stroke survivors completed the survey. RESULTS: Respondents stated that PSF should be regarded as an important medical condition because it is common and can be associated with severe symptoms. Symptoms were perceived to be highly variable and the syndrome was difficult to define objectively. It was felt to have both physical and cognitive components. A variety of different opinions were expressed with regard to causation, conceptualisation and best management. CONCLUSION: Therapists working with stroke survivors conceptualise and manage PSF in different ways. Clinical practice is hampered by a lack of a widely adopted definition, and a small evidence base. Research into causes and management of PSF is a priority.This study was funded by the Malati Kanbur Studentship fund kindly donated by Ravi Kanbur and Margaret Grieco to Lucy Cavendish College, constituent college of the University of Cambridge. JM is supported by an NIHR Senior Investigator award. Views expressed in this written publication are those of the authors and not necessarily those of the funders