Asmal translational neuropsychiatry research
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  • ? For many, the termrefers to the “bench-to-bedside” enterprise of harnessingknowledge from basic sciences to produce new drugs, devices, and treatment options for patients. For this area ofresearch—the interface between basic science and clinicalmedicine—the end point is the production of a promisingnew treatment that can be used clinically or commercialized (“brought to market”). This enterprise is vital, and hasbeen characterized as follows: “effective translation of thenew knowledge, mechanisms, and techniques generated byadvances in basic science research into new approaches forprevention, diagnosis, and treatment of disease is essentialfor improving health.”
  • Panel: Common traits in sub-Saharan Africa A tropical location with near uniform climate with alternating wet and hot seasons that is remarkable for the complete absence of winter Wide-based age-specific pyramid with high fertility and mortality rates and short life expectancy: 50–60% of the population are children age 50 years Mainly rural populations with recent but rapid rural to urban migration Widespread poverty and uneven distribution of infrastructure, financial, human and material resources in the health sector Absence of sound strategies for the collection and standardisation of data that make health statistics unreliable Social and political instability that leads to disorganisation of health services and sometimes emigration of populations Gross underdevelopment and unfavourable health conditions Presence of environmental factors (vectorial, toxic, infectious, mineral deficiencies, etc) with poorly understood causal association with epilepsy and progression of disease
  • pre-transitional diseases and poverty related conditions eg childhood undernutrition and infections, maternal mortality emerging chronic diseases eg obesity, heart disease, diabetes injuries - including interpersonal violence HIV/AIDS and TB epidemics (TB cases increased from 109,000 in 1996 to 341,165 in 2006. 55% cases also have HIV)
  • Studies in SSH are not easily accessible>1/2 epilepsy studies published in regional journals with low distributions and are not indexed in the international databasesMethodological constraints and inconsistencies make epidemiological studies difficult to compare. The biggest constraint in these studies is data collection—clear endpoints are difficult to measure and representative populations hard to recruit. Screening questionnaires, typically used to identify patients with epilepsy, cannot be used across different populations with diverse social or cultural backgrounds; moreover medical records are commonly incomplete. The lack of specialised personnel, particularly in neurology, and the almost complete absence of diagnostic equipment (there are 75 EEGs and 25 CT scanners in tropical Africa, and these are frequently out of order), means that the accuracy of diagnosis cannot be confidently ascertained. The use of different terminologies to classify seizures and epilepsy also hinders study comparison.
  • In China, for example, 49% of patients with dementia were classified as normally ageing and only 21% had adequate access to diagnostic assessment,7 compared with 20% and more than 70%, respectively, in Europe.
  • Figure. Sporadic and familial dementias in developing countriesRed-shaded countries have prevalence or incidence estimates of all dementias that have beendetermined to be similar (>5%) to those in developed countries (grey-shaded countries).Blue-shaded countries have significantly lower prevalence (<3%) of dementia. Sample sizesfor the estimates in the various studies were between 700 and 3200 individuals. Green-shaded areas show countries where there are published cases of dementia or subtypes (ADor VaD), where risk factors have been examined but prevalence or incidence are unknown.Reliable information was not available for countries without shading. Red spots showlocations of families with neurodegenerative and vascular disorders causing dementiaincluding AD, Parkinson's disease, Lewy body disease, frontotemporal lobar degeneration,Huntington's disease, amyotrophic lateral sclerosis, and CADASIL. Information ondementia prevalence and types was derived from many sources.22,29,31,35,37–39,41,45,46,49– 52,58,62–73
  • Clearly progress has been made. A recent Lancet review[41] highlights both the growing awareness of the importance of dementia in developing countries and the burgeoning evidence base. Nevertheless, much more research is needed to close the 10/66 gap. There is still a need for a definitive multi-centric prevalence survey in India with true nationwide scope, encompassing regional, cultural, ethnic, religious, socioeconomic and rural/ urban diversity. Such a survey, whether or not it used the 10/66 methodology, would be enhanced by a common protocol in all centers, with a one phase design including the ascertainment of comorbid chronic diseases, disability, needs for care, care arrangements and health service utilization. It would provide a much needed baseline to monitor, in future surveys, trends in demographic ageing and the health transition. Also missing, for India, is any large-scale prospective study of risk factors for dementia, with biological samples (DNA, hematology, fasting glucose and lipids and frozen serum for later evaluation), other cardiovascular risk factor exposures, diet and anthropometry all collected at baseline. The 10/66 Dementia Research Group has succeeded in establishing such a study across our Latin American network and, to an extent in China, but not yet in India where the need is just as great. Finally, there is a great need, as indicated above, to develop packages and programs of care for people with dementia and their caregivers, which, their cost-effectiveness having been established, would be capable of being scaled up across India’s complex mixed healthcare system.

Asmal translational neuropsychiatry research Presentation Transcript

  • 1. Bridging Bedside and Bench Translational Neuropsychiatry Research in Africa
    University of Stellenbosch, Cape Town, South Africa
  • 2. Schizophrenia Research Overview
    120 FEP participants (matched controls)
    Treated with Flupenthixoldecanoate, 2 year follow-up
    Predictors of outcome, course of illness, ethnic differences, structural brain changes
    Confluence subsample
    RCT, risperidone or flupenthixolimi
    Structural and functional MRI changes
    Stanley discontinuation study
    Omega 3 and ALA
    Other – cochrane, genetics, family therapy study, metabolic disease, early childhood trauma, criminality
  • 3. Translational Neuropsychiatry Research in Africa
  • 4. Bedside to bench and back
    1. Woolf SH, 2009
  • 5. Translational Neuropsychiatry Research in Africa
  • 6. Africa is not a country!
  • 7. But what do we have in common?
    Wide-based age pyramid
    Rural populations with recent but rapid urban migration
    Social and political instability
    Widespread poverty and unevenly distributed health resources
    Absence of sound strategies for data collection
    Quadruple burden of disease
    Preux PM, 2005
  • 8. Quadruple burden of disease
    Pre-transitional diseases and poverty related conditions
    childhood undernutrition and infections, maternal mortality
    Emerging chronic diseases
    obesity, heart disease, diabetes
    including interpersonal violence
    HIV/AIDS, TB, malaria
    MRC Burden of Disease Unit, 2004
  • 9. World Land Area
  • 10. Urban slums
  • 11. Undernourishment
  • 12. HIV Prevalence
  • 13. Syphilis deaths
  • 14. Epilepsy deaths
  • 15. Stroke deaths
  • 16. Translational NeuropsychiatryResearch in Africa
  • 17. What is Neuropsychiatry?
    Mental disorders caused by:
    Structural brain dysfunction
    Electrical malfunction
    Extrinsic toxic-metabolic derangements
    Emphasises neurological basis of mental illness
    Utilises modern neurodiagnostic investigations in evaluation and treatment
    Hurwitz M, 2009
  • 18. Challenges facing Neuropsychiatry Research in Africa
    Studies in SSH are not easily accessible
    Methodological constraints make epidemiological studies difficult to compare.
    Clear endpoints difficult to measure
    Questionnaires not suitable for diverse populations
    Medical records are commonly incomplete
    Lack of specialised personnel, diagnostic equipment
    Use of different terminologies to classify disorders.
    Preux, 2005
  • 19. Dementia: a Developed World problem?
    71% of dementia in developing countries by 20406
    Prevalence is increasing in developing countries5
    shorter survival, lack of awareness, inadequate diagnostic assessments, variability of costs of care – under-reporting
    Research focus on elderly population
    Some work on HIV
    Kalaria R, 2008
    Prince M, 2009
  • 20. Dementia Developing Countries
    6. Kalaria J, 2008
  • 21. Case vignettes
  • 22. Alternate pathophysiology?
    • Economic deprivation
    • 23. Low education
    • 24. Unemployment
    • 25. Inadequate housing
    • 26. Lack of basic eminities
    • 27. Overcrowding
    • Higher prevalence
    • 28. Earlier onset
    • 29. Poor/lack of care
    • 30. More severe course
    • 31. Infectious diseases
    • 32. High stressors
    • 33. Inadequately treated depression
    • 34. Reduced access to social capital
    • 35. Malnutrition
    • 36. Obstetric risks
    • 37. Epilepsy
    • 38. Violence and trauma
  • Layering of risk factors
  • 39. What do we need?
    Multi-centric prevalence survey across Africa
    Sufficient participantsencompassing diversity
    Common protocol
    Focus on co-morbidity
    Carer, need for care, disability, health care use
    Biological samples (DNA, haematology, fasting glucose and lipids and frozen serum)
    Longitudinal studies to better estimate incidence, morbidity, and mortality.
    Dissemination of knowledge
  • 40. References
    Woolf SH. JAMA, Jan 2008; 299(2) The Meaning of Translational Research and why it matters: 211-213
    Preux PM, Druet-CabanacM. Epidemiology and aetiology of epilepsy in sub-Saharan Africa. Lancet Neurol 2005; 4: 21–31
    MRC Burden of Disease Unit, 2004
    Hurwitz, Fundamentals of Neuropsychiatry, UBC, 2009
    Kalaria et al. Alzheimer'sdisease and vasculardementia in developing countries: prevalence, management, and riskfactors. Lancet Neurol. 2008 Sep; 7(9): 812–826.
    Prince MJ, The 10/66 dementia research group - 10 years on. Indian J Psychiatry. 2009 January; 51(Suppl1): S8–S15.