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Neurobehavioural performances associated with occupational hazards The poor state of

Neurobehavioural performances associated with occupational hazards The poor state of Neurobehavioural testing Prof. Craig Jackson Professor of Occupational Health Psychology Birmingham City University Hon Senior Lecturer in Occupational Psychology Institute of Occ & Env Medicine

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Neurobehavioural performances associated with occupational hazards The poor state of

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  1. Neurobehavioural performances associated with occupational hazards The poor state of Neurobehavioural testing Prof. Craig Jackson Professor of Occupational Health Psychology Birmingham City University Hon Senior Lecturer in Occupational PsychologyInstitute of Occ & Env Medicine University of Birmingham ResearchConsultants.co.uk

  2. Principles of Neurobehavioural Testing Damage to CNS due to exposure to Neurotoxic substances Neurotoxic medicines Metabolic disorders Neurotoxic diseases in top ten work-related diseases in USA Occupational exposures to toxins such as Lead Manganese Solvents Pesticides Herbicides Insecticides Contributors to the development of neurobehavioral dysfunction

  3. Neurobehavioural Testing Standard tests Evaluate different aspects of functioning of the CNS including Cognition Motor Skills Memory Reaction Time Coordination Attention Visuospatial Reasoning General Affect Non-invasive Portable Cheap Range of behavioural functions affected is extremely wide Investigators typically use sets (batteries) of tests.

  4. n Numbers recalled Rationale of Neurobehavioural Testing Evaluate functioning in individuals exposed to pathogens Normal population exhibits a range of performance function Exposure places individuals outside of that normal range Some factors affect performance: age sex education

  5. History Behavioural testing began in 1960s Hanninen (1979) developed first behavioural test battery Assess effects of chemicals and neurotoxins 1980 - 60 unique tests 1990 - 250 unique tests 1983 – WHO wanted battery to screen / identify nervous system effects

  6. Neurobehavioural Core Test Battery (NCTB) 1983 WHO & NIOSH Seven behavioural tests: Digit Span Santa Ana Dexterity Digit Symbol Pursuit Aiming II Benton Visual Retention Profile of Mood States Simple Reaction Time Johnson et al. 1987

  7. Minnesota Manual Dexterity Test

  8. Tower of Hanoi

  9. Finger Tapper

  10. Testing Must Be Cross-Cultural, Valid, & Reliable Higher proportion of: Minorities Foreign born > exposures to neurotoxins Poor status & pathogens May not speak English May be “developmentally delayed” Test batteries must be suitable for people of all abilities & backgrounds

  11. Testing Conditions All subjects tested under same conditions Standardized testing Not always possible in the field Furniture Lighting Visual distraction Ambient sound Temperature

  12. Factors to be Aware of in Testing STABLE FACTORSSITUATIONAL FACTORS Age Alcohol (recent use) Education Caffeine (recent use) Sex Nicotine (recent use) Socioeconomics Medication (recent use) Language Paints, glues, pesticides (recent) Handedness Near visual acuity Computer experience Restricted movement (injury) Caffeine (habitual use) Cold / flu Alcohol (habitual use) Stress Nicotine (habitual use) Arousal / Fatigue Medication (habitual use) Sleep Paint, glue, pesticide (habitual use) Screen luminance Diabetes Time of day Epilepsy Time of year Other CNS / PNS disease Alcohol / drug addiction Head injury (out >1 hr) Physical activity

  13. Problems of Neurobehavioural Testing Used since the 1960s in occ and env health toxicology Interpretation of different test scores is not straightforward Less straightforward role in the regulation of chemicals Difficulties neurobehavioural studies encountered by regulators (1) Studies lack scientific rigor (2) Interpretation of results of scientific studies e.g. clinically meaningful? which domains effected? smallest level of exposure associated with impairment? Stephens & Barker 1998

  14. Landmark Occupational Neurobehavioural Papers Stollery & Flindt 1988 Memory sequelae of solvent intoxication Stephens et al. 1995 Neuropsychological effects of long-term exposure to organophosphates in sheep dip Lucchini et al.1995 Neurobehavioral effects of manganese in workers from a ferroalloy plant after temporary cessation of exposure Kishi et al. 1994 Residual neurobehavioural effects associated with chronic exposure to mercury vapour Sjögren et al. 1996 Effects on the nervous system among welders exposed to aluminium and manganese Gamberale 1985 Use of behavioral performance tests in the assessment of solvent toxicity

  15. Landmark Occupational Neurobehavioural Papers Rosenstock et al. 1991 Chronic central nervous system effects of acute organophosphate pesticide intoxication. The Pesticide Health Effects Study Group Verberk et al. 1990 Health effects of pesticides in the flower-bulb culture in Holland Mackay et al. 1987 Behavioral changes during exposure to 1,1,1-trichloroethane: time-course and relationship to blood solvent levels.  Chia et al. 1994 Impairment of color vision among workers exposed to low concentrations of styrene Echeverria et al. 1995 A behavioral evaluation of PCE exposure in patients and dry cleaners: a possible relationship between clinical and preclinical effects

  16. “Careless” Neurobehavioural Testing and the Manganese Problem Current Problem in USA Steel Welding Parkinson’s Disease Neurobehavioural Testing Systematic Review Conclusion

  17. Litigation October 1st 2004 Larry Elam versus A.O. Smith Elam, former welder, aged 65 Developed PD Lifetime welder Wins £1M from Welding Rod Manufacturers

  18. Litigation

  19. Current Problem in USA March 25th 2005 Fed Judge Kathleen O’Malley “Valid scientific evidence supports the conclusion that manganese exposure is connected to dangerous side effects.” February 27th 2006 Fed Judge Kathleen O’Malley Ruled welding can cause serious neurological damage to welders Out of court settlement for 2 welders, made by welding rod manufacturing company ($ undisclosed )

  20. The Current Manganese Situation 1) Manganese Overload = Parkinson’s Disease 2) Welding Work = High Manganese Exposure Therefore . . . “Neurobehavioural testing is used to identify or screen workers with early symptoms of Parkinson’s disease” Could this be a flawed assumption?

  21. Welding of Steel Joins pieces of metal that have been made liquid by heat Metal pieces to be joined and a filler metal (rod) coming from a consumable Heat produced as electricity passes from one conductor to another Temperatures >4000 oC in the arc At least 80 different types of welding processes 365,000 welders in USA 1,000,000 full time welders globally 5,000,000 paid welders globally

  22. Welding Rods

  23. Review of the Neurobehavioural Mn Literature Three Objectives 1) Is there any evidence of occupational manganese exposure impairing neurobehavioural performance? 2) Which tests (domains) are best at demonstrating such impaired performance? 3) What is the smallest level of Mn exposure associated with test impairment?

  24. Systematic Review of the Literature 16 Databases Searched Medline & Pubmed HSE Line CISDOC NIOSHTIC & NIOSHTIC2 PsychoInfo Excerpta Medica Toxfile Embase SciSearch Biosis Previews Web of Science Web of knowledge Science Citation Index Social Science Citation Index

  25. Limitations: Human English Language 1970-2006 Systematic Review of the Literature Search Terms Cognition disorder Neurobehavioral / Neurobehavioural (deficit / impairment) Neurological Neuromotor Neuropsychiatric Neuropsychological (test(ing)) Neurotoxicology Neurotoxic Manganese Manganate Manganese alloy / dioxide / dust / ore / oxide Steel Welding Welders

  26. Systematic Review of the Literature The Better Quality Studies EU Guidelines for qualitative evaluation of neurobehavioural studies (1997) 1. Population of an adequate size relative to the number of tests used 2. Subject selection method which avoids bias for the exposed group 3. Subject selection method which avoids bias for the control group 4. Pre-stated exclusion/inclusion criteria for study participants 5. High response rate for the exposed group (usually > 60%) 6. High response rate for the control group (usually > 60%) where applicable 7. Control or adjustment for important confounders / modifiers of performance 8. Inclusion of quantitative or semi-quantitative assessment of long-term exposure 9. Control for recent exposure (where applicable) 10. An indication of the standardization of testing conditions After applying Quality Criteria, only 12 studies were of “Better Quality”

  27. Expected Neurobehavioural Differences Cognition Motor Skills Memory Reaction Time Coordination Attention Visuospatial Reasoning exposed controls poorer better faster slower better poorer better poorer faster slower better poorer better poorer

  28. Systematic Review of the Literature Initial Search Results 153 articles 42 symptoms alone – not NB Exclusion Criteria Investigations of non-occupational exposure Investigations of multiple substances Animal studies Child studies Test development studies Single case studies of living patients Pathological reports of deceased individuals Investigations involving only neurophysiology Investigations involving only sensory outcome Studies of clinical / pharma intervention Review papers Meta-analyses of neurobehavioural studies 25 editorials 15 not occupational 14 technical / theoretical 5 multiple chemical exposures e.g. Pb Al 1 single-case follow up 1 intervention study 1 meta-analysis 37 journal articles 12 conference abstracts 49 articles

  29. Systematic Review of the Literature The Better Quality Studies EU Guidelines for qualitative evaluation of neurobehavioural studies (1997) 1. Population of an adequate size relative to the number of tests used 2. Subject selection method which avoids bias for the exposed group 3. Subject selection method which avoids bias for the control group 4. Pre-stated exclusion/inclusion criteria for study participants 5. High response rate for the exposed group (usually > 60%) 6. High response rate for the control group (usually > 60%) where applicable 7. Control or adjustment for important confounders / modifiers of performance 8. Inclusion of quantitative or semi-quantitative assessment of long-term exposure 9. Control for recent exposure (where applicable) 10. An indication of the standardization of testing conditions After application of Quality Criteria, only 12 studies were of “Better Quality”

  30. Systematic Review of the Literature The 12 Better Quality Studies Functional domains where differences were found

  31. Systematic Review of the Literature The 12 Better Quality Studies 1. Showed mostly negative results (absence of effects) when comparing exposed versus non-exposed workers 2. Few studies showed differences between exposed and non-exposed workers, all to the detriment of exposed workers, and concerned Eye-Hand Coordination and Tremor (e.g. motor tasks) 3. Balance of evidence suggests no differences between exposed and non-exposed workers that can be measured by neurobehavioural tests However . . .

  32. Counter-Intuitive Neurobehavioural Findings The 12 Better Quality Studies Many studies measured Mn Bloods & Mn Urine Estimated cumulative exposures to Mn Six studies found workers with higher exposures performed significantly worse than workers with low or medium exposures All but one of these tests were motor-function: (Eye-Hand Coordination, Aiming, Finger tap, Tremor, Reaction time) Only one of these tests was cognitive: (Digit Symbol)

  33. Counter-Intuitive NeurobehaviouralConclusions 1. Neurobehavioural test literature does not provide convincing evidence of widespread or adverse effects of occupational manganese exposure upon neurobehavioural functions 2. Lack of consistently demonstrable adverse effects among better quality studies suggests this conclusion in comparisons between exposed and non-exposed workers 3. When better quality studies suggested effects in relation to higher doses and levels of exposures, such effects were consistently detected by motor functioning tests 4. Such dose-related effects are counterintuitive in the absence of effects between exposed and non-exposed, and it is proposed that such “effects” can be attributed to poor methodological standards in many neurobehavioural investigations.

  34. Locuria Manganica Indeed! Perilous Neurobehavioural Interpretations Very serious implications for litigants and defendants in USA Currently large numbers of plaintiffs filing cases in USA Share prices dropped globally e.g. BOC Major concern to US Dept of Defence / USA MRMC currently funding research Serious concern to International Manganese Institute Serious concern to International Institute of Welding

  35. The Way Forward . . . “Traditional” Computerised testing lacks context and obvious situational factors Simulators and simulation equipment may be the way forward for increased validity Video game generation (b. 1970 onwards) have raised the bar of human performance A return to the “Novelty value” of solid-state tests . . . . Guitar Hero Wii Fitness Direct Interfaces

  36. The Way Forward . . .

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