Acute symptom-reporting Acute symptom-reporting after routine exposure after routine exposure

to OP pesticides to OP pesticides in sheep dipin sheep dip

Using data reduction to provideUsing data reduction to provide a clinical profile of symptoms:a clinical profile of symptoms:

Prof. Craig A. Jackson Prof. Craig A. Jackson Division of PsychologyDivision of Psychology

Birmingham City UniversityBirmingham City University

AimsAims

Using data reduction to provide a useful clinical profile of Using data reduction to provide a useful clinical profile of symptomssymptoms

Subjectivity of objective methods – even in quantitative studiesSubjectivity of objective methods – even in quantitative studies

• Factor AnalysisFactor Analysis• Kaiser CriteriaKaiser Criteria• Scree AnalysisScree Analysis• K-means ClusteringK-means Clustering

Prevalence of non-specific symptoms(Western Australia n = 3016)

Symptom Prevalence % Symptom Prevalence % Stuffy nose 46.2 Headaches 33.0Tiredness 29.8 Cough 25.9Itchy eyes 24.7 Sore throat 22.4Skin rash 12.0 Wheezing 10.1Respiratory 10.0 Nausea 9.0Diarrhoea 5.7 Vomiting 4.0

Heyworth & McCaul, 2001

Symptom reporting in societySymptom reporting in society

Common Present Day Symptoms

• Multiple Chemical Sensitivity (MCS) 90’s• Chronic Fatigue Syndrome (formerly ME) 90’s

• Sick Building Syndrome 80’s• Gulf War Syndrome 90’s• Musculoskeletal problems 90’s• Electrical Sensitivity 90’s

Historical Symptoms

• Railway Spine 1860’s• Combat Syndrome 1850’s onward• Wool sorter’s syndrome 1860’s

Unexplained symptom syndromesUnexplained symptom syndromes

Sheep DippingSheep Dipping

Sheep Dipping Sheep Dipping

Sheep DippingSheep Dipping

Organophosphate Pesticides (OPs) & Sheep DippingOrganophosphate Pesticides (OPs) & Sheep Dipping

UK Sheep dipped twice yearly, and was compulsory 1984–1988

OPs were the dip of choice & recommended by HSE

Routine sheep dipping is wet and messy work

NOT usually an acute exposure

Chronic and low level exposure

Non-specific symptoms alleviate 48 hours post-dip

“Dippers’ Flu”Anxiety Depression Fatigue Aches & PainsHeadache FeverNeurobehavioural problems (memory, concentration)

The UK Sheep Dipping SagaThe UK Sheep Dipping Saga

Dippers’ FluDippers’ Flu

• Dipping sheep with Organophosphate Pesticides • Traditionally tied to collection of non-specific symptoms • Manifests shortly after dipping• Spontaneously remits usually after 48 hours

Is there really any Is there really any truth in this truth in this collection of collection of symptoms?symptoms?

Or is it just “background” symptomology

General weaknessMuscle weakness

FeverAches and pains

HeadachesLoss of appetite

“Does Dippers’ Flu really exist?”

Past workPast work

Previous study – Stephens Previous study – Stephens et al. et al. 19951995

Investigated symptom reports in 82 farmers recently exposed to Investigated symptom reports in 82 farmers recently exposed to OPs when dipping sheepOPs when dipping sheep

Compared with controls (quarry workers)Compared with controls (quarry workers)

Overall symptom Overall symptom reporting, and reporting of symptom groups reporting, and reporting of symptom groups was was notnot elevated in exposed relative to controls elevated in exposed relative to controls

This was not consistent for all symptomsThis was not consistent for all symptoms

Possible that this (intuitive) grouping of symptoms may mask Possible that this (intuitive) grouping of symptoms may mask some genuine symptom patterns.some genuine symptom patterns.

A statistical approach was needed . . .

Aims & ObjectivesAims & Objectives

a) a) Establish a plausible basis for grouping of symptomsEstablish a plausible basis for grouping of symptoms

b) b) Identify recognisable core-symptoms consistently Identify recognisable core-symptoms consistently present in exposed workerspresent in exposed workers

c) c) Determine if exposed and controls differ in these Determine if exposed and controls differ in these core-symptomscore-symptoms

e) e) Determine if any excess in core-symptoms is dose-Determine if any excess in core-symptoms is dose-related (e.g. number of sheep, or years dipping)related (e.g. number of sheep, or years dipping)

Strategy for Re-analysisStrategy for Re-analysis

a) a) Cluster analysis of symptom data using original Cluster analysis of symptom data using original symptom groupssymptom groups

b) b) Rank individual symptoms by frequencyRank individual symptoms by frequency

c) c) Chi square analyses of individual symptomsChi square analyses of individual symptoms

d) d) Factor analysis of 73 original symptomsFactor analysis of 73 original symptoms

e)e) Investigation of dose-effect relationshipsInvestigation of dose-effect relationships

f)f) Cluster analysis of the symptom dataCluster analysis of the symptom data

v

Individual symptoms at 24 hours after dippingIndividual symptoms at 24 hours after dipping

12 symptoms reported more by exposed than controls12 symptoms reported more by exposed than controls

15 symptoms reported more by controls than exposed15 symptoms reported more by controls than exposed

Factor Analysis of all symptomsFactor Analysis of all symptoms

Kaiser Criteria – use factors with Eigenvalue >1Kaiser Criteria – use factors with Eigenvalue >1

Factor Analysis of all symptomsFactor Analysis of all symptoms

Twenty-one unwieldy factorsTwenty-one unwieldy factors

Number of Eigenvalues / Factors

Valu

e

0

2

4

6

8

10

12

14

16

18

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

Scree AnalysisScree Analysis

Factor AnalysisFactor Analysis

• 6 factors remained as the best representation of symptom data

• The product of 38 individual symptoms

• Accounted for 47% of the variance in symptom scores

Factor AnalysisFactor Analysis

Little physiologicalcommonality between symptoms in each factor

Kaiser Criteria versus Scree AnalysisKaiser Criteria versus Scree Analysis

• Twentyone factors representing 81% of varianceor• Six factors representing 46% of variance

Dilemma!!!!!

• Kaiser criteria of gives too many factors

• Scree analysis often gives too few factors

• Both good under optimal conditions....

• This study not optimal – 73 variables and 100 cases!!!

Flock size

Sum

of F

acto

rs 1

-6

0

10

20

30

40

0 400 800 1200 1600 2000 2400 2800

Regression95% confid.

Dose-effect relationship?Dose-effect relationship?

• Weak association between 6 factors & flock size (RWeak association between 6 factors & flock size (R22=0.4)=0.4)• Flock size as surrogate exposure estimate is too simplisticFlock size as surrogate exposure estimate is too simplistic• Statistical problem - 38 symptoms and only 82 casesStatistical problem - 38 symptoms and only 82 cases

K means Clustering K means Clustering

A method for reducing data based on differences not A method for reducing data based on differences not similarities (as in Factor Analysis)similarities (as in Factor Analysis)

Uses Euclidean Distances between factors Uses Euclidean Distances between factors • All 73 symptomsAll 73 symptoms• 21 symptoms reported most frequently 21 symptoms reported most frequently • 12 symptoms reported sig more by dippers than 12 symptoms reported sig more by dippers than

controlscontrols

Subjected to “K-Means” cluster analysisSubjected to “K-Means” cluster analysisProduced 5 distinct symptom clusters Produced 5 distinct symptom clusters With seemingly useful physiological explanationsWith seemingly useful physiological explanations

12 symptoms reported more – K means Clustering 12 symptoms reported more – K means Clustering

12 symptoms reported more – K means Clustering 12 symptoms reported more – K means Clustering

12 symptoms reported more by dippers than controls12 symptoms reported more by dippers than controlsSubjected to “K-Means” cluster analysisSubjected to “K-Means” cluster analysisProduced 3 distinct symptom clusters Produced 3 distinct symptom clusters With seemingly useful physiological explanationsWith seemingly useful physiological explanations

Top 21 symptoms – K means Clustering Top 21 symptoms – K means Clustering

Top 21 symptoms – K means Clustering Top 21 symptoms – K means Clustering

21 symptoms reported most frequently 21 symptoms reported most frequently Subjected to “K-Means” cluster analysisSubjected to “K-Means” cluster analysisProduced 5 distinct symptom clusters Produced 5 distinct symptom clusters With seemingly useful physiological explanationsWith seemingly useful physiological explanations

“Gross”“Shiver”

“Flu-like”

“Muscular”

“Global”?

Testing the 5 cluster modelTesting the 5 cluster model

Scores on the 5 clusters compared between exposed and Scores on the 5 clusters compared between exposed and controlscontrols

Significant differences were consistently to the detriment of the Significant differences were consistently to the detriment of the exposedexposed

grossgrossshivershiverflu-likeflu-like

muscularmuscularglobalglobal

ConclusionsConclusions

• High frequency of symptoms in both occupational groups (approx. 50-50)High frequency of symptoms in both occupational groups (approx. 50-50)

• No evidence of more dippers’ flu symptoms in exposed than the controlsNo evidence of more dippers’ flu symptoms in exposed than the controls

• No plausible pattern was evident in symptoms reported by the exposedNo plausible pattern was evident in symptoms reported by the exposed

• Cluster analysis of the original 9 symptom groups showed globalized and Cluster analysis of the original 9 symptom groups showed globalized and non-specific symptoms were being reported more than localised specific non-specific symptoms were being reported more than localised specific symptoms - suggesting general malaise than specific target organ systemssymptoms - suggesting general malaise than specific target organ systems

• Factor analysis provided little clarification of the data Factor analysis provided little clarification of the data - it reduced 21 - it reduced 21 unwieldy factors down to 6 factors, though with little physiological unwieldy factors down to 6 factors, though with little physiological plausibility in the grouping together of some symptomsplausibility in the grouping together of some symptoms

• K means cluster analysis identified K means cluster analysis identified 5 distinct symptom clusters of 5 distinct symptom clusters of better plausibility, better plausibility, 3 of which were significantly worse in exposed3 of which were significantly worse in exposed

SummarySummary

Tentative support for the view that certain symptoms can be Tentative support for the view that certain symptoms can be identified occurring more frequently in those exposed to OPs. identified occurring more frequently in those exposed to OPs.

Such symptoms are consistent with a flu like illness. Such symptoms are consistent with a flu like illness.

Further verification is needed from studies specifically targeted Further verification is needed from studies specifically targeted at a definition of symptom groups following acute OP exposure.at a definition of symptom groups following acute OP exposure.