ࡱ > a c ^ _ ` bjbjVV 4 < < E ( |
|
S S S g g g 8 D 4 g 6} 7! ( _! _! _! $$ $$ $$ c| e| e| e| e| e| e| $ ~ < | Q S - # ^ $$ - - | _! _! g | `9 `9 `9 - ( " _! S _! u `9 - c| `9 `9 2 m r p _! T g 3 n . u | < 6} n N ʁ 6 P ʁ \ p ʁ S p $$ & `9 ( * B $$ $$ $$ | | 9 X $$ $$ $$ 6} - - - - ʁ $$ $$ $$ $$ $$ $$ $$ $$ $$ |
: [1] Title: Adherence to ACE inhibitors and illness beliefs in older heart failure patients.
[2] Gerard J. Molloy1, Chuan Gao2, Derek W. Johnston2, Marie Johnston2, Miles D. Witham3, Allan D. Struthers4, Marion E.T. McMurdo3.
[3] Ninewells Hospital & Medical School, Section Ageing & Health, University of Dundee, Dundee DD1 9SY, Scotland.
[4]
Psychobiology Group, Department of Epidemiology & Public Health, University College London, London WC1E 6BT, England. (GJM: Research Fellow)
School of Psychology, University Aberdeen, Aberdeen AB24 2UB, Scotland. (DWJ & MJ: Professors of Psychology, CG: Research Fellow)
Ninewells Hospital & Medical School, Section Ageing & Health, University of Dundee, Dundee DD1 9SY, Scotland. (MDW: Lecturer, MMcM Professor of Medicine)
Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital & Medical School, University of Dundee, Dundee DD1 9SY, Scotland. (ADS: Professor of Pharmacology).
[5] Corresponding author: Dr Gerard Molloy, Psychobiology Group, Department of Epidemiology & Public Health, University College London, 1-19 Torrington Place
London WC1E 6BT. Phone + 44 (020) 76791846. Fax +44 (020) 79168542. Email: g.molloy@ucl.ac.uk
Abstract
Objective: Patient beliefs about heart failure may be important determinants of adherence. This study assessed levels of adherence to angiotensin-converting enzyme inhibitors (ACEI) and examined whether beliefs about heart failure were associated with adherence to ACEI.
Method: Fifty-eight patients with chronic stable heart failure (80.22 years SD: +4.62, 43% female) were recruited from outpatient clinics in Dundee Scotland. The Illness Perception Questionnaire-Revised (IPQ-R) was used to assess beliefs about heart failure. Adherence to ACEI was assessed by measuring serum levels of angiotensin-converting enzyme (sACE).
Results: Adherence to ACEI (defined as sACE <5 (/l) was 72%. Beliefs about the time-line of heart failure and the consequences of heart failure accounted for 19% of the variability in adherence to ACE inhibitors in this sample. HF patients who believed that their illness had a more chronic (longer term) time frame and had beliefs about greater consequences of heart failure on their lives were less likely to adhere to ACEI.
Conclusion: Adherence to ACEI is sub-optimal. Beliefs about heart failure appear to be associated with objectively measured adherence to ACEI. Future studies should attempt to identify beliefs that consistently predict adherence and examine whether modifying these beliefs can increase adherence to heart failure medications.
Introduction
Adherence to medical regimens is sub-optimal in heart failure populations, particularly amongst older people ADDIN REFMGR.CITE van der Wal20078Adherence in heart failure in the elderly: Problem and possible solutions
5Journal8Adherence in heart failure in the elderly: Problem and possible solutions
5van der Wal,M.H.Jaarsma,T.2007/11/19Quality of LifeNot in FileInt.J Cardiol.Department of Cardiology, University Medical Center Groningen, University of Groningen, The NetherlandsPM:18031843Int.J Cardiol.1(1). As the medical management of heart failure has pharamacotherapy as its mainstay, this is of considerable clinical importance ADDIN REFMGR.CITE Swedberg200569Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology
69Journal69Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology
69Swedberg,K.Cleland,J.Dargie,H.Drexler,H.Follath,F.Komajda,M.Tavazzi,L.Smiseth,O.A.Gavazzi,A.Haverich,A.Hoes,A.Jaarsma,T.Korewicki,J.Levy,S.Linde,C.Lopez-Sendon,J.L.Nieminen,M.S.Pierard,L.Remme,W.J.2005/6Acute DiseaseCardiac Surgical ProceduresCardiovascular AgentsChronic DiseasediagnosisDiagnostic Techniques,CardiovascularetiologyExercise TherapyHeart FailureHeart-Assist DevicesHumansLife StyleRisk AssessmentTerminology as Topictherapeutic usetherapyNot in File11151140Eur.Heart J2611Sahlgrenska Academy at the Goteborg University, Department of Medicine, Sahlgrenska University Hospital, Sweden. karl.swedberg@hjl.gu.sePM:15901669Eur.Heart J1(2). Estimates for non-adherence to medication in elderly heart failure patients have varied from 10% to 99%, with older patients reporting the lowest adherence rates ADDIN REFMGR.CITE van der Wal200536Non-compliance in patients with heart failure; how can we manage it?
8Journal36Non-compliance in patients with heart failure; how can we manage it?
8van der Wal,M.H.Jaarsma,T.van Veldhuisen,D.J.2005/1AdultDirective CounselingFood HabitsHeart FailureHumansLife StylemethodsNetherlandsPatient Education as TopicpsychologyQuality of LifeRisk Reduction BehaviortherapyTreatment RefusalNot in File517Eur.J Heart Fail.71Department of Cardiology, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. m.h.l.van.der.wal@thorax.azg.nlPM:15642526Eur.J Heart Fail.1(3).
One objective method of assessing patient adherence involves assessing levels of adherence to specific drugs in serum assays ADDIN REFMGR.CITE Struthers199929Nonadherence with angiotensin-converting enzyme inhibitor therapy: a comparison of different ways of measuring it in patients with chronic heart failureJournal29Nonadherence with angiotensin-converting enzyme inhibitor therapy: a comparison of different ways of measuring it in patients with chronic heart failureStruthers,A.D.MacFadyen,R.Fraser,C.Robson,J.Morton,J.J.Junot,C.Ezan,E.1999/12AgedAngiotensin IAngiotensin IIAngiotensin-Converting Enzyme InhibitorsBiological MarkersbloodChronic DiseasediagnosisDiureticsdrug therapyDrug Therapy,CombinationEchocardiographyFurosemideHeart FailureHumansLisinoprilmetabolismmethodsOligopeptidesPeptidyl-Dipeptidase ARadionuclide Ventriculographystatistics & numerical datatherapeutic usetherapyTreatment OutcomeTreatment RefusalurineNot in File20722077J Am.Coll.Cardiol.347Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, UKPM:10588226J Am.Coll.Cardiol.1(4). The measurement of serum ACE in heart failure patients can indicate whether heart failure patients are adhering to ACE inhibitor medication ADDIN REFMGR.CITE Struthers199976Non-adherence with ACE inhibitor treatment is common in heart failure and can be detected by routine serum ACE activity assays
4Journal76Non-adherence with ACE inhibitor treatment is common in heart failure and can be detected by routine serum ACE activity assays
4Struthers,A.D.Anderson,G.MacFadyen,R.J.Fraser,C.MacDonald,T.M.1999/11AgedAged,80 and overAngiotensin-Converting Enzyme InhibitorsBiological Markersblooddrug therapyenzymologyFemaleHeart FailureHumansMaleMedical Record LinkageMiddle AgedPeptidyl-Dipeptidase APharmaciestherapeutic useTreatment RefusalNot in File584588Heart825Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital, Dundee DD1 9SY, UKPM:10525514Heart1(5). Serum ACE has 86% sensitivity and 95% specificity and an area under the curve (AUC) of the Receiver Operating Characteristic (ROC) curve of 0.9 at identifying nonadherence ADDIN REFMGR.CITE Struthers199929Nonadherence with angiotensin-converting enzyme inhibitor therapy: a comparison of different ways of measuring it in patients with chronic heart failureJournal29Nonadherence with angiotensin-converting enzyme inhibitor therapy: a comparison of different ways of measuring it in patients with chronic heart failureStruthers,A.D.MacFadyen,R.Fraser,C.Robson,J.Morton,J.J.Junot,C.Ezan,E.1999/12AgedAngiotensin IAngiotensin IIAngiotensin-Converting Enzyme InhibitorsBiological MarkersbloodChronic DiseasediagnosisDiureticsdrug therapyDrug Therapy,CombinationEchocardiographyFurosemideHeart FailureHumansLisinoprilmetabolismmethodsOligopeptidesPeptidyl-Dipeptidase ARadionuclide Ventriculographystatistics & numerical datatherapeutic usetherapyTreatment OutcomeTreatment RefusalurineNot in File20722077J Am.Coll.Cardiol.347Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, UKPM:10588226J Am.Coll.Cardiol.1(4). Previous research has indicated that over a third of heart failure patients are less than 85% adherent to their medication ADDIN REFMGR.CITE Struthers200173Nonadherence with ACE inhibitors is common and can be detected in clinical practice by routine serum ACE activity
3Journal73Nonadherence with ACE inhibitors is common and can be detected in clinical practice by routine serum ACE activity
3Struthers,A.D.Anderson,G.MacFadyen,R.J.Fraser,C.MacDonald,T.M.2001/1Heart FailurePharmaciesNot in File4346Congest.Heart Fail.71Departments of Clinical Pharmacology and Therapeutics, Ninewells Hospital, Dundee, DD1 9SY, UKPM:11828135Congest.Heart Fail.1(6).
There have been systematic attempts to understand the modifiable determinants of adherence ADDIN REFMGR.CITE DiMatteo200784Health beliefs, disease severity, and patient adherence: a meta-analysis
2Journal84Health beliefs, disease severity, and patient adherence: a meta-analysis
2DiMatteo,M.R.Haskard,K.B.Williams,S.L.2007/6Attitude to HealthHealth StatusHumansmethodsPatient CompliancePhysician-Patient RelationspsychologyRiskSeverity of Illness IndexNot in File521528Med.Care456Department of Psychology, University of California, Riverside, California 92521, USA. robin@ucr.eduPM:17515779Med.Care1DiMatteo200487Social support and patient adherence to medical treatment: a meta-analysis
8Journal87Social support and patient adherence to medical treatment: a meta-analysis
8DiMatteo,M.R.2004/3AdultAffectConflict (Psychology)FamilyHealth StatusHumansMarital StatusPatient CompliancepsychologySocial SupportNot in File207218Health Psychol.232Department of Psychology, University of California, Riverside, CA 92521, USA. robin@citrus.ucr.eduPM:15008666Health Psychol.1DiMatteo200089Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence
18Journal89Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence
18DiMatteo,M.R.Lepper,H.S.Croghan,T.W.2000/7/24AdultAnxietyArthritis,RheumatoidcomplicationsDepressionepidemiologyHealth StatusHumansKidney Failure,ChronicmethodsNeoplasmsOdds RatioOutcome Assessment (Health Care)Patient CompliancepsychologyQuestionnairesRetrospective StudiesRiskRisk FactorstherapyTreatment RefusalNot in File21012107Arch.Intern.Med.16014Department of Psychology, University of California, Riverside, CA 92521, USA. robin@citrus.ucr.eduPM:10904452Arch.Intern.Med.1(7-9). As adherence is a behavioral phenomenon, psychological theories of self-regulation have made a significant contribution to this body of work. One area has focused on individual beliefs about illness and treatment ADDIN REFMGR.CITE Ekman2006100Adherence and perception of medication in patients with chronic heart failure during a five-year randomised trial
1Journal100Adherence and perception of medication in patients with chronic heart failure during a five-year randomised trial
1Ekman,I.Andersson,G.Boman,K.Charlesworth,A.Cleland,J.G.Poole-Wilson,P.Swedberg,K.2006/6Activities of Daily LivingAdrenergic beta-AntagonistsAgedAged,80 and overAnalysis of VarianceCarbazolesChi-Square DistributionChronic Diseasedrug therapyFemaleFollow-Up StudiesHealth Knowledge,Attitudes,PracticeHealth StatusHeart FailureHumansMalemethodsMetoprololMulticenter Studies as TopicnursingPatient CompliancePatient Education as TopicPerceptionPropanolaminespsychologyQuestionnairesRandomized Controlled Trials as TopicSeverity of Illness Indexstatistics & numerical dataStroke VolumeSwedentherapeutic useTime FactorsNot in File348353Patient Educ.Couns.613The Sahlgrenska Academy, Faculty of Health and Caring Sciences, Institute of Nursing, Goteborg University, Box 457, SE 405 30, Goteborg, Sweden. inger.ekman@fhs.gu.sePM:16139468Patient Educ.Couns.1Cooper200779Assessing patients' beliefs about cardiac rehabilitation as a basis for predicting attendance after acute myocardial infarctionJournal79Assessing patients' beliefs about cardiac rehabilitation as a basis for predicting attendance after acute myocardial infarctionCooper,A.F.Weinman,J.Hankins,M.Jackson,G.Horne,R.2007Myocardial InfarctionrehabilitationNot in File5358Heart931WOS:000242851500014Heart1Horne19994Patients' beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illnessJournal4Patients' beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illnessHorne,R.Weinman,J.1999/12AdultAgedAsthmaCardiovascular DiseasesChronic Diseasedrug therapyFemaleGreat BritainHealth Knowledge,Attitudes,PracticeHumansKidney FailureMaleMiddle AgedNeoplasmsPatient CompliancepsychologyQuestionnairesRegression AnalysisSampling StudiesSeverity of Illness IndexNot in File555567J Psychosom.Res.476Centre for Health Care Reserach, University of Brighton, UK. r.horne@brighton.ac.ukPM:10661603J Psychosom.Res.1Horne19997The beliefs about medicines questionnaire: The development and evaluation of a new method for assessing the cognitive representation of medicationJournal7The beliefs about medicines questionnaire: The development and evaluation of a new method for assessing the cognitive representation of medicationHorne,R.Weinman,J.Hankins,M.1999Not in File124Psychology & Health1410887-0446ISI:000079471100001Psychology & Health1Weinman199677The illness perception questionnaire: A new method for assessing the cognitive representation of illnessJournal77The illness perception questionnaire: A new method for assessing the cognitive representation of illnessWeinman,J.Petrie,K.J.MossMorris,R.Horne,R.1996PerceptionNot in File431445Psychology & Health1130887-0446ISI:A1996UD24900010Psychology & Health1(10-14). This work has found that beliefs about illness and treatment are associated with patient self-management in a range of conditions including heart failure and coronary heart disease ADDIN REFMGR.CITE Horowitz200482A story of maladies, misconceptions and mishaps: effective management of heart failure
1Journal82A story of maladies, misconceptions and mishaps: effective management of heart failure
1Horowitz,C.R.Rein,S.B.Leventhal,H.2004/2Chronic DiseaseDisease ManagementHealth BehaviorHealth Knowledge,Attitudes,PracticeHeart FailureHumansInterviews as TopicmethodsPerceptionpsychologySelf CaretherapyUnited StatesNot in File631643Soc.Sci.Med.583Department of Health Policy, Mount Sinai School of Medicine, Box 1077, One Gustave L. Levy Place, New York, NY 10029, USA. carol.horowitz@mountsinai.orgPM:14652059Soc.Sci.Med.1Petrie200271Changing illness perceptions after myocardial infarction: an early intervention randomized controlled trial
35Journal71Changing illness perceptions after myocardial infarction: an early intervention randomized controlled trial
35Petrie,K.J.Cameron,L.D.Ellis,C.J.Buick,D.Weinman,J.2002/7AgedAttitude to HealthbloodCholesterol,LDLConvalescenceetiologyFemaleHealth BehaviorHospitalizationHumansMaleMiddle AgedMyocardial InfarctionPerceptionProspective StudiespsychologyQuestionnairesrehabilitationStress,PsychologicalNot in File580586Psychosom.Med.644Department of Health Psychology, Faculty of Medical and Health Sciences, University of Auckland, New Zealand. kj.petrie@auckland.ac.nzPM:12140347Psychosom.Med.1(15, 16). For example beliefs relating to the symptoms that individuals associate with their illness (illness identity), beliefs relating to the perceived duration of the illness (time-line) and beliefs regarding the curability or controllability of the illness (personal and treatment control) are hypothesized to predict behavioural and emotional adaptation to illness ADDIN REFMGR.CITE Weinman199677The illness perception questionnaire: A new method for assessing the cognitive representation of illnessJournal77The illness perception questionnaire: A new method for assessing the cognitive representation of illnessWeinman,J.Petrie,K.J.MossMorris,R.Horne,R.1996PerceptionNot in File431445Psychology & Health1130887-0446ISI:A1996UD24900010Psychology & Health1(14). This approach focusing on how these beliefs about illness influence adaptation to illness is referred to as self-regulation i.e. how people direct their thoughts, feelings, and actions, so that strivings to obtain goals are effective.
In previous studies measures of illness perception such as the illness perception questionnaire (IPQ) ADDIN REFMGR.CITE Weinman199677The illness perception questionnaire: A new method for assessing the cognitive representation of illnessJournal77The illness perception questionnaire: A new method for assessing the cognitive representation of illnessWeinman,J.Petrie,K.J.MossMorris,R.Horne,R.1996PerceptionNot in File431445Psychology & Health1130887-0446ISI:A1996UD24900010Psychology & Health1(14) and the revised IPQ, the IPQ-R ADDIN REFMGR.CITE Moss-Morris200281The revised Illness Perception Questionnaire (IPQ-R)Journal81The revised Illness Perception Questionnaire (IPQ-R)Moss-Morris,R.Weinman,J.Petrie,K.J.Horne,R.Cameron,L.D.Buick,D.2002PerceptionNot in File116Psychology & Health171WOS:000176071800001Psychology & Health1(17), have been found to be reliable (internally consistent and have adequate test-retest reliability) and valid (concurrent, discriminant and predictive validity) in asthma, myocardial infarction, diabetes, rheumatoid arthritis, multiple sclerosis, HIV, chronic fatigue and pain patient groups. This early work establishing the psychometric properties of the IPQ and the IPQ-R has been further advanced by meta-analytic studies that have systematically reviewed studies using these measures ADDIN REFMGR.CITE Hagger200399A meta-analytic review of the common-sense model of illness representations
12Journal99A meta-analytic review of the common-sense model of illness representations
12Hagger,M.S.Orbell,S.2003/4CHRONIC-FATIGUE-SYNDROMEclassification of copingCognitionCOGNITIVE REPRESENTATIONSCOPING STRATEGIESDIABETES-MELLITUSEmotionsEnglandillness cognitionsPerceptionPERCEPTION QUESTIONNAIREPERSONAL MODELSQUALITY-OF-LIFEresearch synthesisSELF-MANAGEMENTself-regulation modelSEVERE PSORIASISTHEORETICAL PERSPECTIVENot in File141184Psychology & Health1820887-0446Univ Essex, Dept Psychol, Colchester CO4 3SQ, Essex, EnglandISI:000181925800001Psychology & Health1(18). These studies provide evidence for theoretically predictable relations between beliefs about illness and self-management behaviour in individuals with chronic illness.
In this study we aimed to measure heart failure patient beliefs about their illness using a measure systematically developed from self-regulation theory. Patient adherence to ACEI was measured using serum analysis of ACE. We aimed to answer the following question: Are patient beliefs about heart failure associated with objectively measured serum ACE in older heart failure patients?
Methods
Design and setting
This was a cross-sectional study of older patients with chronic stable heart failure that were recruited into an exercise intervention trial that has been reported elsewhere ADDIN REFMGR.CITE Witham200710Using an individualised quality of life measure in older heart failure patientsJournal10Using an individualised quality of life measure in older heart failure patientsWitham,M.D.Crighton,L.J.McMurdo,M.E.2007/3/2Activities of Daily LivingAge FactorsAgeddiagnosisFemaleHeart FailureHumansIndividualityInterpersonal RelationsMalemethodspsychologyQuality of LifeQuestionnairesReproducibility of ResultsNot in File4045Int.J Cardiol.1161Section of Ageing and Health, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom. m.witham@dundee.ac.ukPM:16806536Int.J Cardiol.1Witham200517Effect of a seated exercise program to improve physical function and health status in frail patients > or = 70 years of age with heart failureJournal17Effect of a seated exercise program to improve physical function and health status in frail patients > or = 70 years of age with heart failureWitham,M.D.Gray,J.M.Argo,I.S.Johnston,D.W.Struthers,A.D.McMurdo,M.E.2005/5/1AgedAged,80 and overExerciseExercise TherapyFemaleFrail ElderlyHeart FailureHumansMaleMotor ActivityphysiologyPostureProgram EvaluationQuality of LifetherapyWalkingNot in File11201124Am.J Cardiol.959Section of Ageing and Health and Department of Clinical Pharmacology, University of Dundee, Ninewells Hospital, Dundee, United Kingdom. m.witham@dundee.ac.ukPM:15842989Am.J Cardiol.1Molloy200695Effects of an exercise intervention for older heart failure patients on caregiver burden and emotional distress
5Journal95Effects of an exercise intervention for older heart failure patients on caregiver burden and emotional distress
5Molloy,G.J.Johnston,D.W.Gao,C.Witham,M.D.Gray,J.M.Argo,I.S.Struthers,A.D.McMurdo,M.E.2006/6adverse effectsAgedAged,80 and overAmbulatory CareAnxietyCaregiversCost of IllnessDepressionEmotionsExerciseExercise TherapyFemaleHeart FailureHome Care ServicesHumansMalemethodsMiddle AgedpsychologyrehabilitationResearch DesignStress,PsychologicalNot in File381387Eur.J Cardiovasc.Prev.Rehabil.133School of Psychology, University of Aberdeen, Aberdeen, Scotland, UK. g.molloy@abdn.ac.ukPM:16926668Eur.J Cardiovasc.Prev.Rehabil.1(19-21). All data presented in this paper were collected pre-randomisation at baseline.
Participants
Heart failure patients were recruited from the local specialist heart failure clinic and from the local Medicine for the Elderly clinics in Dundee Scotland. Patients aged >70 years with a clinical diagnosis of chronic heart failure according to European Society of Cardiology guidelines, New York Heart Association class II or III symptoms, and evidence of left ventricular systolic dysfunction on echocardiography, contrast ventriculography, or radionuclide ventriculography were eligible to participate. Exclusion criteria were patients with uncontrolled atrial fibrillation, significant aortic stenosis, sustained ventricular tachycardia, recent myocardial infarction, inability to walk without human assistance, abbreviated mental test score >6 of 10, or those currently undergoing physiotherapy or rehabilitation. The study was approved by the Tayside Committee on Medical Research Ethics. Written informed consent was obtained from participants.
Measures
Background socio-demographic and clinical data was collected from medical notes and interview at outpatient clinics. Blood was drawn by a research nurse or clinical research fellow. Serum ACE activity was assayed using serum from clotted blood. The change in absorbance at 340nm due to hydrolysis of furylacrylolylphenylalanylglycylglycine was measured using a Roche MIRA analyzer (Roche Diagnostic systems, Welwyn Garden City, Herts UK). Serum ACE activity of <5U/L was taken as denoting adherence to ACE inhibitor therapy; a level previously validated by the authors ADDIN REFMGR.CITE MacFadyen199715The practical assessment of compliance with ACE-inhibitor therapy--a novel approachJournal15The practical assessment of compliance with ACE-inhibitor therapy--a novel approachMacFadyen,R.J.Struthers,A.D.1997/1AdultAngiotensin-Converting Enzyme InhibitorsAngiotensinsBiological MarkersbloodBlood PressureDiureticsDouble-Blind Methoddrug effectsHeart FailureHumansLisinoprilMalePatient CompliancePeptidyl-Dipeptidase ApharmacologytherapyNot in File119124J Cardiovasc.Pharmacol.291Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Scotland, U.KPM:9007680J Cardiovasc.Pharmacol.1(22).
The illness perception questionnaire-revised (IPQ-R) ADDIN REFMGR.CITE Moss-Morris200281The revised Illness Perception Questionnaire (IPQ-R)Journal81The revised Illness Perception Questionnaire (IPQ-R)Moss-Morris,R.Weinman,J.Petrie,K.J.Horne,R.Cameron,L.D.Buick,D.2002PerceptionNot in File116Psychology & Health171WOS:000176071800001Psychology & Health1(17) was used to assess patient beliefs about their illness. This measure has been systematically developed and refined in a range of clinical conditions and is based on a psychological theory of self-regulation ADDIN REFMGR.CITE Moss-Morris200281The revised Illness Perception Questionnaire (IPQ-R)Journal81The revised Illness Perception Questionnaire (IPQ-R)Moss-Morris,R.Weinman,J.Petrie,K.J.Horne,R.Cameron,L.D.Buick,D.2002PerceptionNot in File116Psychology & Health171WOS:000176071800001Psychology & Health1Weinman199677The illness perception questionnaire: A new method for assessing the cognitive representation of illnessJournal77The illness perception questionnaire: A new method for assessing the cognitive representation of illnessWeinman,J.Petrie,K.J.MossMorris,R.Horne,R.1996PerceptionNot in File431445Psychology & Health1130887-0446ISI:A1996UD24900010Psychology & Health1(14, 17). Beliefs regarding the symptoms associated with the illness (identity), the perceived temporality (timeline), the perceived consequences of the illness (consequences), the perceived personal control over the illness (personal control), the perceived efficacy or outcome of medical treatment (treatment control), the perceived coherence of the condition (illness coherence) and emotional beliefs relating to the illness were assessed using the IPQ-R (emotional reps).
Statistical Analysis
Logistic regression was used to assess the % variability in adherence to ACEI accounted for by the sub-scales of the IPQ-R.
Results
Patient characteristics
Two hundred and twenty nine patients were approached at the two outpatient clinics. Patients that chose not to participate (n= 147) had a mean age was 79.9 years (SD: 6.0) and 70/147 (48%) were male. Eighty-one patients were enrolled in an exercise study ADDIN REFMGR.CITE Witham200517Effect of a seated exercise program to improve physical function and health status in frail patients > or = 70 years of age with heart failureJournal17Effect of a seated exercise program to improve physical function and health status in frail patients > or = 70 years of age with heart failureWitham,M.D.Gray,J.M.Argo,I.S.Johnston,D.W.Struthers,A.D.McMurdo,M.E.2005/5/1AgedAged,80 and overExerciseExercise TherapyFemaleFrail ElderlyHeart FailureHumansMaleMotor ActivityphysiologyPostureProgram EvaluationQuality of LifetherapyWalkingNot in File11201124Am.J Cardiol.959Section of Ageing and Health and Department of Clinical Pharmacology, University of Dundee, Ninewells Hospital, Dundee, United Kingdom. m.witham@dundee.ac.ukPM:15842989Am.J Cardiol.1(20). Fifty-eight (72%) of these patients were prescribed ACEI and these comprised the sample for the present study. Table 1 shows the demographic and clinical characteristics of the sample.
Insert table 1
Adherence to ACEI:
Analysis of serum levels of ACE showed that 42 out of the 58 patients in the study had serum ACE levels that were < 5 (/l suggesting that adherence to ACEI in this sample was 72%. Comparing adherent and non-adherent groups, they were of a similar mean age (t(56) = -.60, p = .55) and there were no significant differences in gender ((2(1) = 1.56, p = .21) or NYHA functional classification ((2(1) = .67, p = .41).
Illness perceptions as predictors of adherence to ACEI
Figure 1 shows the comparisons of the mean scores in illness beliefs between the ACEI adherent and non-adherent groups. Higher scores relate to stronger beliefs that the illness will last a long time as opposed to a short time, that the illness will be cyclical, that the illness will have greater consequences, that you have greater personal control over the illness, that treatments will be effective in managing illness, that the illness makes sense, that the illness makes you emotionally distressed and that the illness has more symptoms. Logistic regression analysis showed that Timeline-acute/chronic (( = -.92, SE = .48, Wald = 3.65, Odds Ratio = 0.40, p = .06) marginally and Consequences (( = -1.02, SE = .51, Wald = 3.92, Odds Ratio = 0.36, p = .05) significantly predicted medication-adherence separately, explaining 11% and 10% of the variance, respectively. Further details are provided in table 2 which provides the univariate and multivariate logistic regression analysis predicting adherence to ACEI.
Insert table 2
When both variables were entered into multivariate analysis, both Timeline-acute/chronic (( = -.92, SE = .51, Wald = 3.26, Odds Ratio = 0.40, p = .07) and Consequences (( = -.97, SE = .52, Wald = 3.47, Odds Ratio = 0.38, p = .06) were found to be marginal predictors of medication-adherence, and explained 19% of the variance. The results indicate that with every increase of 1 in Timeline-acute/chronic or Consequences score, participants were 2.5 times or 2.6 times less likely to be adherent to ACEI medication, respectively. That is, participants who believed that they had a more chronic timeline of illness or perceived more Consequences of illness were less likely to adhere to ACEI.
Discussion
Certain patient beliefs about heart failure were associated with objectively measured serum ACE in older heart failure patients. Heart failure patients who believed that their illness would last a long time (i.e. a chronic timeline, example questionnaire items: My illness is likely to be permanent rather than temporary, I expect to have this illness for the rest of my life) and had more consequences (example questionnaire items: My illness has major consequences on my life, My illness causes difficulties for those who are close to me) were less likely to adhere to ACEI. Adherence to ACEI was 72% in this sample of older heart failure patients. Patient beliefs about the duration of heart failure as an illness and the consequences of this condition may be important determinants of medication adherence that warrant attention in health-care provider and patient interactions concerning medication regimens. It is possible that patients may intentionally decide to stop or intermittently adhere to ACEI if they view ACEI as unnecessary in managing an illness that is permanent and has serious consequences ADDIN REFMGR.CITE Horne19994Patients' beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illnessJournal4Patients' beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illnessHorne,R.Weinman,J.1999/12AdultAgedAsthmaCardiovascular DiseasesChronic Diseasedrug therapyFemaleGreat BritainHealth Knowledge,Attitudes,PracticeHumansKidney FailureMaleMiddle AgedNeoplasmsPatient CompliancepsychologyQuestionnairesRegression AnalysisSampling StudiesSeverity of Illness IndexNot in File555567J Psychosom.Res.476Centre for Health Care Reserach, University of Brighton, UK. r.horne@brighton.ac.ukPM:10661603J Psychosom.Res.1(12).
A larger previous study in older heart failure patients found that overall adherence to physicians recommendations was 72% ADDIN REFMGR.CITE van der Wal200632Compliance in heart failure patients: the importance of knowledge and beliefs
32Journal32Compliance in heart failure patients: the importance of knowledge and beliefs
32van der Wal,M.H.Jaarsma,T.Moser,D.K.Veeger,N.J.van Gilst,W.H.van Veldhuisen,D.J.2006/2AgedCross-Sectional StudiesDietFemaleHealth BehaviorHealth Knowledge,Attitudes,PracticeHeart FailureHumansMalemethodsPatient ComplianceQuestionnairesRegression AnalysisRisk FactorstherapyNot in File434440Eur.Heart J274Department of Cardiology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. m.h.l.van.der.wal@thorax.umcg.nlPM:16230302Eur.Heart J1(23). The similarity of this estimate with the present study is striking, however the previous study found that medication adherence of older heart failure patients was almost 99%. This estimate was based on self-report question asking about all medications simultaneously. This level of adherence is not supported by the present data on adherence to ACEI and other studies that have used more objective measures of adherence ADDIN REFMGR.CITE van der Wal20078Adherence in heart failure in the elderly: Problem and possible solutions
5Journal8Adherence in heart failure in the elderly: Problem and possible solutions
5van der Wal,M.H.Jaarsma,T.2007/11/19Quality of LifeNot in FileInt.J Cardiol.Department of Cardiology, University Medical Center Groningen, University of Groningen, The NetherlandsPM:18031843Int.J Cardiol.1(1). It is likely that self-reports about general medication adherence may be particularly prone to error, perhaps due to social desirability or recall biases of study participants.
There are also considerable data showing that depression ADDIN REFMGR.CITE DiMatteo200089Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence
18Journal89Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence
18DiMatteo,M.R.Lepper,H.S.Croghan,T.W.2000/7/24AdultAnxietyArthritis,RheumatoidcomplicationsDepressionepidemiologyHealth StatusHumansKidney Failure,ChronicmethodsNeoplasmsOdds RatioOutcome Assessment (Health Care)Patient CompliancepsychologyQuestionnairesRetrospective StudiesRiskRisk FactorstherapyTreatment RefusalNot in File21012107Arch.Intern.Med.16014Department of Psychology, University of California, Riverside, CA 92521, USA. robin@citrus.ucr.eduPM:10904452Arch.Intern.Med.1(9) and measures of social support ADDIN REFMGR.CITE Molloy200891Social networks and partner stress as predictors of adherence to medication, rehabilitation attendance, and quality of life following acute coronary syndrome
1Journal91Social networks and partner stress as predictors of adherence to medication, rehabilitation attendance, and quality of life following acute coronary syndrome
1Molloy,G.J.Perkins-Porras,L.Strike,P.C.Steptoe,A.2008/1epidemiologyFemaleHospitalizationmortalityOdds RatioQuality of LiferehabilitationRiskNot in File5258Health Psychol.271Department of Epidemiology and Public Health, University College London, United Kingdom. g.molloy@ucl.ac.ukPM:18230014Health Psychol.1DiMatteo200487Social support and patient adherence to medical treatment: a meta-analysis
8Journal87Social support and patient adherence to medical treatment: a meta-analysis
8DiMatteo,M.R.2004/3AdultAffectConflict (Psychology)FamilyHealth StatusHumansMarital StatusPatient CompliancepsychologySocial SupportNot in File207218Health Psychol.232Department of Psychology, University of California, Riverside, CA 92521, USA. robin@citrus.ucr.eduPM:15008666Health Psychol.1(8, 24) are associated with non-adherence to medication and other aspects of self-care and secondary prevention. It is possible that the illness beliefs associated with non-adherence in this study were more typical of those with higher levels of depression, however emotional beliefs about the illness such as feeling depressed about the illness were not different in the adherent and non-adherent groups in the present study and there were no differences in adherence between married and unmarried patients. It is possible that depressed and non-depressed patients and those with high and low levels of social support have a different set of beliefs about illness and treatment, which may in turn determine adherence. Social support in the form of informal care may be particularly important for understanding the self-management of heart failure ADDIN REFMGR.CITE Molloy200596Family caregiving and congestive heart failure. Review and analysis
6Journal96Family caregiving and congestive heart failure. Review and analysis
6Molloy,G.J.Johnston,D.W.Witham,M.D.2005/6AffectCaregiversepidemiologyFamilyFamily HealthHealth Status IndicatorsHeart FailureHospitalizationHumansPatient CompliancePrevalencepsychologySelf CareStress,PsychologicaltherapyNot in File592603Eur.J Heart Fail.74School of Psychology, University of St. Andrews, St. Andrews KY16 9JU, Scotland. gjm6@st-andrews.ac.ukPM:15921800Eur.J Heart Fail.1(25) and beliefs about illness and treatment may be shaped by those in the patients immediate social environment. Future studies could examine the mediating role of illness and treatment beliefs in explaining the associations between depression and social support and adherence to heart failure medications. The evidence showing that beliefs about illness can be changed to improve return to work and angina symptoms in coronary heart disease patients ADDIN REFMGR.CITE Petrie200271Changing illness perceptions after myocardial infarction: an early intervention randomized controlled trial
35Journal71Changing illness perceptions after myocardial infarction: an early intervention randomized controlled trial
35Petrie,K.J.Cameron,L.D.Ellis,C.J.Buick,D.Weinman,J.2002/7AgedAttitude to HealthbloodCholesterol,LDLConvalescenceetiologyFemaleHealth BehaviorHospitalizationHumansMaleMiddle AgedMyocardial InfarctionPerceptionProspective StudiespsychologyQuestionnairesrehabilitationStress,PsychologicalNot in File580586Psychosom.Med.644Department of Health Psychology, Faculty of Medical and Health Sciences, University of Auckland, New Zealand. kj.petrie@auckland.ac.nzPM:12140347Psychosom.Med.1(16) suggests that beliefs about illness may be important targets for intervention work to improve adherence ADDIN REFMGR.CITE Goodyer199598Does encouraging good compliance improve patients' clinical condition in heart failure?
2Journal98Does encouraging good compliance improve patients' clinical condition in heart failure?
2Goodyer,L.I.Miskelly,F.Milligan,P.1995/7AgedAged,80 and overdrug therapyExerciseFemaleHeart FailureHumansMalePatient CompliancePatient Education as TopicPharmaciesProspective StudiesTreatment OutcomeNot in File173176Br.J Clin.Pract.494Department of Pharmacy, King's College LondonPM:7547154Br.J Clin.Pract.1(26) and subsequent health outcomes in heart failure patients. Future work should first however, identify illness beliefs that consistently predict adherence in heart failure patients.
There are a number of important limitations to the present study which should be acknowledged. The data set did not provide the statistical power to permit the use of large multivariate models with multiple adjustments for other known predictors of medication adherence. Further data on patient beliefs about heart failure and multiple measures of adherence (both self-report and objective measures) are required from larger samples of heart failure patients. The study did not include a measure of beliefs about medications ADDIN REFMGR.CITE Horne19997The beliefs about medicines questionnaire: The development and evaluation of a new method for assessing the cognitive representation of medicationJournal7The beliefs about medicines questionnaire: The development and evaluation of a new method for assessing the cognitive representation of medicationHorne,R.Weinman,J.Hankins,M.1999Not in File124Psychology & Health1410887-0446ISI:000079471100001Psychology & Health1(13), which may be more proximal predictors of medication adherence than beliefs about the illness. Including beliefs about medications in future studies of heart failure patients would also allow investigators to observe how beliefs about illness and beliefs about medications interact to determine adherence behaviour. It is also possible that adherence behaviour and beliefs about the illness reciprocally determine each other making the interpretation of cross-sectional associations problematic; however this is an acknowledged difficulty of all observational studies of psychological factors and adherence behaviour. On the other hand there are clear strengths to the present study in terms of the objective measurement of adherence to ACEI, the sample of older heart failure patients (mean age 80.2 years SD: +4.6) who are often underrepresented in clinical research despite being most at risk ADDIN REFMGR.CITE McMurdo200513Including older people in clinical researchJournal13Including older people in clinical researchMcMurdo,M.E.Witham,M.D.Gillespie,N.D.2005/11/5AgedBiomedical ResearchClinical Trials as TopicHumansPatient SelectionNot in File10361037BMJ3317524PM:16269472BMJ1(27) and the use of systematically developed psychological theory and measurement, which can provide a framework around which a cumulative body of findings on patients beliefs about heart failure and its treatment and adherence behaviour in heart failure can emerge. Such a body of knowledge is necessary to develop interventions that target heart failure beliefs to enhance adherence behaviour.
Conclusion
The present study adds to evidence suggesting that adherence to medication is sub-optimal in older heart failure patients and that adherence is associated with beliefs about the condition. Further research using the measures included in this study will confirm which beliefs consistently predict medication adherence in heart failure patients. The next generation of work in this area will establish whether changing beliefs about heart failure and treatment of the condition can improve adherence to medication and medical advice and consequently reduce morbidity and mortality from heart failure.
ADDIN REFMGR.REFLIST Reference List
1. van der Wal MH, Jaarsma T. Adherence in heart failure in the elderly: Problem and possible solutions. Int J Cardiol 2008; 125;203-208.
2. Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, Tavazzi L, SmisethOA, GavazziA, Haverich A, Hoes A, JaarsmaT, Korewicki J, Levy S, Linde C, Lopez-Sendon JL, Nieminen MS, Pierard L, Remme WJ. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J 2005 ;26:1115-1140.
3. van der Wal MH, Jaarsma T, van Veldhuisen DJ. Non-compliance in patients with heart failure; how can we manage it? Eur J Heart Fail 2005;7:5-17.
4. Struthers AD, MacFadyen R, Fraser C, Robson J, Morton JJ, Junot C, Ezan E. Nonadherence with angiotensin-converting enzyme inhibitor therapy: a comparison of different ways of measuring it in patients with chronic heart failure. J Am Coll Cardiol 1999;34:2072-2077.
5. Struthers AD, Anderson G, MacFadyen RJ, Fraser C, MacDonald TM. Non-adherence with ACE inhibitor treatment is common in heart failure and can be detected by routine serum ACE activity assays Heart 1999;82:584-588.
6. Struthers AD, Anderson G, MacFadyen RJ, Fraser C, MacDonald TM. Nonadherence with ACE inhibitors is common and can be detected in clinical practice by routine serum ACE activity. Congest Heart Fail 2001;7:43-46.
7. DiMatteo MR, Haskard KB, Williams SL. Health beliefs, disease severity, and patient adherence: a meta-analysis. Med Care 2007;45:521-528.
8. DiMatteo MR. Social support and patient adherence to medical treatment: a meta-analysis. Health Psychol 2004;23:207-218.
9. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med 2000;160:2101-2107.
10. Ekman I, Andersson G, Boman K, Charlesworth A, Cleland JG, Poole-Wilson P, et al. Adherence and perception of medication in patients with chronic heart failure during a five-year randomised trial. Patient Educ Couns 2006;61:348-353.
11. Cooper AF, Weinman J, Hankins M, Jackson G, Horne R. Assessing patients' beliefs about cardiac rehabilitation as a basis for predicting attendance after acute myocardial infarction. Heart 2007;93:53-58.
12. Horne R, Weinman J. Patients' beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illness. J Psychosom Res 1999;47:555-567.
13. Horne R, Weinman J, Hankins M. The beliefs about medicines questionnaire: The development and evaluation of a new method for assessing the cognitive representation of medication. Psychology & Health 1999;14:1-24.
14. Weinman J, Petrie KJ, MossMorris R, Horne R. The illness perception questionnaire: A new method for assessing the cognitive representation of illness. Psychology & Health 1996;11:431-445.
15. Horowitz CR, Rein SB, Leventhal H. A story of maladies, misconceptions and mishaps: effective management of heart failure. Soc Sci Med 2004;58:631-643.
16. Petrie KJ, Cameron LD, Ellis CJ, Buick D, Weinman J. Changing illness perceptions after myocardial infarction: an early intervention randomized controlled trial. Psychosom Med 2002;64:580-586.
17. Moss-Morris R, Weinman J, Petrie KJ, Horne R, Cameron LD, Buick D. The revised Illness Perception Questionnaire (IPQ-R). Psychology & Health 2002;17:1-16.
18. Hagger MS, Orbell S. A meta-analytic review of the common-sense model of illness representations. Psychology & Health 2003;18:141-184.
19. Witham MD, Crighton LJ, McMurdo ME. Using an individualised quality of life measure in older heart failure patients. Int J Cardiol 2007;116:40-45.
20. Witham MD, Gray JM, Argo IS, Johnston DW, Struthers AD, McMurdo ME. Effect of a seated exercise program to improve physical function and health status in frail patients > or = 70 years of age with heart failure. Am J Cardiol 2005;95:1120-1124.
21. Molloy GJ, Johnston DW, Gao C, Witham MD, Gray JM, Argo IS, Struthers AD, McMurdo ME. Effects of an exercise intervention for older heart failure patients on caregiver burden and emotional distress. Eur J Cardiovasc Prev Rehabil 2006;13:381-387.
22. MacFadyen RJ, Struthers AD. The practical assessment of compliance with ACE-inhibitor therapy--a novel approach. J Cardiovasc Pharmacol 1997;29:119-124.
23. van der Wal MH, Jaarsma T, Moser DK, Veeger NJ, van Gilst WH, van Veldhuisen DJ. Compliance in heart failure patients: the importance of knowledge and beliefs. Eur Heart J 2006;27:434-440.
24. Molloy GJ, Perkins-Porras L, Strike PC, Steptoe A. Social networks and partner stress as predictors of adherence to medication, rehabilitation attendance, and quality of life following acute coronary syndrome. Health Psychol 2008 Jan;27:52-58.
25. Molloy GJ, Johnston DW, Witham MD. Family caregiving and congestive heart failure. Review and analysis. Eur J Heart Fail 2005;7:592-603.
26. Goodyer LI, Miskelly F, Milligan P. Does encouraging good compliance improve patients' clinical condition in heart failure? Br J Clin Pract 1995;49:173-176.
27. McMurdo ME, Witham MD, Gillespie ND. Including older people in clinical research. BMJ 2005;331(7524):1036-1037.
Table 1
Demographic and clinical characteristics of the study population (n=58).
Age (years + SD)80.2 +4.6 (58)Sex (female)43% (25)Married38% (22)Mean school leaving age (SD)14.3 (+1.27)Left Ventricular Ejection FractionMild/ Moderate/ Severe.26% (15) / 33% (19) / 41% (24).NYHA functional classII / III59% (34) / 41% (24)Ischemic aetiology74% (43)Co-morbiditiesHypertension 17% (10)Diabetes10% (6)COPD19% (11)Previous MI60% (35)Angina Pectoris35% (20)Previous stroke16% (9)Peripheral vascular disease17% (10)MedicationsACE inhibitors100% (58)Beta-blockers24% (14)Spironolactone33% (19)Digoxin28% (16)Diuretics86% (50)Six minute walk distance (Metres + SD)257 + 111BMI (kg/m2) (mean + SD)26.8 + 4.6
Table 2 Logistic regression predicting adherence to ACEI (1= adherent, 0 =non-adherent).
UnivariateMultivariatePredictorOdds ratio95% CIOdds ratio95% CITime-line acute0.400.15-1.000.400.15-1.08Time-line cyclical0.870.38-2.02----------------------Consequences0.360.12-0.990.380.14-1.05Personal control1.360.46-4.02----------------------Treatment control2.190.48-9.99----------------------Illness coherence0.950.45-2.00----------------------Emotional representations1.050.37-2.98----------------------Identity0.940.75-1.20----------------------
Figure1. The comparison of the mean scores of illness beliefs between ACEI adherent (n=42) and non-adherent groups (n=16). Bars represent stand error of the mean.
P A G E 7
P A G E 1
E x a m p l e i t e m s f r o m t h e I P Q - R q u e s t i o n n a i r e .
T i m e - l i n e a c u t e / c h r o n i c ( T L - a c u t e , = 0 . 8 5 ) : M y i l l n e s s w i l l l a s t a s h o r t t i m e .
T i m e - l i n e c y c l i c a l ( T L - c y c l i c a l , = 0 . 7 8 ) : T h e s y m p t o m s o f m y i l l n e s s c h a n g e a g r e a t d e a l f r o m d a y t o d a y .
C o n s e q u e n c e s ( C o n s e q , = 0 . 7 3 ) : M y i l l n e s s h a s m a j o r c o n s e q u e n c e s o n m y l i f e .
P e r s o n a l c o n t r o l ( = 0 . 6 6 ) : W h a t I d o c a n d e t e r m i n e w h e t h e r m y i l l n e s s g e t s b e t t e r o r w o r s e .
T r e a t m e n t c o n t r o l ( = 0 . 5 7 ) : M y t r e a t m e n t w i l l b e e f f e c t i v e i n c u r i n g m y i l l n e s s .
I l l n e s s c o h e r e n c e ( 0 . 8 1 ) : M y i l l n e s s d o e s n t m a k e a n y s e n s e t o m e .
E m o t i o n a l r e p r e s e n t a t i o n s ( r e p s , = 0 . 7 6 ) : W h e n I t h i n k a b o u t m y i l l n e s s I g e t u p s e t .
I d e n t i t y ( = n o t a p p l i c a b l e ) : B r e a t h l e s s n e s s / F a t i g u e / e t c & i s r e l a t e d t o m y i l l n e s s .
R a
' , \ q r s t } ~ T U Z m o .
h
þ÷þþþþþêêêêêê hb hb \h ; PJ nH tH hb PJ nH tH hb hb PJ nH tH h ; h_t H*h_t h_t h_t hb H*hb h ; hb B*ph h ; hb h ; hb 0J" h ; hb 0J" 6hb 0J" 56 hb hb 0J" 6 1 \ ] U V Z i
O
$d a$gd~ d 7$ 8$ H$ gd ;
9r d gd ;
9r hd ^hgd ;
& F
9r d gd ;
& F d gd ; d gd ; $Ld ^La$gd ;
$d a$gd ; 7 9 ^ _ ` y
&
>
?
\
g
h
l
m
q
r
{
ÿ~yun hn2 hn2 h~ h~ 5 h~ hA
h B*ph hd& hl B*ph hrX B*ph hn2 hl B*ph hn2 hl hl h>@ h hA
hn2 hA
5 hw3 5 h+ 5 h]% 5 hsA6 5 hb 5 h ; \hb hb \h ; hb hb hb *
, , `' G f ֚ X ` s * $hd `ha$gd~ d 7$ 8$ H$ `gdK d 7$ 8$ H$ `gd~ d 7$ 8$ H$ gd~
$d a$gd~ ( ) * > H P c q r | } # % & * , 4 5 6 B F G H S T Y [ \ ŷޯ֏|xppi_ j h'G( hk h'G( hk hk B*ph hk hrX hr hr h>@ hA
hn2 hA
5h B*ph hrX B*ph hQ B*ph hn2 B*ph h~ PJ mH nH sH tH hk h~ PJ mH nH sH tH h&u B*ph hn2 hn2 B*ph hn2 hn2 h p h p >*h p hn2 %\ ^ _ d f g i j N Y Z \ p ~ ¾¾¾ꉄ}y}u}pi h. l h. l hQ 5h>@ hrX hQ hQ hn2 5hn2 hn2 5h$:b B*]ph hrX B*]ph h'G( h$:b B*]ph ho6 h. l h{rC h#(i h$:b ht} hnX hn2 hnX h8n' hnX hA
hnX h!H hA
hTJ hr hr hk h'G( hk & S ` d m t + , v w ȷm_m_m hUU PJ mH nH sH tH #j hUU PJ UmH nH sH tH h ( PJ mH nH sH tH h PJ mH nH sH tH hqw PJ mH nH sH tH h PJ mH nH sH tH h^;W h^;W PJ mH nH sH tH h]% 5h]% h]% 5 h&u 5h p ho6 hQ hHF hrX hn2 hn2 hn2 h. l hn2 % " # ' r s ! ! ! ̪r]K] #hYO B*PJ mH nH ph sH tH )h^;W h^;W B*PJ mH nH ph sH tH h PJ mH nH sH tH h
PJ mH nH sH tH h ( PJ mH nH sH tH hUU PJ mH nH sH tH #j hUU PJ UmH nH sH tH h
hF. hB h p h hB hB PJ mH nH sH tH hs PJ mH nH sH tH h^;W h^;W PJ mH nH sH tH ! $! ,! u! v! w! W' X' [' \' ^' _' `' d' m' ' ƴvaO=+= #h{rC B*PJ mH nH ph sH tH #hr B*PJ mH nH ph sH tH #h B*PJ mH nH ph sH tH )hN5J h B*PJ mH nH ph sH tH )hN5J h^;W B*PJ mH nH ph sH tH #hUU B*PJ mH nH ph sH tH ,j hUU B*PJ UmH nH ph sH tH #h p B*PJ mH nH ph sH tH )h^;W h^;W B*PJ mH nH ph sH tH #hTw B*PJ mH nH ph sH tH #h#i B*PJ mH nH ph sH tH ' ' ' ' 0 0 0 0 0 1 1 L1 W1 X1 .8 /8 28 38 48 58 8 8 IJIJ۠|IJIJĠjUJ hb h. l B*ph )hb hr B*PJ mH nH ph sH tH #hr B*PJ mH nH ph sH tH #h 5 B*PJ mH nH ph sH tH #h#i B*PJ mH nH ph sH tH #h ( B*PJ mH nH ph sH tH #hUU B*PJ mH nH ph sH tH ,j hUU B*PJ UmH nH ph sH tH #hr B*PJ mH nH ph sH tH #h?l B*PJ mH nH ph sH tH 8 8 8 8 8 8 8 A A A A A A A A A mm[I7I #h B*PJ mH nH ph sH tH #h#D B*PJ mH nH ph sH tH #h. l B*PJ mH nH ph sH tH #hUU B*PJ mH nH ph sH tH ,j hUU B*PJ UmH nH ph sH tH )hb h. l B*PJ mH nH ph sH tH )hb ho6 B*PJ mH nH ph sH tH )hb hr B*PJ mH nH ph sH tH )hb ho6 B*CJ OJ QJ ^J aJ ph )hb h. l B*CJ OJ QJ ^J aJ ph A A A A B B JB KB G G G G G G G ;G TG _G zG {G 4X ɷ||jXF4F|#h. B*PJ mH nH ph sH tH #hYO B*PJ mH nH ph sH tH #h{rC B*PJ mH nH ph sH tH #h^;W B*PJ mH nH ph sH tH #hUU B*PJ mH nH ph sH tH ,j hUU B*PJ UmH nH ph sH tH #h
B*PJ mH nH ph sH tH #h B*PJ mH nH ph sH tH #h 5 B*PJ mH nH ph sH tH #h#D B*PJ mH nH ph sH tH #h(2 B*PJ mH nH ph sH tH 4X 5X :X ;X =X >X eX fX X
Y Y Y Y mu nu uu vu xu yu ų}kYD/)hUU hHF B*PJ mHnH ph sHtH )hUU hYO B*PJ mHnH ph sHtH #hUU B*PJ mHnH ph sHtH #h. B*PJ mH nH ph sH tH #ho P B*PJ mH nH ph sH tH #h%P B*PJ mH nH ph sH tH #hYO B*PJ mH nH ph sH tH #hpu B*PJ mH nH ph sH tH #h[ B*PJ mH nH ph sH tH #hUU B*PJ mH nH ph sH tH ,j hUU B*PJ UmH nH ph sH tH yu u u u u u u u u v -v .v /v ɷ퓁jXjXjF4 #h.4 B*PJ mH nH ph sH tH #h. B*PJ mH nH ph sH tH #hUU B*PJ mH nH ph sH tH ,j hUU B*PJ UmH nH ph sH tH #h 5 B*PJ mH nH ph sH tH #hrX B*PJ mH nH ph sH tH #hX B*PJ mH nH ph sH tH #h%P B*PJ mH nH ph sH tH #hHF B*PJ mH nH ph sH tH #hj#- B*PJ mH nH ph sH tH #h>@ B*PJ mH nH ph sH tH d l m h i j r s w x ~ ӈ ֈ ۷||jXFjXX #ho6 B*PJ mH nH ph sH tH #hd& B*PJ mH nH ph sH tH #h9z B*PJ mH nH ph sH tH #hUU B*PJ mH nH ph sH tH ,j hUU B*PJ UmH nH ph sH tH #hLb B*PJ mH nH ph sH tH #h B*PJ mH nH ph sH tH #h.4 B*PJ mH nH ph sH tH #hao B*PJ mH nH ph sH tH #h B*PJ mH nH ph sH tH 2 3 c d f lj ʉ ˉ ̉ ͉ Ս ֍ ڍ ۍ ؑ ّ ݑ ޑ ߑ Y Ɠ Ǔ ȓ % & * + , - . ՚ ƿƿƿƒ~zzvi h '& h '& PJ nH tH h '& hqS- hK hK ]hUU j hUU UhSB #hUU B*PJ mH nH ph sH tH ,j hUU B*PJ UmH nH ph sH tH hK hK hK hd& hd& hd& )hd& h B*PJ mH nH ph sH tH )hd& hd& B*PJ mH nH ph sH tH '՚ ֚ ) 0 2 9 n q ɛ ݛ ޛ ߛ 䐥{ϥiWEW #h 5 B*PJ mH nH ph sH tH #h B*PJ mH nH ph sH tH #h< B*PJ mH nH ph sH tH )hnX hrX B*PJ mH nH ph sH tH )hnX hd& B*PJ mH nH ph sH tH )hnX h8n' B*PJ mH nH ph sH tH )hnX h 5 B*PJ mH nH ph sH tH )hnX h< B*PJ mH nH ph sH tH )hnX h>@ B*PJ mH nH ph sH tH h '& hK ߛ W X ^ _ ` f r s ǜ ! " ± ñ ʱ ˱ ̱ ~~p^P^P^? hl h PJ mH nH sH tH hUU PJ mH nH sH tH #j hUU PJ UmH nH sH tH h@ PJ mH nH sH tH h PJ mH nH sH tH h h PJ mH nH sH tH hjF 6PJ mH nH sH tH h ,t 6PJ mH nH sH tH h]% 5 h ,t 5h]% h]% 5 h ,t h]% h]% h< #h< B*PJ mH nH ph sH tH #hj#- B*PJ mH nH ph sH tH ̱ ͱ * 8 @ O j w Ų ղ ֲ ] }kdSD h ,t 6PJ mH nH sH tH h*PJ mH nH sH tH h7 PJ mH nH sH tH hk hk PJ mH nH sH tH hk PJ mH nH sH tH #h ,t h ,t 6PJ mH nH sH tH hl hjF PJ mH nH sH tH hl h|g/ PJ mH nH sH tH hl hS PJ mH nH sH tH hl h=C PJ mH nH sH tH H ^ # $ % > ? C D E F s t y z { | X Y ] ^ ´xj\N\Nj hS PJ mH nH sH tH hZ PJ mH nH sH tH h7 PJ mH nH sH tH hwi PJ mH nH sH tH hUU PJ mH nH sH tH #j hUU PJ UmH nH sH tH ho6 PJ mH nH sH tH h*~: PJ mH nH sH tH h!# PJ mH nH sH tH h^ w h0 PJ mH nH sH tH hHF PJ mH nH sH tH h^ w h7 PJ mH nH sH tH F ` i T U d e x j $d $d &d N P a$gd~ d 7$ 8$ H$ gd~
$d a$gd~ d 7$ 8$ H$ `gd~ Q d 7$ 8$ Eƀ CF H$ `gd74 . / 0 = ? ~ , 0 A E ] _ ` ĶĶ䥔uf_[W[S[_O h0 h|g/ hrX hS hS hS h ,t 6PJ mH nH sH tH hVO PJ mH nH sH tH h h PJ mH nH sH tH h h PJ mH nH sH tH h ht} PJ mH nH sH tH hUU PJ mH nH sH tH #j hUU PJ UmH nH sH tH h PJ mH nH sH tH h PJ mH nH sH tH ht} PJ mH nH sH tH ` h i I n p 5 H R S T U c d e r v ߵzsnidi_ hrX 6 h~ 6 h ,t 6 h`d 6 hg\ hnX hS PJ mH nH sH tH hN PJ mH nH sH tH hrX PJ mH nH sH tH hS hS PJ mH nH sH tH h`d PJ mH nH sH tH hUU j hUU Uh=C hrX h F hg\ hN #hS hS 6PJ mH nH sH tH h]% 5 h ,t 5 $v w x " + , 6 O y z
I M N V W % s ŸŸŭŸŭŸŞߌh74 hv hZ hXH hrX 6 hj#- ] h#i ]h'G( h H*] j ch'G( h ]h'G( h 6 h ]h'G( h ]hrX h j h'G( h h'G( h hk
; h`d h`d h`d h ,t 6 hj#- 6 4 N J K Z [
! ! y0 0 2 2 2 3
$d a$gd5>y 7$ 8$ H$ gd5>y $hd `ha$gd~ hd 7$ 8$ H$ `hgd~ $d $d &d N P a$gdnX
$d a$gd~ o p
# , 0 1 6 8 : = ? @ F V t u I J ԽԽԽԽԹԹԽԽԽԽԽԽ
hnX aJ( hnX h aJ( hnX hNO aJ(
hNO aJ(
hZ aJ( h& h/- h'G( h 6] j bh'G( h 6] h'G( h h'G( h 6]aJ(
h/- aJ( h'G( h aJ(
h aJ( hZ 5J K Z [
# $ & * + 0 3 4 6 7 9 : B F ƿӿ
h= aJ(
h aJ( h/- h'G( h 6] h j bh'G( h 6] h'G( h h'G( h B*aJ( ph h'G( h 6B*]aJ( ph h'G( h aJ(
hnX aJ( hnX 6hnX hnX aJ( : @ C O S X ] xkaWaM h B*]ph h#` B*]ph h.4 B*]ph h'G( h|g/ B*]ph h'G( h|g/ B*aJ( ph h|g/ B*aJ( ph h/- h h]% h #h B*PJ mH nH ph sH tH h B*ph h ,t h ,t 5 h e h h'G( h B*]ph hrX h B*aJ( ph h'G( h 6B*]aJ( ph h'G( h B*aJ( ph " 7 8 9 W [ \ ] ^ " F
ȾȆ~zvrzrzrnjfb^nbjbjn h" h: hD hn` hC5 h h h~ h#` h|g/ hrX h|g/ h|g/ B*]ph h 6PJ \mH nH sH tH h B*]aJ( ph h#` B*]ph h.4 B*]ph h'G( h|g/ B*]ph &h h 6PJ \mH nH sH tH h B*]ph h'G( h B*]ph $ 0 ; u v w
P X d p : ; ? @ < = L g h k l n ! ' + 0 Y Z [ & ȼļܼļ촰ļh[ h6 hp hc hWW hrX h hf hbO h e h
hHF h h#` h % hUU j hUU UhC5 hn` h: D& * A y z
7
c
7 @ v \ ] ! 8 F P Q S T ? D Z w #hti B*PJ mH nH ph sH tH #hUU B*PJ mH nH ph sH tH ,j hUU B*PJ UmH nH ph sH tH #hp B*PJ mH nH ph sH tH h e h74 hUU j hUU UhnX h h" hj hon h/- h.4 h@ hWW hp .Z [ ! ! 1! ! ! ! ! ! ! ! " " &" S" ųygUCC #h$\% B*PJ mH nH ph sH tH #hTw B*PJ mH nH ph sH tH #hn` B*PJ mH nH ph sH tH #hWW B*PJ mH nH ph sH tH hti #hti B*PJ mH nH ph sH tH #h`q B*PJ mH nH ph sH tH #hp B*PJ mH nH ph sH tH #hP B*PJ mH nH ph sH tH #hUU B*PJ mH nH ph sH tH ,j hUU B*PJ UmH nH ph sH tH S" " " " " " %# 3# \# # # # ' ' ' ' ' ( ( ( ( ( ( ) ) ɷۥ|j|j|XFB>B>h$\% h#` #h % B*PJ mH nH ph sH tH #hTw B*PJ mH nH ph sH tH #hUU B*PJ mH nH ph sH tH ,j hUU B*PJ UmH nH ph sH tH #hj B*PJ mH nH ph sH tH #hp B*PJ mH nH ph sH tH #h$\% B*PJ mH nH ph sH tH #hC5 B*PJ mH nH ph sH tH #h" B*PJ mH nH ph sH tH #h e B*PJ mH nH ph sH tH ) V) * * K* S* * * * * * * -+ .+ /+ . . . . . =/ / / / / / / / / / 70 X0 Y0 m0 °{i{i{eaaa]aeaYY h hvu! h` hTw #hUU B*PJ mH nH ph sH tH ,j hUU B*PJ UmH nH ph sH tH #hr B*PJ mH nH ph sH tH h p h@ >*h@ #hql B*PJ mH nH ph sH tH #h@ B*PJ mH nH ph sH tH #hc B*PJ mH nH ph sH tH #hTw B*PJ mH nH ph sH tH h$\% h#` !m0 w0 x0 y0 0 0 0 1 1 @1 1 42 `2 v2 2 2 2 2 2 2 2 2 2 2 2 2 p3 q3 r3 3 3 3 3 3 3 3 3 3 3 3 4 4 4 4
4 4 4
4 4 4 !4 "4 #4 $4 )4 *4 +4 ,4 24 34 44 C4 E4 ȼȴȧh~n PJ mH sH h5>y h5>y PJ mH sH hUU hUU 6h5>y j hUU UhUU h@- h~ h~ 5h%P h" h e h.4 hTw hTw hTw 5hp h h
>3 3 5 5 7 7 8 9 9 : ; < = = > M? @ @ BA A B C pD 3E -F F _G
h d ^ `gd5> 4 4 4 4 4 4 4 4 4 4 4 4 4 >5 5 5 5 5 5 ;6 6 6 6 6 6 6 7 7 7 8 8 8 ,9 49 99 9 9 9 9 9 : : : ; ; ; ; ; < T< < = = = = > > 0? ;? @? ? @ 室廠廠廜廜廜廜廜廜廜 h0 h~n h0 PJ mH sH h~n h~n PJ mH sH hUU hUU 6hUU hUU mHsH h5>y hUU mH sH h5>y hUU 6mH sH hUU h5>y h5>y PJ mH sH h~n PJ mH sH =@ @ @ @ A 0A 5A A A A B B B C /C C C C HD ^D cD E E E !E &E F F %F F F F F F >G MG RG G G G G G G G G %H (H )H *H +H -H 8H :H CH DH MH NH dH eH vH wH H H H H H H H I I I 5I 6I ļļļ h(6 hS >* hZ5 hS h(6 hS 5 hS 5hZ5 hS 5hS j hUU Uh S hUU hUU 6hUU h0 H_G G G G G +H ,H -H >H MH u A kd $$If l ," "
t 6 4 4
l a yt(6 $d $If a$gd(6 l
$d a$gdS hd 7$ 8$ H$ ^hgd5>y
h d ^ `gd5>y MH NH [H dH eH mH vH > T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 $d $If a$gd(6 l T kdX $$If l 0 ," L L
t 6 4 4
l a yt(6 vH wH H H H H H > T kd\ $$If l 0 ," L L
t 6 4 4
l a yt(6 $d $If a$gd(6 l T kd
$$If l 0 ," L L
t 6 4 4
l a yt(6 H H H H u $d $If a$gd(6 l $d $If ^a$gd(6 l T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 H I I I I > T kdR $$If l 0 ," L L
t 6 4 4
l a yt(6 $d $If a$gd(6 l T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 I !I 5I 6I II RI u [ d $7$ 8$ H$ If gd(6 l T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 $d $If a$gd(6 l $d $If ^a$gd(6 l 6I II RI SI bI dI {I |I I I I I I I I I J J 3J 4J KJ LJ dJ eJ vJ wJ J J J J J J J J J J J J J J J J J >K @K XK ?M @M HM IM vM }M M M M M M M M ԺDzDzDzǡ !j hS U]mH nH sH uh'G( hS ]h'G( hS B*]ph hS ]h/b hS 5hS h(6 hS >*h(6 hS 5 hZ5 hS h(6 hS PJ mH nH sH tH :RI SI bI cI dI > T kdH $$If l 0 ," L L
t 6 4 4
l a yt(6 $d $If a$gd(6 l T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 dI rI {I |I I I u T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 $d $If a$gd(6 l $d $If ^a$gd(6 l I I I I u $d $If a$gd(6 l $d $If ^a$gd(6 l T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 I I I I u $d $If a$gd(6 l $d $If ^a$gd(6 l T kd> $$If l 0 ," L L
t 6 4 4
l a yt(6 I I I I u $d $If a$gd(6 l $d $If ^a$gd(6 l T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 I I I I u $d $If a$gd(6 l $d $If ^a$gd(6 l T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 I I J J u $d $If a$gd(6 l $d $If ^a$gd(6 l T kd4 $$If l 0 ," L L
t 6 4 4
l a yt(6 J J J J J > T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 $d $If a$gd(6 l T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 J )J 3J 4J BJ KJ u T kd* $$If l 0 ," L L
t 6 4 4
l a yt(6 $d $If a$gd(6 l $d $If ^a$gd(6 l KJ LJ [J dJ u $d $If a$gd(6 l $d $If ^a$gd(6 l T kd| $$If l 0 ," L L
t 6 4 4
l a yt(6 dJ eJ mJ vJ u $d $If a$gd(6 l $d $If ^a$gd(6 l T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 vJ wJ J J u $d $If a$gd(6 l $d $If ^a$gd(6 l T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 J J J J J > T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 $d $If a$gd(6 l T kdr $$If l 0 ," L L
t 6 4 4
l a yt(6 J J J J J J >K ?K @K KK x m m m m T $d $If a$gd(6 l
$d a$gdS T kd $$If l 0 ," L L
t 6 4 4
l a yt(6 $d $If a$gd(6 l d $7$ 8$ H$ If gd(6 l KK XK YK cK nK uK K K f f f f f $d $If a$gd(6 l g kdv $$If l F
!
@ @
t 6 4 4
l a yt(6 $d $If a$gd(6 l K K K K K K K r Y Y Y Y Y $d $If a$gd(6 l kd $$If l r
,l !
t 6 4 4
l a yt(6 K K K K K K K r Y Y Y Y Y $d $If a$gd(6 l kdr $$If l r
,l !
t 6 4 4
l a yt(6 K K K L L L L r Y Y Y Y Y $d $If a$gd(6 l kd $$If l r
,l !
t 6 4 4
l a yt(6 L L /L 4L >L JL VL r Y Y Y Y Y $d $If a$gd(6 l kdp
$$If l r
,l !
t 6 4 4
l a yt(6 VL WL iL nL xL L L r Y Y Y Y Y $d $If a$gd(6 l kd
$$If l r
,l !
t 6 4 4
l a yt(6 L L L L L L L r Y Y Y Y Y $d $If a$gd(6 l kd` $$If l r
,l !
t 6 4 4
l a yt(6 L L L L L M M r Y Y Y Y Y $d $If a$gd(6 l kd $$If l r
,l !
t 6 4 4
l a yt(6 M
M M M %M 1M =M r Y Y Y Y Y $d $If a$gd(6 l kdP $$If l r
,l !
t 6 4 4
l a yt(6 =M >M ?M M M M M M r g \ \ \ \ Q
$d a$gdS
$d a$gdS
$d a$gdS kd $$If l r
,l !
t 6 4 4
l a yt(6 M M M M M M M M M M M M M M M M N N N N N N N N N *N ,N {w{w{w{wmg]RmgNmgm h'G( h 0J mH nH uj h 0J U
h'G( 0J j h'G( 0J Uh(6 j h(6 U.h5>y CJ OJ PJ QJ ^J aJ mH nH sH tH hS
hS aJ( h'G( hS 5\]!j hS U]mH nH sH uh'G( hS ]5jN
hkN hS CJ OJ PJ QJ U^J aJ mH sH 6j hS CJ OJ PJ QJ U^J aJ mH nH sH uM M M M M M M M M M M M M M M M N N N N h]h &`#$ hd 7$ 8$ H$ ^hgd5>y gdS d gdS
h d ^ `gdS
$d a$gdS
d gdS N N 2N 4N 6N 8N :N N @N BN DN FN N N DO P P vQ R R NS S S gdS 7$ 8$ H$ gdS $a$gdS h]h h &`#$]h &`#$ ,N .N 0N 4N 8N :N FN ~N N N N N N N N N N >O @O BO DO O O ʻʩʻʻʍoTo9ʻ4hgi* hS CJ OJ PJ QJ ^J aJ mH nH sH tH 4hS 6CJ OJ PJ QJ \^J aJ mH nH sH tH :hgi* hS 6CJ OJ PJ QJ \^J aJ mH nH sH tH 7hgi* hS CJ OJ PJ QJ \^J aJ mH nH sH tH #hgi* hS 6CJ OJ QJ ^J aJ hS 5CJ OJ QJ ^J aJ #h%I hS 5CJ OJ QJ ^J aJ h(6 h'G(
h'G( 0J j h'G( 0J Uh!` 0J mH nH u O O O O O P P P DP XP \P ^P P P P P P P P HQ JQ {fT{T6 :h%I hS 6CJ OJ PJ QJ \^J aJ mH nH sH tH #h~ hS 5CJ OJ QJ ^J aJ (hgi* hS CJ OJ QJ ^J aJ mH sH hS 5CJ OJ QJ ^J aJ 7hgi* hS 6CJ OJ PJ QJ ^J aJ mH nH sH tH 4hS 6CJ OJ PJ QJ \^J aJ mH nH sH tH :hgi* hS 6CJ OJ PJ QJ \^J aJ mH nH sH tH hS CJ OJ QJ ^J aJ #h%I hS 5CJ OJ QJ ^J aJ JQ tQ vQ Q Q Q Q R R R R R >R LR NR PR R R R R R R R JS LS NS ^S ѿwwfwQCwQhS CJ OJ QJ ^J aJ (h%I hS CJ OJ QJ ^J aJ mH sH hgi* hS CJ OJ QJ ^J aJ 4hS 6CJ OJ PJ QJ \^J aJ mH nH sH tH :h%I hS 5CJ OJ PJ QJ \^J aJ mH nH sH tH hS 5CJ OJ QJ ^J aJ #h%I hS 5CJ OJ QJ ^J aJ h%I hS CJ OJ QJ ^J aJ :h%I hS 6CJ OJ PJ QJ \^J aJ mH nH sH tH ^S `S xS S S S S S S S T ^
̾xgxgxgxgVVR h!# hWQ hS CJ OJ QJ ^J aJ h\ hS CJ OJ QJ ^J aJ hS CJ OJ QJ ^J aJ h'G( hRdl hS CJ OJ QJ ^J aJ U hS 6CJ OJ QJ ^J aJ #h%I hS 6CJ OJ QJ ^J aJ hS CJ OJ QJ ^J aJ #h%I hS 5CJ OJ QJ ^J aJ #h!S hS 5CJ OJ QJ ^J aJ hS 5CJ OJ QJ ^J aJ n g e f o r a l l s c a l e s 1 - 5 , e x c e p t I d e n t i t y : 0 - 1 4 .
( = C r o n b a c h s a l p h a )
T L a c u t e T L c y c l i c a l C o n s e q P e r s o n a l T r e a t m e n t I l l n e s s E m o t i o n a l I d e n t i t y
C o n t r o l C o n t r o l C o h e r e n c e r e p s
y = M e a n I S ^ 4
hd 7$ 8$ H$ ^hgd5>y $a$gdS gdS gdWQ $a$gdS PQ-R rating.
.h5>y CJ OJ PJ QJ ^J aJ mH nH sH tH 2 1h:pO\X / =!"#$6% V $$If !v h5 "#v ":V l
t 65 "/ yt(6 ^ $$If !v h5 L5L#v L:V l
t 65 L/ yt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 P $$If !v h5 L5L#v L:V l
t 65 Lyt(6 ^ $$If !v h5 L5L#v L:V l
t 65 L/ yt(6 t $$If !v h5
5@ 5@ #v
#v@ :V l
t 65
5@ / yt(6 $$If !v h5
5555#v
#v:V l
t 65
5/ yt(6 $$If !v h5
5555#v
#v:V l
t 65
5/ yt(6 v $$If !v h5
5555#v
#v:V l
t 65
5yt(6 v $$If !v h5
5555#v
#v:V l
t 65
5yt(6 v $$If !v h5
5555#v
#v:V l
t 65
5yt(6 v $$If !v h5
5555#v
#v:V l
t 65
5yt(6 v $$If !v h5
5555#v
#v:V l
t 65
5yt(6 v $$If !v h5
5555#v
#v:V l
t 65
5yt(6 $$If !v h5
5555#v
#v:V l
t 65
5/ yt(6 D d
" 0
# A " Z Bvwkm( vk 6
@=. Bvwkm( vk{ Q V |@ x] tTI6!W $Klr4(5*'D|@$
Q A
> EA[=TEU*UKk#T+*`mO Ri%;sݙ{w6s {3wBf xBQ Ca/B"BI $>p~PB H |6T;ۺk9;suk}엲}'}(y>}t5dr糸ߦ ;K( -}ci: DM T;K+ƕ[8Vr $*R8%d:'SAYVz2 ~ V pd?> L5v[{u|C yR~{x e |} : }X^aUëG g [@~g ( w?Ǥj_G#9h9
6^d\Qɉ|uPjo:OUǭT1,?U )x>p\a1RW?fA^A4*~@G>vگH|
g=mm=&h[riJ3gc
'U
$XjճNОd x&-5~ N`E-hgvf1
4?.b1UP y9>A j` NxTbZ:A (94lOUb
L$ Wぃa2FIAf4 ؠǥXK1]Y
>gR| |dA=v ; 0yM1I'| VfEC^ B`1=XLaE cqba5;$\@6r}F˕J
Rcl2*w= IxipҘĜ[ x'm7B)du4U:.gLj]<>O.քQ,5fsu5r ).u5wv%= */
ܹvqqrcqr*[kCx,V~"vXQ+8=5xC}1 @r=&؝eӸűX6- _~l @dl _H ))ۈ;hc-G| q|nֽ^ G|RqlSoB+1 nLH0yn Fo<Ӱu1oL6u>ǰ,ys#& =0ӚE!հڨ <L豺CHLODszXrߒct-b;b 缿+ڱ/#ڸq<詾e,} }.~yR_s >I44c;_%ޞUbo=' lj&O _%7c\\_ǀiv.#9;8oNc+ۑ[gbVvp>RMM\_Iϑx_.'9TfNrTfe`d>ync;{{s}r;D>(
Y;(}An` |ֿ[%vqKus}kvnTڝ,_k ٤LĘ/Y ]kVI\KaH5UoBl:l`L[f36 ;Y8~`bgY
vUIω1mco3%v.mY{0]-s d ٔ;&qm܍1m Lm|Zbg~ !)&qtiv~_;B&`mׁ1Q }0ɞOe.?hlDϫ%FnC?>Yk*S7$u 'AnfyGc=.$ % ' #ۮցAvSwAcƘ E½(qRXoK7߸ؗ.Z|Dw`
889 d@ 'H ť lhOO~6sm̏] 2~dc b$ɉP\`>]3h
82G'9㟬O/)?8 d@ 2fK3H /a9]x=b1?YYN?rb)?vgv bX\v \ݙN=?>es!jGK1?Zr;[rq)8{#?9 d@ F*& z~$+txl4~ c~|=jpy pE; babBqb\ Bޖ)? _KH/*&hƏ?Ģ#&Io u}8wf0%&ɕ%ӹ ;q1@,W:UL(. ڗD wb t=F<x$~nM}Z? k8 d@ 5 m*&65 ä́ ?ܟV*ծw>8G! bQBńDϏ S mfZMmK m p)?Z9 d@ V_bBqe:[aǛ K' "1Nb !7c^cȏN d@ Rו*&+AzK.%
LO_{^ޟ/tBsM Xߵ_?]w- 'Ѭm!{[B7-T$p ;@^~}b{0[; q88,Ͷ;l{ON>1Vظoele= < +q:V>C sƀYhlݵ*ȝ= QG2%y/&Gޜ)d4wN.w9ZˮAW%VN,PF '>_?_ _-/D Zzz(hk
_, ?GAnoլ|;/DaO605"WZL){~{q^9hs$>wM-wVDZ_|
fH %/nMjH绽v lpiVw{_{#ԇ7%|/>cN&>'=ߢ][o.x_Q ?[uew ӍP ^$ 2 0 @ P ` p 2 ( 0 @ P ` p 0 @ P ` p 0 @ P ` p 0 @ P ` p 0 @ P ` p 0 @ P ` p 8 X V ~ _HmH nH sH tH H ` H 'G( N o r m a l CJ PJ _HaJ mH nHsH tHP P 'G( H e a d i n g 1 $5$ 7$ 8$ 9D @& H$ >*aJ tH T T 'G( H e a d i n g 2 $5$ 7$ 8$ 9D @&H$ 5CJ aJ tH N N 'G( H e a d i n g 3 $$d @&a$ 5>*aJ tH H H 'G( H e a d i n g 4 $@& 6aJ mH sH tH B B 'G( H e a d i n g 5 $@& 56aJ tH N N 'G( H e a d i n g 6 $$d @&a$ 56aJ tH @ @ 'G( H e a d i n g 7 $@& 5aJ tH N N 'G( H e a d i n g 8 $$d @&a$ 5\aJ tH N N 'G( H e a d i n g 9 $$dh @&a$ 5CJ \tH D A` D D e f a u l t P a r a g r a p h F o n t R i@ R T a b l e N o r m a l 4
l 4 a ( k ( N o L i s t \ C \ 'G( B o d y T e x t I n d e n t $0dh ^`0a$ tH > B > 'G( B o d y T e x t $dh a$ tH R P R 'G( B o d y T e x t 2 05$ 7$ 8$ 9D H$ `0 aJ tH L "L 'G( H e a d e r
!5$ 7$ 8$ 9D H$ aJ tH 8 @ 28 'G( F o o t e r
9r tH : " : 'G( C a p t i o n 6CJ aJ tH @ R@ 'G( C o m m e n t T e x t CJ aJ tH @ & a@ 'G( F o o t n o t e R e f e r e n c e H* B rB 'G(
F o o t n o t e T e x t CJ aJ tH @ j QR@ 'G( C o m m e n t S u b j e c t 5\F Q F 'G( B o d y T e x t 3 $d a$ aJ tH P R P 'G( B o d y T e x t I n d e n t 2
h^h CJ$ tH . )@ . 'G( P a g e N u m b e r H H 'G( B a l l o o n T e x t CJ OJ QJ ^J aJ j @ j 2
T a b l e G r i d 7 :V 0 B ' B C o m m e n t R e f e r e n c e CJ aJ $ $ c v o l u m e " " c i s s u e " " c p a g e s . X@ !. ` E m p h a s i s 6]. 1. nX j o u r n a l n a m e PK ! [Content_Types].xmlj0Eжr(Iw},-j4 wP-t#bΙ{UTU^hd}㨫)*1P' ^W0)T9<l#$yi} ;~@(Hu* Dנz/0ǰ $ X3aZ,D0j~3߶b~i>3\`?/[G\!-Rk.sԻ..a濭? PK ! ֧ 6 _rels/.relsj0 }Q%v/C/} (h"O
= C?hv=Ʌ%[xp{۵_Pѣ<1H0ORBdJE4b$q_ 6LR7`0̞O,En7Lib/Se е PK ! ky theme/theme/themeManager.xml M
@}w7c(Ebˮ CAǠҟ7՛K
Y,
e.|,H ,lxɴIsQ}#Ր ֵ+!,^$j=GW)E+&
8 PK ! P theme/theme/theme1.xmlYOo6w toc'vuر-Mn iP@I}úama[إ4:l ЯGRX^6؊>$ !)O^rC$y@ /yH*)UDb`}"qۋJחX^)I`nEp)liV[]1M<OP6r=zgbIguSe bORD۫qu gZo~ٺlAplxpT0+[}`j zA V2Fi@qv֬5\|ʜ̭NleXd sjcs7f
W+Ն7` g ȘJj|h(KD-
dXiJ؇(x$( :;˹! I_TS 1?E ??ZBΪmU/ ?~xY'y5g&/ɋ>GMGeD3Vq%'#q$8K )fw 9:ĵ
x}rxwr:\TZaG*y8IjbRc|XŻǿI
u3KGnD 1NIBs
RuK>V.E L+M2#'fi ~V vl{u8z H
* :( W ☕
~JTe\O*tHGHY }KNP*ݾ˦ TѼ9/#A7qZ $*c?qUnwN%Oi4 =3ڗP
1Pm \\9Mؓ2aD];Yt\[x]}Wr|]g-
eW
)6-rC Sj
id DЇAΜIqbJ#x꺃 6k#ASh&ʌt(Q% p%m&]caS l=X\P1Mh9MVdDAaVB[݈fJíP|8 քAV^f
Hn- "d>znNJ ة>b&2vKyϼD:,AGm\nziÙ .uχYC6OMf3or$5N HT[XF64T,ќM0E)`#5XY`פ ;%1U٥m;R>QD DcpU'&LE/pm%]8firS4d 7y\`JnίI R 3U~7+#m qBiDi*L69mY&iHE=(K&N!V.KeLDĕ{D vEꦚdeNƟe(MN9ߜR6&3(a/DUz<{ˊYȳV)9Z[4^n5!J?Q3eBoCM m<.vp IYfZY_p[=al-Y}Nc͙ŋ4vfavl'SA8|*u{-ߟ0%M07% < ҍ PK !
ѐ ' theme/theme/_rels/themeManager.xml.relsM
0wooӺ&݈Э5
6?$Q
,.aic21h:qm@RN;d`o7gK(M&$R(.1r'JЊT8V"AȻHu}|$b{ P8g/ ]QAsم(#L[ PK- ! [Content_Types].xmlPK- ! ֧ 6 + _rels/.relsPK- ! ky theme/theme/themeManager.xmlPK- ! P theme/theme/theme1.xmlPK- !
ѐ ' theme/theme/_rels/themeManager.xml.relsPK ]
* J * J ' ' ' * \ ! ' 8 A 4X yu ՚ ߛ ̱ ` v J & Z S" ) m0 E4 @ 6I M ,N O JQ ^S 3 _G MH vH H H I RI dI I I I I I J J KJ dJ vJ J J KK K K K L VL L L M =M M N S
v W [ ( ( W) .0 20 0 9 9 J: ? ? z? 4P :P Q mm um .n z z i| r w ́ Յ څ ؉ ݉ Nj % * ! © ʩ $ > C { X ] / v : ? g k Z \
Z .# & & * * ? J QQQQQQQQQQQQQQQQQQQQQQQQQQQQQQ " * !! / X 2 $ e5} w_~ 2 $ Vxv1;:Uߚ @ \ (
V
# " ?
b
3 # " ` ?
\
# # " ` ?
B
S ? E E E J ` h A
t t < t 3 +l t ,l -l * .l /l 7 0l 1l d 2l F 3l \ 4l 5l 6l 7l T 8l 9l :l ;l l D} ?l J @l Ԧ Al 4
Bl t
Cl Lg Dl g El . Fl / Gl 8 Hl 8 Il ] Jl 4] Kl ; Ll < Ml $w Nl dw Ol n Pl n Ql 䩞 Rl $ Sl |e Tl e Ul e Vl Lz Wl z Xl z Yl $ Zl d [l \l ̄ ]l % 3 ; ; B K % i s 9 C V ^ l t t { 9 9 O O [ [ J
! " # $ % ' & ( ) * + , - . / 0 1 2
/ 9 A I S S # - - r B U \ h r z N N U U c c Ū Ū J
! " # $ % ' & ( ) * + , - . / 0 1 2 : *urn:schemas-microsoft-com:office:smarttagsStreet > , *urn:schemas-microsoft-com:office:smarttags
PostalCode = 3 *urn:schemas-microsoft-com:office:smarttags PlaceName = 2 *urn:schemas-microsoft-com:office:smarttags PlaceType 8 . *urn:schemas-microsoft-com:office:smarttagsCity ;
*urn:schemas-microsoft-com:office:smarttagsaddress 9 - *urn:schemas-microsoft-com:office:smarttagsplace B + *urn:schemas-microsoft-com:office:smarttagscountry-region 9 3 2 2 2 3 . - , + 2 2 . . - , + 2 3 . . - , + 3 2 2 2 3 . - , + 3 2 2 2 3 . - , +
. - + - + - + - t y i r 9 B > I % ) S W R b 0 0 om um 9| D| X d ӫ W ] > + + + + + #+ r+ u+ x+ + + + + + + + + + + + + + + + + + + , , , , !, -, 2, <, B, G, O, T, [, _, d, >- - - - - - - - - - . . 3. 8. <. @. D. P. V. a. . . . . "/ +/ / 0 #0 /0 0 0 0 0 K1 S1 1 1 1 1 1 1 1 1
2 2 2 2 2 2 2 2 2 2 w3 {3 |3 3 3 3 s4 z4 4 4 !5 (5 5 5 6 6 6 6 47 77 }7 7 7 7 )8 08 8 8 8 8 S9 [9 9 9 9 9 : : : : ; ; ; ; ; ; ; ; ; ; J< T< U< ^< z< }< ~< < < < < < < < < < = = L= R= > > ]> g> > > > > > > C? G? H? M? ?A HA LB ZB eB lB @C JC E E E E E E E E E F F F F F F F G "G 4I >I `I fI I I J J T O _ ` z { y { + + J- W- _- b- c- - - - . . / / 0 0 91 @1 1 1 1 1 2 2 3 3 Y4 _4 5 5 5 5 6 6 @7 G7 t7 y7 8 8 8 8 8 9 59 <9 l9 9 9 9 : : : : 1; ; ; ; ; G< c< j< q< < &= -= "> (> .> > > > > > > > ? ? ? ? ? ? E E E E E E E # F F H H I I 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 g ⳾ * * * + + + - - 0 0 ,1 1 1 1 2 2 3 3 4 4 4 5 5 5 6 6 07 7 7 8 8 8 9 9 9 9 : : ; ; < q< = 4= > .> > > >? ? ? ? - ɰ @ B B B B ? E E E E E E E E E E E / I I E E E E E E E E E <P^ ~P ?h* CfU >ܪ~ G_$ 0 %. @)E+G 9+qpN -:sD |=N 8?M~ xF CG2d F G LKKtF _a} ,GzeVti =Ze,
< GPyo h ^` . h ^` . h pL p^p`L . h @ @ ^@ ` . h ^` . h L ^`L . h ^` . h ^` . h PL P^P`L . h
^`h H . h
^`h H . h
pL p^p`Lh H . h
@ @ ^@ `h H . h
^`h H . h
L ^`Lh H . h
^`h H . h
^`h H . h
PL P^P`Lh H . \ ^`\o( \ ^`\o( . 0 ^`0o( . . 0 ^`0o( . . . 8 8^8`o( . . . . 8 8^8`o( . . . . .
` ^``o(
. . . . . .
` ^``o( . . . . . . .
^`o( . . . . . . . . \ ^`\o( \ ^`\o( . 0 ^`0o( . . 8 8^8`o( . . . 8 8^8`o( . . . . ` ^``o( . . . . .
` ^``o(
. . . . . .
^`o( . . . . . . .
p p^p`o( . . . . . . . . h h^h`o( h h^h`o( . 0 ^`0o( . . 0 ^`0o( . . . 8 8^8`o( . . . . 8 8^8`o( . . . . .
` ^``o(
. . . . . .
` ^``o( . . . . . . .
^`o( . . . . . . . . h h^h`o( h h^h`o( . 0 ^`0o( . . 8 8^8`o( . . . 8 8^8`o( . . . . ` ^``o( . . . . .
` ^``o(
. . . . . .
^`o( . . . . . . .
p p^p`o( . . . . . . . .
^`h H .
^`h H .
pL p^p`Lh H .
@ @ ^@ `h H .
^`h H .
L ^`Lh H .
^`h H .
^`h H .
PL P^P`Lh H . ^`o( ^`o( . 0 ^`0o( . . 8 8^8`o( . . . 8 8^8`o( . . . . ` ^``o( . . . . .
` ^``o(
. . . . . .
^`o( . . . . . . .
p p^p`o( . . . . . . . .
^`h H .
^`h H .
pL p^p`Lh H .
@ @ ^@ `h H .
^`h H .
L ^`Lh H .
^`h H .
^`h H .
PL P^P`Lh H . ^`o( ^`o( . 0 ^`0o( . . 8 8^8`o( . . . 8 8^8`o( . . . . ` ^``o( . . . . .
` ^``o(
. . . . . .
^`o( . . . . . . .
p p^p`o( . . . . . . . . \ ^`\o( \ ^`\o( . 0 ^`0o( . . 0 ^`0o( . . . 8 8^8`o( . . . . 8 8^8`o( . . . . .
` ^``o(
. . . . . .
` ^``o( . . . . . . .
^`o( . . . . . . . . h h^h`o( h h^h`o( . 0 ^`0o( . . 8 8^8`o( . . . 8 8^8`o( . . . . ` ^``o( . . . . .
` ^``o(
. . . . . .
^`o( . . . . . . .
p p^p`o( . . . . . . . . ^`B* o( ph . ^` . pL p^p`L . @ @ ^@ ` . ^` . L ^`L . ^` . ^` . PL P^P`L . 8 8^8`o( . ^` . L ^ `L . ^ ` . x x^x` . HL H^H`L . ^` . ^` . L ^`L . h h^h`o( h h^h`o( . 0 ^`0o( . . 8 8^8`o( . . . 8 8^8`o( . . . . ` ^``o( . . . . .
` ^``o(
. . . . . .
^`o( . . . . . . .
p p^p`o( . . . . . . . . ^`6o( . ^` . pL p^p`L . @ @ ^@ ` . ^` . L ^`L . ^` . ^` . PL P^P`L . \ ^`\o( \ ^`\o( . 0 ^`0o( . . 0 ^`0o( . . . 8 8^8`o( . . . . 8 8^8`o( . . . . .
` ^``o(
. . . . . .
` ^``o( . . . . . . .
^`o( . . . . . . . . h
^`h H . h
^`h H . h
pL p^p`Lh H . h
@ @ ^@ `h H . h
^`h H . h
L ^`Lh H . h
^`h H . h
^`h H . h
PL P^P`Lh H . ^`o( ^`o( . 0 ^`0o( . . 8 8^8`o( . . . 8 8^8`o( . . . . ` ^``o( . . . . .
` ^``o(
. . . . . .
^`o( . . . . . . .
p p^p`o( . . . . . . . . : :^:`o( : :^:`o( . 0 ^`0o( . . 8 8^8`o( . . . 8 8^8`o( . . . . ` ^``o( . . . . .
` ^``o(
. . . . . .
^`o( . . . . . . .
p p^p`o( . . . . . . . . LKK CG xF ? |= _a 8? G_$ C @)E+ GPyo - =Ze F G ~ ,Gze m|< % 9+ &G$ PT c b 4 5 K _t &u
s 0. 7 % wi % C b U G_ #
hK
g2 G o Z NO rX VO ._ A
[ %P #` D0 ! >! vu! !#
# % $\% '& OI' ^L' 8n' ( 'G( E) ~) * gi* P;+ , z, @- j#- qS- F. y. |g/ j`0 l2 n2 _3 w3 W4 74 5 C5 (6 sA6 >O6 &m6 c7 I8 {8 9 N9 j: +m: *~: ; k
; K; = Ns= (? SB {rC y +{ 5{ sg{ q| 1Z 2- >@ Xq Tw x ;& x \ j tq [ ] Q S H l Xn K ao on *M ^+ !: B + N
e nX Y _D )& n: 7 0 X 2 UU r= k s z R " (2 v 6 pu z ! D F g U4 m] ` n` hn /- Q |r P ~ p 5 -l vX % ) N ~n ? !# ]% M AO 9z D Me n & ^ ?l (g Z 2 ` `q _ Z5 B .4 4 XH BS ti - /( b s < I 4 << ?t # r * o6 D . q "2 2I '. |
`d Z & s #i f =C #D W hz HF J F : !` r t S ) @ pk 6 ~ b; \< o = # xX ul 0 P ^ Z& t} d& ~N E E R E F M G R . I n s t a n t F o r m a t z
R E F M G R . L a y o u t 8f R E F M G R . L i b r a r i e s 3
s < I n s t a n t F o r m a t > < E n a b l e d > 0 < / E n a b l e d > < S c a n U n f o r m a t t e d > 1 < / S c a n U n f o r m a t t e d > < S c a n C h a n g e s > 1 < / S c a n C h a n g e s > < / I n s t a n t F o r m a t > >< L a y o u t > < S t a r t i n g R e f n u m > E u r o p e a n H e a r t J o u r n a l < / S t a r t i n g R e f n u m > < F o n t N a m e > T i m e s N e w R o m a n < / F o n t N a m e > < F o n t S i z e > 1 2 < / F o n t S i z e > < R e f l i s t T i t l e > R e f e r e n c e L i s t < / R e f l i s t T i t l e > < S p a c e A f t e r > 1 < / S p a c e A f t e r > < R e f l i s t O r d e r > 0 < / R e f l i s t O r d e r > < C i t a t i o n O r d e r > 0 < / C i t a t i o n O r d e r > < N u m b e r R e f e r e n c e s > 1 < / N u m b e r R e f e r e n c e s > < F i r s t L i n e I n d e n t > 0 < / F i r s t L i n e I n d e n t > < H a n g i n g I n d e n t > 0 < / H a n g i n g I n d e n t > < L i n e S p a c i n g > 0 < / L i n e S p a c i n g > < S h o w R e p r i n t > 1 < / S h o w R e p r i n t > < S h o w N o t e s > 0 < / S h o w N o t e s > < S h o w K e y w o r d s > 0 < / S h o w K e y w o r d s > < S h o r t F o r m F i e l d s > 0 < / S h o r t F o r m F i e l d s > < S h o w R e c o r d I D > 0 < / S h o w R e c o r d I D > < S h o w A b s t r a c t > 0 < / S h o w A b s t r a c t > < / L a y o u t > [ < D a t a b a s e s > < L i b r a r i e s > < i t e m > i p q - r a n d a d h e r e n c e t o a c e p a p e r < / i t e m > < / L i b r a r i e s > < / D a t a b a s e s > @ 0 L F G H I J J @ N P R @ U n k n o w n T e s t G * T i m e s N e w R o m a n 5 S y m b o l 3. * A r i a l K T i m e s N e w R o m a n P S M T ; S i m S u n [SO 5. * a T a h o m a A B C a m b r i a M a t h " 1 h 4Rf4Rf& 0 O O 0 O O ! 24 d OE OE 3q HX ? 'G( 2 ! x x 3 T e s t g j m 4 \
Oh +'0
0 < H
T ` h p x 3 Test Normal.dotm gjm4 2 Microsoft Office Word @ F# @ l>)@ 8@ 8 0 O ՜. +,0 h p
$ Epidemiology & Public Health, UCL O OE 3 Title
! " # $ % & ' ( ) * + , - . / 0 1 2 3 4 5 6 7 8 9 : ; < = > ? @ A B C D E F G H I J K L M N O P Q R S T U V W X Y Z [ \ ] ^ _ ` a b c d e f g h i j k l m n o p q r s t u v w x y z { | } ~
! " # $ % & ' ( ) * + , - . / 0 1 2 3 4 5 6 7 8 9 : ; < = > ? @ A B C D E F G H I J K L M O P Q R S T U W X Y Z [ \ ] b R o o t E n t r y F hd D a t a
, 1 T a b l e & W o r d D o c u m e n t 4 S u m m a r y I n f o r m a t i o n ( N D o c u m e n t S u m m a r y I n f o r m a t i o n 8 V C o m p O b j y
F' Microsoft Office Word 97-2003 Document
MSWordDoc Word.Document.8 9q