- Integration of Psychiatry into Primary Health Care

Report
Mood & Anxiety
Disorders in Primary
Care: A Review
Arun V. Ravindran, MB, MSc, PhD, FRCPC, FRCPsych
Professor and Director, Global Mental Health and Office of Fellowship Training, Department of
Psychiatry; Graduate Faculty, Department of Psychology and Institute of Medical Sciences; University
of Toronto
Chief, Division of Mood and Anxiety Disorders, Centre for Addiction and Mental Health
Toronto, Ontario, Canada
1
Anxiety Disorders
2
Anxiety
What is Anxiety?
• Diffuse, unpleasant, vague sense of
apprehension often accompanied by autonomic
symptoms
When do you treat Anxiety?
• “Anxiety symptoms exist on a continuum and milder forms of
recent onset often remit without treatment.”
• Need for treatment determined by:
•
•
•
•
Severity and persistence of symptoms
Presence of co-morbidity
Disability + Impaired function
Impact on social function
3
The Spectrum of Anxiety Disorders
Posttraumatic
stress disorder
Social
anxiety disorder
Depression
Panic disorder
Obsessive-compulsive disorder
Generalized anxiety disorder
4
Co-morbidity in Anxiety
Disorders
Anxiety
Disorders
Somatoform
Disorders
Medical
Conditions
Mood
Disorders
Substance
Use
Disorders
5
Anxiety Disorders – DSM-IV –
Fear vs. Distress Disorders
Panic Disorder
Agoraphobia
Specific Phobia
Social Phobia
PTSD
ASD
OCD
GAD
AD / GMC / SU / NOS
6
Key Fears in Anxiety Disorders
•
•
•
•
•
•
PD/A – Dying, going crazy or losing control
SP – Harm from an external object or situation
SAD – Humiliation or embarrassment
GAD – Future events involving real life concerns
PTSD – Re-experiencing trauma in memories/dreams
OCD – Harm, uncertainty, uncontrollable actions
7
Epidemiology of Anxiety
Disorders
Disorder
Life Time Prevalence
Panic Disorder
Specific Phobias
Agoraphobia
Social Phobia
General Anxiety Disorder
Post Traumatic Stress Disorder
Obsessive-Compulsive Disorder
As a group
2 – 5%
1 – 19%
0.2 – 5%
5 – 12%
1 – 6%
2 – 8%
2 – 3%
20-30%
8
Psychophysiology of Anxiety
Disorders
Triple Vulnerability Model
Genetic contribution to temperament
Generalized Biological
Vulnerability
Generalized Psychological
Vulnerability
Disorder
Early Learning
Experiences and Familial/Social
Environment
Sense of diminished
control
9
Key Decision Points in the Management of
Anxiety Disorders
A. Identify anxiety symptoms
Determine if anxiety causing distress or functional impairment
Assess suicidality
B. Differential diagnosis
•Is anxiety due to other medical or psychiatric condition?
•Is anxiety comorbid with other medical or psychiatric condition?
•Is anxiety medication-induced or drug-related?
•Perform physical exam & baseline laboratory assessment
C. Identify specific anxiety disorder
Panic, specific, SAD, OCD, GAD, PTSD
Co-morbid mental disorders
•If substance abuse: avoid BZDs
•If another anxiety disorder: consider therapies that
are 1st-line for both disorders
•If mood disorder: consider therapies that are
effective for both disorders, also refer to depression or
bipolar disorder guidelines
D. Consider psychological and pharmacological treatment
•Patient preference and motivation extremely important when choosing treatment modality
•If formal psychological treatment not applied, all patients should receive education
and support to encourage them to face their fears
Comorbid medical conditions
If medical: assess benefits and risks of
medication for the anxiety disorder, but
consider impact of untreated anxiety
BZD=benzodiazepine, SSRI=selective serotonin reuptake inhibitors, SNRIs=serotonin norepinephrine reuptake inhibitors
MAOIs=monoamine oxidase inhibitors
10
Treatment of Anxiety Disorders in
Primary Care: General Principles
• Screening
• Beck Anxiety Inventory (BAI; 21 items)
• Interventions
• Pharmacotherapy (mild to moderate)
• CBT (mild to moderate)
• Antidepressants + CBT (moderate to severe)
• Maintain antidepressants + CBT boosters – 1-2 years
11
The “CBT Package” – The Proven
Intervention
•
•
•
•
•
•
Psychoeducation
Monitoring/early cue detection
Applied relaxation
Imaginal and in vivo exposure
Coping skills rehearsal
Cognitive restructuring
12
Case History
Jenny, 56-year-old accountant, married with three grown
children
• Describes herself as a ‘worrier’
• Has worried more “for the past 1 year” about her children’s
health, finances, marital relationship, the future
Jenny is likely suffering from:
 Clinical Depression
 Generalized Anxiety Disorder
 Adjustment Disorder
 Alcohol dependence
What further information is useful in her diagnosis?
13
Generalized Anxiety Disorder
(GAD): The Facts
“Inappropriate and/or extreme worry with multiple somatic
anxiety”
- Restlessness
- Poor concentration
- Fatigue
- Irritability
- Sleep difficulties
- Tension
• 5% of the general population
• Onset in adolescence, disability and chronic course
• Comorbidity and vulnerability to MDD
14
Treatment of GAD
• Pharmacotherapy
•
•
•
•
•
Antidepressants
Beta blockers
Benzodiazepines
Anticonvulsants
Buspirone
• Psychotherapy
• CBT
• Recent advances
• Focus on “worries”
• Mindfulness and acceptance
15
Case History
Sam, 24-year-old computer programmer, single and living on his
own
• 1 year history of physical symptoms
• Has seen several physicians – multiple investigations
• Convinced that he has heart disease and believes that it is
being missed
Which of the following is most likely?
 Hypothyroidism
 Panic Disorder
 Schizophrenia
 Incompetent Physicians
16
Panic Disorder and Panic Disorder
with Agoraphobia (PD/A)
“Characterized by panic attacks and avoidance behaviour”
• Prevalence
• Lifetime 3-5%
• Specialty clinics 10-60%
•
•
•
•
Impaired function
High rates of utilization
Early evidence of anxiety
Common medical/psychiatric co-morbidity
17
PD/A Diagnosis (DSM-IV)
Diagnostic criteria: recurrent panic attacks
4 or more of the following:
 Dyspnea or the sensation of being smothered
 Depersonalization or derealization
 Fear of going crazy or of losing self-control
 Fear of dying
 Palpitations or tachycardia
 Sweating
 Trembling or shaking
 Feeling of choking
 Chest pain or discomfort
 Nausea or abdominal upset
 Dizziness, feeling of unsteadiness or faintness
 Numbness or tingling sensation
 Flushes or chills
Cognitive
symptoms
Physical
symptoms
18
BillyCrystalandRobertDe Niroin AnalyzeThis–PanicDisorder
19
Treatment of PD/A
• Pharmacotherapy
• Antidepressants
• Benzodiazepines
• Psychotherapy
• CBT plus
• Breathing retraining
• Relaxation exercises
• Recent advances
• Mindfulness based CBT (MBCT)/Mindfulness based stress
reduction (MBSR)
• Sensation focused intensive treatment (SFIT)
• Virtual reality exposure therapy
20
PD/A: Treatment Outcomes
• CBT vs. pharmacotherapy vs. combination
•
•
•
•
Similar benefit short-term
CBT better on long term
CBT useful
Sequential PT + CBT – new trend
• In General
• Low remission rate – 20-50%
• High rates of relapse – 25-85% on discontinuation
Good initial response – less probability of relapse
21
Case History
Brian, 30-year-old graduate student, engaged to be
married in 6 months
• Is very anxious and apprehensive about the event
• “I don’t like being looked at”, “I think people will laugh at
how I look or what I say”
• History of shyness, being ‘quiet’
What further information would be useful for diagnosis?
What is the likely diagnoses?
22
Social Phobia/Social Anxiety Disorder (SAD)
23
Barbra Streisand
Donny Osmond
Carly Simon
SAD: Signs and Symptoms
Cognitive:
• Fear of scrutiny, humiliation and
embarrassment,
• Exposure promotes anxiety
Physical:
• Blushing, sweating, tremor
Behavioural:
• Avoidance and anticipatory anxiety in
social/performance situations
• Good Insight
24
NicholasCageinAdaptation–SocialPhobia
25
Treatment of SAD
Pharmacotherapy vs. CBT vs. combination
Goals:
• Improve cognitive and physical symptoms
• Reduce anticipatory anxiety and avoidance
• Treat comorbid conditions
• Improve functioning
Methods
• Psychoeducation
• CBT plus
• Social skills training
• Exposure therapy
26
27
Performance-Specific Anxiety
• SAD vs. shyness vs. performance anxiety
• Proposed overlap with non-generalized SAD
• Evidence for benefit with propranolol (RCTs)
• Surgical patients and surgeons
• Dental patients
• Medical students
• Benzodiazepines – decrease anticipatory anxiety but may
impair performance
28
Specific Phobias
Specific phobia is excessive or irrational fear of object or
situation, and is usually associated with avoidance of feared
object
• Lifetime prevalence: 12.5%
• Median age of onset: 7 years
Common Phobias: animal and blood-injection,
claustrophobia, heights
Treatment
• Pharmacotherapy: Difficult to use and unproven
• Psychotherapy: In vivo and virtual exposure
29
Case History
Sonya – 33 year old housewife brought against her wishes by
her husband
• Vague complaints – 3-4 years
• “I don’t understand what is wrong with her” – husband
• Superstitious about leaving the house without knocking on the
door posts. “It’s bad luck if I don’t.”
• Spends half an hour each night checking and double-checking
that the doors and windows are locked and all kitchen
appliances are turned off
• Not able to cope with housework because she spends too
much time on one task. “I’m a perfectionist.”
What would your diagnosis be?
30
Obsessive Compulsive Disorder (OCD)
• Obsessions and/or compulsions
• Recurrent, persistent ideas, thoughts, impulses or images
• Repetitive, purposeful and intentional behaviours that are performed
in response to an obsession
• Repetitive, unpleasant and ego dystonic + resisted
• Excessive/unreasonable
• Marked distress and impact on functioning
• Affects 2-3 % of the population, with onset in teens
31
OCD: Common Obsessions and Compulsions
• Obsessions
• Repetitive thoughts about
contamination
• Repetitive doubts
• Intense need for
orderliness and symmetry
• Aggressive impulses
• Repeated sexual imagery
• Compulsions
• Behaviours
•
•
•
•
•
Hand washing
Ordering
Checking
Demanding reassurance
Repeating actions
• Mental Acts
• Counting
• Repeating words silently
32
JackNicholsoninAsGoodAsItGets-OCD
33
Treatment of OCD
• Pharmacotherapy
• Serotonergic agents
• AAPs
• Combination
• Psychotherapy
• CBT with focus on
•
•
Exposure and response prevention
Cognitive interventions
• Poorer outcomes in
• Males
• Early onset
• Delayed treatment
34
Case History
Goran, a 47-year-old parking attendant
• Complains of feeling tired and ‘down’ for the past 5-6 months,
since being robbed and beaten up at work last year
• Has difficulty sleeping due to nightmares, is ‘jumpy’ and
irritable
• Feels distant from family and friends
• Constant sense of inner and physical tension
Do you think Goran is suffering from:
 Fibromyalgia
 Fatigue
 Post traumatic stress
 Overwork
35
PTSD: Key Features
• Exposure to threat to life or physical integrity
AND
• Emotional reaction of fear, helplessness or horror






Persistent intrusive reexperience of the event
Avoidance of trauma-associated stimuli and
+
numbing – emotional and behavioural withdrawal
Persistent symptoms of increased arousal
Duration 1 month to years
Prevalence 3-4 %
High risk of suicide
36
DamianLewisinBandofBrothers-PTSD
37
PTSD - Treatment
Both Pharmacotherapy and Psychotherapy are
useful
Pharmacotherapy
• Antidepressants and atypical antipsychotics
Psychotherapy
• Trauma focused therapies best results
• CBT, exposure therapy beneficial
• Less effective - IPT, psychodynamic therapy, supportive
therapy
• Different types of trauma may respond to different
psychotherapies, benefit across subtypes
38
Acute Stress Disorder
Follows within 1 month acute exposure to threat and lasts few
days to 4 weeks
Intervention: Brief and immediate
Focus on high risk population
Components:
• Information Education
• Psychological support
• Crisis intervention
• “Emotional first aid”
Does immediate intervention prevent PTSD?
39
Anxiety Disorders: Primary Care
Perspectives
• Often present with somatic symptoms or complaints related
to co-morbid conditions
• High utilizers of primary care
• May need to treat multiple anxiety disorders
• Education and CBT-based brief interventions useful
• Deal with barriers to care
40
Unipolar Depression
41
A Case History
Maria, a 47-year-old married lady, reports feeling
‘not her usual self’ for the past 6-8 months
• She reports feeling both sad and anxious
• She has difficulty sleeping and is always tired
• Her appetite has decreased and she has lost 15
lbs. in the past 6 months
• Her brother died in a car accident about 1 year
ago. She feels guilty about an argument they had
just before, and thinks about it a lot.
What is your diagnosis?
42
Mood/Affective Disorders
Definition: Mental illnesses presenting with
altered mood/affect as the primary symptom
• Affect: External expression of an internal state
(i.e. mood)
• Affect is more transient, mood is more sustained
• Two broad syndromes of mood disorders
• Depression
• Mania
43
How Common Are Mood Disorders
and What is Their Disease Burden?
• Life time prevalence
• Unipolar depression 8-20%
• Bipolar disorder 1%
• WHO: Depression is the leading cause of disability
• Impact on:
•
•
•
•
Quality of life
Impaired function (occupational, social)
Suicide
Physical health
44
What Causes Mood Disorders?
• Genetic vulnerability
• Social and environmental factors
• Life stressors
• Early childhood experiences
• Social determinants
• Neurobiological factors
• Neurotransmitter/neurohormonal challenges
• Neural circuitry
Usually a multi-factorial etiology
45
Defining a Depressive Disorder
(DSM)
• Clinically significant behavioural or psychological syndrome,
associated with
• Distress/disability
• Increased risk of death/pain
• Not simply
• Lowered mood
• Response to loss
• Maladaptive reaction to stress
• Two key forms
• Major depressive disorder (MDD)
• Dysthymic disorder (DD)/Persistent depressive disorder (DSM5)
46
Depression is Complex, Multidimensional
Emotional Symptoms
•
•
•
•
Feelings of guilt
Suicidal
Lack of interest
Sadness
Associated Symptoms
Physical Symptoms
• Lack of energy
• Decreased
concentration
• Change in appetite
• Change in sleep
• Change in
psychomotor skills
APA. DSM-IV-TR; 2000:352,356.
•
•
•
•
Brooding
Obsessive rumination
Irritability
Excessive worry over
physical health
• Pain
• Tearfulness
• Anxiety or phobias
47
NicoleKidmaninTheHours-Depression
48
What Are the Important Subtypes
of MDD and DD?
•
•
•
•
•
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Chronic depression
Melancholic depression
Atypical depression
Psychotic depression
Postpartum depression
Seasonal affective disorder
49
How Do Patients with Depression
Present in Primary Care?
•
•
•
•
Less than 20% seek help from family physicians
Only 50% are recognized as depressed
2/3 present in practice with somatic symptoms only
Common screening tools for primary care
• Brief Hamilton Depression Rating Scale (HDRS; 7 items)
• Beck Depression Inventory (BDI-II; 21 items)
• Patient Health Questionnaire (depression only) (PHQ-9; 9 items)
• Screening tools are specially useful in high risk populations
50
High Risk Groups and Symptomatic
Presentation of MDD
High Risk Clinical Groups
High Risk Symptom Presentations
Past history of depression
Unexplained physical symptoms
Family history of depression
Pain
Psychosocial adversity
Fatigue
High users of the medical system
Insomnia
Chronic medical conditions
Anxiety
Other psychiatric conditions
Substance abuse
Times of hormonal challenge
51
Patten et al., 2009; J Affect Disord.
Managing Depression in Primary
Care
• Assessment
•
•
•
•
Suicide risk
Physical health
Psychosocial issues
Psychiatric morbidity
• Management: “Stepped care approach”
•
•
•
•
Watchful waiting
Guided self-management
Brief psychological/pharmacological interventions
Referral to specialists
• Determine diagnosis and point in continuum of care
52
What Are the Phases of Treatment
for Depression and Their Goals?
• Acute
• Target goals
• Remission
• Restoration of function
• Outcome measures
• Maintenance
• Resolve residual symptoms
• Treat co-morbidities
• Prevent recurrence
Use chronic disease management model
53
What Are the Effective
Interventions for Depression?
• Pharmacotherapy
• Antidepressant agents
• Older agents – TCAs, MAOIs
• Newer agents – SSRIs, SNRIs, atypical antipsychotics, novel agents
• Psychological therapies
• Cognitive Behaviour Therapy (CBT)
• Interpersonal Therapy (IPT)
• Other modalities, supportive therapy
• Combination: Medication + psychotherapy
• Psychosocial interventions
• Neurostimulation
• Electroconvulsive Therapy (ECT)
• Rapid transcranial magnetic therapy (rTMS)
• Investigational modalities
• Chronic disease management model
54
Psychotherapy: Best Modalities
• Cognitive behaviour therapy (CBT)
• Basis: Thoughts, emotions and behaviours are inter-related
• Focus on dispelling cognitive misperceptions of self, others and
surroundings and modifying maladaptive emotional and
behavioural responses
• Interpersonal therapy (IPT)
• Basis: Problematic interpersonal relationships may contribute to
depressive onset and maintenance
• Focus on at least 1 key area: Role transitions, Interpersonal role
disputes, Grief, Interpersonal deficits
• Pick the most appropriate form based on the need
• Both forms effective in acute and maintenance treatment
55
Psychotherapy: Other
Modalities
Psychodynamic psychotherapy
Behavioural activation
Basis: Psychological dysfunction results from
conscious or unconscious conflicts and defense
mechanisms
Basis: “Depression is a consequence of
compromised environmental sources of positive
reinforcement”
Focus on recognizing the conflict and
understanding sources/influences to promote
psychological healing
Focus on increasing patient activity and rewarding
experiences, and de-emphasizing particular
cognitions/ mood states
Motivational interviewing
Computer/internet/telephone
psychotherapy
Basis: Individuals with dysfunctional behaviours
wish to change but lack initiative/commitment
CBT, IPT, supportive therapy, etc. in distance
delivery formats
Focus on resolving ambivalence, building
motivation, and working towards specific, realistic
goals to achieve the desired change
Advantages: Immediate help, anonymity, low
cost, flexible schedule, ease of access for remote
communities
56
Neurostimulation Therapies
ECT
rTMS
Induction of a convulsion (seizure) by
the application of electrical current to
the brain
Application of a magnetic field (1.52.5T), delivered through the skull
Indications: Treatment resistance,
intolerant of antidepressants,
psychotic depression
Indication: Treatment resistance,
severe depression
Physical and cognitive side effects
Short term side effects: Headache and
scalp pain.
Investigational therapies
VNS, DBS and MST
57
How does Depression Affect
Physical Health?
• Increase the effect of risk factors
•
•
•
•
•
•
•
•
Obesity
Smoking
Cardiovascular
Immune
Increase the risk of chronicity
Worsen pain disorders
Reduce treatment adherence
Reduce participation in prevention
58
What is the Long-term Outcome of
Depressive Disorders?
• MDD
•
•
•
•
•
Variable duration
Spontaneous recovery in many
Longer illness  poor outcome
Often recurrent
20% non-recovery and chronic course
• Dysthymia/Persistent depressive disorder
• Chronic fluctuating course
• Superimposed MDD  double depression
• Poor function
59
Bipolar Disorder
60
Case History
Susan, a 20-year-old university student, presents with symptom
of 2 months’ duration (worsening in last 2 weeks)
• Has started many projects, but is easily distracted and does
not complete them – has affected her grades
• Is sleeping less (but does not feel tired)
• Has been buying unneeded things impulsively from the
internet
• Her friends say her mood is unpredictable, and that she gets
overly excited or angry about even little things.
What is your assessment of this patient?
61
Symptom Overlap: The Complexity of Mood
Disorders
Psychosis
Bipolar Mania
Mixed
State
Bipolar Depression
Agitated Depression
Treatment
Resistant
Depression
Unipolar Depression
62
*All have potential for psychotic presentation/escalation
Bipolar Disorder and Bipolar Spectrum
Disorders
• BP I: Mania with/without depression
• BP II: Depression with hypomania - Recurrent MDE with clearcut hypomanic episodes (lasting at least 4 days)
• BP Spectrum/ Complex Subtypes
• Mixed states: Mania and depression
• Rapid cycling, Ultra-rapid cycling, Ultradian
• Cyclothymia
• Substance/Antidepressant-induced hypomania
• Prevalence:
• Bipolar I Disorder: 1.2-1.6%
• Bipolar II Disorder: 2-6%
• Bipolar Spectrum Disorders: 6.4%
63
Bipolar Disorder: Burden of Disease
• High degree of psychiatric/physical co-morbidity and
psychosocial consequences:
•
•
•
•
Suicidality
Substance abuse
Medical illnesses
Employment and family problems
• Increased mortality than those without bipolar disorder:
• 2.5 times more likely to die in 12 months, if untreated
• One of the world’s 10 most disabling conditions
• DALYs highest in 14-44 year olds
64
Diagnosing Mania
Mood: Abnormally and persistently elevated, expansive or
irritable
Duration: At least one week or requiring admission
PLUS
Three (four if irritable mood) or more of the following:
• Grandiosity
• More talkative
• Flight of ideas
• Distractibility
• Less need for sleep
• More goal-directed activity
• Excessive involvement in pleasurable activities
65
Hypomania: Presentation
A distinct period of persistently elevated, expansive
or irritable mood, lasting at least 4 days
PLUS
Three (four if irritable mood) or more of the
following:
•
•
•
•
•
•
•
Grandiosity
More talkative
Flight of ideas
Distractibility
Less need for sleep
More goal-directed activity
Excessive involvement in pleasurable activities
More commonly seen in primary care than mania
66
BradleyCooperinSilverLiningsPlaybook-Hypomania
67
What are the common presentations of
Bipolar I and II Disorder to the Family
Physician?
Psychological
Physical
Depression
Alcohol/substance use
Anxiety
Sexually transmitted diseases
Sleep difficulties
Fatigue
Poor concentration
Social
Other
Marital/relationship problems
Episodic impulsivity/risk taking
Financial
Suicide attempts
Occupational
68
The Complex Bipolar Patient
• Mixed episodes
• Both manic and depressive symptoms
•  comorbid substance use disorders
•  risk of suicide and psychosis
• Rapid cycling
• 4 or more cycles/year with > 8 weeks of well periods
• Occurs in Bipolar I and II
69
The Complex Bipolar Patient:
Co-morbidities/Complications
• Personality disorders
(cluster B)
• High co-morbidity (up to 92%)
• Risk factor for bipolar disorder • Medical conditions
• Anxiety disorders
• May elevate risk of suicide
• Substance abuse
• High rates of co-morbidity vs.
the general population
• Higher prevalence of complex
subtypes
• ADHD
• Bi-directional relationship
• Overlap of symptoms
• ADHD as a prodrome
•
•
•
•
Obesity
Cardiovascular
Endocrine
Cerebral pathology
• Suicide
• 15% suicide rate
• 25-50% attempt suicide in
lifetime
70
Bipolar Disorders: Management
Chronic disease management model: Long term, interdisciplinary,
education focused and integrated
• Bipolar I Disorder
•
•
•
•
•
Emergency management
Acute care/short-term
Mixed/rapid cycling states
Bipolar mania
Bipolar depression
• Bipolar II Disorder
• Mainly depression
• Maintenance treatment and prophylaxis
71
Issues Specific to Primary Care
• Diagnostic difficulties – screening tools
• Patient Health Questionnaire (depression only) (PHQ-9; 9 items)
• Mood Disorder Questionnaire (mania only; 17 items)
•
•
•
•
•
•
•
Check for “destabilization”/non response to antidepressants
Use antidepressants with caution
Referral for consultation/shared care
Treatment adherence
Risk of suicide /financial difficulties
Medical issues, e.g. obesity, cardiovascular disease
Psychoeducation and support through life transition for patient and
family
72
• Relapse prevention
What Interventions are Useful for
Bipolar Disorders?
• Pharmacotherapy
• Antipsychotics
• Mood stabilizers
• Lithium carbonate
• Anticonvulsants
• Psychotherapy
•
•
•
•
Psychoeducation
CBT, IPT
Family interventions
Benefits: Improve adherence and function, early identification of
relapse and suicidal ideation, prevent suicide
• Neurostimulation
• ECT
73
Bipolar Patients: Baseline
Investigations and Monitoring
•
•
•
•
•
CBC electrolytes
Fasting lipids and glucose
Liver function levels
TSH + ECG
Urine analysis
Regular monitoring:
• The above +
• Weight, smoking status and alcohol use
• Medication serum levels
• Cognitive function
74
75
On a Lighter Note…
76
END
77

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