General Practice

Key Facts

Type 2 diabetes is a metabolic disorder characterised by insulin resistance and progressive beta-cell dysfunction, leading to chronic hyperglycaemia. It accounts for 90% of all diabetes and is a major contributor to cardiovascular disease, CKD, retinopathy, and neuropathy.

Epidemiology

• 4.7 million people in the UK with diabetes (90% type 2)
• Rising prevalence linked to obesity and ageing population
• Higher prevalence in South Asian (6× risk), Black African/Caribbean (3× risk), and deprived communities
• Pre-diabetes (HbA1c 42-47 mmol/mol): affects approximately 5 million in the UK
• Accounts for 10% of NHS spending (~£10 billion/year)

Aetiology

• Insulin resistance: skeletal muscle, liver, adipose tissue
• Progressive beta-cell failure: ongoing decline in insulin secretion
• Risk factors: obesity (especially central), family history, ethnicity, physical inactivity, gestational diabetes history, PCOS, age

Pathophysiology

• Insulin resistance leads to compensatory hyperinsulinaemia
• Over time, beta-cell exhaustion leads to relative insulin deficiency
• Chronic hyperglycaemia causes glucotoxicity and lipotoxicity, further impairing beta-cell function
• Microvascular complications: retinopathy, nephropathy, neuropathy
• Macrovascular complications: coronary artery disease, stroke, peripheral arterial disease
• Advanced glycation end-products (AGEs) and oxidative stress drive tissue damage

Typical Presentation

• Often asymptomatic - detected on routine blood testing or screening
• Polyuria, polydipsia, weight loss (if significantly hyperglycaemic)
• Fatigue
• Recurrent infections (UTIs, candidiasis)
• Blurred vision
• Slow wound healing

Complications at Presentation

• May present with established complications (up to 50% have complications at diagnosis)
• Diabetic foot ulcer
• Visual impairment (retinopathy)
• Proteinuria (nephropathy)
• Cardiovascular event

Red Flags

• DKA/HHS (rare in T2DM but can occur): vomiting, dehydration, altered consciousness
• Rapidly declining glycaemic control (consider latent autoimmune diabetes in adults - LADA)
• Young, lean patient diagnosed with T2DM (consider MODY or LADA)
• Foot ulcer with signs of infection/ischaemia
• Sudden visual loss (vitreous haemorrhage from proliferative retinopathy)

Diagnosis

• HbA1c ≥48 mmol/mol (6.5%) on two separate occasions if asymptomatic
• HbA1c ≥48 mmol/mol on one occasion if symptomatic
• Fasting plasma glucose ≥7.0 mmol/L or random glucose ≥11.1 mmol/L with symptoms
• Note: HbA1c unreliable in haemoglobinopathies, anaemia, pregnancy, CKD stage 5

Baseline Assessment

• HbA1c
• Lipid profile (total cholesterol, LDL, HDL, triglycerides)
• U&Es, eGFR
• Urine ACR (albumin:creatinine ratio)
• LFTs
• TFTs (associated autoimmune thyroid disease)
• BMI, BP
• ECG if cardiovascular risk factors

Annual Review (8 Care Processes)

1. HbA1c
2. Blood pressure
3. Cholesterol (total, HDL)
4. Serum creatinine/eGFR
5. Urine ACR
6. BMI
7. Foot examination
8. Retinal screening

Special Tests

• GAD antibodies, C-peptide: if LADA/T1DM suspected
• Genetic testing: if MODY suspected
• QRISK3: cardiovascular risk assessment

Non-pharmacological

• Structured education: DESMOND (newly diagnosed), X-PERT, DAFNE-equivalent programmes
• Weight loss: target 5-10% body weight reduction; consider low-calorie diet programmes
• Diet: low glycaemic index, reduce refined carbohydrates, Mediterranean diet
• Exercise: 150 minutes/week moderate intensity
• Smoking cessation: most important CVD risk reduction

Pharmacological - Glycaemic Management (NICE NG28)

• Step 1: Metformin 500mg OD, titrate to 1g BD (or MR if GI intolerance)
  • HbA1c target: 48 mmol/mol (6.5%)
• Step 2 (if HbA1c rises above target): add second agent to metformin:
  • SGLT2 inhibitor (empagliflozin 10mg OD, dapagliflozin 10mg OD): preferred if established CVD, HF, or CKD
  • DPP-4 inhibitor (sitagliptin 100mg OD): weight-neutral, well tolerated
  • Sulfonylurea (gliclazide 40-320mg/day): effective, cheap, risk of hypos and weight gain
  • Pioglitazone 15-45mg OD: if others unsuitable; avoid in HF, bladder cancer risk
• Step 3: triple therapy or consider GLP-1 receptor agonist (semaglutide, liraglutide) if BMI ≥35
• Step 4: add insulin (usually basal: insulin glargine or detemir) if above measures fail

Cardiovascular Risk Management

• Atorvastatin 20mg OD: all T2DM patients >40 years or QRISK3 ≥10%
• BP target: <140/80 mmHg (<130/80 if renal, eye, or cerebrovascular disease)
• ACEi/ARB: first-line antihypertensive if microalbuminuria or proteinuria
• Antiplatelet: aspirin 75mg only if established CVD (not for primary prevention)

Referral Criteria

• Diabetologist: uncertain diagnosis, LADA, MODY, complex insulin regimens, recurrent DKA
• Ophthalmology: retinopathy detected on screening
• Podiatry: diabetic foot disease
• Renal: progressive CKD (eGFR <30 or rapidly declining)
• Bariatric surgery: BMI ≥35 with diabetes (NICE recommendation)

• UKPDS: intensive glycaemic control reduces microvascular complications by 25%; legacy effect persists for decades
• Each 1% (11 mmol/mol) reduction in HbA1c reduces microvascular complications by 37% and MI by 14%
• Life expectancy reduced by 6-7 years on average vs general population
• Cardiovascular disease is the leading cause of death (50-60%)
• SGLT2 inhibitors: EMPA-REG showed 38% reduction in CV death with empagliflozin; DAPA-CKD showed 39% reduction in kidney disease progression
• With comprehensive management (glycaemia + BP + lipids + lifestyle), outcomes are significantly improved
• Remission possible with significant weight loss (>15kg) in early disease (DiRECT trial: 46% remission at 1 year)

NICE NG28 - Glycaemic Drug Selection Guide

Key Landmark Trials in Type 2 Diabetes

Diabetic Foot Risk Assessment

Key Facts

Asthma is a chronic inflammatory disease of the airways characterised by variable symptoms of wheeze, breathlessness, chest tightness, and cough, with variable expiratory airflow limitation. Effective management focuses on achieving and maintaining control through a stepwise approach.

Epidemiology

• 5.4 million people in the UK; 1 in 11 children, 1 in 12 adults
• UK has among the highest prevalence and mortality rates in Europe
• 1,400 deaths/year in the UK (most preventable - NRAD 2014)
• Costs the NHS approximately £1.1 billion/year

Aetiology

• Complex interaction of genetic susceptibility and environmental factors
• Atopy (genetic predisposition to IgE-mediated hypersensitivity) is the strongest risk factor
• Triggers: allergens (house dust mite, animal dander, pollen, moulds), infections (viral URTI), exercise, cold air, pollution, occupational sensitisers, drugs (NSAIDs, beta-blockers), emotional stress

Pathophysiology

• Chronic eosinophilic airway inflammation driven by Th2 cytokines (IL-4, IL-5, IL-13)
• Airway hyperresponsiveness: exaggerated bronchoconstriction to stimuli
• Airway remodelling: smooth muscle hypertrophy, goblet cell metaplasia, subepithelial fibrosis, basement membrane thickening
• Reversible airflow obstruction: bronchospasm, mucosal oedema, mucus plugging
• Type 2 (T2-high) asthma: eosinophilic, responsive to ICS
• Non-T2 asthma: neutrophilic or paucigranulocytic, less responsive to ICS

Typical Symptoms

• Episodic wheeze (polyphonic, expiratory)
• Breathlessness
• Chest tightness
• Cough (particularly nocturnal or early morning)
• Symptoms variable, intermittent, worse at night/early morning
• Triggered by exercise, allergens, cold air, infections

Examination

• May be normal between attacks
• Widespread polyphonic wheeze on auscultation
• Prolonged expiratory phase
• Hyperinflation (if chronic)

Red Flags - Acute Severe/Life-Threatening Asthma

• Acute severe: PEF 33-50%, RR ≥25, HR ≥110, inability to complete sentences
• Life-threatening: PEF <33%, SpO2 <92%, silent chest, cyanosis, bradycardia, hypotension, altered consciousness, exhaustion
• Near-fatal: raised PaCO2 (normal or rising CO2 in acute asthma is a danger sign - indicates exhaustion)

Diagnostic Tests (NICE NG80)

1. FeNO (fractional exhaled nitric oxide): ≥40ppb in adults supports eosinophilic inflammation (first-line test)
2. Spirometry with reversibility: FEV1/FVC ratio reduced; ≥12% AND ≥200ml improvement post-bronchodilator
3. Peak flow variability: ≥20% diurnal variation over 2-4 weeks
4. Bronchial challenge testing (methacholine/histamine): if diagnostic uncertainty; PC20 <8mg/ml positive

Monitoring

• Asthma control questionnaire (ACT or RCP 3 questions)
• Peak flow diary
• FeNO monitoring (assess adherence to ICS)
• Spirometry annually

Bloods

• FBC (eosinophil count)
• Total IgE (if allergic asthma suspected)
• Specific IgE or skin prick testing (identify triggers)

Imaging

• CXR: usually normal; exclude differentials (pneumonia, pneumothorax, heart failure)
• HRCT: if bronchiectasis or alternative diagnosis suspected

Non-pharmacological

• Personalised asthma action plan: traffic light system (green/amber/red zones)
• Inhaler technique review: at every consultation (most common cause of poor control)
• Trigger avoidance: allergens, smoking (passive and active), occupational sensitisers
• Annual influenza vaccination: recommended for all asthma patients
• Weight loss: if overweight/obese
• Breathing exercises: Papworth, Buteyko

Pharmacological - BTS/SIGN Stepwise Approach (Adults)

• Step 1: SABA as needed (salbutamol 100mcg, 2 puffs PRN) - reliever only for infrequent symptoms
• Step 2: Low-dose ICS (beclometasone 200-400mcg/day or budesonide 200-400mcg/day)
• Step 3: Low-dose ICS + LABA (e.g. Seretide 100/50, Symbicort 200/6); OR increase ICS to medium dose
  • MART regime: Symbicort 200/6 - 1-2 puffs BD maintenance + 1 puff as needed (up to 12/day)
• Step 4: Medium-dose ICS + LABA; consider adding LTRA (montelukast 10mg ON), LAMA (tiotropium 2.5mcg), or theophylline
• Step 5: Specialist referral; high-dose ICS; oral prednisolone (lowest dose); biologic therapy for severe eosinophilic asthma
  • Omalizumab (anti-IgE, NICE TA278)
  • Mepolizumab (anti-IL5, NICE TA431)
  • Benralizumab (anti-IL5R, NICE TA565)
  • Dupilumab (anti-IL4R, NICE TA751)

Acute Asthma Management

• Oxygen: target SpO2 94-98%
• Salbutamol: 5mg via oxygen-driven nebuliser (back-to-back if severe)
• Ipratropium bromide: 500mcg nebulised (severe/life-threatening)
• Prednisolone: 40-50mg PO for 5-7 days (or IV hydrocortisone 100mg if unable to swallow)
• IV magnesium sulphate: 1.2-2g over 20 minutes (single dose for acute severe/life-threatening)
• IV aminophylline: specialist use for life-threatening asthma

Referral Criteria

• Specialist respiratory referral: diagnostic uncertainty, occupational asthma, severe/difficult asthma (step 4-5), frequent exacerbations despite adherence
• Emergency: acute severe or life-threatening asthma

• Well-controlled asthma: normal life expectancy and activity levels
• 1,400 deaths/year in the UK; 90% considered preventable (NRAD 2014)
• Key risk factors for asthma death: previous near-fatal attack, hospitalisation in past year, ≥3 drug classes, heavy SABA use (≥3 canisters/year), poor adherence to ICS, psychosocial factors
• Childhood asthma: 50-60% of children 'grow out' of asthma by adulthood, though airway hyperresponsiveness may persist
• SABA overuse (≥3 inhalers/year) is an independent risk factor for asthma death
• Biologic therapy: significantly reduces exacerbations and oral steroid use in severe eosinophilic asthma

RCP 3 Questions (Asthma Control)

Key NRAD (National Review of Asthma Deaths) Findings

ICS Dose Equivalence (BDP-HFA equivalent mcg/day)

Key Facts

COPD is a common, preventable, and treatable disease characterised by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities, usually caused by significant exposure to noxious particles or gases, most commonly tobacco smoke.

Epidemiology

• 1.2 million diagnosed, estimated 3 million total (including undiagnosed) in the UK
• Third leading cause of death worldwide (WHO)
• Approximately 30,000 deaths/year in the UK
• Prevalence: 2% overall; >10% in smokers >40 years
• Significant health inequality: 3-5× more prevalent in most deprived quintile

Aetiology

• Smoking: >85% of cases; risk proportional to pack-years
• Alpha-1 antitrypsin deficiency: 1-2% of cases; suspect if young onset, non-smoker, lower lobe emphysema
• Occupational exposure: coal dust, silica, cadmium, grain dust
• Air pollution: indoor (biomass fuel) and outdoor
• Childhood lung infections: severe childhood pneumonia

Pathophysiology

• Chronic bronchitis: mucus hypersecretion, goblet cell metaplasia, squamous metaplasia of bronchial epithelium
• Emphysema: destruction of alveolar walls distal to terminal bronchioles; loss of elastic recoil; air trapping
• Small airway disease: inflammation and fibrosis of small airways (<2mm)
• Neutrophilic inflammation (unlike asthma's eosinophilic predominance)
• Progressive, largely irreversible airflow limitation
• Systemic effects: skeletal muscle wasting, cardiovascular disease, osteoporosis, depression, lung cancer risk

Typical Presentation

• Exertional dyspnoea (progressive over years)
• Chronic productive cough (particularly morning)
• Wheeze
• History of smoking (typically >10 pack-years)
• Age typically >35 years
• Reduced exercise tolerance

Examination

• Hyperinflation (barrel chest, reduced cricosternal distance)
• Pursed lip breathing
• Use of accessory muscles
• Wheeze and reduced air entry on auscultation
• Cyanosis (if hypoxic)
• Peripheral oedema (cor pulmonale)

Red Flags

• Rapidly progressive dyspnoea (exclude PE, pneumothorax, heart failure)
• Haemoptysis (exclude lung cancer)
• Significant weight loss (exclude lung cancer, TB)
• Young onset without smoking history (alpha-1 antitrypsin deficiency)
• Cor pulmonale (peripheral oedema, raised JVP)

Diagnostic

• Post-bronchodilator spirometry: FEV1/FVC <0.7 confirms airflow obstruction
  • Mild: FEV1 ≥80% predicted
  • Moderate: FEV1 50-79%
  • Severe: FEV1 30-49%
  • Very severe: FEV1 <30%
• Reversibility testing: limited reversibility (<12% or <200ml) - distinguishes from asthma

Baseline

• CXR: hyperinflation, flat diaphragms, bullae; exclude other pathology
• FBC: polycythaemia (chronic hypoxia), anaemia
• BMI: track nutritional status
• Pulse oximetry: SpO2 <92% → refer for ABG and LTOT assessment
• Alpha-1 antitrypsin level: in all patients (one-time test)

Monitoring

• Spirometry annually
• MRC dyspnoea scale (grade 1-5)
• Exacerbation frequency
• BMI
• CAT score (COPD Assessment Test)

Special Tests

• ABG: for LTOT assessment (PaO2 ≤7.3kPa)
• TLCO (transfer factor): reduced in emphysema
• HRCT: if bronchiectasis or alternative diagnosis suspected
• Echocardiography: if cor pulmonale or concurrent heart failure suspected

Non-pharmacological

• Smoking cessation: single most important intervention; offer NRT, varenicline (1mg BD for 12 weeks), or cytisine
• Pulmonary rehabilitation: 6-12 week supervised exercise + education programme; offer to all MRC grade ≥3; NNT 4 to prevent hospitalisation
• Annual influenza vaccination + pneumococcal vaccination
• Self-management plan: recognising and managing exacerbations
• Nutritional support (if BMI <20)
• Psychological support (anxiety, depression common)

Pharmacological - NICE NG115 Inhaler Pathway

• Initial: SABA (salbutamol) or SAMA (ipratropium) PRN
• If persistent symptoms/exacerbations:
  • No asthmatic features/lower eosinophils: LABA (formoterol/salmeterol) + LAMA (tiotropium/glycopyrronium) - e.g. Ultibro Breezhaler
  • Asthmatic features/higher eosinophils (≥300): LABA + ICS - e.g. Symbicort, Seretide
• If still uncontrolled: Triple therapy - LABA + LAMA + ICS (e.g. Trimbow, Trelegy Ellipta)
• Mucolytics: carbocisteine 750mg TDS if chronic productive cough
• Oral theophylline: consider after inhaler optimisation (narrow therapeutic index - monitor levels)
• Prophylactic antibiotics: azithromycin 250mg 3×/week for patients with ≥3 exacerbations/year (specialist initiation; check ECG/QTc, LFTs, sputum culture for NTM)

Long-Term Oxygen Therapy (LTOT)

• Indications: PaO2 ≤7.3kPa on two ABGs 3 weeks apart (stable), or PaO2 ≤8kPa with secondary polycythaemia, pulmonary hypertension, or peripheral oedema
• Use for ≥15 hours/day (MRC LTOT trial: improved survival)
• Target SpO2 88-92% in exacerbation
• NEVER prescribe LTOT without confirming smoking cessation (fire/explosion risk)

Acute Exacerbation Management

• Controlled oxygen: 24-28% Venturi mask, target SpO2 88-92%
• Nebulised bronchodilators: salbutamol 2.5-5mg + ipratropium 500mcg
• Prednisolone 30mg OD for 5 days (no need to taper)
• Antibiotics: if purulent sputum - amoxicillin 500mg TDS 5 days, doxycycline 200mg stat then 100mg OD, or clarithromycin 500mg BD
• NIV (BiPAP): for acute hypercapnic respiratory failure (pH 7.25-7.35) despite initial treatment

Referral Criteria

• Respiratory specialist: diagnostic uncertainty, FEV1 <30%, frequent exacerbations (≥3/year), LTOT assessment, alpha-1 antitrypsin deficiency, lung volume reduction surgery consideration
• Palliative care: severe COPD with significant symptom burden

• COPD is a progressive disease; FEV1 decline can be slowed by smoking cessation but not reversed
• Smoking cessation: reduces rate of FEV1 decline from 60ml/year to ~30ml/year (Lung Health Study)
• BODE index (BMI, Obstruction, Dyspnoea, Exercise capacity) predicts mortality
• Median survival with FEV1 <30%: approximately 3-4 years
• Acute exacerbation requiring hospitalisation: 10% in-hospital mortality, 25% 1-year mortality
• LTOT improves survival in hypoxic patients (MRC LTOT trial: reduced mortality by ~50% at 5 years)
• Pulmonary rehabilitation improves exercise capacity and quality of life but does not alter FEV1
• Lung cancer risk is significantly increased in COPD (independent of smoking)

MRC Dyspnoea Scale

NICE NG115 Inhaler Selection Summary

GOLD ABCD Assessment Tool

Key Facts

Depression is a common mental health disorder characterised by persistent low mood, loss of interest or pleasure (anhedonia), and a range of cognitive, behavioural, and physical symptoms. It is a leading cause of disability worldwide and is predominantly managed in primary care.

Epidemiology

• Lifetime prevalence: 15-20%; point prevalence: 5-10%
• Female:male ratio 2:1
• Peak onset: 20-30 years; second peak in elderly
• Recurrence: 50% after first episode; 80% after third episode
• Only one-third of depressed individuals seek help
• Associated with significant morbidity, reduced productivity, and increased mortality

Aetiology

• Biopsychosocial model: biological, psychological, and social factors interact
• Biological: monoamine hypothesis (serotonin, noradrenaline, dopamine deficiency), genetic predisposition (heritability ~40%), HPA axis dysregulation, neuroinflammation, structural brain changes
• Psychological: cognitive distortions (Beck), learned helplessness (Seligman), attachment difficulties
• Social: life events (bereavement, job loss, relationship breakdown), social isolation, childhood adversity, poverty, chronic illness

Pathophysiology

• Reduced serotonergic, noradrenergic, and dopaminergic neurotransmission
• HPA axis overactivity: elevated cortisol
• Reduced hippocampal neurogenesis and BDNF (brain-derived neurotrophic factor)
• Neuroinflammation: elevated pro-inflammatory cytokines (IL-6, TNF-α)
• Antidepressants increase monoamine availability and promote neuroplasticity

Core Symptoms (ICD-11)

• Persistent low mood (most of the day, nearly every day, for ≥2 weeks)
• Anhedonia (loss of interest or pleasure in activities)
• Fatigue/reduced energy

Associated Symptoms

• Reduced concentration and attention
• Reduced self-esteem and confidence
• Ideas of guilt and unworthiness
• Disturbed sleep (insomnia or hypersomnia)
• Appetite and weight change (reduced or increased)
• Psychomotor agitation or retardation
• Suicidal ideation or acts of self-harm

Severity Classification

• Mild: 2 core + 2 associated symptoms; minimal functional impairment
• Moderate: 2 core + 3-4 associated symptoms; considerable difficulty with daily activities
• Severe: 3 core + ≥4 associated symptoms; marked functional impairment; may have psychotic features

Red Flags

• Active suicidal ideation with plan and intent
• Psychotic features (hallucinations, delusions of guilt/worthlessness)
• Self-neglect (not eating, drinking, personal hygiene)
• Catatonia
• Severe agitation
• Risk to children/dependants

Screening/Assessment Tools

• PHQ-9 (Patient Health Questionnaire-9): scores 0-27; ≥5 mild, ≥10 moderate, ≥15 moderately severe, ≥20 severe
• PHQ-2: 2-item screen (first 2 questions of PHQ-9); ≥3 warrants full PHQ-9
• GAD-7: for comorbid anxiety
• Suicide risk assessment: direct questioning about suicidal thoughts, plans, means, protective factors

Bloods (Exclude Organic Causes)

• TFTs: hypothyroidism
• FBC: anaemia
• Vitamin B12 and folate: deficiency
• Glucose/HbA1c: diabetes
• U&Es, LFTs: baseline
• Calcium: hypercalcaemia

Special Tests

• ECG: before starting certain antidepressants (citalopram QTc prolongation risk)
• Drug and alcohol screening if substance misuse suspected
• Cognitive assessment (ACE-III): if depression in elderly (differentiate from dementia)

NICE NG222 Stepped-Care Model

• Step 1: Recognition, assessment, watchful waiting for subthreshold/mild depression
• Step 2: Low-intensity psychological interventions (guided self-help, computerised CBT, group physical activity, behavioural activation)
• Step 3: High-intensity psychological therapy (individual CBT, IPT, EMDR, couples therapy) OR antidepressant medication, or combination
• Step 4: Complex/crisis: specialist mental health services, inpatient care, ECT

Pharmacological

• First-line SSRI: sertraline 50mg OD (start 50mg, increase to 100-200mg); or fluoxetine 20mg OD (start 20mg, increase to 40-60mg)
• Alternative SSRIs: citalopram 20mg OD (max 40mg; 20mg if >65 years - QTc risk), escitalopram 10-20mg OD
• Second-line: switch SSRI, or consider SNRI (venlafaxine 75-375mg/day, duloxetine 60-120mg/day), mirtazapine 15-45mg ON (sedating, appetite stimulating)
• Augmentation (specialist): lithium, atypical antipsychotic (quetiapine, aripiprazole)
• Duration: continue for ≥6 months after remission (first episode); ≥2 years for recurrent depression
• Taper gradually when discontinuing (over 4+ weeks) to avoid discontinuation syndrome
• Warn about: delayed onset of benefit (2-4 weeks), initial anxiety increase, SSRI side effects (nausea, sexual dysfunction, headache)

Psychological Therapies

• CBT: 16-20 sessions; as effective as antidepressants for moderate depression (NICE NG222)
• IPT (Interpersonal Therapy): 16 sessions; focuses on relationships
• Behavioural Activation: structured increase in rewarding activities
• MBCT (Mindfulness-Based Cognitive Therapy): for relapse prevention (NICE recommended)

Referral Criteria

• Crisis/home treatment team: active suicidal ideation with plan, psychotic features, severe self-neglect
• Community mental health team: treatment-resistant depression (failed ≥2 adequate antidepressant trials), complex comorbidity
• Psychiatrist: diagnostic uncertainty, bipolar suspected, augmentation strategies
• IAPT (Improving Access to Psychological Therapies): for Steps 2-3 psychological therapies
• Emergency: immediate risk to self or others

• 60-70% respond to first-line antidepressant treatment (STAR*D: 33% remission with first trial)
• Average episode duration: 6-9 months if untreated; shorter with treatment
• 50% relapse after first episode; 80% after third episode
• With continuation treatment (≥6 months), relapse rate reduced to 25%
• Chronic (persistent) depression: 20% of cases
• Depression is associated with 2× increased risk of cardiovascular disease and 4× increased risk of completed suicide
• CBT has comparable long-term efficacy to antidepressants and may have lasting protective effect after therapy ends
• Suicide risk: 6% lifetime risk in severe depression

PHQ-9 Scoring

SSRI Side Effects and Comparison

Serotonin Syndrome - Key Features

Key Facts

Anxiety disorders are characterised by excessive worry, fear, and associated behavioural disturbance. They are the most common mental health conditions and are frequently encountered in primary care. GAD is the most common type, but other anxiety disorders (panic disorder, social anxiety, specific phobias, agoraphobia) are also prevalent.

Epidemiology

• GAD prevalence: 5-6% (lifetime prevalence ~10%)
• Panic disorder: 1-2%
• Social anxiety disorder: 3-7%
• Anxiety disorders overall: 15-20% lifetime prevalence
• Female:male ratio 2:1
• Peak onset: late adolescence to early adulthood
• Comorbid depression: 50-60%

Aetiology

• Biopsychosocial model
• Biological: genetic predisposition (heritability 30-40%), GABAergic dysfunction, serotonergic dysfunction, HPA axis dysregulation
• Psychological: cognitive distortions (catastrophic thinking, overestimation of threat), conditioning, maladaptive coping
• Social: childhood adversity, life stressors, social deprivation, loneliness

Pathophysiology

• Overactive amygdala (threat detection centre) with reduced prefrontal cortical regulation
• Dysregulation of GABA (inhibitory) and glutamate (excitatory) neurotransmitter balance
• Chronic sympathetic nervous system activation (fight-or-flight)
• Altered serotonergic neurotransmission in raphe nuclei
• Locus coeruleus noradrenergic hyperactivity (panic disorder)

GAD

• Excessive, uncontrollable worry about multiple life domains (health, finances, family, work)
• Duration: most days for ≥6 months (DSM-5)
• Associated symptoms: restlessness, fatigue, poor concentration, irritability, muscle tension, sleep disturbance
• Physical symptoms: palpitations, sweating, tremor, GI symptoms, headache, dizziness

Panic Disorder

• Recurrent unexpected panic attacks: sudden surge of intense fear peaking in minutes
• Symptoms: palpitations, chest pain, breathlessness, dizziness, paraesthesiae, derealization, fear of dying
• Anticipatory anxiety and avoidance of situations where attacks occurred

Social Anxiety Disorder

• Marked fear of social/performance situations (scrutiny by others)
• Fear of embarrassment, humiliation, or negative evaluation
• Avoidance of social situations

Red Flags

• Suicidal ideation (anxiety is an independent risk factor for suicide)
• Severe functional impairment (unable to work, leave house)
• Substance misuse (self-medication with alcohol/benzodiazepines)
• Psychotic features (rare, suggests alternative diagnosis)
• Sudden onset in elderly (consider organic cause)

Screening Tools

• GAD-7: 7-item questionnaire; ≥8 clinically significant; ≥10 moderate; ≥15 severe
• PHQ-9: for comorbid depression
• SPIN (Social Phobia Inventory): for social anxiety disorder
• Panic Disorder Severity Scale: for panic disorder

Bloods (Exclude Organic Causes)

• TFTs: hyperthyroidism
• FBC: anaemia
• Glucose/HbA1c: hypoglycaemia/diabetes
• Calcium: hypercalcaemia
• ECG: if palpitations or cardiac symptoms

Special Tests

• 24h urinary metanephrines: if phaeochromocytoma suspected
• 24h Holter monitor: if cardiac arrhythmia suspected
• Drug/alcohol screening: if substance misuse suspected

NICE CG113 Stepped-Care Model

• Step 1: Psychoeducation, self-help resources, monitoring
• Step 2: Low-intensity interventions - guided self-help (based on CBT), psychoeducation groups, computerised CBT
• Step 3: CBT (12-15 sessions) OR SSRI medication, or combination
• Step 4: Specialist mental health services: complex/treatment-resistant cases, crisis care

Pharmacological

• First-line SSRI (NICE CG113):
  • Sertraline 50mg OD (unlicensed for GAD but NICE recommended; start 25mg to reduce initial anxiety)
  • Escitalopram 10mg OD (licensed for GAD)
  • Paroxetine 20mg OD (licensed for GAD, panic, social anxiety)
• Allow 4-6 weeks for therapeutic effect; increase dose if insufficient response at 4-6 weeks
• If first SSRI fails: switch to another SSRI or SNRI (venlafaxine 75-225mg OD)
• Continue for at least 12 months after remission
• Second-line: pregabalin 150-600mg/day (licensed for GAD); duloxetine 60-120mg OD
• Benzodiazepines: AVOID for routine use; maximum 2-4 weeks for acute crisis only; risk of dependence
• Buspirone: 5-HT1A agonist; alternative for GAD (limited availability)
• Beta-blockers (propranolol 10-40mg): for somatic symptoms (tremor, palpitations) in performance anxiety; NOT for underlying anxiety

Psychological Therapies

• CBT: gold standard; 12-15 sessions (individual or group); addresses cognitive distortions and avoidance behaviour
• Applied relaxation: alternative to CBT if preferred
• Self-help: books (e.g. 'Overcoming Anxiety' series), apps (e.g. SilverCloud, Beating the Blues)
• IAPT (Improving Access to Psychological Therapies): NHS talking therapies; self-referral available

Referral Criteria

• IAPT: for psychological therapy (Steps 2-3)
• Community mental health team: treatment-resistant anxiety (failed ≥2 adequate treatments), complex comorbidity, severe functional impairment
• Emergency/crisis: suicidal ideation, severe agitation, psychotic features

• CBT: response rate 50-60%; durable effects - may prevent relapse better than medication alone
• SSRIs: response rate 50-60%; relapse rate 25-30% after discontinuation
• GAD follows a chronic relapsing course in many patients; 25% achieve full remission at 2 years
• Panic disorder: good prognosis with CBT; 70-80% improvement
• Social anxiety disorder: tends to be chronic without treatment; CBT effective in 50-65%
• Comorbid depression worsens prognosis and should be treated concurrently
• Substance misuse complication: 20-30% of anxiety patients develop alcohol use disorder
• Early intervention improves long-term outcomes significantly

GAD-7 Scoring

Antidepressant Comparison for Anxiety Disorders

Panic Attack vs Panic Disorder

Key Facts

Insomnia is the most common sleep disorder and one of the most frequent complaints in primary care. It is both a symptom and an independent disorder with significant health consequences. Management should prioritise non-pharmacological approaches.

Epidemiology

• Intermittent insomnia symptoms: 30-35% of adults
• Chronic insomnia disorder: 6-10%
• Female:male ratio 1.5:1
• Prevalence increases with age
• Strong bidirectional association with depression and anxiety

Aetiology

• Primary insomnia: no identifiable medical or psychiatric cause (diagnosis of exclusion)
• Comorbid insomnia: depression, anxiety, chronic pain, COPD, heart failure, GORD, menopause, nocturia
• Substance-related: caffeine, alcohol, nicotine, stimulants, medication effects (SSRIs, steroids, beta-blockers)
• Other sleep disorders: OSA, restless legs syndrome, circadian rhythm disorders
• 3P model (Spielman): Predisposing (personality, genetics) + Precipitating (life events, illness) + Perpetuating (maladaptive sleep behaviours, worry about sleep)

Pathophysiology

• Hyperarousal model: physiological (increased cortisol, metabolic rate, heart rate), cognitive (rumination, worry), and cortical (increased beta EEG activity during sleep)
• Disrupted circadian rhythm regulation (melatonin, cortisol)
• Conditioned arousal: bed/bedroom becomes associated with wakefulness rather than sleep
• Compensatory behaviours (sleeping late, napping, excessive time in bed) perpetuate insomnia

Symptoms

• Difficulty falling asleep (sleep-onset insomnia)
• Difficulty staying asleep (sleep-maintenance insomnia)
• Early morning awakening with inability to return to sleep
• Non-restorative sleep
• Daytime consequences: fatigue, poor concentration, mood disturbance, reduced performance, irritability
• Preoccupation or worry about sleep

Assessment

• Sleep history: sleep-wake pattern, bedtime, wake time, time to fall asleep, number of awakenings, total sleep time
• Sleep diary: 2 weeks minimum
• Daytime functioning
• Bedroom environment
• Caffeine, alcohol, drug use
• Screen for depression (PHQ-9), anxiety (GAD-7), OSA (STOP-BANG)

Red Flags

• Excessive daytime sleepiness with snoring (OSA)
• Restless legs/periodic limb movements
• Narcolepsy symptoms (cataplexy, sleep paralysis)
• Parasomnias (sleepwalking, REM sleep behaviour disorder)
• Insomnia with cognitive decline in elderly (delirium, dementia)

Bedside

• Sleep diary: 2 weeks; record bedtime, wake time, sleep latency, awakenings, daytime naps
• Validated questionnaires: Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI)
• PHQ-9, GAD-7: screen for comorbid depression and anxiety
• STOP-BANG: screen for OSA
• Epworth Sleepiness Scale: if excessive daytime sleepiness

Bloods

• TFTs (hyper/hypothyroidism)
• FBC (anaemia, restless legs - ferritin if RLS suspected)
• Ferritin (if restless legs suspected; treat if <75mcg/L)
• HbA1c (diabetes - nocturia)

Special Tests

• Polysomnography: NOT routinely indicated for insomnia; reserved for suspected OSA, PLMD, narcolepsy, or diagnostic uncertainty
• Actigraphy: wrist-worn device measuring sleep-wake patterns over 1-2 weeks; useful for circadian rhythm disorders

Non-pharmacological - First-Line

• CBT-I (Cognitive Behavioural Therapy for Insomnia): first-line treatment (NICE, AASM)
  • Components: sleep restriction, stimulus control, cognitive restructuring, relaxation, sleep hygiene
  • Sleep restriction: limit time in bed to match actual sleep time (initially may be 5-6 hours); gradually increase
  • Stimulus control: bed only for sleep and sex; leave bed if awake >15-20 minutes; fixed wake time
  • Delivery: face-to-face, group, digital (Sleepio app - NHS approved)
  • Efficacy: 70-80% improvement; durable effects lasting months-years
• Sleep hygiene (component of CBT-I, limited evidence alone):
  • Regular sleep-wake schedule
  • Avoid caffeine after midday, alcohol before bed
  • Cool, dark, quiet bedroom
  • Avoid screens 1 hour before bed
  • Regular exercise (but not within 4 hours of bed)

Pharmacological - Second-Line/Short-Term Only

• Melatonin MR 2mg (Circadin): licensed for patients ≥55 years; up to 13 weeks; relatively safe
• Z-drugs (zopiclone 3.75-7.5mg, zolpidem 5-10mg): maximum 2-4 weeks; risk of dependence, rebound insomnia, falls, daytime sedation
• Short-acting benzodiazepines (temazepam 10-20mg): maximum 2-4 weeks; AVOID in elderly
• Low-dose amitriptyline (10-25mg ON): off-label; useful if comorbid chronic pain or depression
• Antihistamines (promethazine 25mg, diphenhydramine): short-term; anticholinergic side effects; AVOID in elderly
• Orexin receptor antagonists (suvorexant, lemborexant): newer agents; not widely used in UK

Referral Criteria

• Sleep clinic: suspected OSA, narcolepsy, parasomnia, complex circadian rhythm disorder
• Psychology/IAPT: for CBT-I (available through NHS talking therapies)
• Psychiatry: insomnia with severe mental health comorbidity
• Avoid ongoing hypnotic prescriptions without review

• CBT-I: sustained benefit in >70% at 12 months; superior to medications long-term
• Hypnotics: effective short-term; high relapse on discontinuation; dependence risk
• Chronic insomnia is often a long-term condition requiring ongoing self-management
• Untreated insomnia: associated with 2× risk of depression, 1.5× risk of hypertension, cardiovascular disease, and impaired immune function
• Insomnia in elderly: associated with increased falls, cognitive decline, and mortality
• Most patients can achieve significant improvement with appropriate management

CBT-I Components Summary

Insomnia Severity Index (ISI)

Hypnotic Prescribing Safety (NICE CKS)

Key Facts

Chronic pain is a major public health issue and one of the most common reasons for GP consultation. NICE NG193 has significantly changed the approach to chronic primary pain, moving away from pharmacological management towards exercise, psychological therapy, and self-management.

Epidemiology

• Chronic pain: 28 million UK adults (~43%)
• Moderate-severe chronic pain: 14% of adults
• Higher prevalence in women, older adults, lower socioeconomic groups
• Associated with significant disability, mental health comorbidity, and social isolation
• Accounts for 4.6 million GP appointments/year in England

Aetiology

• Chronic primary pain: no identifiable underlying condition; includes fibromyalgia, chronic widespread pain, complex regional pain syndrome (CRPS), chronic pelvic pain, chronic headache, IBS
• Chronic secondary pain: identifiable underlying cause - neuropathic pain (diabetic neuropathy, post-herpetic neuralgia), musculoskeletal (OA, RA), cancer pain, post-surgical

Pathophysiology

• Central sensitisation: amplification of neural signalling within the CNS resulting in pain hypersensitivity
• Peripheral sensitisation: lowered threshold of nociceptors
• Neuroplasticity: structural and functional changes in pain-processing areas (somatosensory cortex, prefrontal cortex, limbic system)
• Descending modulation dysfunction: impaired inhibitory pain pathways
• Psychosocial amplification: fear-avoidance, catastrophising, depression, anxiety, social factors all modulate pain experience
• Chronic primary pain is not 'imagined' - it reflects real neurobiological changes in pain processing

Chronic Primary Pain

• Widespread pain without identifiable tissue damage or pathology
• Often associated with: fatigue, sleep disturbance, cognitive difficulties ('fibro fog'), low mood
• Disproportionate to any identifiable pathology
• Affects function and quality of life significantly

Assessment

• Comprehensive biopsychosocial assessment
• Pain characteristics: location, duration, quality, severity (VAS/NRS), aggravating/relieving factors
• Impact on function: work, sleep, mood, relationships, activities
• Psychological: PHQ-9, GAD-7, catastrophising (PCS)
• Current medications and previous treatments tried
• Medication use: opioid dose, escalation pattern, aberrant behaviour

Red Flags (Exclude Serious Pathology)

• New onset pain in patient >50 years with weight loss (malignancy)
• Neurological deficit (cauda equina, cord compression)
• Bone pain with raised calcium (metastases)
• Night pain/morning stiffness >45 min (inflammatory arthritis)
• Fever with pain (infection)

Bedside

• Pain assessment scales (VAS 0-10, NRS)
• Functional assessment
• PHQ-9, GAD-7 (comorbid depression/anxiety)
• Brief Pain Inventory
• DN4 (Douleur Neuropathique 4): screening for neuropathic pain component

Bloods

• FBC, ESR, CRP (exclude inflammatory/infectious cause)
• TFTs (hypothyroidism can cause myalgia)
• Vitamin D (deficiency common in chronic pain patients)
• HbA1c (diabetic neuropathy)
• Calcium (bony metastases, hyperparathyroidism)

Imaging

• Not routinely indicated for chronic primary pain (may reinforce unhelpful beliefs)
• Targeted imaging for suspected chronic secondary pain (X-ray for OA, MRI for suspected structural pathology)

Special Tests

• Nerve conduction studies/EMG: if neuropathic pain suspected
• DEXA: if osteoporosis suspected
• DN4 questionnaire: ≥4/10 suggests neuropathic component

Chronic Primary Pain (NICE NG193)

• Recommended:
  • Supervised group exercise programme: most effective intervention
  • Psychological therapy: CBT or ACT (acceptance and commitment therapy)
  • Acupuncture: consider a single course
  • Antidepressant for pain: ONLY if also treating comorbid depression/anxiety; NOT for pain alone
  • Pain neuroscience education
  • Self-management support
• NOT recommended (NICE NG193 - for chronic primary pain specifically):
  • Paracetamol, NSAIDs, opioids, gabapentinoids, benzodiazepines, antidepressants (for pain), ketamine, local anaesthetics, corticosteroid injections, TENS

Chronic Secondary Pain - Neuropathic Component (NICE CG173)

• First-line: amitriptyline 10mg ON (titrate to 75mg), duloxetine 60mg OD, gabapentin 300mg TDS (titrate to 1200mg TDS), or pregabalin 75mg BD (titrate to 300mg BD)
• Second-line: switch or combine first-line agents
• Third-line: tramadol (short-term), specialist referral
• Topical: capsaicin 0.075% cream, lidocaine 5% patches (post-herpetic neuralgia)

Opioid Management

• Avoid long-term opioids for chronic non-cancer pain wherever possible
• If already on long-term opioids: discuss dose reduction, agree tapering plan
• Review all patients on opioids: risks (dependence, OIH, falls, endocrine effects), benefits (often diminishing)
• Use opioid risk tools (ORT) before initiating

Referral Criteria

• Multidisciplinary pain clinic: complex chronic pain, failed primary care management, opioid reduction support
• Psychology/IAPT: for CBT/ACT
• Physiotherapy: for supervised exercise
• Addiction services: if problematic opioid/gabapentinoid use

• Chronic primary pain is a long-term condition requiring ongoing self-management
• CBT/ACT: reduces pain-related disability and distress in 40-60%; does not necessarily reduce pain intensity
• Exercise: improves function and pain by 20-30% in most studies
• Opioids: no evidence of long-term benefit beyond 3 months for chronic non-cancer pain; significant risk of harm
• Prognosis is improved by: early intervention, active coping strategies, psychological support, sustained physical activity
• Poor prognostic factors: catastrophising, fear-avoidance, ongoing compensation/litigation, depression, social isolation
• Many patients achieve meaningful improvement in function and quality of life with multimodal management

NICE NG193 vs CG173 - Key Differences

Fibromyalgia - ACR 2016 Revised Diagnostic Criteria

Opioid Concerns in Chronic Pain

Key Facts

Low back pain is an extremely common condition that is the leading cause of years lived with disability globally. The vast majority of cases are non-specific and self-limiting. Management focuses on reassurance, activity, and avoiding over-investigation.

Epidemiology

• Lifetime prevalence: 80%; point prevalence: 20-30%
• Most common cause of sickness absence in the UK
• Peak prevalence: 35-55 years
• Annual cost to NHS: >£1 billion; total UK economic cost: >£12 billion/year
• 90% improve within 6 weeks; 7-10% develop chronic pain (>12 weeks)

Aetiology

• Non-specific (>90%): no identifiable pathological cause; likely multifactorial (muscle, ligament, disc, facet joint)
• Radiculopathy/sciatica (5-10%): nerve root compression (disc prolapse most common, L4/5 and L5/S1)
• Serious pathology (<1%): cauda equina syndrome, spinal fracture, malignancy, infection, inflammatory spondyloarthropathy
• Risk factors for chronicity: psychosocial ('yellow flags') - fear-avoidance, catastrophising, depression, job dissatisfaction, compensation claims

Pathophysiology

• Degenerative changes in discs, facet joints, and ligaments (universal with ageing, poorly correlated with symptoms)
• Muscle deconditioning and spasm
• Central sensitisation in chronic pain
• Disc herniation: nucleus pulposus protrusion irritating/compressing nerve root
• Cauda equina syndrome: large central disc prolapse or other mass compressing cauda equina (below L2)

Non-Specific Low Back Pain

• Pain between costal margin and gluteal folds
• May radiate to thighs (not below knee)
• Mechanical: worse with movement, better with rest (or worse with sustained postures)
• No neurological deficit

Sciatica (Radiculopathy)

• Leg pain worse than back pain
• Pain radiating below the knee in a dermatomal distribution
• Positive straight leg raise (SLR) <45°
• Neurological signs: reduced reflexes, weakness, sensory loss in nerve root distribution
• L5 root: foot drop, weakness of great toe dorsiflexion, sensory loss dorsum of foot
• S1 root: reduced ankle jerk, weakness of plantarflexion, sensory loss lateral foot

Red Flags (Exclude Serious Pathology)

• Cauda equina: bilateral sciatica, saddle anaesthesia, urinary retention/incontinence, loss of anal tone, bilateral neurological deficit - EMERGENCY
• Cancer: age >55, history of cancer, unexplained weight loss, pain at rest, night pain, thoracic pain
• Fracture: osteoporosis, steroid use, significant trauma, structural deformity
• Infection: fever, IV drug use, immunocompromised, recent surgery, tuberculosis risk
• Inflammatory: age <40, morning stiffness >30 min, improves with exercise, family history of spondyloarthropathy

Bedside

• Comprehensive clinical examination: range of motion, SLR, neurological assessment (power, sensation, reflexes)
• STarT Back tool: risk stratification (low, medium, high)
• PR examination: if cauda equina suspected (anal tone)

Bloods

• Not routinely indicated for non-specific LBP
• ESR, CRP: if inflammatory/infectious cause suspected
• PSA, calcium, ALP: if malignancy suspected
• HLA-B27: if ankylosing spondylitis suspected

Imaging

• Do NOT routinely image non-specific low back pain (NICE NG59)
• MRI: gold standard when imaging indicated
  • Cauda equina syndrome: EMERGENCY MRI within hours
  • Red flags suggesting serious pathology
  • Sciatica not improving after 6 weeks (if surgery being considered)
• X-ray: limited utility; consider for suspected fracture
• MRI SIJ: if inflammatory spondyloarthropathy suspected

Special Tests

• Nerve conduction studies: rarely needed; if diagnostic uncertainty regarding radiculopathy vs peripheral neuropathy

Non-pharmacological (NICE NG59)

• Reassurance and education: back pain is common, not dangerous, self-limiting in most cases
• Encourage staying active: bed rest is harmful; return to normal activities as soon as possible
• Group exercise programme: biomechanical, aerobic, mind-body (yoga, Pilates) - any form of exercise beneficial
• Manual therapy (spinal manipulation, mobilisation, massage): as part of a treatment package including exercise
• CBT/psychological therapy: for medium-high risk on STarT Back
• Self-management support

Pharmacological (NICE NG59)

• First-line: NSAID (ibuprofen 400mg TDS or naproxen 250-500mg BD) - shortest effective course; PPI cover if risk factors
• If NSAID contraindicated: weak opioid (codeine 30mg QDS) with or without paracetamol - SHORT TERM ONLY
• Paracetamol alone: NOT recommended for LBP (insufficient evidence - Cochrane)
• Do NOT offer opioids for chronic LBP (NICE NG59)
• Do NOT offer gabapentinoids for non-specific LBP
• Neuropathic agents (amitriptyline, gabapentin, pregabalin): for sciatica with neuropathic pain component

Surgical

• Spinal decompression (discectomy/laminectomy): for sciatica with confirmed nerve root compression not improving with conservative management after 6-12 weeks
• Spinal fusion: rarely; for specific indications after comprehensive MDT assessment
• Do NOT offer facet joint injections, disc replacement for non-specific LBP (NICE NG59)

Referral Criteria

• Emergency: cauda equina syndrome (same-day MRI and neurosurgical assessment)
• Urgent: progressive neurological deficit, suspected malignancy or infection
• Routine: physiotherapy, pain management programme, orthopaedic/spinal surgeon if surgery candidate
• Occupational health: advice on work modifications and return to work

• 90% of acute LBP improves within 6 weeks
• 7-10% develop chronic pain (>12 weeks)
• Psychosocial factors ('yellow flags') are the strongest predictors of chronicity, NOT imaging findings
• Disc degeneration on MRI is universal with ageing and does NOT correlate with symptoms (up to 80% of asymptomatic individuals have disc changes)
• Sciatica: >50% improve within 6 weeks; >90% within 12 months
• Surgery for sciatica: faster recovery but similar outcomes at 1-2 years vs conservative management
• Cauda equina syndrome: outcome depends on timing of decompression; delay >48 hours associated with worse outcome

STarT Back Risk Stratification

Sciatica - Key Nerve Roots

Yellow Flags (Psychosocial Risk Factors for Chronicity)

Key Facts

Neck pain is the second most common musculoskeletal presentation after low back pain. Most cases are non-specific and self-limiting. Careful clinical assessment is essential to identify the minority with serious pathology requiring urgent intervention.

Epidemiology

• Annual prevalence: 30-50% of adults
• Point prevalence: 10-15%
• Chronic neck pain: 15%
• More common in women and office workers
• Peak age: 40-60 years

Aetiology

• Non-specific (mechanical): poor posture, muscle strain, cervical spondylosis
• Cervical radiculopathy: disc prolapse or osteophyte compressing nerve root
• Cervical myelopathy: spinal cord compression (spondylosis, disc prolapse, OPLL)
• Whiplash-associated disorder: acceleration-deceleration injury (usually RTA)
• Serious pathology: fracture, malignancy (metastases), infection (discitis, epidural abscess), inflammatory arthritis (RA - atlantoaxial subluxation)

Pathophysiology

• Cervical spine is highly mobile with complex anatomy; vulnerable to degenerative changes and injury
• Cervical spondylosis (degenerative disc disease and osteophyte formation) is universal with ageing
• Disc prolapse: typically posterolateral, compressing exiting nerve root
• Myelopathy: narrowed spinal canal (spondylosis, disc, ligament hypertrophy) compresses spinal cord
• Non-specific pain: likely involves muscles, facet joints, discs, ligaments

Non-Specific Neck Pain

• Axial pain in the posterior neck
• May radiate to shoulder/trapezius
• Mechanical: worse with sustained postures, better with position change
• Limited range of motion
• No neurological deficit

Cervical Radiculopathy

• Arm pain worse than neck pain, dermatomal distribution
• Paraesthesiae and numbness in nerve root distribution
• Weakness (muscle group specific to root)
• Spurling test positive (neck extension + lateral flexion + axial load reproduces arm symptoms)

Cervical Myelopathy

• Subtle, progressive gait disturbance (spastic ataxia)
• Hand clumsiness (loss of fine motor control)
• Upper motor neurone signs: hyperreflexia, spasticity, upgoing plantars, clonus
• Lhermitte sign: electric shock sensation down spine on neck flexion
• Bladder dysfunction (late)

Red Flags

• Progressive neurological deficit (myelopathy)
• Lhermitte sign
• Bilateral arm symptoms
• Bladder/bowel dysfunction
• Fever, IV drug use, immunosuppression (infection)
• History of malignancy, unexplained weight loss
• Severe trauma (fracture)
• Rheumatoid arthritis (atlantoaxial subluxation)

Bedside

• Full neurological examination of upper and lower limbs
• Spurling test (cervical radiculopathy)
• Hoffman sign, Babinski reflex (UMN signs - myelopathy)
• Grip and release test (impaired in myelopathy)
• Assessment of gait (spastic ataxia in myelopathy)

Bloods

• Not routinely required for non-specific neck pain
• ESR, CRP: if inflammatory/infectious cause suspected
• RF, anti-CCP: if RA suspected

Imaging

• Not routinely indicated for non-specific neck pain
• MRI cervical spine: investigation of choice if red flags, myelopathy, or persistent radiculopathy
• CT cervical spine: after trauma (Canadian C-spine rules or NEXUS criteria)
• X-ray: limited role; flexion/extension views for RA instability assessment

Special Tests

• Nerve conduction studies: if diagnostic uncertainty between radiculopathy and peripheral neuropathy
• CT myelogram: if MRI contraindicated

Non-pharmacological

• Reassurance: most neck pain is not serious and improves within 4-6 weeks
• Stay active: avoid prolonged rest, maintain normal activities
• Exercise programme: stretching, strengthening, range of motion; supervised or home-based
• Manual therapy: mobilisation or manipulation (physiotherapy/chiropractic) - part of multimodal treatment
• Ergonomic advice: workstation assessment, posture correction, regular breaks
• Whiplash: early return to activity; NO cervical collar (delays recovery); exercises

Pharmacological

• NSAIDs: ibuprofen 400mg TDS or naproxen 250-500mg BD (short course)
• Paracetamol: as adjunct
• Muscle relaxant: diazepam 2-5mg TDS for acute spasm (maximum 1 week)
• Neuropathic agents: amitriptyline 10-75mg ON or gabapentin for radicular neuropathic pain
• Avoid opioids for chronic neck pain

Surgical

• Cervical myelopathy (progressive): urgent neurosurgical decompression (anterior cervical discectomy and fusion - ACDF, or posterior decompression)
• Cervical radiculopathy: surgery if failure of 6-12 weeks conservative management with persistent significant symptoms
• Cervical fracture: stabilisation as indicated

Referral Criteria

• Emergency neurosurgery: progressive myelopathy, acute spinal cord injury
• Urgent: suspected myelopathy, progressive neurological deficit, suspected malignancy/infection
• Routine: persistent radiculopathy >6 weeks, failed conservative management
• Physiotherapy: all patients with neck pain for exercise and manual therapy

• Non-specific neck pain: >60% improve within 4-6 weeks; 30% develop chronic symptoms
• Whiplash: >80% recover within 3 months; 10-20% develop chronic pain (Quebec Task Force classification)
• Cervical radiculopathy: >80% resolve with conservative management
• Cervical myelopathy: progressive without treatment; surgery stabilises or improves in >70% but recovery depends on duration and severity pre-operatively
• Psychosocial factors (yellow flags) are the strongest predictors of chronicity
• Cervical spondylosis is radiographically present in >85% of those >60 years and poorly correlates with symptoms

Canadian C-Spine Rules (Post-Trauma)

Cervical Nerve Root Syndromes

Cervical Myelopathy - Clinical Features

Key Facts

Shoulder pain is extremely common and a significant cause of functional limitation. Most cases are due to soft tissue pathology around the shoulder, particularly the rotator cuff. Management is predominantly conservative, with physiotherapy as the cornerstone.

Epidemiology

• Point prevalence: 16-26% of adults
• Annual incidence in primary care: 15 per 1,000 registrations
• Increases with age, peaking at 45-64 years
• Rotator cuff pathology accounts for 70% of shoulder pain

Aetiology

• Rotator cuff tendinopathy/tears: supraspinatus most common; degeneration, impingement, overuse
• Adhesive capsulitis (frozen shoulder): idiopathic, diabetes, thyroid disease, immobility
• Acromioclavicular joint: OA, osteolysis, injury
• Glenohumeral OA: less common than hip/knee OA
• Instability: anterior dislocation (young, traumatic), multidirectional (hypermobility)
• Referred pain: cervical spine, cardiac, diaphragmatic, apical lung tumour (Pancoast)

Pathophysiology

• Rotator cuff: four muscles (supraspinatus, infraspinatus, teres minor, subscapularis) stabilise the humeral head in the glenoid
• Tendinopathy: degenerative rather than inflammatory; failed healing response, collagen disorganisation
• Impingement: mechanical compression of rotator cuff between humeral head and acromion during overhead activities
• Adhesive capsulitis: fibrosis and contracture of glenohumeral joint capsule; three phases - freezing, frozen, thawing
• Calcific tendinopathy: calcium hydroxyapatite deposits within rotator cuff tendons, causing acute inflammatory pain

Rotator Cuff Tendinopathy

• Lateral/anterolateral shoulder pain
• Painful arc (60-120° abduction)
• Worse with overhead activities
• Night pain (sleeping on affected side)
• Positive impingement tests (Neer, Hawkins-Kennedy)

Adhesive Capsulitis (Frozen Shoulder)

• Global restriction of both active AND passive movement
• Especially external rotation and abduction
• Three phases: freezing (painful, 2-9 months), frozen (stiff, 4-12 months), thawing (recovery, 5-24 months)
• Total duration: 12-30 months; may not fully resolve

Acute Rotator Cuff Tear

• Sudden weakness after trauma or fall
• Unable to initiate abduction (complete supraspinatus tear)
• Drop arm test positive

Red Flags

• Acute traumatic injury with deformity (fracture/dislocation)
• Hot, swollen joint with fever (septic arthritis)
• Progressive weakness (complete rotator cuff tear, neurological cause)
• Shoulder pain with weight loss/malaise (malignancy - Pancoast tumour)
• Shoulder pain radiating to arm with cervical signs (referred from C-spine)

Bedside

• Full shoulder examination: inspection, palpation, range of motion (active and passive), strength, special tests
• Painful arc (60-120°): rotator cuff impingement
• Neer test, Hawkins-Kennedy: impingement
• Empty can test (Jobe): supraspinatus
• Drop arm test: complete rotator cuff tear
• External rotation lag sign: infraspinatus
• Belly press, lift-off: subscapularis
• Cross-body adduction: AC joint

Imaging

• X-ray: first-line if trauma, OA suspected, or persistent symptoms; assess acromion morphology, calcification, OA
• USS: excellent for rotator cuff assessment; operator-dependent; first-line soft tissue imaging
• MRI: gold standard for comprehensive assessment; rotator cuff tears, labral pathology, bone marrow

Bloods

• Not routinely required
• CRP, WCC: if septic arthritis suspected
• HbA1c: screen for diabetes in adhesive capsulitis
• TFTs: associated with adhesive capsulitis

Non-pharmacological

• Physiotherapy and exercise: first-line for all shoulder conditions; supervised exercise programme for rotator cuff (progressive loading, strengthening, range of motion)
• Activity modification: avoid aggravating overhead activities temporarily
• Adhesive capsulitis: physiotherapy (gentle stretching, not aggressive mobilisation); may use hydrodilatation

Pharmacological

• NSAIDs: ibuprofen 400mg TDS or naproxen 250-500mg BD (short course for acute pain)
• Paracetamol: as adjunct
• Subacromial corticosteroid injection: methylprednisolone 40mg + 1% lidocaine; short-term benefit (4-6 weeks); maximum 3 injections/year
• Intra-articular injection: for adhesive capsulitis or glenohumeral OA

Surgical

• Arthroscopic subacromial decompression: controversial; CSAW trial showed no benefit over placebo (Lancet 2018)
• Rotator cuff repair: for complete tears in active patients, acute traumatic tears
• Manipulation under anaesthesia or arthroscopic capsular release: for refractory adhesive capsulitis
• Shoulder arthroplasty: for severe glenohumeral OA (total or reverse shoulder replacement)

Referral Criteria

• Urgent: suspected septic arthritis, acute traumatic complete rotator cuff tear (young/active)
• Routine orthopaedic: failed 3-6 months conservative management, significant rotator cuff tear, adhesive capsulitis >12 months, glenohumeral OA for arthroplasty consideration
• Physiotherapy: all shoulder pain for exercise programme

• Rotator cuff tendinopathy: >70% improve with physiotherapy at 6 months
• Adhesive capsulitis: natural history 12-30 months; most recover good function; 20-50% have persistent minor restriction
• Rotator cuff tear: small tears may be managed conservatively; large/complete tears in young active patients usually require surgery
• Subacromial decompression: CSAW trial (Lancet 2018) showed no significant benefit over placebo surgery
• Corticosteroid injections: effective short-term (4-6 weeks); no long-term benefit; may weaken tendons if repeated
• Psychosocial factors (fear-avoidance, kinesiophobia) influence outcomes significantly

Rotator Cuff Muscles - SITS

Adhesive Capsulitis - Three Phases

CSAW Trial (Lancet 2018)

Key Facts

Knee pain is the most common large joint complaint in primary care. In adults over 45, osteoarthritis is the most common cause. In younger patients, ligament and meniscal injuries predominate. Systematic assessment helps distinguish the common causes.

Epidemiology

• 25% of adults >55 have significant knee pain
• OA of the knee: affects >4.7 million in the UK
• ACL injuries: approximately 20,000/year in the UK
• Patellofemoral pain syndrome: most common cause of anterior knee pain in adolescents/young adults

Aetiology

• Osteoarthritis: degenerative, age-related, obesity, previous injury, genetic predisposition
• Ligament injuries: ACL (pivot/twist), MCL (valgus force), PCL (dashboard injury), LCL (varus force)
• Meniscal tears: twisting on weight-bearing knee; medial more common than lateral
• Inflammatory arthritis: RA, gout, pseudogout, reactive arthritis, psoriatic arthritis
• Patellofemoral pain: anterior knee pain in young, active patients; overuse, malalignment
• Referred pain: hip OA, L3/4 radiculopathy
• Other: prepatellar bursitis (housemaid's knee), Baker cyst, iliotibial band syndrome

Pathophysiology

• OA: cartilage degeneration, subchondral bone sclerosis, osteophyte formation, synovial inflammation
• ACL: pivot/twisting mechanism ruptures anterolateral band; often combined with meniscal and MCL injury (unhappy triad)
• Meniscal tears: degenerative (>40 years, minimal trauma) or traumatic (young, sport)
• Gout: monosodium urate crystal deposition; pseudogout: calcium pyrophosphate deposition

Osteoarthritis

• Pain worse with activity, better with rest
• Morning stiffness <30 minutes
• Crepitus on movement
• Bony enlargement
• Reduced range of motion
• Gradually progressive over months/years

ACL Tear

• Acute injury: pivot/twist, often with audible 'pop'
• Immediate swelling (haemarthrosis within 2 hours)
• Feeling of instability/giving way
• Positive Lachman test (most sensitive), anterior drawer test, pivot shift

Meniscal Tear

• Twisting injury or insidious onset (degenerative)
• Delayed swelling (24-48 hours)
• Mechanical symptoms: locking, catching, giving way
• Joint line tenderness
• Positive McMurray test

Inflammatory Arthritis (Gout/Pseudogout)

• Acute hot, swollen, red, exquisitely tender joint
• Gout: typically first MTP but can affect knee
• Pseudogout: knee is the most commonly affected joint
• Rapid onset (hours)

Red Flags

• Hot, swollen joint with fever (septic arthritis - emergency joint aspiration)
• Acute locked knee (meniscal fragment, loose body)
• Significant trauma with inability to weight-bear (fracture)
• Rapidly progressive deformity (malignancy, infection)

Bedside

• Full knee examination: inspection, palpation, range of motion, stability testing
• Lachman test (ACL - most sensitive), anterior/posterior drawer
• McMurray test (meniscus)
• Valgus/varus stress (MCL/LCL)
• Patellar apprehension test, Clarke test (patellofemoral)
• Assess for effusion: cross fluctuance, patellar tap, sweep test

Bloods

• Not required for OA diagnosis
• Serum urate: for gout (may be normal in acute attack)
• ESR, CRP: inflammatory or infectious causes
• RF, anti-CCP: if RA suspected

Imaging

• X-ray (weight-bearing AP, lateral, skyline): for OA (joint space narrowing, osteophytes, subchondral sclerosis, cysts), fracture, chondrocalcinosis
• NOT required to diagnose OA if clinical criteria met (NICE NG226)
• MRI: gold standard for soft tissue pathology (ACL, meniscus, cartilage)
• USS: Baker cyst, effusion assessment

Special Tests

• Joint aspiration: if effusion present (especially if septic arthritis or crystal arthropathy suspected)
  • Septic: turbid, WCC >50,000, positive culture
  • Gout: negatively birefringent needle-shaped crystals
  • Pseudogout: positively birefringent rhomboid crystals
  • OA: clear/straw-coloured, low WCC

Osteoarthritis (NICE NG226)

• Non-pharmacological (first-line):
  • Exercise: quadriceps strengthening, aerobic exercise, flexibility; supervised or home-based
  • Weight loss: if overweight; every 1kg loss reduces knee load by 4kg
  • Education and self-management: Arthritis Action, Versus Arthritis resources
  • Walking aids if needed
• Pharmacological:
  • Topical NSAID (diclofenac gel): first-line before oral NSAIDs
  • Oral NSAID (ibuprofen/naproxen): if topical insufficient; lowest dose, shortest duration; PPI cover
  • Paracetamol: adjunct (limited evidence for OA - Cochrane)
  • Intra-articular corticosteroid injection: for flares; short-term benefit (6-8 weeks)
  • Do NOT offer glucosamine, chondroitin, hyaluronic acid injections (NICE NG226)
• Surgical: total knee replacement for severe OA with significant impact on QoL

Ligament Injuries

• ACL: physiotherapy (rehabilitation) for low-demand patients; ACL reconstruction (hamstring/patellar tendon graft) for young, active, unstable knee
• MCL: usually conservative (bracing, physiotherapy)

Meniscal Tears

• Degenerative: physiotherapy first-line; arthroscopic partial meniscectomy NOT superior to physiotherapy (FIDELITY trial)
• Traumatic with locking: arthroscopic meniscal repair or partial meniscectomy

Crystal Arthropathy

• Acute gout: NSAID (naproxen 750mg stat then 250mg TDS), or colchicine 500mcg BD-TDS, or short-course prednisolone 30mg/day
• Urate-lowering: allopurinol 100mg (start 2 weeks after acute attack), titrate to target urate <360μmol/L

Referral Criteria

• Emergency: suspected septic arthritis (joint aspiration), acute locked knee
• Orthopaedic: ACL reconstruction candidate, refractory meniscal symptoms, severe OA for arthroplasty
• Rheumatology: inflammatory arthritis, recurrent crystal arthropathy
• Physiotherapy: first-line for all knee pain

• OA: progressive but variable; exercise and weight loss significantly reduce pain and disability; >90% of knee replacements last >15 years
• ACL tear: without reconstruction, risk of further meniscal damage and early OA; post-reconstruction, >85% return to sport
• Meniscal tear: degenerative tears - physiotherapy as effective as surgery (FIDELITY trial); traumatic tears in young patients often require surgery
• Gout: excellent prognosis with urate-lowering therapy; chronic tophaceous gout is preventable
• Septic arthritis: requires emergency treatment; delay increases risk of joint destruction and mortality (10-15%)

NICE NG226 - OA Clinical Diagnosis Criteria (No Imaging Needed)

Knee Examination Special Tests

Key Trial: FIDELITY (Meniscal Tears)

Key Facts

Headache accounts for approximately 4% of all GP consultations. The vast majority are primary headaches (tension-type, migraine, cluster), but a systematic approach is required to identify the small proportion with secondary causes requiring urgent investigation or referral.

Epidemiology

• Tension-type headache: lifetime prevalence 60-80%
• Migraine: affects 15% of UK adults; 6% of men and 18% of women
• Cluster headache: prevalence 0.1%; male-to-female ratio 3:1
• Medication overuse headache affects approximately 1-2% of the general population
• Headache is the most common neurological reason for GP consultation

Aetiology

• Primary headaches: tension-type (peripheral and central sensitisation), migraine (cortical spreading depression, trigeminovascular activation), cluster (hypothalamic dysfunction)
• Secondary headaches: medication overuse, intracranial pathology (tumour, haemorrhage, infection), giant cell arteritis, idiopathic intracranial hypertension, cervicogenic headache
• Triggers: stress, sleep disturbance, hormonal changes (menstruation), dietary factors (alcohol, caffeine withdrawal, cheese), environmental factors

Pathophysiology

• Tension-type: peripheral myofascial nociception with central sensitisation in chronic forms
• Migraine: cortical spreading depression triggers trigeminovascular system activation, leading to release of CGRP and vasoactive peptides causing neurogenic inflammation
• Cluster: hypothalamic activation with parasympathetic outflow via the trigeminal-autonomic reflex
• Medication overuse: chronic analgesic use causes downregulation of endogenous pain-modulating pathways and central sensitisation

Tension-Type Headache

• Bilateral, pressing or tightening quality ('band-like')
• Mild to moderate intensity
• Not aggravated by routine physical activity
• No nausea or vomiting (mild photophobia OR phonophobia may be present but not both)
• Duration: 30 minutes to 7 days

Migraine

• Unilateral (60%), pulsating/throbbing quality
• Moderate to severe intensity
• Aggravated by routine physical activity
• Associated nausea/vomiting, photophobia, and phonophobia
• Duration: 4-72 hours
• With aura in 25%: visual (scotomata, fortification spectra), sensory, speech disturbance lasting 5-60 minutes

Cluster Headache

• Strictly unilateral, severe periorbital/temporal pain
• Associated ipsilateral autonomic features: lacrimation, conjunctival injection, rhinorrhoea, ptosis, miosis
• Duration: 15-180 minutes
• Frequency: 1-8 attacks per day in bouts lasting 6-12 weeks

Medication Overuse Headache

• Present on ≥15 days/month
• Develops or worsens during regular overuse of analgesics
• Typically bilateral, dull, worse on waking

Red Flags

• Thunderclap headache (maximal intensity within 5 minutes) - subarachnoid haemorrhage
• New headache in patient >50 years - giant cell arteritis, intracranial pathology
• Progressive headache with focal neurological signs - space-occupying lesion
• Headache with papilloedema - raised intracranial pressure
• Headache with fever, neck stiffness, rash - meningitis
• Headache worse on coughing/straining/lying flat - raised ICP
• New headache in immunocompromised or cancer patients

Bedside

• Blood pressure measurement
• Fundoscopy (papilloedema screening)
• Neurological examination including cranial nerves
• Temporal artery palpation in patients >50 years
• Visual acuity assessment

Bloods

• ESR and CRP: if giant cell arteritis suspected (ESR often >50 mm/hr)
• FBC: if systemic symptoms
• U&Es, TFTs: if secondary causes considered

Imaging

• CT head: urgent if thunderclap headache, acute neurological deficit
• MRI brain: if red flags present, progressive headache, new neurological signs, suspected space-occupying lesion
• CT/MR angiography: if subarachnoid haemorrhage or cerebral venous sinus thrombosis suspected

Special Tests

• Lumbar puncture: if CT negative but SAH suspected (xanthochromia); for measuring opening pressure in suspected IIH
• Temporal artery biopsy: if GCA suspected
• Headache diary: minimum 8 weeks, documenting frequency, duration, triggers, medication use

Non-pharmacological

• Reassurance and patient education about primary headache diagnosis
• Headache diary to identify and avoid triggers
• Regular sleep pattern, adequate hydration, regular meals
• Stress management techniques (CBT, relaxation therapy, mindfulness)
• Limit caffeine intake; address screen time and posture
• For medication overuse headache: abrupt withdrawal of overused analgesic (except opioids/barbiturates - gradual taper)

Pharmacological

Acute treatment - Tension-type headache:

• Paracetamol 1g QDS or ibuprofen 400mg TDS (first-line)
• Aspirin 900mg as alternative
• Avoid codeine-containing preparations (risk of medication overuse)

Acute treatment - Migraine:

• Oral triptan (sumatriptan 50-100mg) + NSAID (naproxen 500mg) or + paracetamol 1g (NICE CKS)
• Sumatriptan 50mg is available OTC
• Anti-emetic if needed: metoclopramide 10mg or prochlorperazine 10mg buccal
• Avoid opioids

Prophylaxis - Migraine (if ≥4 attacks/month or significantly disabling):

• Propranolol 40-240mg daily (first-line; NICE CKS)
• Topiramate 25-100mg daily (contraindicated in pregnancy - teratogenic)
• Amitriptyline 10-75mg nocte (off-label; also useful if coexistent tension-type)
• Candesartan 8-16mg daily (off-label alternative)
• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) - NICE TA for episodic/chronic migraine after ≥3 preventive failures

Cluster headache:

• Acute: sumatriptan 6mg SC or high-flow oxygen 12-15 L/min via non-rebreather mask for 15-20 minutes
• Prophylaxis: verapamil 240-960mg daily (first-line, requires ECG monitoring); short course prednisolone 60-100mg tapering

Surgical

• Occipital nerve stimulation for refractory chronic cluster headache (specialist centres)
• Greater occipital nerve block with local anaesthetic ± corticosteroid for refractory cases

Referral Criteria

• Red flag features: urgent/2-week-wait referral as appropriate
• Suspected cluster headache: refer to neurologist
• Migraine refractory to ≥2 prophylactic agents: refer to headache specialist
• Suspected medication overuse headache not responding to withdrawal: neurology referral
• Diagnostic uncertainty or atypical features

• Tension-type headache: chronic form (≥15 days/month) develops in 2-3% of episodic sufferers
• Migraine: improves in 60-70% of women after menopause; remission rates of 40% over 10 years
• Cluster headache: episodic form may become chronic in 10-15%; spontaneous remission in 10-20%
• Medication overuse headache: 50-70% improve within 2 months of withdrawal; relapse rate 30-45% at 1 year
• Secondary headache prognosis depends on underlying cause
• Migraine with aura carries a small increased risk of ischaemic stroke, particularly in women using combined hormonal contraception

ICHD-3 Migraine Without Aura Criteria

Headache Red Flags (SNOOP Mnemonic)

Key Facts

Dizziness is an umbrella term encompassing vertigo (illusion of movement), presyncope (feeling of impending faint), disequilibrium (unsteadiness), and non-specific light-headedness. Careful history-taking to characterise the symptom type is the cornerstone of diagnosis.

Epidemiology

• Lifetime prevalence of dizziness: approximately 20-30% in the general population
• Incidence increases with age, affecting >30% of those aged over 65
• BPPV is the commonest vestibular disorder, with a lifetime prevalence of 2.4%
• Vestibular neuritis is the second most common cause of peripheral vertigo

Aetiology

• Peripheral vestibular: BPPV (otolith displacement), vestibular neuritis (viral inflammation of vestibular nerve), Meniere disease (endolymphatic hydrops), labyrinthitis
• Central vestibular: posterior circulation stroke/TIA, vestibular migraine, MS, posterior fossa tumour
• Cardiovascular: postural hypotension, arrhythmia (AF, heart block, long QT), aortic stenosis, carotid sinus hypersensitivity
• Other: anaemia, hypoglycaemia, medication side effects (antihypertensives, antiepileptics, aminoglycosides), anxiety/hyperventilation

Pathophysiology

• BPPV: otoconia (calcium carbonate crystals) become displaced from the utricle into the semicircular canals (usually posterior), causing abnormal endolymph flow with head position changes
• Vestibular neuritis: viral inflammation (often HSV-1) of the vestibular nerve causes acute unilateral vestibular failure
• Meniere disease: endolymphatic hydrops causes distension of the membranous labyrinth, leading to episodic vertigo, hearing loss, and tinnitus
• Postural hypotension: inadequate baroreceptor response on standing leads to cerebral hypoperfusion

BPPV

• Brief episodes of vertigo (<60 seconds) triggered by head position changes
• Commonly provoked by rolling over in bed, looking up, or bending forward
• No hearing loss or tinnitus
• Positive Dix-Hallpike test with rotatory nystagmus and latency

Vestibular Neuritis

• Acute onset of severe prolonged vertigo (hours to days)
• Nausea and vomiting
• Unsteadiness with falling towards affected side
• No hearing loss (if hearing loss present, consider labyrinthitis)
• Often preceded by viral illness

Meniere Disease

• Episodic vertigo lasting 20 minutes to several hours
• Fluctuating low-frequency sensorineural hearing loss
• Tinnitus (typically low-pitched roaring)
• Aural fullness

Presyncope

• Feeling of impending faint
• Visual greying, tunnel vision
• Pallor, sweating, nausea
• May occur on standing (postural hypotension) or with exertion (cardiac cause)

Red Flags

• Acute vertigo with cerebellar signs (ataxia, dysarthria, dysphagia) - posterior circulation stroke
• Vertical or direction-changing nystagmus - central cause
• Sudden sensorineural hearing loss - requires urgent ENT referral
• New neurological deficit with dizziness
• Dizziness on exertion with syncope - cardiac arrhythmia or structural heart disease
• Risk factors for stroke (hypertension, diabetes, AF, smoking) with acute vestibular syndrome

Bedside

• Dix-Hallpike test: diagnostic for posterior canal BPPV
• Supine roll test: for horizontal canal BPPV
• HINTS exam: Head Impulse test, Nystagmus pattern, Test of Skew - differentiates peripheral from central in acute vestibular syndrome
• Lying and standing blood pressure: orthostatic drop ≥20mmHg systolic or ≥10mmHg diastolic
• Romberg test, tandem gait, cerebellar examination
• ECG: arrhythmia screen
• Blood glucose: hypoglycaemia

Bloods

• FBC (anaemia)
• U&Es (electrolyte disturbance)
• TFTs (thyroid dysfunction)
• HbA1c/glucose
• Lipid profile if vascular risk assessment needed

Imaging

• MRI brain: if central cause suspected (cerebellar signs, vertical nystagmus, new neurological deficit)
• CT head: acute stroke work-up if MRI unavailable
• Echocardiogram: if structural cardiac disease suspected

Special Tests

• Audiometry: essential if Meniere disease suspected or hearing loss present
• 24-hour Holter monitor: if paroxysmal arrhythmia suspected
• Tilt table test: if recurrent unexplained presyncope
• Caloric testing: specialist vestibular function assessment

Non-pharmacological

• BPPV: Epley manoeuvre (canalith repositioning) - success rate 80% after single treatment, 90% after repeated treatments
• Vestibular rehabilitation: graded exercise-based programme for vestibular hypofunction; effective for vestibular neuritis and chronic dizziness (Cochrane evidence)
• Postural hypotension: slow positional changes, adequate hydration, compression stockings, review culprit medications
• Patient education: nature of condition, expected time course, driving restrictions if applicable
• Dietary modifications for Meniere disease: salt restriction (<1.5g/day), caffeine and alcohol avoidance

Pharmacological

Acute vestibular symptoms (short-term use only, <1 week):

• Prochlorperazine 5mg TDS oral or 3mg buccal BD
• Cyclizine 50mg TDS
• Betahistine 16mg TDS (specifically for Meniere disease; limited evidence for other causes)

Vestibular neuritis:

• Short course of vestibular sedatives (prochlorperazine) for first 24-72 hours only
• Early mobilisation and vestibular rehabilitation (avoid prolonged sedative use as it delays central compensation)

Meniere disease prophylaxis:

• Betahistine 16mg TDS (may increase to 48mg TDS)
• Consider diuretics (bendroflumethiazide 2.5mg OD) in refractory cases

Postural hypotension (if non-pharmacological measures fail):

• Fludrocortisone 50-300mcg OD
• Midodrine 2.5-10mg TDS

Surgical

• Meniere disease: endolymphatic sac decompression, intratympanic gentamicin (chemical labyrinthectomy), or surgical labyrinthectomy for refractory cases
• Posterior semicircular canal occlusion for intractable BPPV (very rare)

Referral Criteria

• Suspected central cause (urgent neurology/stroke referral)
• Sudden sensorineural hearing loss (urgent ENT within 2 weeks, ideally within 72 hours)
• Meniere disease (ENT referral)
• BPPV not responding to Epley manoeuvre after 2-3 attempts
• Recurrent syncope/presyncope (cardiology)
• Persistent dizziness >6 weeks impacting function

• BPPV: 80-90% resolve with Epley manoeuvre; recurrence rate 15-20% per year
• Vestibular neuritis: most recover spontaneous vestibular function within 6-12 weeks; 10-15% develop BPPV subsequently
• Meniere disease: burns out in 60-70% over 5-10 years with progressive hearing loss; bilateral involvement in 30-50%
• Postural hypotension: associated with 30% increased risk of falls in the elderly
• Central vestibular causes: prognosis depends on underlying pathology (posterior circulation stroke carries 20% 30-day mortality in basilar territory)

Differentiating Peripheral from Central Vertigo

HINTS Exam Interpretation

Key Facts

Fatigue is one of the most common symptoms in primary care. It encompasses physical tiredness, mental exhaustion, and lack of motivation. A structured approach is needed as the differential is broad, spanning organic disease, psychological conditions, medications, and lifestyle factors.

Epidemiology

• Prevalence of significant fatigue in the community: 10-20%
• More common in women (1.5:1 ratio)
• Accounts for approximately 5-7% of GP consultations
• An organic cause is identified in about 50% of cases
• Psychological cause identified in 20-30%

Aetiology

• Haematological: iron deficiency anaemia, B12/folate deficiency, haemolytic anaemia
• Endocrine: hypothyroidism, diabetes mellitus, Addison disease, hypercalcaemia
• Infection: post-viral fatigue, EBV, hepatitis, HIV, TB
• Cardiac: heart failure, valvular disease
• Respiratory: COPD, sleep apnoea
• Autoimmune: coeliac disease, SLE, rheumatoid arthritis
• Malignancy: any cancer (fatigue may be presenting symptom)
• Psychological: depression, anxiety, chronic stress
• Lifestyle: sleep deprivation, excessive alcohol, sedentary behaviour, poor nutrition
• Medications: beta-blockers, statins, SSRIs, antihistamines, opioids

Pathophysiology

• Fatigue is a complex symptom with central (brain-mediated) and peripheral (muscular) components
• In anaemia, reduced oxygen-carrying capacity leads to tissue hypoxia
• Hypothyroidism reduces basal metabolic rate
• Depression is associated with altered serotonin, noradrenaline, and dopamine signalling
• CFS/ME pathophysiology is incompletely understood but may involve immune dysregulation, autonomic dysfunction, and altered energy metabolism

History Assessment

• Duration and onset (acute vs chronic)
• Character: physical vs mental vs both
• Impact on daily activities and function
• Sleep quality and quantity (screen for obstructive sleep apnoea)
• Mood assessment (PHQ-9 for depression, GAD-7 for anxiety)
• Menstrual history in women (menorrhagia)
• Weight change, appetite change
• Medications and alcohol/substance use
• Occupational and psychosocial history

Clinical Features Suggesting Specific Diagnoses

• Pallor, tachycardia, koilonychia - anaemia
• Cold intolerance, weight gain, constipation, dry skin - hypothyroidism
• Polyuria, polydipsia, weight loss - diabetes
• Lymphadenopathy, night sweats, weight loss - lymphoma/malignancy
• Joint pain, rash, oral ulcers - SLE/autoimmune
• Bloating, diarrhoea, weight loss - coeliac disease
• Snoring, daytime somnolence, obesity - obstructive sleep apnoea

Red Flags

• Unexplained weight loss (>5% over 3 months)
• Night sweats
• Lymphadenopathy
• New focal neurological signs
• Rectal bleeding or change in bowel habit in patients >50
• Progressive breathlessness
• Suicidal ideation

Bedside

• BMI and weight
• Blood pressure
• Urinalysis (glycosuria, proteinuria)
• PHQ-9 and GAD-7 questionnaires
• Epworth Sleepiness Scale if sleep apnoea suspected

Bloods

• FBC: anaemia (microcytic, macrocytic), lymphocytosis, pancytopenia
• Ferritin: iron deficiency (low ferritin <30 mcg/L is diagnostic; consider <50 mcg/L as cut-off in presence of inflammation)
• U&Es: renal failure, electrolyte disturbance
• TFTs: hypothyroidism
• HbA1c: diabetes mellitus
• LFTs: liver disease
• CRP/ESR: inflammation, infection, malignancy
• Coeliac screen: anti-tTG IgA + total IgA
• Calcium: hypercalcaemia
• B12 and folate: macrocytic anaemia

Imaging

• CXR if respiratory or cardiac cause suspected
• Echocardiogram if heart failure suspected

Special Tests

• Polysomnography/home sleep study if obstructive sleep apnoea suspected
• Short Synacthen test if Addison disease suspected
• HIV test if risk factors present
• CT chest/abdomen/pelvis if malignancy suspected

Non-pharmacological

• Sleep hygiene education
• Graded return to physical activity (unless CFS/ME - energy management approach per NICE NG206)
• Dietary advice: balanced diet, adequate iron and B12 intake
• Alcohol reduction advice
• Psychological support: CBT for fatigue, depression, anxiety
• Address occupational and psychosocial stressors
• Self-management support

Pharmacological

• Treat underlying cause:
  • Iron deficiency: ferrous sulphate 200mg BD-TDS for 3 months after Hb normalises
  • Hypothyroidism: levothyroxine, starting dose 25-50mcg OD (lower in elderly/cardiac disease), titrate to normalise TSH
  • B12 deficiency: hydroxocobalamin 1mg IM on alternate days for 2 weeks, then every 3 months
  • Depression: SSRI (sertraline 50mg OD, increase to 100-200mg) as first-line; consider mirtazapine 15-45mg nocte if insomnia prominent
  • Diabetes: manage per NICE NG28
• CFS/ME: no specific pharmacological treatment recommended; manage symptoms (pain: low-dose amitriptyline 10mg nocte; sleep disturbance: melatonin 2mg MR)

Surgical

• Not generally applicable unless specific surgical cause (e.g. uterine artery embolisation for menorrhagia)

Referral Criteria

• Suspected malignancy: 2-week-wait referral
• Suspected CFS/ME: refer to specialist CFS/ME service if no improvement after 3 months (NICE NG206)
• Suspected sleep apnoea: sleep clinic referral
• Refractory or unexplained fatigue after initial investigation: secondary care review

• Iron deficiency anaemia: Hb normalises within 6-8 weeks of iron supplementation; fatigue often improves within 2-4 weeks
• Hypothyroidism: symptoms improve within 3-6 months of levothyroxine replacement
• Depression: 50-60% respond to first-line SSRI; recurrence rate 50% after single episode
• CFS/ME: 40-60% show some improvement over time; full recovery in 5-10%; 25% remain severely affected
• Post-viral fatigue: most recover within 6-12 months
• In cases with no identified cause, 50-70% report improvement over 1-2 years with supportive management

Recommended Fatigue Screening Bloods

CFS/ME Diagnostic Criteria (NICE NG206)

Key Facts

UTI is one of the most frequently encountered infections in primary care. Most are uncomplicated lower UTIs in women that respond well to empirical antibiotic therapy. Recognition of complicated UTI, upper tract involvement, and appropriate investigation of atypical presentations is essential.

Epidemiology

• Lifetime risk in women: approximately 50%; 27% will have at least one recurrence within 6 months
• Male UTI is less common and should prompt investigation for underlying cause
• Peak incidence in young sexually active women and postmenopausal women
• UTI in pregnancy: 2-10% develop asymptomatic bacteriuria; untreated, 30-40% progress to pyelonephritis

Aetiology

• E. coli: 70-90% of uncomplicated community-acquired UTI
• Staphylococcus saprophyticus: 5-15%, particularly in young women
• Klebsiella, Proteus, Enterococcus: together account for 5-10%
• Proteus mirabilis: more common in men and with urinary catheters; associated with struvite stones
• Risk factors: female sex, sexual activity, pregnancy, menopause (vaginal atrophy), diabetes, urinary catheterisation, urinary tract abnormalities, immunosuppression

Pathophysiology

• Ascending infection: uropathogens colonise the periurethral area, ascend the urethra, and adhere to urothelial cells via fimbriae (type 1 and P fimbriae)
• Shorter female urethra (4 cm vs 20 cm in males) explains higher female prevalence
• Virulence factors of E. coli (adhesins, toxins, siderophores) promote colonisation and invasion
• Complicated UTI involves structural or functional abnormalities impairing urinary flow or host defences

Uncomplicated Lower UTI (Cystitis)

• Dysuria (burning on micturition)
• Frequency and urgency
• Suprapubic pain or discomfort
• Haematuria (visible or non-visible)
• Cloudy or malodorous urine
• No systemic symptoms

Upper UTI (Pyelonephritis)

• Loin/flank pain (unilateral or bilateral)
• Fever ≥38°C, rigors
• Nausea and vomiting
• Costovertebral angle tenderness
• May have lower urinary tract symptoms

UTI in the Elderly

• May present atypically: confusion, falls, functional decline
• Avoid attributing non-specific symptoms to UTI on dipstick alone (asymptomatic bacteriuria is common)

Red Flags

• Signs of sepsis: fever >38°C, tachycardia, hypotension, altered mental state
• Loin pain with systemic symptoms - pyelonephritis
• Visible haematuria in patients >45 years - requires 2-week-wait urology referral to exclude malignancy
• UTI in men - investigate for underlying cause
• Recurrent UTI - consider investigation for structural abnormality
• UTI in pregnancy - risk of pyelonephritis and preterm labour

Bedside

• Urine dipstick: nitrites (high specificity >90%, sensitivity 50-70%), leucocyte esterase (high sensitivity, lower specificity), blood
• Observations: temperature, HR, BP (sepsis screen)
• In women <65 with ≥2 of dysuria, frequency, urgency: treat empirically without dipstick (NICE NG109)

Bloods

• Not required for uncomplicated lower UTI
• FBC, CRP, U&Es, blood cultures if pyelonephritis or sepsis suspected

Microbiology

• MSU for culture and sensitivity: not required for uncomplicated lower UTI in young women
• MSU recommended for: men, pregnant women, children, recurrent UTI, treatment failure, atypical symptoms, catheter-related UTI
• Significant bacteriuria: ≥10⁵ CFU/mL (some labs use ≥10³ for symptomatic patients)

Imaging

• Not required for uncomplicated UTI
• USS renal tract: if recurrent UTI, male UTI, suspected complications (abscess, obstruction)
• CT urogram: if haematuria persisting after UTI treatment or structural abnormality suspected

Special Tests

• Residual urine assessment if voiding dysfunction suspected
• Urodynamics if recurrent UTI with voiding symptoms
• Cystoscopy for recurrent UTI in patients >45 or with risk factors for malignancy

Non-pharmacological

• Adequate fluid intake (aim 2-3 L/day during acute infection)
• Paracetamol or ibuprofen for pain/fever
• Voiding habits: regular voiding, post-coital voiding
• Cranberry products: limited evidence; NICE does not recommend for prevention
• Vaginal oestrogen for postmenopausal women with recurrent UTI (reduces recurrence by 50%)

Pharmacological

Uncomplicated lower UTI in non-pregnant women (NICE NG109):

• First-line: nitrofurantoin 100mg MR BD for 3 days (avoid if eGFR <45 mL/min)
• Second-line: trimethoprim 200mg BD for 3 days (avoid if used in preceding 3 months or local resistance >30%)
• Third-line: pivmecillinam 400mg initial dose then 200mg TDS for 3 days; or fosfomycin 3g single dose

Lower UTI in men:

• Trimethoprim 200mg BD for 7 days or nitrofurantoin 100mg MR BD for 7 days

UTI in pregnancy:

• First-line: nitrofurantoin 100mg MR BD for 7 days (avoid at term - risk of neonatal haemolysis)
• Alternative: amoxicillin 500mg TDS for 7 days (if culture-sensitive); cefalexin 500mg BD for 7 days
• Treat asymptomatic bacteriuria in pregnancy

Acute pyelonephritis (managed in community if mild):

• Cefalexin 500mg BD-TDS for 7-10 days or co-amoxiclav 500/125mg TDS for 7-10 days
• Hospital admission if systemically unwell, unable to take oral medication, pregnant

Recurrent UTI prophylaxis:

• Self-start antibiotic courses for women with ≥3 UTIs/year
• Low-dose prophylaxis: nitrofurantoin 50-100mg nocte or trimethoprim 100mg nocte for 6 months
• Vaginal oestrogen in postmenopausal women
• D-mannose 2g daily (some evidence of benefit)

Surgical

• Not generally applicable unless structural abnormality requiring correction

Referral Criteria

• Male UTI: urology referral for investigation of underlying cause
• Visible haematuria >45 years: 2-week-wait urology referral
• Recurrent UTI not responding to prophylaxis: urology or urogynaecology referral
• Complicated UTI with suspected structural abnormality
• Pyelonephritis in pregnancy: hospital admission

• Uncomplicated UTI: 90-95% resolution with appropriate antibiotics; symptom improvement within 24-48 hours
• Recurrence: 27% recur within 6 months; 44-70% within 1 year
• Pyelonephritis: full recovery in >90% with appropriate treatment; <5% develop complications (perinephric abscess, sepsis)
• UTI in pregnancy: untreated asymptomatic bacteriuria leads to pyelonephritis in 30-40%; associated with preterm birth and low birth weight
• Antimicrobial resistance: trimethoprim resistance in E. coli approximately 30% in UK; nitrofurantoin resistance <5%

NICE NG109 Treatment Summary

Dipstick Interpretation

Key Facts

URTIs encompass the common cold (acute nasopharyngitis), pharyngitis, tonsillitis, acute rhinosinusitis, and acute otitis media. They are overwhelmingly viral and self-limiting, making antimicrobial stewardship a key management principle.

Epidemiology

• Adults average 2-4 URTIs per year; children 6-8 per year
• Peak incidence in autumn and winter months
• Account for approximately 60% of all antibiotic prescriptions in UK primary care
• Group A Streptococcus (GAS) causes only 5-15% of adult pharyngitis

Aetiology

• Viral (>90%): rhinovirus (30-50%), coronavirus (10-15%), influenza A and B, parainfluenza, RSV, adenovirus, EBV
• Bacterial (<10%): Group A Streptococcus (pharyngitis/tonsillitis), Streptococcus pneumoniae, Haemophilus influenzae (sinusitis), Moraxella catarrhalis
• Fungal: rare; consider in immunosuppressed (oropharyngeal candidiasis)

Pathophysiology

• Viral entry through respiratory epithelium via nasal or conjunctival mucosa
• Incubation period typically 1-3 days
• Local inflammatory response with mucosal oedema, increased mucus production, and vascular engorgement
• Cytokine release (IL-1, IL-6, TNF-α, interferons) mediates systemic symptoms
• Bacterial superinfection may complicate viral URTI, particularly rhinosinusitis

Common Cold

• Nasal congestion and rhinorrhoea (initially clear, may become mucopurulent)
• Sore throat (usually mild)
• Sneezing, mild malaise
• Low-grade fever
• Duration: typically 7-10 days

Acute Pharyngitis/Tonsillitis

• Sore throat (predominant symptom)
• Odynophagia (painful swallowing)
• Tonsillar enlargement ± exudate
• Cervical lymphadenopathy
• Fever

Acute Rhinosinusitis

• Nasal congestion and purulent nasal discharge
• Facial pain/pressure (worse on bending forward)
• Reduced sense of smell
• Duration: symptoms >10 days or worsening after initial improvement suggest bacterial component

Red Flags

• Trismus, unilateral swelling, uvular deviation - peritonsillar abscess (quinsy)
• Stridor or drooling - epiglottitis or airway compromise
• Persistent unilateral symptoms >3 weeks - consider nasopharyngeal malignancy
• Systemically unwell (high fever, rigors, inability to swallow) - consider hospital admission
• Recurrent tonsillitis meeting Paradise criteria - ENT referral for tonsillectomy

Bedside

• Observations: temperature, HR, RR, oxygen saturations
• Throat examination with tongue depressor
• Centor score or FeverPAIN score for sore throat

Bloods

• Not routinely required for uncomplicated URTI
• FBC and monospot test if glandular fever suspected
• CRP point-of-care testing may guide antibiotic decisions (NICE NG120)

Microbiology

• Throat swab for culture: not routinely recommended; consider if recurrent tonsillitis, treatment failure, or outbreak setting
• Rapid antigen detection test (RADT) for GAS: not widely used in UK primary care but high specificity

Imaging

• Not required for uncomplicated URTI
• CT sinuses if complicated sinusitis suspected (orbital/intracranial extension)
• Lateral neck X-ray if epiglottitis suspected (thumb sign)

Special Tests

• FeverPAIN/Centor scores to risk-stratify sore throat for antibiotic need
• CRP point-of-care testing (NICE NG120): CRP <20 mg/L supports no antibiotics; CRP 20-100 mg/L supports delayed antibiotics; CRP >100 mg/L supports immediate antibiotics

Non-pharmacological

• Reassurance: explain viral aetiology and expected time course
• Adequate fluid intake and rest
• Honey and lemon in warm water for sore throat (evidence for honey in cough in children >1 year)
• Saline nasal irrigation for rhinosinusitis
• Steam inhalation (limited evidence but widely used)
• Provide safety-netting advice and expected illness duration

Pharmacological

Symptomatic relief:

• Paracetamol 1g QDS or ibuprofen 400mg TDS for pain and fever
• Nasal decongestants: xylometazoline 0.1% spray (max 7 days) for congestion
• Throat lozenges/sprays for local analgesia

Antibiotics for sore throat (NICE NG84):

• No antibiotic: FeverPAIN 0-1 or Centor 0-1
• Delayed antibiotic (back-up prescription): FeverPAIN 2-3 or Centor 2-3
• Immediate antibiotic: FeverPAIN 4-5 or Centor 3-4
• First-line: phenoxymethylpenicillin 500mg QDS for 5-10 days
• Penicillin allergy: clarithromycin 250-500mg BD for 5 days

Antibiotics for acute rhinosinusitis (NICE NG79):

• Most cases do not require antibiotics (symptom duration >10 days or worsening after initial improvement)
• First-line: phenoxymethylpenicillin 500mg QDS for 5 days
• Alternative: doxycycline 200mg on day 1 then 100mg OD for 5 days; or clarithromycin 500mg BD for 5 days

Surgical

• Tonsillectomy: consider if Paradise criteria met (≥7 episodes in 1 year, ≥5/year for 2 years, or ≥3/year for 3 years)
• Incision and drainage for peritonsillar abscess

Referral Criteria

• Peritonsillar abscess: same-day ENT referral
• Epiglottitis: emergency admission
• Recurrent tonsillitis meeting criteria: ENT referral
• Persistent unilateral nasal symptoms: 2-week-wait ENT referral (exclude malignancy)

• Common cold: resolves in 7-10 days; cough may persist for 3-4 weeks
• Bacterial tonsillitis: symptom resolution in 3-4 days with antibiotics; without antibiotics, 85% resolve within 7 days
• Acute rhinosinusitis: 80% resolve within 2-3 weeks without antibiotics
• Complications: peritonsillar abscess in <1% of sore throat cases; post-streptococcal complications (rheumatic fever, glomerulonephritis) very rare in UK
• Antibiotic prescription reduces sore throat duration by approximately 16 hours (NNT 6 to prevent 1 sore throat at day 3)

FeverPAIN Score

Centor Criteria

Key Facts

Gastroenteritis causes acute diarrhoea (≥3 loose stools/day) with or without vomiting. Most community-acquired cases are viral and self-limiting. Assessment of dehydration status and identification of patients requiring investigation or hospital admission are key primary care skills.

Epidemiology

• Estimated 17 million cases of infectious intestinal disease annually in England
• Norovirus: most common cause in adults, responsible for >3 million cases/year in UK
• Campylobacter: most common bacterial cause; incidence 100 per 100,000
• Salmonella: approximately 8,000 cases/year in UK
• Rotavirus cases in children reduced by >80% since vaccine introduction in 2013

Aetiology

• Viral: norovirus (most common in adults), rotavirus (children, now less common with vaccination), adenovirus, astrovirus
• Bacterial: Campylobacter jejuni (most common bacterial), Salmonella spp., Shigella, E. coli (STEC O157), Clostridium difficile, Staphylococcus aureus (toxin-mediated)
• Parasitic: Giardia lamblia, Cryptosporidium, Entamoeba histolytica (travel-related)
• Toxin-mediated: Bacillus cereus (reheated rice), Staphylococcus aureus (rapid onset <6 hours)

Pathophysiology

• Viral: invasion and destruction of enterocytes leading to villous blunting, reduced absorption, and secretory diarrhoea
• Bacterial: varies by organism - invasive (Campylobacter, Salmonella), toxin-mediated (S. aureus, B. cereus), cytotoxic (C. difficile, STEC)
• Toxin-mediated gastroenteritis typically has shorter incubation (<6 hours for preformed toxins)
• Dehydration results from fluid loss through diarrhoea and vomiting exceeding oral intake

Typical Viral Gastroenteritis

• Acute onset watery diarrhoea
• Nausea and vomiting (often prominent with norovirus)
• Abdominal cramps
• Low-grade fever
• Duration: 24-72 hours typically

Bacterial Gastroenteritis

• May present with bloody diarrhoea (Campylobacter, Shigella, STEC)
• Higher fever
• More severe abdominal pain
• Longer duration (5-7 days)
• Campylobacter: bloody diarrhoea with severe cramping, mimics appendicitis

Dehydration Assessment

• Mild: thirst, dry mucous membranes, reduced urine output
• Moderate: tachycardia, reduced skin turgor, sunken eyes
• Severe: hypotension, oliguria/anuria, altered consciousness

Red Flags

• Bloody diarrhoea - invasive bacterial infection, STEC (risk of HUS)
• Severe dehydration or inability to maintain oral intake
• Immunosuppressed patients - higher risk of complicated/prolonged illness
• Symptoms >7 days - consider non-infectious cause or parasitic infection
• Recent antibiotic use - C. difficile
• Recent travel - parasitic or tropical infections
• Outbreak setting - notification to public health required

Bedside

• Observations: HR, BP, temperature, capillary refill
• Assessment of hydration status
• Weight (especially in children)

Bloods

• Not routinely required for mild self-limiting gastroenteritis
• FBC, U&Es, CRP if systemically unwell or dehydrated
• Blood cultures if sepsis suspected

Microbiology

• Stool culture: recommended for bloody diarrhoea, immunocompromised, recent travel, >7 days duration, suspected outbreak, food handlers
• C. difficile toxin: if antibiotic-associated diarrhoea
• Stool ova, cysts, and parasites: if travel history or prolonged symptoms
• Norovirus PCR: in outbreak settings (care homes, hospitals)

Imaging

• Not routinely required
• Abdominal X-ray if concern about toxic megacolon or obstruction

Special Tests

• Faecal calprotectin: to differentiate IBD from functional bowel disease if chronic symptoms
• STEC testing: if bloody diarrhoea (request E. coli O157 culture + PCR for Shiga toxin)
• Giardia antigen test: if persistent diarrhoea with travel history or waterborne outbreak

Non-pharmacological

• Oral rehydration: first-line for all patients; oral rehydration salts (ORS) in moderate dehydration
• Maintain regular small sips of fluid
• Bland diet as tolerated; avoid dairy if significant vomiting
• Handwashing and infection control advice (48-hour rule after last episode for return to work/school)
• Advise food handlers to stay off work until 48 hours symptom-free

Pharmacological

• Loperamide: 4mg initially then 2mg after each loose stool (max 16mg/day) - for symptomatic relief in non-bloody, non-febrile gastroenteritis; avoid in bloody diarrhoea and suspected STEC
• Oral rehydration salts (Dioralyte): for moderate dehydration
• IV fluids (0.9% saline): if unable to maintain oral intake or severe dehydration

Antibiotics (only for specific indications):

• Campylobacter (if severe or immunocompromised): clarithromycin 250-500mg BD for 5 days or ciprofloxacin 500mg BD for 3 days
• Shigella (moderate-severe): ciprofloxacin 500mg BD for 3 days or azithromycin 500mg OD for 3 days
• Salmonella (only if invasive/bacteraemia or immunocompromised): ciprofloxacin 500mg BD for 5-7 days
• C. difficile: stop causative antibiotic; oral vancomycin 125mg QDS for 10 days (first-line per PHE guidance) or fidaxomicin 200mg BD for 10 days
• Giardia: metronidazole 400mg TDS for 5 days

Surgical

• Not applicable unless surgical complication (e.g. toxic megacolon, perforation)

Referral Criteria

• Severe dehydration or inability to maintain oral intake: hospital admission
• Suspected HUS (STEC, bloody diarrhoea, thrombocytopenia, renal failure): emergency referral
• Immunocompromised with severe infection: hospital admission
• Outbreak: notification to local Public Health team (notifiable disease)

• Viral gastroenteritis: self-limiting in >95% within 48-72 hours
• Campylobacter: resolution within 5-7 days in most; post-infectious IBS in 10-15%; Guillain-Barré syndrome risk 1 in 1,000
• Salmonella: carrier state in 1-5% after acute infection
• STEC O157: HUS develops in 5-15% of infected children; mortality of HUS 3-5%
• C. difficile: recurrence rate 20-30% after first episode; 40-60% after multiple recurrences
• Dehydration-related mortality: very low in UK with access to healthcare; higher risk in extremes of age

Common Causes by Incubation Period

When to Send Stool Samples

Key Facts

Iron deficiency anaemia results from insufficient iron to support normal erythropoiesis. In primary care, the emphasis is on identifying the underlying cause, as IDA in men and postmenopausal women may be the presenting feature of gastrointestinal malignancy.

Epidemiology

• Prevalence of IDA: 2-5% in adult men and postmenopausal women; 10-20% in premenopausal women
• Iron deficiency without anaemia is even more common (up to 30% of premenopausal women)
• Most common cause of anaemia in UK primary care
• GI malignancy is found in approximately 6-13% of patients with unexplained IDA

Aetiology

• Blood loss: menorrhagia (commonest in premenopausal women), GI blood loss (peptic ulcer, colorectal cancer, gastric cancer, angiodysplasia, NSAIDs, oesophagitis)
• Malabsorption: coeliac disease, inflammatory bowel disease, gastrectomy/bariatric surgery, H. pylori infection
• Increased demand: pregnancy, growth (children/adolescents)
• Dietary insufficiency: vegan/vegetarian diet (rare as sole cause in developed countries)

Pathophysiology

• Iron is absorbed in the duodenum and proximal jejunum, regulated by hepcidin
• Iron is transported bound to transferrin and stored as ferritin
• Depletion of iron stores leads to iron-deficient erythropoiesis and eventually microcytic hypochromic anaemia

Common Symptoms

• Fatigue and lethargy (most common)
• Shortness of breath on exertion
• Palpitations
• Pallor
• Headache and dizziness

Specific Signs of Iron Deficiency

• Koilonychia (spoon-shaped nails)
• Angular cheilitis (stomatitis)
• Glossitis (smooth, red tongue)
• Pica (craving non-food substances, e.g. ice)
• Restless leg syndrome
• Brittle hair

Symptoms Suggesting Underlying Cause

• Change in bowel habit, rectal bleeding - GI malignancy
• Heavy menstrual bleeding - menorrhagia
• Weight loss, bloating, diarrhoea - coeliac disease or GI malignancy
• Dyspepsia, epigastric pain - peptic ulcer

Red Flags

• IDA in men or postmenopausal women - exclude GI malignancy
• Weight loss
• Rectal bleeding or change in bowel habit
• Abdominal mass
• Dysphagia (consider Plummer-Vinson syndrome)
• Severe anaemia (Hb <70 g/L or symptomatic)

Bedside

• Full history including diet, medications (NSAIDs, anticoagulants), menstrual history, GI symptoms
• Examination: pallor, koilonychia, glossitis, abdominal mass, rectal examination

Bloods

• FBC: low Hb, low MCV (<80 fL), low MCH
• Ferritin: <30 mcg/L diagnostic of iron deficiency (consider <50 mcg/L if concurrent inflammation)
• Iron studies: low serum iron, low transferrin saturation (<16%), raised TIBC
• Blood film: microcytic hypochromic red cells, pencil cells, target cells
• Reticulocyte count: low or inappropriately normal
• CRP/ESR: to assess for concurrent inflammation (ferritin is acute phase reactant)
• Coeliac screen: anti-tTG IgA + total IgA (NICE NG20)
• U&Es, LFTs: baseline
• H. pylori testing: consider if dyspeptic symptoms

Imaging/Endoscopy

• Men and postmenopausal women with IDA: OGD + colonoscopy (BSG guidelines)
• CT colonography: alternative if colonoscopy declined or inappropriate
• Premenopausal women: GI investigation if GI symptoms, family history of GI cancer, failed response to iron, or age ≥50

Special Tests

• Faecal immunochemical test (FIT): may be used as part of initial assessment in primary care
• Bone marrow biopsy: rarely needed; gold standard for iron stores assessment

Non-pharmacological

• Dietary advice: red meat, green leafy vegetables, fortified cereals, dried fruit
• Vitamin C enhances iron absorption (take iron with orange juice)
• Avoid tea, coffee, calcium supplements at time of iron ingestion (inhibit absorption)
• Treat underlying cause (e.g. manage menorrhagia, treat H. pylori, gluten-free diet for coeliac)

Pharmacological

• First-line: ferrous sulphate 200mg BD-TDS (contains 65mg elemental iron per tablet)
• Alternative: ferrous fumarate 210mg BD-TDS (68mg elemental iron per tablet)
• Duration: continue for 3 months after Hb normalises to replenish iron stores
• Check Hb after 2-4 weeks: expect rise of approximately 20 g/L over 3-4 weeks
• If intolerant: try alternate day dosing, switch preparation (ferrous gluconate 300mg BD), or liquid formulations
• IV iron (ferric carboxymaltose [Ferinject] 1000mg single infusion, or iron sucrose): if oral iron not tolerated, malabsorption, ongoing blood loss, or rapid correction needed
• Blood transfusion: reserved for acute symptomatic anaemia or Hb <70 g/L with haemodynamic compromise

Surgical

• Treat underlying surgical cause (e.g. colorectal cancer resection, endoscopic treatment of angiodysplasia)

Referral Criteria

• Men and postmenopausal women with IDA: 2-week-wait referral if age ≥60 or suspected GI malignancy (NICE NG12)
• GI referral for OGD and colonoscopy in all men and postmenopausal women with IDA
• Haematology referral if no cause found after GI investigation, refractory to treatment, or suspected haematological malignancy
• Gynaecology referral for menorrhagia not responding to medical management

• Hb typically normalises within 6-8 weeks of adequate oral iron supplementation
• Ferritin normalises after 3-6 months of continued treatment
• Response failure (no Hb rise after 2-4 weeks): reassess compliance, consider malabsorption or ongoing blood loss
• GI malignancy found in 6-13% of men/postmenopausal women investigated for IDA
• With treatment of underlying cause, prognosis for IDA itself is excellent
• Untreated IDA in pregnancy associated with preterm birth and low birth weight

BSG Guidelines for Investigation of IDA

Iron Preparation Comparison

Key Facts

Hypothyroidism results from insufficient thyroid hormone production. It is one of the most common chronic conditions managed in primary care. Primary hypothyroidism (thyroid gland failure) accounts for >95% of cases.

Epidemiology

• Prevalence: 2-5% of the UK adult population
• More common in women (10:1 ratio) and increases with age
• Subclinical hypothyroidism: prevalence 5-10%, particularly in elderly women
• Hashimoto thyroiditis prevalence: approximately 2% of women

Aetiology

• Autoimmune (Hashimoto thyroiditis): most common cause in UK; associated with anti-TPO antibodies in >90%
• Iatrogenic: post-thyroidectomy, post-radioiodine therapy, post-external radiotherapy to neck
• Drugs: amiodarone (can cause hypo- or hyperthyroidism), lithium, carbimazole, interferon-alpha, immune checkpoint inhibitors
• Iodine deficiency: most common cause worldwide (uncommon in UK)
• Secondary (central): pituitary failure (low TSH, low fT4) - rare
• Congenital hypothyroidism: detected by newborn screening (Guthrie test)

Pathophysiology

• In Hashimoto thyroiditis, autoimmune destruction of thyroid follicular cells by anti-TPO and anti-thyroglobulin antibodies leads to progressive thyroid failure
• Reduced T4 and T3 production causes loss of negative feedback on the hypothalamus and pituitary, resulting in elevated TSH
• Thyroid hormones regulate metabolic rate, thermogenesis, growth, and development
• Deficiency leads to widespread metabolic slowing affecting cardiovascular, neurological, GI, and musculoskeletal systems

Common Symptoms

• Fatigue and lethargy
• Weight gain (modest, typically 2-5 kg)
• Cold intolerance
• Constipation
• Dry skin and hair
• Hair loss (diffuse)
• Menorrhagia or oligomenorrhoea
• Depression and cognitive slowing
• Myalgia and arthralgia
• Hoarse voice

Clinical Signs

• Bradycardia
• Non-pitting oedema (myxoedema)
• Goitre (in Hashimoto thyroiditis)
• Delayed relaxation of deep tendon reflexes
• Periorbital oedema
• Dry, coarse skin
• Carpal tunnel syndrome

Red Flags

• Myxoedema coma: hypothermia, altered consciousness, bradycardia, hypotension - medical emergency
• Severe untreated hypothyroidism in pregnancy - risk of neurodevelopmental impairment in offspring
• Rapidly enlarging goitre or compressive symptoms - exclude thyroid lymphoma (especially in Hashimoto) or anaplastic carcinoma
• Pituitary symptoms (headache, visual field defects) - consider secondary hypothyroidism

Bedside

• Weight, BMI
• Heart rate and blood pressure
• Thyroid examination (goitre, nodules)
• Deep tendon reflexes (delayed relaxation phase)

Bloods

• TSH: primary screening test; elevated in primary hypothyroidism
• Free T4: low in overt hypothyroidism; normal in subclinical
• Anti-TPO antibodies: positive in Hashimoto thyroiditis (>90%); helps confirm autoimmune aetiology and predicts progression of subclinical hypothyroidism
• FBC: macrocytic anaemia may be present
• Lipid profile: hypercholesterolaemia common in hypothyroidism
• U&Es: hyponatraemia may occur
• Cortisol/Short Synacthen test: if secondary hypothyroidism suspected (must exclude adrenal insufficiency before starting levothyroxine)

Imaging

• Thyroid ultrasound: if nodule detected on examination or asymmetric goitre
• Not routinely required for diagnosis of hypothyroidism

Special Tests

• Fine needle aspiration: if suspicious thyroid nodule on USS
• Pituitary function tests and MRI pituitary: if secondary hypothyroidism suspected (low/normal TSH with low fT4)

Non-pharmacological

• Patient education about lifelong nature of treatment
• Take levothyroxine consistently, preferably 30-60 minutes before breakfast on empty stomach
• Awareness of symptoms of over- and under-replacement
• Inform about drug interactions affecting absorption

Pharmacological

• Levothyroxine (T4): treatment of choice
  • Standard starting dose: 50-100mcg OD in young, fit adults
  • Lower starting dose: 25mcg OD in elderly, cardiac disease, or severe/prolonged hypothyroidism
  • Titrate by 25mcg increments every 6-8 weeks based on TSH
  • Target: TSH within reference range (0.4-4.0 mU/L); some patients feel best at lower end
  • Average maintenance dose: 100-150mcg OD (approximately 1.6mcg/kg/day)
• Pregnancy: levothyroxine dose usually needs to increase by 25-50% from first trimester; aim TSH <2.5 mU/L in first trimester
• Myxoedema coma: IV liothyronine (T3) 5-20mcg + IV hydrocortisone 100mg (before levothyroxine, to cover possible coexistent adrenal insufficiency)
• Subclinical hypothyroidism:
  • TSH >10 mU/L: treat with levothyroxine
  • TSH 4-10 mU/L: consider treatment if symptomatic, positive anti-TPO antibodies, or planning pregnancy; otherwise monitor 6-monthly
• Drug interactions: iron, calcium, PPI (separate by ≥4 hours); oestrogen (may increase levothyroxine requirement); carbamazepine, phenytoin (increase clearance)

Surgical

• Thyroidectomy: not for hypothyroidism itself; may be needed for compressive goitre or concurrent thyroid malignancy

Referral Criteria

• Suspected secondary hypothyroidism (low/normal TSH, low fT4): endocrinology referral
• Hypothyroidism in pregnancy: shared care with endocrinology
• Persistent symptoms despite optimised TSH: endocrinology review to consider T3/T4 combination therapy
• Thyroid nodule with suspicious features: 2-week-wait referral
• Children with hypothyroidism: paediatric endocrinology

• With appropriate levothyroxine replacement, life expectancy is normal
• Symptoms typically improve within 3-6 months of treatment initiation
• Subclinical hypothyroidism progresses to overt hypothyroidism at 2-5% per year (higher if anti-TPO positive)
• Myxoedema coma mortality: 30-60% even with treatment
• Cardiovascular risk: untreated hypothyroidism associated with hypercholesterolaemia, accelerated atherosclerosis, and heart failure
• Hashimoto thyroiditis carries a small increased risk of thyroid lymphoma (rare)

Levothyroxine Dose Adjustment Guide

Causes of Persistently Elevated TSH on Levothyroxine

Key Facts

AF is characterised by rapid, irregular atrial activation replacing normal sinus rhythm. It is a major modifiable risk factor for ischaemic stroke. Primary care is central to detection, risk stratification, anticoagulation, and rate/rhythm control.

Epidemiology

• Prevalence: 2% of UK population (approximately 1.4 million people)
• Prevalence rises steeply with age: 0.5% at age 50-59; >10% at age >75
• Lifetime risk of developing AF: 25% for those aged ≥40
• AF-related strokes tend to be more severe and carry higher mortality

Aetiology

• Cardiovascular: hypertension (most common), valvular heart disease (especially mitral), heart failure, coronary artery disease, cardiomyopathy
• Non-cardiovascular: hyperthyroidism, acute infection/sepsis, alcohol excess ('holiday heart'), PE, post-cardiac surgery, obesity, OSA
• Lone AF: no identifiable cause, typically younger patients (<60 years)

Pathophysiology

• Multiple re-entrant circuits and/or rapid focal ectopic firing (commonly from pulmonary veins) cause chaotic atrial depolarisation at 350-600 bpm
• Loss of coordinated atrial contraction leads to irregular ventricular response and loss of atrial 'kick' (15-25% of cardiac output)
• Atrial stasis predisposes to thrombus formation, particularly in the left atrial appendage
• Electrical and structural remodelling ('AF begets AF') promotes persistence

Symptoms

• Palpitations (irregular, rapid heartbeat)
• Breathlessness on exertion
• Fatigue and reduced exercise tolerance
• Dizziness or light-headedness
• Chest tightness
• Many patients are asymptomatic (detected incidentally)

Classification

• Paroxysmal: self-terminating within 7 days (usually <48 hours)
• Persistent: sustained >7 days; requires cardioversion
• Long-standing persistent: continuous >12 months
• Permanent: accepted by patient and clinician; rhythm control not pursued

Presentation as Complication

• Ischaemic stroke or TIA (first presentation in some cases)
• Acute heart failure (fast AF with decompensation)
• Systemic embolisation

Red Flags

• Haemodynamic instability (hypotension, syncope) - emergency DC cardioversion
• Acute stroke symptoms - thrombolysis/thrombectomy pathway
• Very fast ventricular rate (>150 bpm) with chest pain - consider WPW or urgent rate control
• Signs of heart failure - urgent assessment and treatment
• New AF with thyrotoxicosis - treat thyroid disease

Bedside

• Pulse palpation: irregularly irregular rhythm
• 12-lead ECG: absent P waves, irregular R-R intervals, narrow QRS complex (unless bundle branch block)
• Blood pressure
• Heart rate

Bloods

• TFTs: exclude hyperthyroidism (mandatory in new AF)
• FBC: exclude anaemia
• U&Es: baseline renal function for DOAC dosing
• LFTs: baseline for anticoagulation
• Coagulation screen: baseline
• BNP/NT-proBNP: if heart failure suspected

Imaging

• Echocardiogram: assess LV function, valvular disease, left atrial size - recommended for all patients with AF (NICE NG196)
• CXR: if heart failure suspected

Special Tests

• 24-hour or 7-day Holter monitor: if paroxysmal AF suspected but not captured on ECG
• Event recorder or implantable loop recorder: for infrequent episodes
• CHA₂DS₂-VASc score: stroke risk assessment
• HAS-BLED score: bleeding risk assessment (does not contraindicate anticoagulation but identifies modifiable risk factors)
• Ambulatory ECG: assess rate control adequacy

Non-pharmacological

• Lifestyle modification: weight loss (LEGACY trial showed AF burden reduction with 10% weight loss), alcohol reduction, treat OSA, exercise
• Patient education about AF, stroke risk, and anticoagulation
• Pulse self-monitoring

Pharmacological

Stroke prevention (NICE NG196):

• Assess stroke risk with CHA₂DS₂-VASc:
  • Score 0 (men) or 1 (women): no anticoagulation
  • Score 1 (men): consider anticoagulation
  • Score ≥2 (men) or ≥3 (women): offer anticoagulation
• First-line: DOAC - apixaban 5mg BD (reduced to 2.5mg BD if ≥2 of: age ≥80, weight ≤60kg, creatinine ≥133 μmol/L) or rivaroxaban 20mg OD with food (15mg if CrCl 15-49 mL/min) or edoxaban 60mg OD (30mg if CrCl 15-50 mL/min, weight ≤60kg, or certain P-gp inhibitors) or dabigatran 150mg BD (110mg BD if age ≥80 or on verapamil)
• Warfarin: if DOAC contraindicated (mechanical heart valve, moderate-severe mitral stenosis); target INR 2.0-3.0
• Do NOT offer aspirin as sole stroke prevention in AF

Rate control (first-line for most patients, NICE NG196):

• Bisoprolol 2.5-10mg OD (or other beta-blocker)
• Diltiazem 120-360mg daily (non-dihydropyridine CCB; avoid with beta-blocker)
• Digoxin: add if monotherapy inadequate or in sedentary patients; loading dose 500mcg then 125-250mcg OD
• Target resting heart rate <110 bpm (lenient) initially; <80 bpm (strict) if persistent symptoms

Rhythm control (consider if symptomatic despite rate control, young, first episode, or patient preference):

• Flecainide 100-150mg BD (only if no structural heart disease; 'pill-in-the-pocket' for paroxysmal AF)
• Amiodarone 200mg TDS for 1 week, 200mg BD for 1 week, then 200mg OD maintenance (significant side effects: thyroid, pulmonary fibrosis, liver, photosensitivity)
• DC cardioversion: for persistent AF; pre-anticoagulate for ≥3 weeks or exclude LAA thrombus with TOE

Catheter ablation:

• Pulmonary vein isolation for symptomatic paroxysmal or persistent AF refractory to ≥1 antiarrhythmic drug (NICE NG196)
• CASTLE-AF trial: improved outcomes in AF with heart failure

Surgical

• Left atrial appendage occlusion (Watchman device): if anticoagulation contraindicated
• Maze procedure: during concomitant cardiac surgery

Referral Criteria

• Haemodynamically unstable AF: emergency admission
• Suspected underlying structural heart disease: cardiology referral + echo
• Considering rhythm control strategy: cardiology
• AF in WPW (delta wave on ECG): urgent cardiology (avoid AV nodal blocking agents)
• Young patients (<50) with lone AF: cardiology
• Anticoagulation in challenging cases (renal impairment, bleeding history): haematology/cardiology

• AF increases stroke risk 5-fold; anticoagulation reduces this by 60-70% (DOACs) or 65% (warfarin)
• Heart failure develops in approximately 20-30% of AF patients over time
• Mortality: AF associated with 1.5-2 fold increased all-cause mortality
• Catheter ablation: freedom from AF at 1 year in 60-80% (paroxysmal) and 50-60% (persistent); may require repeat procedures
• Anticoagulation-related major bleeding: approximately 2-3% per year with DOACs (lower intracranial haemorrhage rate compared to warfarin)
• Rate control achieves adequate symptom control in >80% of patients

CHA₂DS₂-VASc Score

Landmark DOAC Trials in AF

Key Facts

Heart failure occurs when the heart cannot pump sufficient blood to meet metabolic demands or can only do so at elevated filling pressures. It is classified by ejection fraction into HFrEF, HFmrEF, and HFpEF. Management is guided by ejection fraction and NYHA class.

Epidemiology

• Prevalence: 1-2% of UK adults; 900,000+ people affected
• Incidence increases with age; mean age at diagnosis 75 years
• Accounts for approximately 5% of all emergency hospital admissions
• 1-year mortality after first hospitalisation: 25-30%

Aetiology

• Coronary artery disease: most common cause in UK (60-70% of HFrEF)
• Hypertension: major contributor, particularly to HFpEF
• Valvular heart disease: aortic stenosis, mitral regurgitation
• Cardiomyopathy: dilated (idiopathic, alcohol, familial), hypertrophic, restrictive, peripartum
• Arrhythmia: tachycardia-induced cardiomyopathy, AF
• Other: congenital heart disease, myocarditis, infiltrative disease (amyloidosis, sarcoidosis)

Pathophysiology

• Reduced cardiac output triggers neurohormonal activation: RAAS activation, sympathetic nervous system activation, ADH secretion
• These compensatory mechanisms initially maintain perfusion but cause progressive fluid retention, vasoconstriction, and myocardial remodelling
• Chronic volume and pressure overload leads to progressive ventricular dilatation and fibrosis
• Evidence-based therapies (ACEi, beta-blockers, MRA, SGLT2i) counteract these maladaptive neurohormonal responses

Left Heart Failure

• Breathlessness on exertion (most common symptom)
• Orthopnoea (breathlessness lying flat)
• Paroxysmal nocturnal dyspnoea (PND)
• Fatigue
• Bibasal crepitations on auscultation
• Third heart sound (S3 gallop)
• Tachycardia

Right Heart Failure

• Peripheral oedema (ankle swelling)
• Raised JVP
• Hepatomegaly and hepatojugular reflux
• Ascites (in severe cases)

NYHA Classification

• Class I: no limitation of physical activity
• Class II: slight limitation; comfortable at rest, symptoms with ordinary activity
• Class III: marked limitation; comfortable only at rest
• Class IV: symptoms at rest; unable to carry out any physical activity

Red Flags

• Acute pulmonary oedema: severe dyspnoea at rest, pink frothy sputum, hypoxia
• Cardiogenic shock: hypotension, cold peripheries, oliguria
• New-onset AF with rapid ventricular rate and decompensation
• Syncope in heart failure (consider arrhythmia, may need ICD assessment)

Bedside

• Observations: HR, BP, RR, SpO2, weight
• JVP assessment, auscultation (S3, murmurs, crepitations)
• Peripheral oedema assessment
• ECG: may show LVH, AF, Q waves, bundle branch block (normal ECG makes HFrEF unlikely)

Bloods

• NT-proBNP (or BNP): first-line diagnostic test in primary care
  • NT-proBNP <400 pg/mL: HF unlikely
  • NT-proBNP 400-2000 pg/mL: refer for echocardiogram within 6 weeks
  • NT-proBNP >2000 pg/mL: urgent referral within 2 weeks
• FBC: exclude anaemia
• U&Es: baseline renal function, electrolytes (before ACEi/MRA)
• LFTs: hepatic congestion
• TFTs: exclude thyroid disease
• HbA1c: diabetes screening
• Lipid profile

Imaging

• Echocardiogram: confirms diagnosis, classifies by EF, identifies structural abnormality
• CXR: cardiomegaly, pulmonary oedema, pleural effusions
• Cardiac MRI: gold standard for EF assessment; useful for cardiomyopathy, myocarditis, infiltrative disease

Special Tests

• Coronary angiography: if ischaemic aetiology suspected
• Iron studies: iron deficiency (ferritin <100 or ferritin 100-300 with transferrin saturation <20%) should prompt IV iron

Non-pharmacological

• Fluid restriction (1.5-2L/day in severe HF)
• Daily weight monitoring
• Low-sodium diet
• Cardiac rehabilitation and exercise programme
• Smoking cessation and alcohol moderation
• Annual influenza and pneumococcal vaccination
• Self-management plan with action plan for deterioration

Pharmacological (HFrEF - the 'four pillars')

1. ACE inhibitor:

• Ramipril: start 1.25mg OD, titrate to 10mg OD
• Enalapril: start 2.5mg BD, titrate to 20mg BD
• If intolerant (cough): switch to ARB (candesartan 4-32mg OD or valsartan 40-160mg BD)

2. Beta-blocker:

• Bisoprolol: start 1.25mg OD, titrate to 10mg OD
• Carvedilol: start 3.125mg BD, titrate to 25-50mg BD
• Nebivolol: start 1.25mg OD, titrate to 10mg OD (if age ≥70)

3. Mineralocorticoid receptor antagonist (MRA):

• Spironolactone 25-50mg OD (RALES trial: 30% mortality reduction)
• Eplerenone 25-50mg OD (EMPHASIS-HF trial; less gynaecomastia)

4. SGLT2 inhibitor:

• Dapagliflozin 10mg OD (DAPA-HF trial: 26% reduction in CV death/HF hospitalisation)
• Empagliflozin 10mg OD (EMPEROR-Reduced trial)
• Recommended regardless of diabetes status

Additional therapies:

• Sacubitril/valsartan (Entresto): start 24/26mg BD, titrate to 97/103mg BD - replaces ACEi/ARB if symptomatic despite optimal therapy (PARADIGM-HF: 20% mortality reduction vs enalapril)
• Ivabradine: 2.5-7.5mg BD if sinus rhythm HR ≥75 bpm despite maximally tolerated beta-blocker (SHIFT trial)
• Loop diuretics: furosemide 20-80mg OD for fluid overload (symptomatic, not mortality benefit)
• IV iron (ferric carboxymaltose): if ferritin <100 or ferritin 100-300 + TSAT <20% (IRONMAN, AFFIRM-AHF trials)
• Digoxin: for persistent symptoms or AF rate control
• Hydralazine + isosorbide dinitrate: if ACEi/ARB/ARNI not tolerated (A-HeFT trial; particularly beneficial in Black patients)

Devices

• ICD (implantable cardioverter-defibrillator): primary prevention if EF ≤35% despite ≥3 months optimal therapy (NYHA I-III)
• CRT (cardiac resynchronisation therapy): if EF ≤35%, QRS ≥150ms (LBBB), NYHA II-IV

Surgical

• Coronary revascularisation if ischaemic aetiology
• Valve repair/replacement for significant valvular disease
• Heart transplant: refractory HF in selected patients
• LVAD: bridge to transplant or destination therapy

Referral Criteria

• All patients with suspected HF: cardiology/HF specialist assessment after NT-proBNP
• Acute decompensation: hospital admission
• Consider palliative care referral for NYHA IV refractory symptoms

• 5-year mortality: approximately 50% for all-cause heart failure
• 1-year mortality: 25-30% after first HF hospitalisation
• HFrEF with optimal quadruple therapy: estimated survival benefit of 6-8 additional years compared to no treatment
• NYHA class IV: 1-year mortality >50%
• Each HF hospitalisation associated with progressive decline and increased subsequent mortality
• Heart transplant: 1-year survival 85-90%; 5-year survival 70-75%

Heart Failure Classification by Ejection Fraction

Landmark Heart Failure Trials

Key Facts

CKD is a long-term condition characterised by progressive loss of kidney function. Most patients with CKD G1-G3 are asymptomatic and managed in primary care. The primary goals are cardiovascular risk reduction and slowing progression to end-stage kidney disease.

Epidemiology

• Prevalence: approximately 13% of UK adults (many undiagnosed)
• CKD G3-G5 prevalence: 5-7%
• More common with increasing age: >30% of adults aged >75 have eGFR <60
• CKD is more common in people of Black African and South Asian ethnicity

Aetiology

• Diabetic nephropathy: most common cause in developed countries (25-30%)
• Hypertensive nephrosclerosis: 15-25%
• Glomerulonephritis: 10-15%
• Polycystic kidney disease: 5-10% (most common inherited cause)
• Obstructive uropathy: particularly in older men (BPH)
• Other: renovascular disease, reflux nephropathy, interstitial nephritis (NSAIDs, lithium)

Pathophysiology

• Regardless of initial insult, progressive nephron loss leads to glomerular hyperfiltration in remaining nephrons
• Hyperfiltration activates RAAS, promoting further glomerular injury, proteinuria, and fibrosis
• Proteinuria itself is toxic to tubular cells, driving progressive tubulointerstitial fibrosis
• Reduced kidney function leads to impaired electrolyte handling, acid-base disturbance, reduced EPO production (anaemia), and disordered mineral metabolism (CKD-MBD)

Early CKD (G1-G3a)

• Usually asymptomatic
• Detected on routine blood tests or screening in at-risk groups
• May have non-specific fatigue

Moderate CKD (G3b-G4)

• Fatigue, malaise
• Nocturia, polyuria
• Mild oedema
• Pruritus
• Restless legs

Advanced CKD (G5)

• Severe fatigue, lethargy
• Nausea, vomiting, anorexia
• Peripheral oedema
• Uraemic symptoms: pericarditis, encephalopathy, seizures
• Metabolic bone disease: bone pain, fractures
• Anaemia: pallor, breathlessness