NICE summaries

The fact that the National Institute of Clinical Excellence has its own official biscuits does not bode well for the quality of its recommendations on obesity...

The purpose of this page is to allow you to quickly brush up on the relevant NICE guidance, (and sometimes other national guidelines) in common areas, split up by common topics body system/pathologies. Try to memorise them all in one sitting (really - don't do this)...

Cancer is a huge topic, affecting every organ system, so I've dropped the guidance into each sub section...

Cardiovascular

AF

Atrial fibrillation is very common. If they are haemodynamically stable, then you want to do an ECG to confirm. Once confirmed, consider starting anticoagulation, and think about Rate/Rhythm control.

Anticoagulation

Do a CHA₂DS₂Vasc. Try the free online tool, or calculate yourself:

CHA2DS2Vasc	Score
CCF	1 point
Hypertension	1 point
Age (more than 65)	1 point
(or if more than 75)	2 points
Diabetes	1 point
Stroke	2 points
Vascular Disease	1 point

The proper tool has a point for gender too, but that needlessly confuses things with the guidance. Ignore gender, and anyone that scores 2 or more needs to be considered for anticoagulation.

You then do a HASBLED score, which tells you their risk of bleeding. Score 3 or more, and it becomes less sensible to start warfarin.

HASBLED	Score
Hypertension (uncontrolled >160 syst)	1
Age (65+)	1
Stroke	1
Kidney issues	1
Knackered liver	1
Unstable INR	1
Alcohol use	1

You then start them on Warfarin. You can definitely also consider a NOAC, they appear to be pretty equally good.

Rhythm Control

If fits the criteria below, then refer for cardioversion. (Will need warfarinisation before cardioversion for at least 4 weeks.)

• New onset AF
• AF with reversible cause
• Heart failure suspected to be caused by AF

Rate Control

Most people - your standard 70 year old with an incidental finding of AF on examination - will need rate control. You want to:

1. Keep pulse under 100.
2. Start with bisoprolol.
3. Consider adding in diltiazem or digoxin if not working.
4. Still struggling? Refer.

Chest Pain

Medical Emergency - Likely acute coronary syndrome with active chest pain will need sending to hospital by ambulance.

You need to give them:

• GTN
• Aspirin 300mg
• Do an ECG
• Measure O₂ saturation, consider giving oxygen.

If they have no pain currently, but have had within the last 72 hours, will likely still need to go to hospital for ECG and Troponin.

Stable chest pain

Assess them, looking for cardiac risk factors, especially diabetes, smoking and hyperlipidaemia.

For most of them, you will want to do further tests to identify likelihood of angina. This will often be an exercise ECG, myocardial perfusion scan or similar. Either way, best access route is usually rapid access chest pain clinic.

Managing angina

Once you've confirmed angina, manage it with:

• GTN spray
• Lifestyle interventions
• Beta blocker (or calcium channel blocker)
• Aspirin 75mg
• Statin - atorvastatin 80mg.
• ACE inhibitor if they have diabetes

Familial hypercholesterolaemia

Inherited as an autosomal dominant condition. Anyone with cholesterol over 7.5 or LDL more than 4.9 needs to be considered for this.

• Be alert for tendon xanthomas in the family.
• MI in 1st degree relative under 60
• MI in 2nd degree relative under 50

Management

Pretty simple. They will likely need:

• DNA testing
• Lifelong statins.
• Aggressive lifestyle modification.

Heart Failure

Heart failure diagnosis is pretty easy. Suspect heart failure?

• If they've had a previous MI, just refer them for an urgent echo and specialist review.
• Otherwise, measure a BNP or NTproBNP.
  • If BNP is under 100 (or 400 for NTproBNP), chill out, unlikely to be heart failure.
  • 100-400 (400-2000 NTproBNP), refer for routine assessment.
  • 400+ (2000+ NTproBNP), needs an urgent review like with MI.

Make sure you do an ECG too!

Management of CCF

• Lifestyle management, as ever.
• ACE inhibitor and beta blocker for everyone.
• Diuretics for symptoms.
• Only give aspirin if known CHD - see recommendations in chest pain section.

HGV drivers are disqualified from driving if symptomatic!

Hypertension

Measure their blood pressure (obviously). You will get one of three findings:

1. BP is less than 140/90. Normotensive woohoo! Recheck BP at least every 5 years.
2. BP more than 140/90:
   1. Offer ambulatory BP monitoring (or home BP monitoring if unable to do ABPM)
      1. If ABPM its less than 135/85, they are normotensive
      2. More than 135/85, you need to check their 10 year CVD risk. If above 20%, start treatment. Otherwise, just nag them about lifestyle.
      3. More than 150/95, no need to worry about 10 year CVD risk, just start treatment.
   2. Look for end organ damage with an ACR, urine dip, bloods, ECG and fundoscopy.
3. BP more than 180/110, start treatment straight away, don't bother with ABPM.

Anti-hypertensives

Commence antihypertensives in following order, stepping up if condition not controlled:

1. Look at their age:
   1. Age less than 55? Start an ACE Inhibitor
   2. Age more than 55, or patient is black? Start a Calcium channel blocker.
2. ACE + CCB
3. ACE + CCB + indapamide 2.5mg OM
4. ACE + CCB + indapamide + one of below + consider referral
   1. if K+ less than 4.5, spironolactone
   2. if K+ more than 4.5, increase indapamide
   3. alpha blocker
   4. beta blocker

Peripheral artery disease

In anyone with symptoms of peripheral artery disease, especially intermittent claudication...

• Examine for pale, hairless legs
• Check pedal pulse
• Measure ankle branchial pressure index (ABPI)
  • ABPI less than 0.9 makes PAD likely
  • ABPI less than 0.5 points to critical ischaemia

Management

Start them on clopidogrel 75mg OD, atorvastatin 80mg and refer to vascular!

Statins

Primary prevention with statins is based pretty heavily on the QRISK2 tool (try it here). Start atorvastatin 20mg in anyone with one of these:

• Over 85
• Who scores more than QRISK 10%
• Chronic kidney disease
• Type 1 Diabetes? If over 40, or had diabetes more than 10 years then start the pills!

In anyone with CVD, you'll want to start atorvastatin 80mg.

Monitoring

Before starting, check:

• Lipids (don't need to be fasting)
• HbA1c
• Kidney function
• LFTs
• TSH
• 
  Pregnancy status - should not be started in pregnancy!

After three months

• Check lipids if secondary prevention (aiming 40% reduction in non-HDL)
• Recheck LFTs. If less than three times normal AST/ALT, no need to stop.

Annually

• First year, check LFTs.
• Following years no monitoring required.

Muscle pains

• Check CK.
• If more than 5 times normal, consider stopping or reducing statin.

Dermatology

Acne vulgaris

Managing acne involves some helpful people skills

• Reassure them that it will usually settle without scarring.
• Unrelated to diet or stress.
• Not caused by poor hygiene, can be worsened by washing.
• Smoking can make it worse!

Mild acne

• Wash no more than twice a day.
• Avoid scrubbing.
• Use a water based emollient instead of soap if needed.

1. Try a topical retinoid (isotretinoin) or benzoyl peroxide as first line.
2. Consider azelaic acid if above not tolerated.
3. Offer a COCP to anyone needing contraception, as it can help reduce acne.

Moderate acne

• Add in a topical antibiotics with one of the topical agents above if not helping. Ideally don't give for more than 12 weeks.
• Consider oral antibiotics combined with a topical retinoid or benzoyl peroxide.
  • Use tetracycline, oxytetracycline, doxycyline or lymecycline.
  • Don't use without a topical agent
  • Don't give both topical and oral antibiotics.

Severe acne

If all that has failed, refer them to Dermatology, who will consider starting oral isotretinoin.

Eczema

Robby Robinson, former Mr Universe, opposes use of anabolic steroids in bodybuilding, but finds a little clobetasone just the thing for his eczema...

Medical Emergency - Eczema herpeticum is always a possibility. Basically systemic herpes in someone known to have eczema. Anyone unwell, covered in herpetic blisters, admit immediately!

However, in normal eczema, management is a bit less exciting:

1. Emollients are the mainstay of treatment in eczema. Make sure you explain that it should be applied around 4 times a day, and that they should be getting through buckets of the stuff - or they aren't using it properly.
2. Topical steroids are next, if a decent emollient regime isn't curing it.
   1. Start with mild or moderate steroids (see image on the right)
   2. On the face and thin skin in flexures, don't progress beyond moderate.
   3. With children, especially on the face, start with mild.
   4. Apply steroids once or twice a day, after applying emollient to the area.
   5. If steroids aren't working, consider infected eczema, and consider a blood test to rule out coaeliac disease which can present with dermatitis herpetiformis, which looks a fair bit like eczema.
3. If that's not working, topical tacrolimus is an option, but should be initiation by dermatologists.

Psoriasis

1. As with eczema, the first step of treatment is regular use of emollient.
2. Next add in short term potent topical steroid (betamethasone 0.1%) and/or topical calcipotriol. Recomend maximum 4-8 weeks on steroids, then 4 weeks off (using calcipotriol alone).
3. Stronger steroids should be prescribed by the dermatologist, so refer. They may want to do narrow band UVB therapy. Current evidence says this probably doesn't increase skin cancer risk..

Skin cancer

Malignant Melanoma

Refer to rule out melanoma with any pigmented lesion with 3 or more points (see below).

Major features (worth 2 points each)

• Change in size
• Irregular shape
• Irregular colour

Minor features (worth 1 point each)

• Largest diameter ≥7mm
• Inflammation
• Oozing
• Change in sensation.

Other skin cancers

Also refer under 2WW anything that you feel may be a SCC. Suspected BCC should be sent under a routine referral.

Endocrine

Diabetes (Type 2)

Diagnosing diabetes

• You need two results showing fasting glucose ≥7, or HbA1c ≥ 48mmol/mol.
• If having symptoms of diabetes, such as thirst, polyuria, you only need one.

Lifestyle

Step one is aaaaaaaaaaaaaall about lifestyle changes. Losing 5-10% body weight can even revert HbA1c to normal in some cases.

Obviously, need to sort out their blood pressure, smoking, etc. However, if HbA1c is still more than 48, you'll need to intensify...

Anti-glycaemic drugs

Step	Steps if Metformin tolerated
Monotherapy	Start metformin
First Intensification (Add if HbA1c >58)	Add sulphonylurea (gliclazide) Or gliptin (sitagliptin) Or pioglitazone
Second Intensification (Add if HbA1c >58)	Add third drug... So Metformin + SU + gliptin Or Metformin + SU + pioglitazone Or start insulin therapy (see below)
If second step not tolerated, and super keen to avoid insulin	Consider metformin + gliclazide + GLP 1 (liraglutide) - only use if BMI >35 and big concerns about weight gain/occupational issues regarding insulin.

Step	If Metformin not tolerated
Monotherapy	Start on of the below: Sulphonylurea (gliclazide) Gliptin (sitagliptin) Pioglitazone Repaglinide
First Intensification (Add if HbA1c >58)	Stop repaglinide if using. Try: SU + gliptin SU + pioglitazone Gliptin + pio
Second Intensification (Add if HbA1c >58)	Consider insulin

Insulin therapy

Starting a patient on insulin is a scary prospect, but its pretty simple:

• Keep the metformin going alongside the insulin.
• Start with a single daily dose of long acting insulin - Insulatard is the standard, or Lantus/Levemir (slightly more expensive options).
• If sugars not controlled, may benefit from change to multiple doses/times, but usually will be managed by diabetic specialist nurse clinic.

Diabetes and driving

A key question for drivers is "Have they had an episode of hypoglycaemia requiring the assistance of another person in the last 12m?". If so, cannot drive!

Generally, aside from that, there is slightly more strict guidance for HGV drivers compared to normal divers, but with insulin:

• They need to have full awareness of when they are having a hypo.
• The DVLA always need to be informed of their condition.
• They will expect the driver to measure blood sugar 2 hourly whilst driving.

Hyperhidrosis

This is excessive sweating. Management is mostly in secondary care, but it can be a useful red flag...

1. Step one is to rule out secondary causes of nightsweats or excessive sweating; such as TB, Cancer, Menopause, Diabetes, etc.
2. If you are confident it is primary hyperhidrosis, consider topical aluminium chloride. Apply 12.5% at night, and wash off in morning. Increase up to 30% if needed.
3. If that's ineffective, refer to Dermatology.

Hypothyroidism

If you clinically suspect hypothyroidism, or have an incidental finding in TFTs

• Treat overt hypothyroidism.
  • Start at 50-100micrograms OD
  • Adjust by 25-50mg every 3-4 weeks.
  • Usual maintenance dose is 100-200mg OD.
• With subclinical lab results, treat if:
  • Goitre
  • Rising TSH
  • Pregnant
  • Consider trial of treatment if symptomatic.

Generally you can manage without referral, but go for it if patient unwell, painful goitre, treatment resistant, under 16, or any possibility of Addison's disease.

Eyes and ENT

Conjunctivitis

Evidence shows that antibiotics don't really do much - it might resolve slightly earlier, but by 7 days there's no difference between groups.

• If you have to give something, give Chloramphenicol.
• Kids absolutely no not need to avoid school.

Sinusitis

Very common, sinusitis is almost always self limiting. According to a Cochrane review, "there is no place for antibiotics for the patient with clinically diagnosed, uncomplicated acute rhinosinusitis".

Advised the patient it should get better in 2-3 weeks, and that antibiotics do not reduce how long the pain lasts.

GI

Upper GI cancer

You will want to refer via 2WW anyone with an upper abdominal mass that suggests stomach cancer, or anyone over 40 with jaundice.

Send for urgent OGD

• Dysphagia
• 55+ with weight loss and pain/reflux symptoms.

Send for non-urgent OGD

• Haematemesis
• 55+ with:
  • Non resolving dyspepsia.
  • Upper abdo pain and anaemia
  • Raised platelets with any upper GI symptoms
  • Nausea and vomiting with weight loss/reflux/pain

Send for urgent CT

Hunting for pancreatic cancer, anyone who is 60+ with weight loss and any of these:

• Diarrhoea or constipation
• Back pain
• Abdominal pain
• Nausea/Vomiting
• New diabetes

Some of these are a bit odd, because you would probably already be sending on a Lower GI cancer referral...

Consider urgent USS

Anyone who has a mass that feels like an enlarged liver or gallbladder mass deserves a cheeky USS.

Lower GI cancer

It's 2WW time for any of the following:

• Any age with unexplained anal mass or ulceration.
• 40+ with weight loss and abdo pain
• 50+ with unexplained rectal bleeding
• 60+ with iron deficiency anaemia or changes in bowel habit.
• Positive FOB test.

Consider 2WW referral

• Any abdominal mass
• Younger than 50 with rectal bleeding plus:
  • Abdominal pain
  • Change in bowel habit
  • Weight loss
  • Iron deficiency anaemia

Offer FOB testing

• 50+ with abdominal pain +/- weight loss.
• Less than 60 with change in bowel habit or iron deficiency anaemia.
• More than 60 with any anaemia.

Gynaecology

Ovarian cancer

You need to refer urgently if you suspect ascites, or find any unexpected pelvic/abdominal mass.

Consider ovarian malignancy and do CA125 if

• 50+ woman with bloating, early satiety, pelvic pain, or increased urinary symptoms.
• Any unexplained weight loss, fatigue or bowel habit changes.
• New onset of IBS in women over 50.

The key is that ovarian cancer is easily missed and diagnosed late, so always have it at the back of your mind.

Endometrial cancer

Send anyone 55+ with postmenopausal bleeding via 2WW. Consider it strongly in anyone under 55 too.

Go for an urgent USS if...

• 55+ with unexplained vaginal discharge for the first time, or with thrombocytosis, or with haematuria.
• Haematuria with anaemia, raised platelets or high blood sugars.

Other gynae cancers

If the cervix is abnormal in appearance, they are going to need an urgent referral. Same with any weird vulval lumps, ulcers or bleeding.

Haematology

Leukaemia

Do an FBC within 48 hours in any children or adults with one of these:

• severe pallor or tiredness
• generallised lymphadenopathy
• unexplained persistent infections
• bleeding or bruising issues
• hepatosplenomegaly

In children with these bleeding or bruising issues or hepatosplenomegaly, admit for an immediate specialist review - they coiuld have severe marrow suppression!

Lymphoma

Refer anyone with unexplained lymphadenopathy or splenomegaly for 2WW. Refer kids even more urgently. Especially think about fever, night sweats, SOB, itchiness, weight loss.

Myeloma

In patients over 60 with bone pain, particularly back pain or unexplained fractures do FBC, serum calcium and ESR/plasma viscosity.

If they have raised calcium, or raised viscosity, do protein electrophoresis and Bence Jones protein urine test within 48 hours. Refer with 2WW if these suggest myeloma.

Neurology

Stroke & TIA

Anyone with a suspected TIA needs assessing under ABCD₂:

ABCD2 points
Age (more than 65)	1
Blood pressure (more than 140 or 90)	1
Clinical features	Motor weakness: 2 Speech changes no weakness: 1
Duration	Less than 10 minutes: 0 10-60 minutes: 1 More than 60 minutes: 2
Diabetes	1

• Give them all 300mg aspirin OD until assessed.

Score of 4 or more, or 2 or more TIAs in a week: - High risk of stroke, specialist assessment within 24 hours.

• Score of 3 or less, refer for assessment within 1 week.

After a stroke is confirmed

If haemorrhagic stroke:

• Manage BP, but don't give antiplatelets or statins.

If thrombotic:

• Clopidogrel 75mg OD.
• If not tolerated, can use aspirin 75mg OD and dipyridamole MR 200mg BD.
• Atorvastatin 80mg ON
• Indapamide and ACE inhibitors in all, even if don't have raised BP!

Brain and CNS cancer

Adults with a progressive loss of CNS functions, or any sign of intracranial lesion should have an urgent MRI. Children should have an urgent Neurology review.

Paeds

Childhood cancers

All the below need a 2WW referral to rule out neuroblastomas, retinoblastomas and Wilm's tumours...

• Palpable abdominal mass
• Absent red reflex
• Unexplained visible haematuria

Fever

Hugely common problem, most kids run a temperature when they are unwell. For managing fever, there is no benefit to using both paracetamol and ibuprofen, just recommend one or the other.

In deciding if a child needs urgent help, use the traffic light system:

Any red features? Send to hospital.

• Any amber features? Use clinical judgement
• All green? Can be managed safely at home, with appropriate safety netting.

Respiratory

Asthma

Diagnosis

Asthma likely	Asthma less likely
More than one of these, especially if worse at night or early morning? Wheeze Breathlessness Chest tightness Cough Coupled with: History of atopy Wheeze on examination Low FEV1 or Peak flow Unexplained eosinophilia	Chronic cough without wheeze Voice disturbance Symptoms with colds only 20+ years smoking history Cardiac disease Normal tests + exam when symptomatic

• High probability of asthma? Start treatment, and test if not responding.
• Intermediate probability? Do spirometry to look for obstruction. If present, test for reversibility. If >400ml improvement after 400micrograms salbutamol, highly suggestive of asthma.
• Low probability? Consider other options/specialist referral.

Refer is still symptomatic after treatment, any occupational link suspect, scary CXR findings or eosinophilia > 1x10⁹

Management

Step wise management for everyone, progressing to next step if symptoms not managed. For adults:

1. Start with salbutamol PRN
2. Add in beclometasone 400 micrograms a day (range of 200-800)
3. Add in a long acting beta agonist - salmeterol
4. Increase to 2000 micrograms a day beclometasone (or consider adding in LTRA, theophyllines, slow release beta agonist tablets)
5. Add oral steroids and refer

Similar for children 5-12, but earlier cut off for referral:

1. Start with salbutamol PRN
2. Add in beclometasone 400 micrograms a day (range of 200-800)
3. Add in a long acting beta agonist - salmeterol
4. Increase to 2000 micrograms a day and refer at this point!

Children under 5 its fairly different:

1. Start with salbutamol PRN
2. Add in beclometasone 400 micrograms a day (range of 200-800)
3. Add in a LTRA - Montelukast. Do not add a long acting beta agonist!
4. Refer

Acute Asthma

Moderate asthma:

• Peak flow 50-75% predicted
• Talking normally
• O₂ more than 92%
• RR <25
• P <110

Can be managed with salbutamol via spacer, and oral prednisolone for 5 days. Only give antibiotics if signs of infection.

Acute severe asthma:

• Peak flow 33-50% predicted.
• Can't finish sentence in 1 breath
• O₂ more than 92%
• RR >25
• P >110

Life-threatening asthma - any one of these, then arrange immediate admission

• Peak flow less than 33%.
• Poor respiratory effort/silent chest
• O₂ less than 92% or cyanosis
• Hypotension
• Exhaustion/altered consciousness

Treat these patients with oxygen, and 5mg nebulised salbutamol. Consider adding ipratropium 0.5mg also. If they don't have life threatening signs, and are improving, consider allowing home with steroids, otherwise admit urgently.

Bronchiolitis

1 in 5 children under one years old get this each year. Peak incidence is at 3-6 months.

Needs a 999 referral if:

• Apnoea (in history or in consultation)
• Respiratory distress - grunting, recession, RR >70
• Cyanosis
• O₂ sats <92%

Needs same day referral if:

• RR>60
• Feeding difficulties (less than 75% normal intake)
• Dehydration

Give the kids O₂ - but there's no value in giving antibiotics or bronchodilators, they don't help.

COPD

Diagnosis of COPD is through spirometry. Consider doing it on anyone over 35 who have a smoking history and:

• SOB on exertion
• Chronic cough
• Regular sputum production
• Frequent winter "bronchitis"
• Wheeze

Without asthma symptoms:

• Chronic unproductive cough.
• Significant day-to-day or day/night change in symptoms.
• Night time waking with breathlessness/wheeze

If spirometry shows FEV1/FVC <0.7 without reversibility, treat for COPD. If reversible, consider asthma.

Lung cancers

In

anyone with a suggestive CXR, or anyone over 40 with unexplained haemoptysis you need to refer them through 2WW.

Otherwise, consider:

Urgent CXR if over 40 and 2 of these:

• Significant smoking/asbestos history
• Cough
• Fatigue
• SOB
• Chest pain
• Weight loss or loss of appetite

Consider urgent CXR if over 40 and

Anything weird, such as recurrent chest infections, clubbing, neck or supraclavicular lymphadenopathy or weird chest findings on examination.

Sexual Health

Contraception

UKMEC guidance says the combined pill should be avoided in anyone:

• 35+ who smokes
• BMI over 35
• Breastfeeding, or within 3 weeks of giving birth.
• High blood pressure or vascular disease
• History of DVT (or high risk for one)
• With previous stroke
• Migraine with aura.
• Personal history of breast cancer, or BRCA1 positive.
• Diabetes with end organ damage.
• Liver cancer
• Current gall bladder disease.
• Lupus

Cancer risk

The Combined Oral Contraceptive increases risk of some female cancers. The easy way to remember risk: Oral = Oh no!

Oh no! Outermost, Improves Innermost:

• Increases risk of outermost female cancers - breast and cervical
• Decreases risk of innermost - ovarian and endometrial

Urology

Male Stuff

Refer any of the following via 2WW:

• Lumpy scary-feeling prostate on DRE.
• PSA above the age specific range (Generally anything much over 5).
• Painless enlargement or change in testicle shape.
• Firm penile mass or ulceration after STI excluded/treated.

Consider DRE and PSA test

• Any urinary symptoms, such as urgency, frequency, nocturia, etc.
• Erectile dysfunction
• Visible haematuria

Exclude UTI with these too.

Consider USS

• For any unexplained or unusually persistent testicular symptoms.

Bladder and kidney cancer

Two groups to look for:

• 45+ with visible haematuria without UTI as the cause
• 60+ with microscopic haematuria and dysuria or raised WCC.

Consider non urgent referral

Anyone over 60 with recurrent UTI with no obvious cause.

Women's Health

Breast cancer

Breast clinic under a 2WW for anyone:

• Over 30 with a concerning breast lump with or without pain.
• 50+ with nipple changes or discharge.

Consider 2WW referral for anyone

• With skin changes that suggest breast cancer
• 30+ with axillary lump with no obvious cause.

Clinical Genetics referral

Sarah has a rare X-linked allergy to Jaffa cakes, and has two 1st degree, 2 second degree and a 3rd degree relative suffering from this terrifying disease.

First step is to understand what a first, second and third degree relative is - its simply just the number of steps from you along a family tree:

1. First degree: parents, siblings, children
2. Second degree: grandparents, aunts, nephew, grandchild, half-sibling, etc
3. Third degree: great-grandparents, great aunt/uncle, first cousin, great grandchild, great niece or great nephew

Refer to Clinical Genetics if breast cancer in:

• any 1st degree female relatives under age of 40
• any 1st degree male relatives at any age
• any two 1st and 2nd degree relatives
• any three 1st, 2nd and 3rd
• any 1st or 2nd with breast plus any 1st or 2nd with ovarian cancer

References