Understanding clinical studies - p value

The P (probability) value is used when we wish to see how likely it is that a hypothesis is true. The hypothesis is usually that there is no difference between two treatments, known as the “null hypothesis”.

P = 0.5 means that the probability of the difference having happened by chance is 0.5 in 1, or 50:50.
P = 0.05 means that the probability of the difference having happened by chance is 0.05 in 1, i.e. 1 in 20. = SIGNIFICANT result

The lower the P value, the less likely it is that the difference happened by chance and so the higher the significance of the finding.

P = 0.01 is often considered to be “highly
significant”. It means that the difference will only have happened by chance 1 in 100 times. This is unlikely, but still possible.
P = 0.001 means the difference will have happened by chance 1 in 1000 times, even less likely, but still just possible. It is usually considered to be “very highly significant”.

Resources

http://www.roche.com/research_and_development/what_we_are_working_on/oncology/cancer-immunotherapy/interpreting-clinical-trials-data.htm
MedicalStatisticMadEasy

What's in a name?

What is cancer? 

Cancer is an uncontrolled cell proliferation. The term cancer is synonym with malignancy. Benign tumours are not cancer. 
Because dividing cells do not always copy their DNA perfectly, every division is an opportunity for a cancer-causing mutation. The difference in cancer rates in different tissues can  be the result of different underlying rates of cell division. As an argument,  cells of the large intestine divide frequently,  (approximately 4.3 percent of men and women will be diagnosed with colon and rectum cancer at some point during their lifetime)  while small bowel cancer, which has cells that divide rarely,  is rare (approximately 0.3 percent of men and women will be diagnosed with small intestine cancer at some point during their lifetime).

 Results from a recent study show that random DNA copying mistakes are responsible for 66% of the mutations (aka bad luck according to the authors) 29% are due to environmental factors and 5% of heredity. This study is controversial, and more reliable studies show that roughly 42 percent of cancers are preventable by: not smoking, maintaining a healthy weight, and not being exposed to cancer-causing pollutants. I personally dislike this term "bad luck" and I considere that this is a question to be answered, what causes this mutations or what makes them invisible for the immune system?

What's in a name? Ethymology

 The word cancer comes from the latin  word cancer, meaning crab, since the enlarged veins seen in some cancer resembled with the legs of a crab.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069308/
http://www.sciencemag.org/news/2017/03/debate-reignites-over-contributions-bad-luck-mutations-cancer

Today's thoughts (regarding cancer)

What is growth fraction?

• It is the percentage of cells  in a tumour mass that are actively dividing.

What is doubling time?

• It is the amount of time  it takes for a tumour to double in size ( in Burkitt lymfoma it can be as short as 24 h, in some adenocarcinoma it could be up to 200 days or longer).

The rate of growth slows  as the tumour increases in size, due to limits imposed by tumour microenvironment. Small tumours or micro metastasis might to be more sensitive to chemotherapy, this is the idea that lies behind  adjuvant chemotherapy (chemotherapy that is given after an initial intervention that is designed to cut-reduce the tumour bulk and remove all macroscopic disease)

Resources: Oncology at a glance, Graham G. Dark

Metastatic spinal cord compression MSCC

MSCC is caused by compression of the dural sac and its contents (spinal cord or cauda equina) by an extradural or intradural mass,
and it leads to irreversible neurological damage such as paraplegia or tetraplegia depending on the level of the lesion.
Extradural masses are the more common.


Haematogenous spread with bony metastasis to the vertebral spine causes collapse and compression, accounting for over 85% of MSCC.


How does it present?

• Back pain isthe most common firstsymptom, occurring in 95% of patients for up to two months before signs related to MSCC appear.
• Motor deficit. Limb weakness is the second most common symptom, affecting 60-85% of patients at the time of diagnosis of MSCC. Patients may complain of an unsteady gait or a rapid onset of difficulty in walking, standing, or transferring from bed to chair that has progressed over days or a few weeks.
• Sensory deficit: Patients may complain of paraesthesia, decreased sensation and numbness of toes and fingers which may extend 1-5 dermatomes below the true level of cord compression. Radicular sensory loss and loss of tendon reflex  can be seen on clinical. A combination of rapid onset sensory and motor symptoms should raise a high degree of suspicion of MSCC.
• Autonomic dysfunction: bladder and bowel dysfunction such as urinary retention, urinaryor faecal incontinence, or constipation.
• Cauda equine sd: extreme pressure and swelling of the nerves at the end of the spinal cord. Symtomps: decreased awareness at presentation on passing urine or opening bowels, without a motor deficit and sometimes in the absence of pain. Clinical signs are decreased sensation over the buttocks, posterior-superior thighs, and perineal regionin a saddle distribution, with most patients exhibiting decreased anal sphincter tone on examination. Urinary retention.

How to confirm the diagnosis? MRI of the whole spine.

What to do about MScc:
Offer corticosteroids and analgesia and consider spinal stability while the patient is assessed.loading dose of
16 mg of dexamethasone (given intravenously or orally)
followed by a short course of 16 mg dexamethasone daily (given
in divided doses, such as 8 mg twice daily orally). Steroids are contraindicated if lymphoma isthe suspected cause of the MSCC
as the oncolytic effect of the steroids may impair tissue diagnosis. Steroids have no effect on survival.

Timely referral for neurosurgery or radiotherapy, or both, provides better outcomes longer term, but palliative care is the treatment of choice for some patients.


Box 1: NICE recommendations for diagnosis and management of patients at risk of or with metastatic spinal cord
compression (MSCC)6
• Contact the relevant team urgently (within 24 hours) to discuss the care of patients with
cancer and pain with any of the following characteristics suggestive of spinal metastases:
– Pain in the middle (thoracic) or upper (cervical) spine
– Progressive lower (lumbar) spinal pain
– Severe unremitting lower spinal pain
– Spinal pain aggravated by straining (for example, at stool) or when coughing or sneezing
– Localised spinal tenderness
– Nocturnal spinal pain preventing sleep.








Resources:

Bmj learning
BMJ 2016;353:i2539 doi: 10.1136/bmj.i2539 (Published 19 May 2016)

Loblaw DA, Mitera G, Ford M, Laperriere NJA. A 2011 updated systematic review and
clinical practice guideline for the management of malignant extradural spinal cord
compression. Int J Radiat Oncol Biol Phys 2012;84:312-7. doi:10.1016/j.ijrobp.2012.01.
014 pmid:22420969.

Bucholtz JD. Metastatic epidural spinal cord compression. Semin Oncol Nurs
1999;15:150-9. doi:10.1016/S0749-2081(99)80002-3 pmid:10461699.

 Levack P, Graham J, Collie D, et al. A prospective audit of the diagnosis, management and outcome of malignant spinal cord compression. Clinical Resource and Audit Group,
2001.

Tumour lysis syndrome - what is it?

Povestea unui erizipel

Erizipelul

Infectie cutatana cauzata de streptococ. Infectia este favorizata de factor locali care slabesc bariera epidermica si permit streptococcului sa invadeze dermul, printre acesti factori se numara edemul local, traumatismele, eczema.
Diagnosticul este usor de stabilit, examenul clinic fiind suficient  de cele mai multe ori. Se observa semne de inflamatie  si infectie locala: eritem (inrosirea pielii, bine delimitata, cu marginile usor proeminente), caldura locala, durere.  Diagnosticul diferential (alte posibile cauze) se face cu: tromboza  venoasa, celulita, artrita septica etc.  Nu detaliez,  exista deja f multe surse de informare daca vreti sa aprofundati subiectul.

De data aceasta nu fac nici un sumar al bolii, un good to know asa cum scriu de obicei pe blog.
Scriu insa "Povestea unui erizipel".

Povestea unui erizipel

A fost o data un epizipel, arata ca orice erizipel din familia sa, era rosu, cu marginile usor ridicate, cauza durere si prurit (mancarime). Se stabilise  de catvea saptamani pe gambele unei gazde. Posesorul erizipelului il descria ca fiind dureros, cald si amintea ca erizipelul se intindea succesiv. Ba chiar amintea ca erizipelul isi construise si cateva vezicule. 

Gazda erizipelului se duce la medicul de familie. Aici s-ar fi putut incheia poveste erizipelului. Medicul ar fi putut prescrie, de exemplu, Penicilina V 1g de 3 ori pe zi timp de 10 zile. Posesorul erizipelului ar fi cumparat medicmanetul de la farmacie cu 4.9 ron si ar fi scapat de erizipelul nedorit in cateva zile.  Daca erizipelul se incapatana sa ramana  posesorul ar fi putut suna la policlinica si povesti ca erizipelul nu este sensibil la antibiotic  iar medicul de familie ar fi reconsiderat diagnosticul sau poate ar fi prescris alt antibiotic (poate o cefalosporina daca ar fi considerat ca raufacatorul este de fapt un stafilococ). Daca medicul de familie ar fi considerat  ca exista riscul ca  Eripizelul  sa foloseasca o identitate falsa  si defapt sa fie o tromboza  venoasa profunda ar fi putut trimite pacientul catre investigatii precum ecografie vasculara sau flebografie si intre timp posesorul erizipelului cu nume fals ar fi primit tratament anticoagulant.

Nu a fost  sa fie asa. Medicul de familie se hotaraste sa trimita umilul erizipel in control 
la medicul specialist dermatolog, sa il numim Dr N.A.  Specialistul  dermatolog  se intalneste cu erizipelul  si se hotaraste ca nu se porte decide... pare a fi o infectie isi spune, dar daca este doar o reactie alergica locala...  Dermatologul scoate retetarul si parafa si ia hotararea sa trateze erizipelul cu respect, adica sa nu il trateze cu un simplu antibiotic.   Prescrie tablete cu antialergic (nu alege cea mai ieftina variante, erizipelul era pe semne foarte alergizat), o pomada care contine doua antibiotice si pe deasupra  o crema de corp emolienta cu extract de ovaz (cu scop preventiv, nu care cumva sa se intoarca erizipelul, se pare ca erizipelului nu ii facea bine ovazul) .

Posesorul erizipelului se duce rapid la farmacie si intinde reteta:
1. Xyzal, antialergicul  26 Ron. Ar fi putut scrie substanta activa si nu denumirea comerciala, dar dr  N.A.alege sa scrie numele unui medicament mai scump, probabil pentru ca erizipelul trebuie tratat cu respect.
2. Exomega, 140 Ron, lotiune  emolienta cu extract de ovaz...Pielea uscata trebuie si ea tratata cu aceeasi stima.
2. Pomada cu: Metronidazol, Eritromicina, Bepanthen, Neopreol, Reviken  pe care farmacistul  prepara contra sumei de 100 ron.
Total 266 Ron.

Povestea erizipelului s-ar fi putut incheia dupa vizita la medicul de familie, cu un cost de numai 4.9 Ron cat costa penicilina V Ospen.  
Nu a fost asa, gazda erizipelului plateste 20% din venitul sau lunar pe tratametul prescris de dermatolog. Dintr-un exces de zel greu de inteles, Dr N.A ii recomanda posesorului de erizipel sa se intoarca  peste 10 zile pentru control . Probabil ca poveste nu se termina aici


...... negustor cinstit

MRI nomenclature

Subaraknoidalblödning

N.B. Om CT-undersökningen är normal utförs lumbalpunktion, dock tidigast 6 timmar efter insjuknandet (inte längre 12 timmar som det var indicerat i förut).

Resources:
Akut neurologi, Jean Malm, Johan Liedholm, 2010
www.internetmedicin.se

Adrenal inssuficiency 😩

About this blog 💬

This is a blog about medicine that is intended to be used by doctors, medical students or anyone else that is curious to learn about diseases.

I am a medical doctor, my area of expertise is internal medicine. This is a very complex medical specialty that comprises  diseases from all of the organs, diseases that intricate and superimpose and this means a continuous intellectual challenge. Adding to this the continuous  progress and changes due to research, most of us feel like no matter how  many books you read you are still long behind with your  knowledge. Medicine is not all about studying, but studying is a big part of medicine so my plan is to make it easier, this  is the purpose of this blog. I believe that we need to have some "pillar of rock", the  basic knowledge, that something to build on. After achieving this, we can then  start  making connections, deduct, imagine, invent.

So my plan is to read medicine from reliable sources and to write in this blog the facts that are  relevant in my daily practice, those that I would like to know and remember. I usually use charts and diagrams to gather the information in  a more simpler and visual way.

I will not go deep,  I will make it short!

✌ Tania

Hyperglycemic emergencies

Diabetes Mellius type 2 - Oral and Insulin therapy-

Pharmacological Therapy for Type 2 Diabetes

Recommendations

• Metformin is the preferred initial pharmacological agent for type 2 diabetes. A

 Metformin may be safely continued down to glomerular filtration rate (GFR) of 45 mL/min/1.73 m2 or even 30 mL/min/1.73 m2. If metformin is used in the lower GFR range, the dose should be reduced and patients should be advised to stop the medication for nausea, vomiting, and dehydration.

• If noninsulin monotherapy at maximum tolerated dose does not achieve or maintain the A1C target over 3 months, then add a second oral agent, a glucagon-like peptide 1 receptor agonist, or basal insulin. 

• For patients with type 2 diabetes who are not achieving glycemic goals, insulin therapy should not be delayed. B

Insulin therapy

Basal insulin is usually prescribed in conjunction with metformin and possibly one additional noninsulin agent. 

Resources:
American Diabetes Association. Approaches to glycemic treatment. Sec. 7. In Standards of Medical Care in Diabetes—2016. Diabetes Care 2016;39(Suppl. 1):S52–S59

Diabetes mellitus

Types of DM

DM type 2 is characterised by hyperglycemia and variable degrees of insulin deficiency and resistance. Accounts for 90% of diabetes un adults

DM type 1 is characterised by destruction of the pancreatic beta cells leading to absolute insulin deficienc. Accounts fod 10% of diabetes in adults.
 Testing for islet cell antibodies (ICA) or other islet autoantibodies (antibodies to glutamic acid decarboxylase [GAD] 65, insulin, and to the tyrosine phosphatases, insulinoma-associated protein 2 [IA-2] and IA-2 beta, and zinc transporter ZnT8) in serum may be helpful if establishing the diagnosis is important. 

LADA (Latent autoimmune diabetes in adults) is DM with debut in adult ages that progresses to a insulin dependent phase. These patients may be  ICA or GAD antibodies positive.

Maturity onset diabetes of the young — Maturity onset diabetes of the young (MODY) is a clinically heterogeneous disorder characterized by non-insulin dependent diabetes diagnosed at a young age (<25 years) with autosomal dominant transmission and lack of autoantibodies [1]The diagnosis of MODY is made by performing diagnostic genetic testing by direct sequencing of the gene. It has features of both impaired insulin secretion and insulin resistance. 

Diseases of the exocrine pancreas 
Diseases that damage the pancreas, or removal of pancreatic tissue, can result in diabetes. Ex: pancreatectomy, pancreas cancer, pancreatitis, hemocromatosis. It uw usually insulin requiring but is even more prone to hypoglycemia than DM because glucagon producing cells are also demaged.

DRUG-INDUCED HYPERGLYCEMIA — Drugs can impair glucose tolerance by decreasing insulin secretion, increasing hepatic glucose production, or causing resistance to the action of insulin.
Included in this list are glucocorticoids, oral contraceptives, several classes of antihypertensive drugs such as beta blockers, thiazide diuretics, nicotinic acid, statins, protease inhibitors used for the treatment of human immunodeficiency virus (HIV) infection, gonadotropin-releasing hormone (GnRH) agonists used for the treatment of prostate cancer, tacrolimus

When to look for  antibodies?

We measure autoantibodies when the diagnosis of type 1 or type 2 diabetes is uncertain by clinical presentation:

●In patiens with poor response to initial therapy with sulfonylureas or metformin

●Personal or family history of autoimmune disease

●Overweight or obese children or adolescents presenting with apparent type 2 diabetes, who actually may have an early presentation of type 1 diabetes

References:

1. A difference between the inheritance of classical juvenile-onset and maturity-onset type diabetes of young.people. Tattersall RB, Fajans SS, Diabetes. 1975;24(1):44
2.Drug-induced hyperglycemia Luna B, Feinglos MNJAMA. 2001;286(16):1945.

Diabetes and the eye👀

Types of eye pathology associated with diabetes:

Glaucoma: earlier debut is noticed in patients with DM.
Symptoms typical of acute glaucoma include an acutely red, painful eye with reduced vision. Occurs when new blood vessels hm grow in the iris and block the drainage of fluid.

Rubeotic glaucoma occurs when new blood vessels that are abnormal grow on the iris and block the drainage of fluid, leadingsecondary to raised intraocular pressure. High intraocular pressure can cause headache, nausea, and vomiting.

Diabetic retinopathy that is uncontrolled and proliferative is a common cause of rubeotic glaucoma

Bilateral diabetic papillopathy: a reduction in visual acuity that is sudden, does not fluctuate, and does not improve with a pinhole. A relative afferent pupillary defect may be present if one eye is affected more severely than the other. Direct ophthalmoscopy would reveal swollen discs.

Bilateral macular oedema (exudate within the macula) presents as a a gradual decline in central vision. Some patients describe missing patches of text when they read. 

Variable refractive change:  it is caused by fluctuations and rapid reduction of blood glucose that may alter the composition and thickness of lens (lens hydration). It may manifest with:blurred  vision when driving, watching TV,   reading 

Bilateral cataracts: patients with DM tend to develop cataract earlier than those without DM. It results in a gradual decline in vision.

They classically cause patients to experience a glare with oncoming headlights while driving at night.

Vitreous haemorrhage may occur in patients with diabetes who have proliferative retinopathy (when retinal tissue becomes hypoxic new blood vessels form - proliferative diabetic retinopathy). Bleeding occurs from new vessels at the optic disc or elsewhere. 

Screening for retinopathy should be done in the begging (when DM 1 or 2 is diagnosed) and every 2 years afterwards.

Diabetes mellitus - diagnosis -

Variceal bleeding

TO DO LIST

1. Fluid resuscitation to a target mean arterial blood pressure of 65 mmHg: Ringer acetate.
2. Plan for urgent endoscopy.
3. Intravenous terlipressin 2 mg four times a day  (in patients without a history of ischaemic heart disease or peripheral vascular disease).
4. Blood transfusion given if the haemoglobin falls below 7 g/dL, to a target of 8 g/dL.
5. Nasogastric sond.
6. Consider PPI i.v. ( esomeprazol or pantoprazol) 80 mg bolusdos and after that  infusion 8 mg/h i 72 hours. 
7. Consider reversal of anticoagulation (Ocplex) 1500 IE (10-30 IE/kg)  or Confidex, Konakion 10 mg i.v. 
8. Antibiotic profylax (reduces the risk of repeat bleeding, spontaneous bacterial peritonitis).

Resources:

Jairath V, Rehal S, Logan R, et al. Acute variceal haemorrhage in the United Kingdom: patient characteristics, management and outcomes in a nationwide audit. Dig Liver Dis 2014;46(5):419-26.

Acute liver failure

What happens in acute liver failure?

Acute liver failure  is a deteriorating of liver functions that results in:

1. Coagulopathy, usually with an international normalized ratio (INR) of greater than 1.5. Causes: impaired liver protein synthesis.
2.  Encephalopathy - because of impaired ammonia clearance.
3. Hypoglycemia - because of impaired glyconeogenese.
4. Jaundice- impaired bilirubin metabolism
5. Lactic acidosis - impaired lactate clearance. 
6. Ascites - impaired albumin synthesis 

Dyspepsia - red flags -

Etiology:

• Peptic ulcer or  malignancy
• Gastro-oesophageal reflux disease (GORD)
• Hiatus hernia
• Coeliac disease ( gluten intolerance, test for IgA-transglutaminas(tTG)-antibody)
• Crohn’s disease
• Gastroparesis
• Medications: eg non-steroidal anti-inflammatory drugs (NSAIDs), bisphosphonates (such as alendronic acid or risedronate), iron supplements, nitrates, levodopa
• Pancreaticobiliary disease eg gallstone disease, pancreatic malignancy
• Systemic conditions eg diabetes, Addison’s disease. 

Red flags with indication for further investigation:

• Age greater than 55 with new onset dyspepsia
• Dysphagia
• Unintentional weight loss ( then  order an endoscopy as soon as possible < 2 weeks)
• GI bleeding
• Trombocytose
• Persistent vomiting
• Iron deficiency anaemia
• A palpable epigastric mass
• An abnormal barium meal result

Investigation: endoscopy, if negative then CT abdomen : pancreatobiliary disease, gallstone or malignancy?

Resourses: BMJ learning

Liver function tests

What kind of liver abnormality does the patient have:

• Isolated bilirubin?

• Cholestatic?

• Hepatitic?

1. Isolated raised bilirubin: Most commonly caused by Gilbert’s syndrome (affects 8% of the population); consider haemolysis in patients with anaemia.
2. Cholestatic: Predominantly raised ALP (alkaline phosphatase) and GGT (gamma glutamyltransferase) indicate cholestasis. Common causes include: primary biliary cirrhosis, primary sclerosing cholangitis, biliary obstruction (stones, strictures, neoplasia etc), and drug induced liver injury
3. Hepatitic: Predominantly raised ALT (alanine transaminase) and AST (aspartate aminotransferase) indicate hepatocellular liver injury (hepatitis). Common causes include: viral hepatitis, non-alcoholic fatty liver disease (NAFLD), alcohol related liver disease (ARLD), autoimmune hepatitis, and drug induced liver injury.

 Elevated GGT?

Alcohol consumption, drug induced liver injury, NAFLD, cholestatic liver disorders, liver metastases, hepatic congestion secondary to heart failure.

 ELEVATED GGT and ALP?

Elevated GGT and alkaline phosphatase (ALP) with normal or less pronounced elevations of ALT or AST is suggestive of a cholestatic disorders: gallstones, pancreatic cancer, cholangiocarcinoma, primary biliary cirrhosis, primary sclerosing cholangitis, or drug induced liver injury.

The description of pale stools, dark urine, and itching is characteristic of post hepatic jaundice.

ELEVATED TRANSAMINASE?

In alcohol related disease, AST tends to rise higher than the ALT. In alcoholic hepatitis and cirrhosis, the AST/ALT ratio is greater than 2 in around 70% of patients.
In alcoholic hepatitis, serum AST levels rarely rise above 500 iu/L and ALT rarely rises above 300 iu/L. In comparison, acute infectious hepatitis and drug and toxin injury often cause much higher ALT and AST rises.

In patients with NAFLD (non-alcoholic fatty liver disease), the typical abnormality is mildly raised serum ALT and/or GGT levels.

ELEVATED FERRITIN AND LIVER DISFUNCTION?

Raised ferritin with normal saturation < 45 % and a raised corpuscular volume (MCV) is suggestive of ARLD.

Hepatic function	Clinical feature in acute liver failure
Bilirubin metabolism	Jaundice
Gluconeogenesis	Hypoglycaemia
Ammonia clearance	Hepatic encephalopathy/cerebral oedema
Lactate clearance	Lactic acidosis
Protein synthesis	Coagulopathy
	Neutrophil dysfunction, risk of sepsis
	Ascites

Resources:

• http://learning.bmj.com/learning/modules/flow/JIT.html?execution=e1s3&moduleId=10054395&status=LIVE&action=start&_flowId=JIT&sessionTimeoutInMin=90&locale=en_GB&shouldStartAtQuestionSection=false&page=2
• Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for nclinicians. CMAJ 2005;172(3):367-79.
• Jonston DE, Special considerations in interpreting liver function tests, Am Fam Physicians 1999; 59(8), 2223-30

Decompensated liver disease and acute kidney failure

• It is more common in association with spontaneous bacterial peritonitis. 
•  Search for causes: nefrotoxic,  infection?Perform urinalysis and urine culture, looking for infection or evidence of parenchymal kidney injury. 
• Withdraw diuretics and nephrotoxic drugs.
•  Euvolaemia should be achieved with albumin or a crystalloid.
•  If renal function in a patient with cirrhosis and ascites deteriorates despite initial treatment, the most likely cause is hepatorenal syndrome: Terlipressin and albumin treatment improves renal perfusion. Reduction in the effective circulating blood volume and  hypoperfusion of the kidney is the  underlying pathogenetic mechanism for the development of hepatorenal syndrome.

Terlipressin is a vasopressin analogue that generates vasocontrction . It ncreases mean arterial pressure and systemic vascular resistance; while the heart rate, cardiac output, HVPG and portal venous blood flow decrease significantly. This decrease correlates well with the decrease in plasma renin activity. 

The improvement in hemodynamics with Terlipressin is associated with an increase in glomerular filtration rate and deactivation of the vasoconstrictor and sodium-conserving hormones with reduced activity of the RAAS resulting in increased natriuresis. Patients with HRS who show an improvement in renal function with Terlipressin and albumin seem to have an excellent post-transplantation outcome similar to that of patients without HRS. 

BMJ 2016;352:i124 doi: I/bmj.i124 (Published 26 January 2016)

J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:109-14. doi: 10.1111/j.1440-1746.2010.06583.x.

Acute pancreatitis - The essentials -

Acute pancreatitis is inflammation of the pancreas. The pancreas is "eaten" by the enzymes that it produces.

Causes: ususally gallstones, alkohol, hypertrigliceridemia, viral infections (coxackie, mumps - epidemic parotitis).

Diagnosis: abdominal pain and vomiting  associated with increase in serum amylase or lipase levels at least mare than three times upper limit of normal. Lipase levels remain increased for longer than amylase levels.

Acute pancreatitis is diagnosed when at least 2 of 3 criteria are present:

• typical abdominal pain, 

• raised enzyme levels, 

• appearances of pancreatitis on computer tomography.

Blog tests may reveal hypercalcemia and hypertrigliceridemia

Abdominal US may reveal gallstones.

Differential diagnoses: 

• Perforated peptic ulcer, 

• Myocardial infarction

• Cholecystitis.

Medical management

• Ringer lactat 2,5-4 l the first 24 h or enough to get a normal urine output 0.5-1ml/kg/hr.
• Antibiotics? Only if infection is clinically suspected or found.At present there is no indication for early antibiotics to prevent infection pancreatic necrosis.
• Pain relief (opioid) 
• Enter nutrition - nasogastric intubation.

Source: BMJ 2014;349:g4859 doi: 10.1136/bmj.g4859 

Travelers diarrhoea - how to avoid it -

Travelers diarrhoea - how to avoid it -

Source: BMJ Clinical review

BMJ 2016;353:i1937 doi: 10.1136/bmj.i1937

1.  Boiling water, cooking food Thoroughly, and peeling fruit and vegetables.  
2.  Avoiding ice, shellfish, and condiments on restaurant tables.
3.  Using a straw to drink from bottles, and avoiding salads and buffets where food may have been unrefrigerated forsevera hours. 
4. Drink bottled water where available, including in alcoholic drinks, as alcohol does not sterilise non-bottled water. If bottled water is not available, water can be purified by boiling, filtering, or use of chlorine based tablets.
5.  Use alchohol hand gel may reduce diarrhoea rates in travellers.
6.  Hand washing with soap reduces the risk of diarrhoeal illness by 30-40%.

If you've got it anyway, use rehydration salts (or a mixture of six level teaspoons of sugar and half a teaspoon ofsalt in a litre of clean water if rehydration. 

salts are unavailable) (see http://rehydrate.org/rehydration/index.

html).

Loperamide (anti motility agent)  might be of help, but it should be  avoided in
the presence of severe abdominal pain or bloody diarrhoea which can signify invasive colitis.

Investigations (for diarrhoeal symptoms that persist beyond 14 days following
travel or sooner if there are other concerning features such as
fever or dysentery):

• full blood count,
•  liver and renal function,
•  inflammatory markers;
• stool samples for microscopy and culture; and examination for ova cysts, and parasites. 

The most common cause of long lasting diarrhoea after traveling is Giardia, easy treatable with 5 nitroimidazole, tinidazole 2 g once only or metronidazole 400 mg three times daily for five days.