Hormone Replacement Therapy

This morning we briefly talked about the Women’s Health Initiative (WHI)and hormone replacement therapy. WHI was a set clinical trials including two hormone trials in healthy postmenopausal woman 50-70. The hormone trials were stopped early due to increased risk of cardiac events, VTE, stroke and breast cancer. The study did show benefits in reducing fracture and colorectal cancer risk.

Subsequent analysis of the WHI noted that the increased risk of CHD tended to depend on the timing of exposure, with no excess risk observed in younger menopausal women.

Current recommendations are as follows:

Moderate to severe menopausal symptoms can be treated with short term HRT in peri- or postmenopausal women (and no contraindications to estrogen). HRT should be stopped before five years. HRT should not be used as primary or secondary prevention of CAD.


Here is Endocrine Society’s statement on HRT.

Lets SIGN OUT? at TWH!

Handing over. We do it often. And the information we transfer is critical to patient safety. This morning we talked about SIGN OUT? as a template for our signovers.

S: Is the patient sick? Code status!!!
I: Identifying data
G: General hospital course
N: New events
O: Overall health status right now
U: Upcoming possibilities (if and then statements)
T: Tasks to complete overnight
?: Questions

Every team will function differenly, but sticking to consisten hand over template an style keeps communication flowing, and patients safe.

* it's 5pm...have you Singed Out yet?!

VTE and Malignancy

The questions of screening for an occult malignancy comes up often when a patient presents with unprovoked VTE. There are multiple observational studies that have confirmed the increased incidence of malignancy among those with VTE, however, none has shown improved survival with aggressive diagnostic testing. None of these studies are prospective.

As a result, the current recommendations is that all patients with idiopathic DVT should be evaluated with careful history. A past history of cancer should be a red flag. Other symptoms such as loss of appetite, weight loss, fatigue, pain, hematochezia, hemoptysis, and hematuria should also raise suspicion about cancer.

A complete physical examination (including digital rectal examination and testing for fecal occult blood, pelvic examination in women), and routine laboratory testing (complete blood count, chemistry panel including electrolytes, calcium, creatinine, and liver function tests), urinalysis and CXR should also be performed. Furthermore, age-appropriate cancer screening (PSA, FOB and C-scope, mammogram) should be offered.

Any abnormality observed on initial testing should then be investigated aggressively.

HCV-associated Cryoglobulinemia

Cryoglobulins are immunoglobulins that precipitate in cold and dissolve with warming.

HCV infections is associated with Type II or essential mixed cryoglobulinemia (polyclonal IgG and a monoclonal IgM rheumatoid factor directed against the IgG) and Type III or mixed cryoglobulin (polyclonal IgG and rheumatoid factor IgM).

Deposition of antigen-antibody complexes in small and medium-sized arteries leads to the clinical findings of cyroglobulinemia. It is unclear, however, why cryoglobulins are produced and which antigen triggers this process. HCV RNA itself may serve as the inciting agent.

Clinical features include palpable purpura, nonspecific systemic symptoms, arthralgias, lymphadenopathy, hepatosplenomegaly, peripheral neuropathy, and hypocomplementemia (low C4).

Here is a review on the topic.

*image is papable purpura (non-blanching erythematosus papules) found in a patient with chronic HCV infection with mixed cryoglobulinemia.

"Did the green onion make me yellow"?

Hep A is an RNA virus that spreads by the fecal-oral route. HAV is more prevalent in low socioeconomic areas with lack of adequate sanitation and poor hygienic practices. International travel is the most common risk factor in USA (and Canada).

HAV infection usually results in an acute, self-limited illness and only rarely leads to fulminant hepatic failure in those with underlying liver disease, especially chronic hepatits C infection.

The manifestations also vary with age: HAV is usually silent or subclinical in children. In contrast, infection in adults can vary in severity from a mild flu-like illness to fulminant hepatitis. The incubation period averages 30 days (range 15 to 49 days). Symptoms include fatigue, malaise, nausea, vomiting, anorexia, fever, and right upper quadrant pain followed by dark urine, light stools, jaundice, and pruritus. Lab investigations show marked elevations of serum aminotransferases (usually >1000 IU/dL), bilirubin, and alkaline phosphatase.

Acute HAV infection is diagnosed by the detection IgM anti-HAV in serum.

The treatment is supportive care.

* image: the most widespread hepatitis A outbreak in USA affected 640 people (killing 4) ,in late 2003, was blamed on tainted green onions at a restaurant.

Statin-induced muscle injury

Muscle injury with statin therapy can range from myalgias to myositis to rhabdomyolysis. Muscle symptoms usually begin within weeks to months after starting statins and usually return to normal over days to weeks after drug discontinuation.

You should warn your patients about new onset muscle pain and weakness when you start a statin. A CK level should be obtained at baseline, but routine monitoring of serum CK levels is not recommended.

Patients with acute or chronic renal failure, liver disease, and hypothyroidism are at higher risk of developing muscle injury. Clinical symptoms or a CK level >10X the upper limit of normal should prompt a drug discontinuation.

Pravastatin and fluvastatin appear to have much less intrinsic muscle toxicity than other statins. After the CK has returned to baseline, patients may be tried on a statin less likely to cause muscle toxicity with careful monitoring.

Here is review on the topic.

An assessment of statin safety by muscle experts. Thompson PD, Clarkson PM, Rosenson RS, National Lipid Association Statin Safety Task Force Muscle Safety Expert Panel. Am J Cardiol. 2006;97(8A):69C.

Antibiotics in COPD exacerbation

The use of antibiotics in exacerbations of COPD is based on small placebo-controlled trials and large retrospective population studies. They found that antibiotics improve clinical outcomes in severe COPD exacerbations. There is little evident for the use of antibiotics in mild exacerbation.

A recent cochrane review on the topic concluded that "in COPD exacerbations with increased cough and sputum purulence antibiotics, regardless of choice, reduce the risk of short-term mortality by 77%, decrease the risk of treatment failure by 53% and the risk of sputum purulence by 44%; with a small increase in the risk of diarrhoea These results should be interpreted with caution due to the differences in patient selection, antibiotic choice, small number of included trials and lack of control for interventions that influence outcome, such as use of systemic corticosteroids and ventilatory support. Nevertheless, this review supports antibiotics for patients with COPD exacerbations with increased cough and sputum purulence who are moderately or severely ill".


Choice of antibiotics is an area where not a great deal of evidence exists. Most initial trials were with Amoxicillin, Doxycyclin and Septra. However, these antibiotics are no longer considered first-line for treatment of pathogens such as H.Flu and M. catarrhalis that maybe responsible for COPD exacerbations. When deciding on the antibiotic choice, risk factors such as older age (>65 years), comorbid conditions (especially cardiac disease), severe underlying COPD (defined as FEV1 <50 percent), frequent exacerbations (three or more per year), and antimicrobial therapy within the past three months should be taken into account.

The GOLD guidelines recommend antibiotic therapy for patients with:

1) Severe exacerbation requiring mechanical ventilation
2) With three cardinal symptoms of increased sputum purulence plus either increased dyspnea or increased sputum volume
(thought they don’t provide any guidance regarding the choice of antibiotics)

WITHDRAWN: Antibiotics for exacerbations of chronic obstructive pulmonary disease.
Ram FS, Rodriguez-Roisin R, Granados-Navarrete A, Garcia-Aymerich J, Barnes NC. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD004403.

4 for 2, 2 for 4

This morning we reviewed the drugs involved in treatment of active tuberculosis.

The initial phase of treatment usually consists of two months of therapy with four drugs--typically isoniazid, rifampin, pyrazinamide, and ethambutol. The continuation phase in most cases consists of isoniazid and rifampin for four months (remember “4 for 2, 2 for 4”).

Treatment requires careful monitoring for drug toxicity. Baseline transaminases, bilirubin and ALP, CBD, creatinine, and uric acid should be obtained. When starting ethambutol, patients should be referred to ophthalmology for visual acuity and red-green color discrimination testing. Patients should be monitored closely for signs of hepatic toxicity.

Here is a recent update on TB management.
Current concepts in the management of tuberculosis. Sia IG, Wieland ML. Mayo Clin Proc. 2011 Apr;86(4):348-61

* Ghon's complex, seen in left middle field in the above image, is a lung lesion caused by tuberculosis that consists of a calcified focus of infection and an associated lymph node.

The Right dose at the Right time

This morning we discussed a case of fever and headache. We reviewd the approach to diagnosis and treatment of bacterial meningitis. Two key points from our discussion were:

1. Antibiotic therapy should not be delayed for any reason and should be given immediately after blood cultures are obtained. Dexamethasone should be given shortly before or at the same time as the first dose of antibiotics, when S. pneumoniae is suspected.

2. The "meningitis doses" of the empiric antibiotics in patients with normal renal function is: Vancomycin 1.5-2g IV q12, Ceftriaxone 2 g IV every 12 hours, and if Listeria suspected Ampicillin 2gr IV q4hr.


Here is a previous post on Meningitis.

*Steptococcus Pneumoniae, a gram postive cocci in chains, is the most common cause of community acquired bacterial meningitis in adults.

A case of bloody diarrhea

Today we discussed a case of bloody diarrhea caused by Enterohemorrhagic E. coli (EHEC), strain O157: H7.

Patients with this infection generally present with bloody diarrhea, mild leukocytosis, abdominal pain, but no fever. This bacteria produces a toxin called the Shiga toxin which can result in the dreaded Hemolytic-uremic syndrome (HUS)- the major systemic complication of EHEC infection. HUS is characterized by the triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia

The treatment of EHEC infection consists of supportive care and monitoring for the development of microangiopathic complications. Administering antibiotic therapy to patients with EHEC is not recommended (Grade 1B- though the evidence is only in children <10).

Here is a review article on the topic.

Escherichia coli O157:H7 and the hemolytic-uremic syndrome.Boyce TG, Swerdlow DL, Griffin PM. N Engl J Med. 1995;333(6):364.

* Romanian greenhouse employees destroy tons of cucumbers for fear of E. coli. In May 2011, a new Shiga toxin-producing EHEC strain, O104:H4, was identified as the cause of an outbreak in Germany and other countries in Europe.

"a case of abnormal bone softening"

We talked about a case of newly diagnosed Multiple Myeloma. Here is a previous blog post on the topic.

*Sarah Newbury, the first reported patient with multiple myeloma. (A) Bone destruction in the sternum. (B) The patient with fractured femurs and right humerus. (C) Bone destruction involving the femur. Reported by Solly 1844.

Combined ASA and Plavix in setting of Acute Stroke

This morning we talked about the evidence behind dual therapy with ASA and plavix in the setting of acute stroke.

A large study called the MATCH trial, with over 7500 patients, did not find any benefic with the combined use of aspirin and clopidogrel but found significant increase in the risk of bleeding complications.


The FASTER trial, a much smaller study with 392 patients with TIA or mild stroke, compared either aspirin plus clopidogrel (300 mg loading dose, then 75 mg daily) or aspirin alone. The trial ended prematurely due to slow recruitment. At 90 days, there was no statistically significant difference between the groups but a trend toward decreased primary outcome measure of combined ischemic and hemorrhagic stroke (7.1 versus 10.8 percent).

Silk Road Disease

This morning we discussed a case of oral ulcers and our differential diagnosis included Behcet’s disease.

This disorder is a systemic vasculitis that can effect veins of variable sizes. The disease is characterized by relapsing episodes of oral and genital ulcers, skin lesions, and ocular lesions, and can affect other systems including vascular, gastrointestinal, and neurological systems.

It occurs most frequently in an area that coincides with the Old Silk Route, so the disease is sometimes referred to as the Silk Road Disease.

Mainstay of treatment is immunosuppression with corticosteroids, azathioprine, cychlophosphamide, cyclosporine A, and more recently biologics including interferon-alpha, anti-tumour necrosis factor alpha agents.


Here is a recent feview article on the topic.

Behçet's disease--a contemporary review. Mendes D, Correia M, Barbedo M, Vaio T, Mota M, Gonçalves O, Valente J. J Autoimmun. 2009 May-Jun;32(3-4):178-88. Epub 2009 Mar 26.


* The image is a picture of Hulusi Behçet, a Turkish dermatologist and scientist who first described the illness in 1936.

Tachycardia-induced Cardiomyopathy

We discussed a case of tachycardia-induced cardiomyopathy this morning. This condition results from prolonged periods of rapid ventricular heart rates, and often improves with heart rate control with a good prognosis in most patients.

Patients may present with palpitations, fatigue, decreased exercise tolerance, or symptomatic congestive heart failure.

Treatment of tachycardia-mediated heart failure is the same as any other heart failure (eg, ACE or ARB inhibitors, beta blockers, diuretics), with aggressive control of heart rate.

Here is a recent review article on the topic

Tachycardia-induced cardiomyopathy: evaluation and therapeutic options. Lishmanov A, Chockalingam P, Senthilkumar A, Chockalingam A. Congest Heart Fail. 2010 May;16(3):122-6.


* Chest x ray showing cardiomegaly (panel A) in a patient with tachycardia (panel B). Panel C shows improved cardiomegaly after 3 months of aggressive heart-rate control (panel D). Images in Cardiology. Heart 2001;86:642.

Diabetic Autonomic Neuropathy

This morning our we talked about diabetic autonomic neuropathy (DAN) in long-standing diabetes.

DAN is a common and distressing complication that can affect any or all parts of the autonomic nervous system (ANS). Many organs are innervated dually by the parasympathetic and sympathetic fiber. DAN can cause hypo- or hyperactivity of each or all parts of the ANS.

Clinical manifestations can include the cardiovascular system (tachycardia, exercise intolerance, cardiac denervation leading to silent ischemia, orthostatic hypotension), GI system (esophageal dysfunction, gastroparesis, diarrhea or constipation, fecal incontinence), GU system (erectile dysfunction, neurogenic bladder), skin (impaired sweating), and metabolic dysfunction(hypoglycaemia unawareness).

Here a review article on the topic.
Diabetic autonomic neuropathy. Vinik AI, Freeman R, Erbas T. Semin Neurol.(4):365-7.

* A plain abdominal radiograph showing a very dilated stomach (arrows) secondary to diabetic autonomic neuropathy (Images in Clinical Medicine NEJM)

Water Intoxication

This morning, we discussed a case of hyponatremia.

Remember that disorders of sodium are really problems with water balance, so it is helpful to think of hyponatremia as excess free water. Prior to being able to test for serum sodium concentrations, the clinical syndrome that is now known as hyponatremia, characterized by confusion, muscle cramps, fatigue, delirium, seizures, and death, was called “water intoxication” syndrome.

Here are two previous post on hyponatremia.
Hyponatremia
Hyponatremia - no it's Hyperhydroemia


* MRI scan of person with central pontine myelinolysis (Saggital view, the dark area inside the circle is the region of damage). CPM is a devastating consequence of rapid fluctuations in sodium status.

Equilibrium

Today in morning report a few of the presented cases had disorders of equilibrium with the two cardinal symptoms of either vertigo – an illusion of bodily or environment spinning- or ataxia- incoordination of limbs or gait.

Disorders of disequilibrium can be produced by conditions that affect the vestibular pathways, the cerebellum, or sensory pathways in the spinal cord or peripheral nerves.

We considered the diagnosis of stroke in all of the above cases. A recent article in CMAJ called "Does my dizzy patient have a stroke" addresses that same question. Here is the article.

*Jean Louis Forain's 19th Century Tightrope Walker. How many organ systems is the performer using to maintaining her balance in the dark?

Is This Patient Malnourished?

In our physical exam rounds today, we examined a patient for signs of malnutrition, and reviewed the JAMA RCE article on the topic.

The gist of the articles is to know the “Subjective Global Assessment” which includes the following:
•History (Weight change,Dietary intake change,GI symptoms,Functional capacity)
•Physical exam (Loss of subcutaneous fat, Muscle wasting, Edema)

Based the above, you can categorize patients into “well-nourished”, “moderately malnourished”, or “severely malnourished”. These categories then correlate with patient likelihood of being admitted, and post-operative complications.

Here is the article.
http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed?term=is%20this%20patient%20malnourished%20detsky%20JAMA

* Given our topic of conversation, I like to remind everyone of the famine in East Africa. A devastating drought and crumbling infrastructure have created one of the worst hunger emergencies in our generation. If you would like to make a donation, the Government of Canada has created the East Africa Drought Relief Fund, and will match your donations.

An aspirin a day? ASA in secondary prevention of CVD.

This morning we briefly mentioned the Antithrombotic Trialists' Collaboration overview article. This group reviewed the results of 195 randomized trials of aspirin, among more than 135,000 high-risk patients with prior history of cardiovascular or cerebrovascular events. The following are the major conclusions:

• Aspirin, significantly reduced the relative risk of subsequent vascular events (nonfatal MI, nonfatal stroke, and vascular death) by approximately 22 percent.
• There was no difference in efficacy between doses of 75 to 150 mg/day (called low-dose aspirin) and 160 to 325 mg/day (called medium-dose aspirin).

Here is the link to the paper if you like.
Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Antithrombotic Trialists' Collaboration. BMJ. 2002;324(7329):71.

http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed?term=BMJ.%202002%3B324(7329)%3A71.

* A French advertisement for aspirin from 1923. Aspirin (name originally coined by they Bayer company in 1897) lost its status as a registered trademark became a generic name in many countries. Today, Aspirin, with a capital "A", remains a registered trademark of Bayer Canada.

...and the QT was 580!!

Amuse-Bouche at today’s morning report was prolonged QT interval on the ECG. This conditions is associated with an increased risk of torsades de pointes, which is a life threatening polymorphic ventricular tachycardia.

Long QT can be genetic or acquired. Drugs are a common cause of prolonged QT. Among them are:
• Antiarrhythmic drugs such as sotolol, amiodarone, quinidine, procainamide
• Macrolide and floquinolone antibiotics
• Certain psychotropic medications like TCAs, haloperidol, methadone

Drug-induced prolonged QT is an idiosyncratic event, but there are some identified risk factors.
• Rapid IV infusion of the drug
• Electrolyte abnormalities (hypokalemia, hypocalcemia or hypomagnesemia)
• Use of other drugs known to prolong the QT interval
• Congenital long QT syndrome
• Underlying cardiac abnormalities
• Hypothyroidism
• Females
• Patients with stroke

Here is a review article on the topic.
Long QT syndrome: diagnosis and management. Khan IA. Am Heart J. 2002 Jan;143(1):7-14
http://www.ncbi.nlm.nih.gov/pubmed/11773906

* The term “torsade de pointes” means “twisting around the points in ballet where the dancer rotates around an imaginary axis. On the ECG, the QRS complex appears to twist around the electrical baseline with a continuously changing point of origin, reminiscent of the ballet movement.

Ascites

We talked about examination manoeuvres for clinically diagnosing ascites today in our physical exam rounds. Here is a good review of the topic in a previous post.

http://morningreporttwh.blogspot.com/2009/07/ascites.html

* The image is a painting of Bacchus, the Greek god of wine by Henri Millot,1730. How many stigmata of alcoholic cirrhosis can you identify in him?

Is it hot enough yet?

Given the recent heat wave in Toronto, morning report was aptly about a case of heat stroke today. As we discussed today, the most important causes of severe hyperthermia (greater than 40ºC) are heat stroke, neuroleptic malignant syndrome, thyroid strom, and malignant hyperthermia.

Heat stroke is diagnosed based on history, physical examination and the context in which symptoms developed (eg, high temperature and no air conditioner). Diagnostic studies are nonspecific. Heat stroke can cause cardiovascular, renal, or hepatic dysfunction or coagulopathy.

The management of heat stroke consists of ABC, rapid cooling, and treatment of complications.

Here is a recent review of the topic.

Heat-related illness. Becker JA, Stewart LK. Am Fam Physician. 83(11):1325-30
http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed/21661715

Toxic Epidermal Necrolysis

This morning we discussed an unsolved mystery that involved a skin biopsy showing TEN. Toxic Epidermal Necrolysis (TEN) a severe type of hypsersensitivity reaction, affecting the skin and mucus membranes, that occurs in response to medications and some infections.

Treatment includes stopping the offending agent and supportive care including treating the complications such as superimposed skin infections.

Here is a recent review on the topic if you like to read more!
Toxic epidermal necrolysis and Stevens-Johnson syndrome: a review.
Gerull R, Nelle M, Schaible T. Crit Care Med. 2011 Jun;39(6):1521-32.

*The above picture is Mycoplasma pneumoniae, which is rarely associated with TEN

Systemic Lupus Erythematosis

This morning, we discussed a case of first presentation of lupus. Here is post from last year on the topic
http://morningreporttwh.blogspot.com/2010/07/systemic-lupus-erythematosus.html

* Contrary to popular belief, British singer Seal wasn't bitten by a seal and didn't wrestle a wild boar. His facial scars are manifestations of discoid rash of lupus.<

Neurologic Manifestations of Vitamin B12 Deficiency

In our discussion this morning about the causes of “fall and dementia” we briefly touched on Vitamin B12 deficiently. Vitamin B12 is a water soluble present in animal products (meat and dairy). B12 is involved in myelin synthesis, and hence, it’s deficiency has neurologic consequences.

Neurologic manifestations of B12 deficiency is the classic subacute combined degeneration of the dorsal (posterior) and lateral spinal columns. SCD manifests as symmetrical primarily lower limb neuropathy with loss of vibration and position sense, which can result in ataxia.

Other neurologic findings in B12 deficiency include axonal degeneration of peripheral nerves and central nervous system symptoms including memory loss, irritability, and dementia.

Interestingly, not all patients with neurologic abnormalities secondary to Vit B12 deficiency have hematologic manifestations.

Here is good review of B12 deficiency.
Current concepts in the diagnosis of cobalamin deficiency. Green R, Kinsella LJ. Neurology. 1995;45(8):1435.

*the picture is an axial image of the spinal cord of a patient with B12 Deficiency. Blue is where myeline is stained and you can see the loss of myeline latterally and posteriorly.