April 2016 by Doctor's Review

APRIL 2016

BASE ings A T A ING D m/meet T E E .co +M 2500 rsreview AGE 21 doctoSS CODE P ACCE

MEDICINE ON THE MOVE

Flashlight self-defense Medicine’s truest symbol Patients’ compliance in depression

WIN

THIS MONTH’S

GADGET PAGE 19

CANADIAN PUBLICATIONS MAIL SALES PRODUCT AGREEMENT No. 40063504

ADVENTURES Safari savings in style Silk Road ramblings Sail Spain to Italy PLUS:

Cheese meltdown!

IN E L B ILA A AV

D NA

FORXIGA (dapagliflozin) is a reversible inhibitor of sodium-glucose co-transporter 2 (SGLT2) that improves glycemic control by reducing renal glucose reabsorption leading to urinary excretion of excess glucose (glucuresis)1,2 *â&#x20AC;

The first and only fixed-dose combination of an SGLT2 inhibitor with metforminâ&#x20AC;Ą XIGDUO combines two antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes: dapagliflozin and metformin hydrochloride2 *

There have been no clinical studies conducted with XIGDUO tablets. XIGDUO tablets demonstrated comparable bioavailability of dapagliflozin and metformin with co-administered tablets of dapagliflozin and metformin in a four-way crossover comparative bioavailability study.

XIGDUO

• Increased mean hemoglobin/hematocrit and frequency of patients with abnormally elevated values of hemoglobin/hematocrit

Indications and clinical use:

• Hypoglycemia

XIGDUO is indicated for use as an adjunct to diet and exercise in adults with type 2 diabetes mellitus who are already being treated with dapagliflozin and metformin as separate tablets and achieving glycemic control. XIGDUO is also indicated for use in combination with insulin as an adjunct to diet and exercise in adults with type 2 diabetes mellitus who are already achieving glycemic control with dapagliflozin, metformin and insulin.

• Increased risk of genital mycotic infections • Temporary suspension for any surgical procedure; discontinue 2 days before procedure and should not be restarted until patient’s oral intake has resumed and renal function is normal

Not for use in pediatrics (<18 years).

• Use of concomitant medications that may affect renal function or result in significant hemodynamic change or may interfere with the disposition of metformin

Geriatrics (≥65 years of age): caution as age increases.

• Periodic measurements of fasting blood glucose and A1c levels

Contraindications:

For more information:

• Unstable and/or insulin-dependent (Type I) diabetes mellitus

Please consult the Product Monograph at www.azinfo.ca/xigduo/pm944 for important information relating to adverse reactions, drug interactions and dosing. The Product Monograph is also available by calling 1-800-668-6000.

• Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma, history of ketoacidosis with or without coma, history of lactic acidosis, irrespective of precipitating factors • In patients with serum creatinine levels above the upper limit of normal range or when renal function is not known, renal disease or renal dysfunction, or abnormal creatinine clearance (<60 mL/min), which may result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia • Excessive alcohol intake, acute or chronic • Severe hepatic dysfunction, since severe hepatic dysfunction has been associated with some cases of lactic acidosis, XIGDUO should not be used in patients with clinical or laboratory evidence of hepatic disease • Cardiovascular collapse and in disease states associated with hypoxemia, which are often associated with hyperlactacidemia • Stress conditions

FORXIGA FORXIGA is indicated in monotherapy for use as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus for whom metformin is inappropriate due to contraindications or intolerance. FORXIGA is also indicated in adult patients with type 2 diabetes mellitus to improve glycemic control in add-on combination with metformin, a sulfonylurea, metformin and a sulfonylurea, sitagliptin (alone or with metformin), or insulin (alone or with metformin), when metformin alone or the existing therapy listed above, along with diet and exercise, does not provide adequate glycemic control. Consult the complete Product Monograph at www.azinfo.ca/forxiga/pm367 for important information about:

• Severe dehydration • During pregnancy and breastfeeding

• Contraindications in patients with moderate to severe renal impairment, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, end-stage renal disease and patients on dialysis.

• Period around administration of iodinated contrast materials Most serious warnings and precautions: Lactic acidosis: can occur due to metformin accumulation during treatment. Patients should be cautioned against excessive alcohol intake as it can potentiate the effect of metformin on lactic acidosis. Other relevant warnings and precautions: • Not for use in patients with active bladder cancer and use with caution in patients with a prior history of bladder cancer • Not for use in patients concomitantly treated with pioglitazone • Not recommended for use in patients who are volume-depleted; caution in patients for whom a dapagliflozin-induced drop in blood pressure could pose a risk, or in case of intercurrent conditions that may lead to volume depletion; careful monitoring of volume status is recommended and temporary interruption of XIGDUO should be considered for patients who develop volume depletion until the depletion is corrected

• Relevant warnings and precautions: not for use in type 1 diabetes or for the treatment of diabetic ketoacidosis; not for use in patients with active bladder cancer and use with caution in patients with a prior history of bladder cancer; not recommended for use in patients who are volume depleted; caution in patients for whom a FORXIGA-induced drop in blood pressure could pose a risk, or in case of intercurrent conditions that may lead to volume depletion; careful monitoring of volume status is recommended and temporary interruption of FORXIGA should be considered for patients who develop volume depletion until the depletion is corrected; DKA, caution in patients at higher risk of DKA and when reducing a patient’s insulin dose; risk of hypoglycemia when used in combination with insulin or insulin secretagogues; dose-related LDL-C increases; monitor LDL-C levels; increased mean hemoglobin/hematocrit and frequency of patients with abnormally elevated values of hemoglobin/hematocrit; increased risk of genital mycotic infections and urinary tract infections; not recommended in severe hepatic impairment; renal function should be assessed prior to initiation of FORXIGA and regularly thereafter; not for use in pregnant or nursing women; patients taking FORXIGA will test positive for glucose in their urine.

• Hypoxic states have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur, XIGDUO should be promptly discontinued

• Conditions of clinical use, adverse reactions, drug interactions, and dosing instructions.

• Risk of hypoglycemia when used in combination with insulin

The Product Monograph is also available by calling 1-800-668-6000.

• Dose-related LDL-C increases; monitor LDL-C levels • Laboratory abnormalities or clinical illness should be evaluated promptly in patients previously well controlled on XIGDUO for evidence of ketoacidosis or lactic acidosis; if acidosis occurs, XIGDUO must be stopped immediately and corrective measures initiated

* Clinical significance unknown. † The amount of glucose removed by the kidney through this mechanism is dependent upon the blood glucose concentration and glomerular filtration rate. ‡ Comparative clinical significance unknown.

• Temporary loss of glycemic control when exposed to stress • Decrease in vitamin B12 levels; initial and periodic monitoring of hematologic parameters advised

01/17

References: 1. FORXIGA Product Monograph. AstraZeneca Canada Inc., December 8, 2015. 2. XIGDUO Product Monograph. AstraZeneca Canada Inc., December 9, 2015.

The adventure of walking I went for a long walk yesterday. It’s a very human thing to do. Ever since we managed to struggle onto our hind legs, we’ve walked. It’s what we do and, for better or worse, by now we’ve covered almost the entire planet with our footsteps many times over. Walking is much more than a way of getting from point A to point B. It can be a comfort and a joy or sheer drudgery. Poets, philosophers and prime ministers walk to calm themselves, to find a fresh way of looking at the world, to ruminate. Of course, so do the rest of us, including writers. I just read two books about walking, but that’s where their similarity ends. Bill Bryson’s newest, The Road to Little Dribbling, describes his second walk around the British Isles. Twenty years ago, he penned the best seller Notes from a Small Island about a similar trek. Despite his curmudgeonly comments on the deterioration in beauty and civility in the UK over the last two decades, he’s an optimistic, funny man, and both books are a delight. Not so for Walking the Nile by British modern-day explorer Levison Wood. His ambition was to be the first person ever to walk the 6840 kilometres from the great river’s source to the Mediterranean delta in Egypt. He made it, but it Bill Bryson on the hunt. took him nine months of almost unrelieved grief. He started in Rwanda and walked north through Uganda, South Sudan, Sudan and Egypt. Each of these countries is washed in blood beginning with the Rwandan genocide, not forgetting the brutal rule of Idi Amin, the “Butcher of Uganda,” who killed as many as 500,000; the current fighting in South Sudan, which has brought the new country to its knees; and the suppressive rule in post-Arab Spring Egypt. Across the area, normal family life is constantly under threat if not from war then from disease, pollution, drought and food shortages. The forests are being cut down and wildlife poached almost to extinction. It’s not a pretty picture and Wood is not one to make the best of it. He soldiers on finding what peace he can in putting one foot in front of the other, fed by his ambition to get it done and find his own place in the history books. If what he records is an accurate reflection of the times, it will be a small miracle if Africa — and, for that matter, the rest of us — survives to the end of the century. What makes us kill? On a happier note, adventure has its place and this issue offers good reads about adventures in China, Europe and South Africa. In the latter case, if you’ve ever considered an African safari, the article by Anita Draycott (page 32) is a must-read. She and four friends rent a luxury villa adjacent to Kruger Park that comes with a private guide. They see all of the Big Five on the first day. Need I say more? Happy trails,

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David Elkins, publisher and editor delkins@parkpub.com

@doctorsreview APRIL 2016 • Doctor’s

Review

Experience ANORO ELLIPTA ™

Indications and Clinical Use: ANORO™ ELLIPTA® (umeclidinium/vilanterol) is a combination of a long-acting muscarinic antagonist (LAMA) and a long-acting beta2-agonist (LABA) indicated for the long-term once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. ANORO™ ELLIPTA® is not indicated for the relief of acute deterioration of COPD. ANORO™ ELLIPTA® is not indicated for the treatment of asthma. The safety and efficacy of ANORO™ ELLIPTA® in asthma have not been established. ANORO™ ELLIPTA® should not be used in patients under 18 years of age. Contraindications: • Patients with severe hypersensitivity to milk proteins. Most Serious Warnings and Precautions: • ASTHMA-RELATED DEATH: Long-acting beta2-adrenergic agonists (LABA) increase the risk of asthma-related death. Data from a large placebo-controlled US study that compared the safety of salmeterol (SEREVENT® Inhalation Aerosol) or placebo added to patients’ usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of LABA, including vilanterol, one of the active ingredients in ANORO™ ELLIPTA®. The safety and efficacy of ANORO™ ELLIPTA® in patients with asthma have not been established.

Other Relevant Warnings and Precautions: • ANORO™ ELLIPTA® is not indicated for the treatment of acute episodes of bronchospasm (i.e., as rescue therapy), relief of acute deterioration of COPD or for the treatment of asthma. • ANORO™ ELLIPTA® should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD. • Patients should be instructed to discontinue regular use of short-acting beta2-agonists and to use them only for acute respiratory symptoms. • Exacerbations may occur during treatment. Patients should be advised to continue treatment and seek medical advice if COPD symptoms remain uncontrolled or worsen after initiation of therapy. • ANORO™ ELLIPTA® should not be used more often or at higher doses than recommended. ANORO™ ELLIPTA® should not be used in conjunction with other medicines containing a LABA or LAMA. • Headache or blurred vision may influence the ability to drive or to use machinery. • Anticholinergic Effects: Use with caution in patients with narrow-angle glaucoma or urinary retention. • Cardiovascular effects: ANORO™ ELLIPTA® should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, acute myocardial infarction, cardiac arrhythmias, and hypertension. Cardiovascular effects such as cardiac arrhythmias, may be seen after administration. Treatment may need to be discontinued. ANORO™ ELLIPTA® was associated with a dose-dependent increase in heart rate and QTcF prolongation in healthy subjects receiving steady-state treatment. Caution is recommended in patients with a known history of QTc prolongation, risk factors for torsade de pointes (e.g., hypokalemia), or patients taking medications known to prolong the QTc interval.

A once-daily LAMA/LABA dual bronchodilator for COPD.* • Endocrine and Metabolism: Use with caution in patients with convulsive disorders, thyrotoxicosis and patients who are unusually responsive to sympathomimetic amines. Use with caution in patients predisposed to low levels of serum potassium or patients with ketoacidosis or diabetes. • Respiratory: Treatment should be discontinued if paradoxical bronchospasm occurs and alternative therapy instituted if necessary. • Hypersensitivity: As with all medications, immediate hypersensitivity reactions may occur after administration of ANORO™ ELLIPTA®. Patients with severe milk protein allergy should not take ANORO™ ELLIPTA®. • Use during pregnancy, labour and in breastfeeding women should only occur if the potential benefit justifies the potential risk. Adverse Events: Adverse reactions reported at a frequency of ≥1% and greater than placebo include: pharyngitis, sinusitis, lower respiratory tract infection, diarrhea, constipation, pain in extremity, muscle spasms, neck pain and chest pain.

Recommended Dose: • The recommended dose is one inhalation of ANORO™ ELLIPTA® 62.5/25 mcg once daily. Dosing Considerations: • No dosage adjustment is required in patients over 65 years of age, in patients with renal impairment, or in patients with mild or moderate hepatic impairment. ANORO™ ELLIPTA® has not been studied in patients with severe hepatic impairment. For More Information: Please consult the Product Monograph at http://gsk.ca/anoro/en for important information relating to adverse reactions, drug interactions, and dosing information, which have not been discussed in this piece. The Product Monograph is also available by calling 1-800-387-7374. To report an adverse event, please call 1-800-387-7374. *LAMA=Long-acting muscarinic antagonist [also known as a long-acting anticholinergic (LAAC)]; LABA=Long-acting beta2-agonist

ANORO and ELLIPTA are trademarks of Glaxo Group Limited, used under license by GlaxoSmithKline Inc. ANOROTM ELLIPTA® was developed in collaboration with Theravance, Inc. © 2015 GlaxoSmithKline Inc. All rights reserved. 00656 05/15

Treating IBS-C? Consider CONSTELLA® CONSTELLA® patients showed significant improvement in:

• Abdominal pain

• Bloating • Constipation2

Abdominal pain2 AT WEEK 12 38.9% had ≥30% reduction in abdominal pain for at least 9/first 12 weeks vs. 19.6% placebo (p<0.0001)

(Trial 2, abdominal pain responder, ≥30% reduction from baseline)

Bloating2,3† AT WEEK 12 29% improvement in abdominal bloating from baseline vs. 15% placebo (p<0.0001)

(Trial 2, secondary endpoint, mean change vs. baseline) Baseline: CONSTELLA® 6.6, placebo 6.5. Mean weeks 1-12: CONSTELLA® 4.7, placebo 5.4, 11-point scale.

Spontaneous bowel movements (SBMs)2 67% had an SBM within 24 hours of their first dose vs. 42% placebo (p<0.0001) (Trials 1 and 2, pooled results, secondary endpoint)

Study parameters are available at http://www.actavis.ca/specialty/products/constella

The only prescription medication indicated in Canada for IBS-C in adults1* Visit ConstellaMD.ca to learn more Indications and clinical use: CONSTELLA® (linaclotide) is indicated for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in adults. Clinical studies of CONSTELLA® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. CONSTELLA® is contraindicated in children under 6 years of age and is not recommended for use in children between 6 and 18 years of age as the safety and efficacy of CONSTELLA® in pediatric patients have not been established. Contraindications: • Pediatric patients under 6 years of age • Patients with known or suspected mechanical gastrointestinal obstruction Most serious warnings and precautions: Children: Not recommended in children between 6 and 18 years of age

Other relevant warnings and precautions: • Diarrhea most common adverse reaction; may cause serious diarrhea • Use in pregnant women only if the potential benefit justifies the potential risk to the fetus • Caution should be exercised when CONSTELLA® is administered to nursing women For more information: Please consult the Product Monograph at www.actavis.ca/NR/ rdonlyres/94008767-D103-460E-B854-766C324A3CE8/0/CONSTELLA_ ProductMonograph.pdf for important information relating to adverse reactions, food interactions and dosing information not discussed in this piece. The Product Monograph is also available by calling 1-855-892-8766. IBS-C=irritable bowel syndrome with constipation * Comparative clinical significance has not been established. † Scores self-evaluated on an 11-point numerical rating scale (0=none, 10=very severe).3 References: 1. Data on file, Allergan Inc., August 26, 2015. 2. CONSTELLA® (linaclotide) Product Monograph, Forest Laboratories Canada Inc., May 12, 2014. 3. Data on file, Forest Laboratories Canada Inc.

linaclotide capsules

contents APRIL 2016

COVER: UTOPIA_88 / SHUTTERSTOCK.COM

features 32 Safari extraordinaire An affordable, South African adventure at a private game reserve where the animals are literally your neighbours by Anita Draycott

40 Spain to Italy by sailing ship

A weeklong cruise from Barcelona to Rome aboard a five-masted, 300-passenger luxury yacht by John and Sandra Nowlan

Commanders in cheese Strawberries, brie and bourbon sauce for brunch plus more gooey grilled sandwiches that will make you melt by Heidi Gibson with Nate Pollak

Silk Road rising The old trade route is being resurrected by the new China —10 wonders along the way to take in now by Gary Crallé

40 52 Treating chronic pain, our shared responsibility. APRIL 2016 • Doctor’s

CLIENT: Purdue

DOCKET NUMBER: PQ9818

PROJECT: Magazine Ads

FILE NAME: PQ9818_BL_DR

Review

COLOURS

PRODUCER

Helping you support your patients on ALESSE.

An effective oral contraceptive and a trusted choice in Canada for 18 years.1

New Box Design. Same Formula. DUAL INDICATION: CONCEPTION CONTROL AND TREATMENT OF MODERATE ACNE VULGARIS.2 HELP YOUR PATIENTS SAVE ON ALESSE! Encourage them to visit Alesse.ca, enroll and download the Pfizer Strive Payment Assistance card.* Alesse (levonorgestrel 100 mcg and ethinyl estradiol 20 mcg tablets) is indicated for conception control and the treatment of moderate acne vulgaris in women ≥14 years of age, who have no known contraindications to oral contraceptive therapy, desire contraception and have achieved menarche. Consult the product monograph at http://www.pfizer.ca/pm/en/ALESSE.pdf for contraindications, warnings, precautions, adverse reactions, interactions, dosing, and conditions of clinical use. The product monograph is also available through our medical department. Call us at 1-800-463-6001. * Pfizer Strive Payment Assistance is available in all provinces except Quebec. Availability and coverage vary by province.

References: 1. Alesse NOC. Health Canada, 1997. 2. Alesse Product Monograph, Pfizer Canada Inc., September 18, 2015.

® Pfizer Inc., used under license ALESSE ® Wyeth LLC, owner; Pfizer Canada Inc., Licensee

CA0115ALS016E

Alesse makes sense

contents APRIL 2016

regulars 11

13 19

LETTERS

Multi-purpose tactical flashlights by David Elkins

From cracking jokes to cranking radios

PRACTICAL TRAVELLER Join Chris Hadfield on a cruise to the Arctic, celebrate one of the world’s oldest choirs in Germany, eat fresh with Air Transat’s new menu and more by Camille Chin and David Elkins

GADGETS

TOP 25 The biggest medical meetings scheduled for September

HISTORY OF MEDICINE One snake or two? Is the Asclepius or Caduceus the real symbol of medicine? by Rose Foster

DEPRESSION KEYPOINTS Issues in patient compliance by Mairi MacKinnon

PHOTO FINISH A slippery slope by Dr Errol Billinkoff

Coming in

May

• Prince Edward County, 200 kilometres from Toronto, where the vineyards, farm-to-table restos and beaches beckon • Lake Okanagan calls itself the “Houseboat Capital of Canada” — get ready for a really good time • Lima offers a cornucopia of fine places to dine on local ingredients from farm, sea and forest

• Young adults often try to cover-up depression, and family and friends can dismiss it as a “phase” — must-ask questions APRIL 2016 • Doctor’s

Review

Introducing

Introducing Nesina (alogliptin): a new DPP-4 inhibitor for patients with type 2 diabetes. Pr

Reimbursed by RAMQ as a médicament d’exception (prescribing codes available) Treatment of type 2 diabetic patients:

CODE

As monotherapy, where metformin and sulfonylurea are contraindicated or not tolerated

EN167

In association with metformin, where sulfonylurea is contraindicated, not tolerated or ineffective

EN148

In association with sulfonylurea, where metformin is contraindicated, not tolerated or ineffective

EN149

DPP-4 = Dipeptidyl peptidase-4

As per RAMQ List of Medications and Codes des médicaments d’exception (Updated July 24, 2015).

Nesina is indicated to improve glycemic control in adult patients with type 2 diabetes mellitus • as monotherapy as an adjunct to diet and exercise in patients for whom metformin is inappropriate due to contraindications or intolerance • in combination with metformin when diet and exercise plus metformin alone do not provide adequate glycemic control • in combination with a sulfonylurea (SU) when diet and exercise plus a SU alone do not provide adequate glycemic control • in combination with pioglitazone when diet and exercise plus pioglitazone alone do not provide adequate glycemic control ®

• in combination with pioglitazone and metformin when diet and exercise plus dual therapy with these agents do not provide adequate glycemic control • in combination with insulin (with or without metformin) when diet and exercise plus a stable dose of insulin (with or without metformin) do not provide adequate glycemic control Consult the product monograph at http://www.takedacanada.com/ ca/nesinapm for contraindications, warnings, precautions, adverse reactions, drug interactions, dosing and conditions of clinical use. The product monograph is also available by calling us at 1-866-295-4636.

REFERENCE: 1. NESINA Product Monograph, Takeda Canada Inc., November 7, 2014. ®

See Product Monograph for complete dosing and administration information including dosage adjustment in renal impairment.

LETTERS

EDITOR

David Elkins

MANAGING EDITOR

Camille Chin

CONTRIBUTING EDITOR

Katherine Tompkins

From cracking jokes to cranking radios

TRAVEL EDITOR

Valmai Howe

SENIOR ART DIRECTOR

Pierre Marc Pelletier

DOCTORSREVIEW.COM WEBMASTER

Pierre Marc Pelletier

PUBLISHER

David Elkins

DIRECTOR, SALES & MARKETING

Stephanie Gazo / Toronto

OFFICE MANAGER

Denise Bernier

CIRCULATION MANAGER

Claudia Masciotra

EDITORIAL BOARD

R. Bothern, MD R. O. Canning, MD M. W. Enkin, MD L. Gillies, MD M. Martin, MD C. G. Rowlands, MD C. A. Steele, MD L. Tenby, MD L. Weiner, MD

MD HUMOUR A younger member of the profession passed me the magazine. I enjoyed, hilariously, the several “Medical Quips.” Please keep them coming. On page 20 [One last thing, February 2016], there is a tantalizing, juicy story in bold print titled “Listen Up.” I’d like to read details of the story. Where was the story published? Dr Muri B Abdurrahman, a young septuagenarian with sharp eyes for fun Via email

Editor’s note: Here’s the source for the piece you inquired about: thestar.com/news/ gta/2016/01/16/doctor-sues-mother-ofhis-child-for-emotional-damages.html.

MONTREAL HEAD OFFICE

400 McGill Street, 4th Floor Montreal, QC H2Y 2G1 Tel: (514) 397-8833 Fax: (514) 397-0228 Email: editors@doctorsreview.com www.doctorsreview.com

TORONTO SALES OFFICE

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None of the contents of this publication may be reproduced, stored in a retrieval system or transmitted in any form by any means, without prior permission of the publishers. ISSN 0821-5758 Canadian Publications Mail Sales Product Agreement No. 40063504 Post-paid at St. Laurent, QC. Return undeliverable Canadian addresses to: Circulation Department, 400 McGill Street, 3rd Floor, Montreal, QC, H2Y 2G1. Subscription rates: One year (12 issues) – $17.95 Two years (24 issues) – $27.95* One year U.S. residents – $48.00 *Quebec residents add PST. All prescription drug advertisements appearing in this publication have been precleared by the Pharmaceutical Advertising Advisory Board.

CHARTING DEPRESSION The study reports on those who attended for treatment as 43 percent of those suffering depression [“The high cost of untreated depression,” Depression Snapshot, February 26, page 26]. In other words, an additional 57 percent are not reporting their illness and not getting treatment. That is 3,110,137 persons — approximately 15 percent of the total population of Canadians. A staggering figure for a treatable yet highly disabling illness. Dr Ezzat Guirguis Via DoctorsReview.com

PERFECT TIME I live in a place where the electricity goes out with some regularity. More than the time projected onto the ceiling [“Atomic time,” Gadgets, January 2016], I love the idea of a clock with unquestioned accuracy. Dr John Carroll Via DoctorsReview.com

CONGRATULATIONS!

The winner of an Eton Scorpion II emergency crank radio is Dr Glenn Loy Son, a pediatrician from Guelph, ON.

CRANKED UP Here are a few of the online comments we received about the Eton Scorpion II emergency crank radio: I already wonder how I could have lived the past 73 years without it. Dr Pierre Gagne

Looks like a great gadget to have in emergencies. Dr Rebecca Caces

I really hope it is nothing like [the crank radio] I saw Wednesday night [on the TV show Modern Family]. It seems that this one has a 4:1 play-to-crank ratio, however, whereas others are 1:1 (one minute of airtime per one minute of cranking). [To see the Modern Family clip, go to abc.go.com/shows/modernfamily/video and click on “Cam and Mitch Improvise for Lily’s Party.”] Mitchell Pritchett

A very handy gadget for anyone who wants to survive a severe storm. Dr Yasmin Mussani

APRIL 2016 • Doctor’s

Review

PA R T O F T H E N OVA R T I S C O P D P O R T F O L I O

A once-daily dual LAMA/LABA bronchodilator for COPD1 Indications and clinical use: ULTIBRO® BREEZHALER® (indacaterol maleate and glycopyrronium bromide) is a combination of a long-acting β2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA), indicated for the long-term once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. Consult the complete Product Monograph at www.novartis.ca/UltibroMonograph for important information about: • Contraindications in asthma, severe hypersensitivity to milk proteins or hypersensitivity to any component of ULTIBRO® BREEZHALER® • The most serious warnings and precautions regarding asthma-related death • Other relevant warnings and precautions regarding acute episodes of bronchospasm; acutely deteriorating COPD; concomitant use with other LABAs and LAMAs; use in patients with narrow-angle glaucoma, urinary retention, cardiovascular disorders, especially coronary insufficiency, acute myocardial infarction, cardiac arrhythmias, and hypertension, known history of QTc prolongation, risk factors for torsade de pointes, or patients who are taking medications known to prolong the QTc interval; convulsive disorders, thyrotoxicosis; patients who are unusually responsive to sympathomimetic amines, severe renal impairment, severe hepatic impairment; risk of hypokalemia, hyperglycemia, immediate hypersensitivity reactions including angioedema, urticaria, or skin rash; risk of paradoxical bronchospasm; use during labour, pregnancy/nursing and delivery • Conditions of clinical use, adverse reactions, drug interactions and dosing/administration instructions The Product Monograph is also available by calling the Medical Information Department at 1-800-363-8883.

Reference: 1. ULTIBRO® BREEZHALER® Product Monograph. Novartis Pharmaceuticals Canada Inc., August 18, 2014. ULTIBRO and BREEZHALER are registered trademarks. Product Monograph available on request. PRO/ULT/0050E © Novartis Pharmaceuticals Canada Inc. 2016

P R AC T I C AL T R A V E L L E R

Arctic high Join Colonel Chris Hadfield, the first Canadian Commander of the International Space Station, on an expedition to explore the high Arctic on the icebreaker Kapitan Khlebnikov. “This is the ultimate earthly adventure, where real learning happens,” says Hadfield who calls the trip, “almost like a space expedition of its own.” As a bonus, fellow explorers will be treated to “Chris Hadfield’s Generator,” a science-based variety show hosted by the space walker. Offered by Quark Expeditions, now in its 25th year of providing polar travel, the 18-day adventure begins on August 22 in Ottawa with a charter flight to Kangerlussuaq, Greenland. The all-inclusive price for the Best of the Canadian High Arctic package is US$21,945. quarkexpeditions. com/en/arctic/. [DE]

APRIL 2016 • Doctor’s

Review

P R AC T I C AL T R A V E L L E R

MATTHIAS KRÜGER

A celebration of song One of the world’s oldest choirs is celebrating its 800th anniversary this year — its singers are all boys between the ages of nine and 19. The Dresdner Kreuzchor, or Choir of the Church of the Holy Cross, is one of Germany’s most important cultural institutions. The choir sings at half of all the services and evening prayers at the Church of the Holy Cross in Dresden’s Old Market Square. Concerts are attended by up to 3000 people. Its repertoire ranges from the early Baroque works of the musical director of the Dresden court orchestra Heinrich Schütz, the Passions, Motets and Cantatas by Bach to the choir music of the 19th century up to modernism. About 150 singers attend the Church of the Holy Cross school; half of them live at the adjacent boarding house. For performance dates through 2016 and locations: kreuzchor.com. [CC]

Vienna took the top spot in Mercer’s 2016 Quality of Living Rankings. Headquartered in NYC and based in 43 countries, Mercer is the largest human resources consulting firm in the world. Mercer’s survey is conducted annually to enable multinational companies to compensate employees fairly when placing them on international assignments. Living conditions are analyzed according to 39 factors in 10 categories: politics, economics, socio-cultural, medical and health, schools and education and so on. The survey also identifies personal safety rankings based on internal stability, crime figures, performance of local law enforcement and the home country’s relationship with other countries. For more: imercer.com/content/mobility/quality-ofliving-city-rankings.html. [CC]

Doctor’s Review • APRIL 2016

KAPA1966 / SHUTTERSTOCK.COM

At home in Europe Vienna’s historic Old Town.

QUALITY OF LIVING 1. Vienna, Austria 2. Zurich, Switzerland 3. Auckland, New Zealand 4. Munich, Germany 5. Vancouver, Canada 6. Dusseldorf, Germany 7. Frankfurt, Germany 8. Geneva, Switzerland 9. Copenhagen, Denmark 10. Sydney, Australia

PERSONAL SAFETY 1. Luxembourg 2. Bern, Switzerland 3. Helsinki, Finland 4. Zurich, Switzerland 5. Vienna, Austria 6. Geneva, Switzerland 7. Stockholm, Sweden 8. Singapore 9. Auckland, New Zealand 10. Wellington, New Zealand

Russia underground VIACHESLAV LOPATIN / SHUTTERSTOCK.COM DANIEL KORZENIEWSKI / SHUTTERSTOCK.COM

MOS.RU / WIKIMEDIA

Glacier National Park in Montana’s Rocky Mountains.

Moscow recently opened its 200th metro station and with more expansion in the works, the city’s system is set to be the world’s fourth largest by 2020. The new station, Salaryevo, opened on the metro’s oldest line, the red line, and is now the southernmost stop. The Salaryevo station is decorated in the style of constructivism: the walls, ceiling, pillars and floor are divided into “squares” of different colours. Moscow’s metro stations get a lot of attention for their beautiful mosaics and ornamentation, but the 80-year-old system is also efficient: about nine million people use it every day. [CC] Moscow metro stations from top to bottom: Salaryevo, Mayakovskaya and Komsomolskaya.

APRIL 2016 • Doctor’s

Review

PR A CTICA L T RAVEL L ER

Highclere Castle in Hampshire, England.

The final episode of Downton Abbey aired on March 6 and travel outfitters want to help ease withdrawal symptoms if you were a fan. The new Tribute to Downton Abbey Tour by California-based Zicasso is a nine-day private trip through England and Scotland that visits the most recognizable filming locations of the British drama series that ran for six seasons. Day one in London features afternoon tea at the Ritz where Edith Crawley dined with Aunt Rosamund. Day two includes Belgrave Square, home to Lady Rosamund. You can circle Brooklands Race Track in a classic 20th-century car on day four and tour the Great Hall, the library and more at Highclere Castle, the series’ main filming location, on day five. Day seven features Brancaster Castle, home of Bertie Pelham; day eight in Edinburgh Inveraray Castle aka Duneagle Castle, home of Rose MacClare. From US$4499 per person inclusive of accommodation, breakfast, private driver and guide, and more. For details: zicasso.com. [CC]

DUTOURDUMONDE PHOTOGRAPHY / SHUTTERSTOCK.COM

TV come true

HOT HAM & BRIE SAN SANDW DWICH ICH JAMBON CHAUD AU ET AU BRI torta sesam E e bun,

smoked ham, brie chee se, cranb erry sprea d petit pain aux grain sésame, jamb es de fromage brie, tartin on fumé, ade canneber aux ges

CHICKE N WRAP ROULÉ AU POULET

garden toma to tortilla, chicken strips mild ched , red peppers, dar chee seasoning, se, fajita mild cabbage, salsa, carrots tortilla aux tomates du jardi poulet, poivn, lanières de fromage rons rouges, ched assaisonn dar doux, fajitas, salsa ement pour douce, chou , carottes

HOT SM OKED MEA SANDW T SANDWICH ICH CHA À LA VIA UD NDE

FUMÉE pretzel caramelizedbaguette, smok onions, horse ed meat, mustard radishspread baguette bretzel, fumée, oignviande caramélisé ons s, au raifort tartinade VEGETA et à la RIAN MAK moutarde MAKIS VÉG IS ÉTARIEN avocado, S carrots, red seaweed cabbage, salad, edam ame humm avoc us chou roug at, carottes, d’algues, e, salade d’edamam houmous e

HOT PUL SANDW LED BEEF SAN ICH DWICH AU BŒUF CHAUD EFFILO

CHÉ onion bagu ette, pulle d beef, Mont cheese, coles erey Jack law, maple BBQ dill pickles, spread baguette aux oignons, bœuf effilo monterey ché, fromage chou, cornjack, salade de ichons à l’ane tartinade barbecue th, à l’érable

HOT GRI LLED VEGETA BLE SAN SANDW ICH CHA DWICH UD AUX GRILLÉ S LÉGUME S onion bagu ette, and yellow eggplant, zucch peppers, ini, red spread, provo sun-d lone chee ried tomato se baguette courgettesaux oignons, aube rgine , poivr jaunes, tartin ons rouges et s, ade aux séchées, fromage tomates provolone

Air Transat’s fresh start On April 1, Air Transat launched a new economy-class menu on transatlantic flights between Canada and Europe. Instead of the choice of two frozen meals that are reheated onboard aircraft, passengers now have six fresh options that were made that day. The free-of-charge choices on the new Euro Bistro menu include a chicken wrap, five sandwiches — a hot smoked meat sandwich, hot ham and brie, hot pulled beef, hot grilled veggies — and nine pieces of vegetarian makis. transat.com. [CC]

Doctor’s Review • APRIL 2016

A CANADIAN DEVELOPMENT

INTRODUCING REPATHA (EVOLOCUMAB) – FIRST-IN-CLASS PCSK9 INHIBITOR * TM

In patients with atherosclerotic CVD as adjunct therapy to simvastatin, atorvastatin or rosuvastatin, at 12 weeks

REPATHA 140 MG Q2W – PROVIDED POWERFUL LDL-C REDUCTION TM

O140 NMG ESC O N E EVERY FIXED

DOSE

CLICK

TWO WEEKS

1,2†

Indications and clinical use: Repatha (evolocumab) is indicated as an adjunct to diet and maximally tolerated statin therapy in adult patients with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (CVD), who require additional lowering of low-density lipoprotein cholesterol (LDL-C).

• Use with caution in patients with severe hepatic impairment • Needle cap contains dry natural rubber; may cause an allergic reaction in latex-sensitive patients For more information: Please consult the Product Monograph at www.amgen.ca/Repatha_PM.pdf for important information relating to adverse reactions, drug The effect of Repatha on cardiovascular morbidity and mortality has not been determined. interactions and dosing information which have not been discussed in this piece. Contraindication: The Product Monograph is also available • Hypersensitivity to Repatha or to any by calling Amgen Medical Information at ingredient in the formulation or component 1-866-502-6436. of the container Most serious warnings and precautions: LDL-C=low density lipoprotein cholesterol; PCSK9=proprotein • Refer to Contraindications and Warnings convertase subtilisin/kexin type 9; Q2W=every 2 weeks; and Precautions for any concomitant lipid QM=monthly; SC=subcutaneous lowering medications * Comparative clinical significance has not been established. † Significant LDL-C reduction vs. placebo was consistently seen with Other relevant warnings and precautions: Repatha 140 mg Q2W and 420 mg QM in combination with a • No studies have been conducted with statin, as assessed over 12-week and 52-week treatment periods. Repatha in pregnant women and relevant ‡ LAPLACE-2 was a multicentre, double-blind randomized data from clinical use are very limited controlled trial in which patients with atherosclerotic CVD • Statin product monographs recommend (n=296) received Repatha or placebo as add-on therapy discontinuation when a patient becomes to daily doses of atorvastatin 80 mg, rosuvastatin 40 mg or simvastatin 40 mg. Patients were initially randomized to a pregnant, therefore Repatha should also 4-week lipid stabilization period (open-label statin regimen) be discontinued followed by random assignment to Repatha 140 mg Q2W, • Not recommended for use in nursing women or Repatha 420 mg QM or placebo for 12 weeks. in pediatric patients with primary hyperlipidemia § Overall difference, mean % change from baseline to Week 12 • Use of Repatha in patients with severe in LDL-C, mean difference from placebo with Repatha 140 mg renal impairment is not recommended Q2W (95% CI: -84%, -64%, p<0.0001). ™

™

PATIENT SUPPORT PROGRAM

YOUR PARTNER IN CARE, EVERY STEP OF THE WAY ▪ONE-STEP ENROLMENT ▪REIMBURSEMENT NAVIGATION/SUPPORT ▪GETTING STARTED WITH AUTOINJECTOR TRAINING AND NURSE SUPPORT ▪PATIENT TREATMENT REMINDERS, ONGOING SUPPORT

™

1,2

References: 1. Repatha (evolocumab) Product Monograph. Amgen Canada Inc., September 10, 2015. 2. Robinson JG, et al. Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia. The LAPLACE-2 randomized clinical trial. JAMA 2014;311(18):1870-82. © 2016 Amgen Canada Inc. All rights reserved. Repatha and RepathaREADY are trademarks of Amgen Inc., used with permission. ™

™

Offer your COPD patients feedback that’s

Loud

Now covered in Ontario (Limited Use Benefit) and in Alberta and New Brunswick (Special Authorization Benefit)

Introducing A new LAMA / LABA option for COPD

Positive feedback signals

DUAKLIR GENUAIR

The GENUAIR inhaler was designed to help promote correct use1*

For symptomatic COPD patients who require long-term maintenance bronchodilator treatment1

• Visual signal to indicate the dose is ready for inhalation (red window turns green) • Auditory signal to indicate the inhaler is being used correctly (audible ‘click’) • Visual signal to indicate full dose was inhaled correctly (green window turns red)

• Demonstrated rapid and sustained bronchodilation - Lung function effects were observed within 5 minutes of the first dose and sustained over the dosing interval1 • More patients on DUAKLIR GENUAIR demonstrated clinically meaningful improvements in breathlessness (defined as an increase of ≥1 unit [TDI score]) vs. placebo at week 241,2† - 58.1% vs. 36.6% for placebo (p<0.001; secondary endpoint)

Two feedback signals

SEE dosing start and finish signals

HEAR proper inhalation signal

DUAKLIR GENUAIR (aclidinium bromide/formoterol fumarate dihydrate) is a combination of a long-acting muscarinic antagonist (LAMA) and a long-acting beta2 -agonist (LABA) indicated as a long-term maintenance bronchodilator treatment for airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.1 DUAKLIR GENUAIR is a pre-loaded inhaler administered twice daily.1 Clinical use: DUAKLIR GENUAIR is not indicated for the relief of an acute deterioration of COPD. DUAKLIR GENUAIR is not indicated for the treatment of asthma. Indicated in patients >18 years of age. Contraindication: All long-acting beta2 -adrenergic agonists (LABA) are contraindicated in patients with asthma without use of a long-term asthma control medication Most serious warnings and precautions: Asthma-related death: All LABA increase the risk of asthma-related death. Data from a large placebo-controlled US study that compared the safety of salmeterol (SEREVENT® Inhalation Aerosol) or placebo added to patients’ usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of LABA, including formoterol fumarate, one of the active ingredients in DUAKLIR GENUAIR. DUAKLIR GENUAIR is only indicated for COPD. The safety and efficacy of DUAKLIR GENUAIR in patients with asthma have not been established. Other relevant warnings and precautions: • Should not be used for the initial treatment of acute episodes of bronchospasm (i.e., as rescue therapy) • Should not be initiated in patients with acutely deteriorating COPD • Patients who have been taking inhaled, short-acting bronchodilators on a regular basis should start using them only for symptomatic relief; patients not on a short-acting bronchodilator should be provided one for symptomatic relief of acute symptoms • Should not be used more frequently than twice daily, at higher doses than recommended and concomitantly with other medicines containing a LABA or a long-acting muscarinic antagonist • Worsening of narrow-angle glaucoma • Worsening of urinary retention • Cardiovascular effects; use with caution in patients with certain cardiac conditions DUAKLIRTM and the logo are trademarks of Almirall, S.A., used under license by AstraZeneca Canada Inc. GENUAIR® is a registered trademark of AstraZeneca UK Ltd., used under license by AstraZeneca Canada Inc. The AstraZeneca logo is a registered trademark of AstraZeneca AB, used under license by AstraZeneca Canada Inc. © AstraZeneca Canada Inc. 2016.

FELT demonstrated

improvements in breathlessness1

• Should be used with caution in patients with cardiac arrhythmias, palpitations, myocardial ischaemia, angina pectoris, hypertension or hypotension, electrocardiogram changes • Should be used with caution in patients with a history of QTc prolongation, risk factors for torsade de pointes or taking medications known to prolong the QTc interval • Should be used with caution in patients with convulsive disorders, thyrotoxicosis and phaeochromocytoma and in those who are unusually responsive to sympathomimetic amines • Hypokalemia, hyperglycemia • Immediate hypersensitivity reaction • Should be used with caution in patients with severe milk protein allergy • Paradoxical bronchospasm • Occurrence of headache or blurred vision may influence the ability to drive or use machinery • Should be used with caution during pregnancy, labour and delivery, and in breastfeeding women For more information: Please consult the DUAKLIR GENUAIR Product Monograph at www.azinfo.ca/duaklir/pm382/en, for important information relating to adverse reactions, drug interactions, and dosing information, which have not been discussed in this piece. The Product Monograph is available by calling AstraZeneca Canada at 1-800-668-6000. TDI: Transition Dyspnea Index *Comparative clinical significance has not been established. †AUGMENT-COPD study was a randomized, double-blind, placebo and active-controlled 6-month trial designed to investigate the efficacy and safety of twice-daily DUAKLIR GENUAIR in patients aged ≥40 years (N=1,692) with a clinical diagnosis of stable moderate-to-severe COPD (with post-bronchodilator FEV1 of ≥30% to <80% of predicted normal value) and a history of smoking of at least 10 pack-years. The co-primary endpoints were the changes from baseline in FEV1 at 1 hour post-dose and in trough FEV1 at week 24 compared to aclidinium bromide 400 mcg and formoterol fumarate 12 mcg, respectively.1,2 REFERENCES: 1. DUAKLIRTM GENUAIR® (aclidinium bromide/formoterol fumarate dihydrate inhalation powder) Product Monograph. AstraZeneca Canada Inc. April 9, 2015. 2. D’Urzo AD et al. Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study. Respiratory Research 2014;15:123.

GA D GE T S by

D a v i d Elk i n s

Light up your life Flashlights are emphatically not what they used to be. LED bulbs first appeared five or six years ago mostly in cheap $3-$5 mini-models sold in dollar stores and at hardware check-outs. They’re a big improvement from the old D-cell plastic models and, at the price, well worth having several around the house and another couple in your car. The latest models though are light years ahead of these toys. New tactical models are about the same size, but pack a huge illumination punch. Offering anywhere from 240 to 1000 lumens, the beam is powerful enough to light up distant treetops or temporarily blind an assailant and, as such, is an excellent weapon for self defense. For a demonstration go to earthandhoney.co/carry-a-tactical-flashlight and watch self-defense expert James Williams show how effective they can be against two types of attack. A huge range of tactical flashlights are available. Prices range from about $15 to over $200 depending on power, focus features and batteries with rechargeable lithium-ion models at the high end. The V1 PRO from J5 Tactical (j5tactical. com) produces 300 lumens — more than sufficient for self-defense purposes — using a single AA battery. The high-grade aluminum body is waterproof and the beam can be focused from flood to spot. The unit measures only 9.4 x 2.54 centimetres, and weighs just 65 grams. Consider too the Suaoki 4-in-1 Handheld LED Rechargeable (suaoki.com). It offers three modes with 300 lumens of brightness at maximum output and includes a strobe. A seat-belt cutter and window smasher make it an excellent emergency device for your glove compartment. Another feature: the top unscrews to reveal a USB plug-in and charger for your phone. Measures 3.73 x 16 centimetres, weighs 315 grams. J5 Tactical V1 PRO US$12.95; Suaoki 4-in-1 US$24.99, both on sale at Amazon.com. Note: I always try to source products in Canada, but in this case I could find no domestic suppliers with comparable features and value.

Win both these flashlights (2-for-1 special!) in the Gadget of the Month contest. Enter at doctorsreview.com

MEDICAL QUIPS Patient during colonscopy “Could you write a note for my wife saying that my head is not up there?”

APRIL 2016 • Doctor’s

Review

Treating chronic pain, our shared responsibility. As one of the leading pharmaceutical companies in Canada, Purdue Pharma is dedicated to ongoing research and development in the field of drug delivery and the use of pain medications. However, we also recognize that prescription drug abuse is a public health issue. A recent survey conducted by CAMH showed that 81% of students who use medicines non-medically obtain them from family or friends.1 Purdue Pharma, together with health authorities and the medical community, is actively working to reverse this trend so that the right medications get to the right patients. Through our educational programs and strong community partnerships, we are confident that we can continue to make great strides in addressing the use, abuse and diversion of pain medications. For more information on our products and our role within the community, please contact your Purdue Health Solutions Manager or visit www.purdue.ca.

1. Boak, A., Hamilton, H. A., Adlaf, E. M., & Mann, R. E. (2013). Drug use among Ontario students, 1977-2013: Detailed OSDUHS findings (CAMH Research Document Series No. 36). Toronto, ON: Centre for Addiction and Mental Health.

THE TOP 25 MEDICAL MEETINGS compiled by Camille Chin

Access 2500+ conferences at doctorsreview.com/meetings Code: drcme Canada Calgary, AB September 18-22 22nd World Congress for the International Association for Child and Adolescent Psychiatry and Allied Professions with the 36th Annual Conference of the Canadian Academy of Child and Adolescent Psychiatry iacapap2016.org

Montreal, QC September 29-October 2

October 18-21 21st International Congress on Palliative Care palliativecare.ca

Niagara Falls, ON September 15-18 14th Annual Canadian Society of Hospital Medicine Conference fhs.mcmaster.ca/conted/calendar.html

The pedestrian and cycling Peace Bridge in Calgary.

2016 Annual Scientific Meeting of the Canadian Society of Allergy and Clinical Immunology csaci.ca/annual-scientific-meeting

Quebec City, QC September 14-17

Regina, SK September 30-October 2

7th Canadian Stroke Congress strokecongress.ca

September 30-October 1

9th Annual Meeting of the Canadian Neuromodulation Society neuromodulation.ca

25th Annual Scientific Meeting of the Canadian Academy of Geriatric Psychiatry cagp.ca/conferences

Toronto, ON September 22-24 66th Annual Conference of the Canadian Psychiatric Association cpa-apc.org

September 22-24 62nd Annual Meeting of the Canadian Fertility and Andrology Society cfas.ca

Vancouver, BC August 17-22 28th International Congress of Pediatrics ipa2016.com

August 21-24 149th Annual Meeting of the Canadian Medical Association cma.ca/En/pages/upcoming-annual-meetings.aspx

Winnipeg, MB September 29-30 Winnipeg’s Plug In Institute of Contemporary Art.

5th Biennial Conference of the Eating Disorders Association of Canada edac-atac.ca/upcoming-conferences

APRIL 2016 • Doctor’s

Review

THE TOP 25 MEDICAL MEETINGS

Access 2500+ conferences at doctorsreview.com/meetings Code: drcme Around the world Barcelona, Spain September 8-11 2nd World Congress on Controversies in Breast Cancer congressmed.com/cobrca

PIGPROX / SHUTTERSTOCK.COM

Bali, Indonesia August 22-25 33rd World Congress of Internal Medicine wcimbali2016.org

Denmark, Copenhagen September 3-6 39th Annual Meeting of the European Thyroid Association eurothyroid.com/#eta2016

Glasgow, Scotland September 15-18 5th European Headache and Migraine Trust International Congress ehmtic2016.com

Istanbul, Turkey September 29-October 2 34th World Congress of Sports Medicine fims2016.org

The Antiquarium room at the Munich Residence in Germany.

Prague, Czech Republic September 28-October 1

Munich, Germany September 12-16 52nd Annual Meeting of the European Association for the Study of Diabetes easd.org/images/easdwebfiles/ annualmeeting/52ndmeeting/index.html

15th World Congress on Menopause imsociety.org/world_congress.php

Paris, France September 10-12

26th World Congress on Ultrasound in Obstetrics and Gynecology isuog.org/WorldCongress/2016

Rome, Italy September 25-28

55th Annual Meeting of the European Society for Paediatric Endocrinology espe2016.org

Singapore, Singapore September 19-21 15th World Congress of the International Society for the Diseases of the Esophagus isde.net/singapore_2016_world-congress

Singapore’s Little India.

Tokyo, Japan September 13-16

BULE SKY STUDIO / SHUTTERSTOCK.COM

46th Annual Meeting of the International Continence Society ics.org/2016

Doctor’s Review • APRIL 2016

Vienna, Austria August 31-September 3 16th World Congress on Cancers of the Skin wccs2016.com

Yokohama, Japan September 26-30 16th World Congress on Pain iasp-pain.org

Binge Eating Disorder is a cycle of

Binge. Distress. Repeat.

The twelve-month prevalence of Binge Eating Disorder (BED) is estimated to be 1.2%, affecting about 1 in 83 U.S. adults.2* Though its exact cause is unknown, BED may have a neurobiological basis.3-6 Now recognized as a distinct disorder in the DSM-5, BED is defined as eating large amounts of food in short time periods with a perceived lack of control. During these episodes (occurring one or more times a week for 3 months), patients may eat extremely fast, to the point of physical discomfort, or with no physical hunger. They may eat alone due to shame, feel distress or self-disgust afterwards, and may hide these symptoms, even from you. BED is not associated with compensatory behaviour as in bulimia nervosa.1 Identifying and accurately diagnosing adults with BED is the first step to helping them.

Learn to recognize it. You can help. * Based on twelve-month prevalence rates of BED among U.S. adults over the age of eighteen. Prevalence and correlates of eating disorders from a nationally representative face-to-face household survey (n=9282) were assessed using the WHO Composite International Diagnostic Interview. References: 1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013. 2. Hudson JI, et al. The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biol Psychiatry 2007;61(3):348-58. 3. Manwaring JL, et al. Discounting of various types of rewards by women with and without binge eating disorder: evidence for general rather than specific differences. Psychol Rec 2011;61(4):561-82. 4. Balodis IM, et al. Divergent neural substrates of inhibitory control in binge eating disorder relative to other manifestations of obesity. Obesity 2013;21(2):367-77. 5. Davis CA, et al. Dopamine for “wanting” and opioids for “liking”: a comparison of obese adults with and without binge eating. Obesity 2009;17(6):1220-5. 6. Wang GJ, et al. Enhanced striatal dopamine release during food stimulation in binge eating disorder. Obesity 2011;19(8):1601-8. © 2015 Shire Pharma Canada ULC. All rights reserved. SHI-57022-05-2016-E

HIS T ORY O F MED I C I NE by

Ros e Fos ter

Medicine’s odd confusion ove Caduceus or Asclepius? Why only one of them is correct

hat is the correct symbol of medicine? Those in the know will likely gaze down their noses at anyone foolish enough to proclaim it the winged staff

The Schönbrunn Gardens in Vienna features a classic sculpture of Asclepius with his single rod and snake.

Apollo excised Asclepius from his mother’s womb by caesarean on her funeral pyre 24

Doctor’s Review • APRIL 2016

encircled by twin serpents, otherwise known as the Caduceus. The true symbol, these experts will point out, is the rod of Asclepius, the Greek god of medicine, depicted by a single snake ascending a staff. Why then the ubiquitous use of Caduceus across Canada and the US? The rod of Asclepius has a rich history of association with medicine. Greek myth has it that Asclepius brandished the staff and pursued a career so successful he brought on the wrath of the gods. Indeed, things did not always go so smoothly for Asclepius, whose mortal mother Coronis, consort of Apollo, engaged in a dalliance while pregnant with Asclepius for which she was executed. While flames consumed her on the funeral pyre, Apollo took pity on his son and excised the boy by caesarean. Not being inclined towards parenting himself, Apollo then gave newly born Asclepius to the kind-

hearted centaur Chiron, who instructed Asclepius in the art of medicine.

THE LEAF CURE According to one account, Asclepius acquired his affinity for serpents during a particularly tough case early in his career. Unable to cure the son of Minos, ruler of Crete, he was sealed into a room with the dying boy. When a snake slithered under the door, Asclepius killed it. Moments later, another snake made its way under the door and placed a leaf on the dead snake’s body, restoring it to life. Asclepius gave the leaf to the boy, who was cured. Another theory has it that Asclepius adopted the rod and snake as his symbol because it depicted the treatment for the then common filarial worm Dracunculus medinensis aka “the fiery serpent,” a horrible parasite that crept around just below the skin and could The removal of Dracunculus medinensis, once called “the fiery serpent,” is a possible basis for the staff and serpent of Asclepius.

er symbols only be extracted by trapping its front end and winding it slowly around a stick. The cure is much the same to this day, though somewhat more hygienic. Before long, Asclepius became proficient at saving lives and this angered Hades, King of the Underworld, who complained to Zeus that his realm was being depopulated. Zeus thought Hades’ point a good one, and struck Asclepius down with a thunderbolt. Always the diplomat, Zeus soothed Apollo’s fury at the killing of his son with the tried-and-true Greek god’s panacea for murderous acts, placing the dead physician’s body among the stars as the constellation Ophiuchus or “the Serpent Holder.” Later, some sources say, Zeus resurrected Asclepius as a god to further mollify Apollo, though Asclepius was given strict instructions never to revive the dead without permission. Asclepius’s influence on medicine did not end there. A cult of Asclepius sprang up and reached a zenith of popularity in the third century BCE, with over 500 temples spanning the ancient world from Scotland to Egypt and as far east as modern-day Iraq. The temples were a combination of health spas and religious centres that employed the help of non-venomous rat snakes in their healing rituals. Contemporary herpetologists think that the spread of the temples correlates with the population dispersion of the snake, now known popularly as the “aesculapian snake” and scientifically as Zamenis longissimus. Hippocrates himself is thought to have been trained as a priest at one such temple in Kos. And although the great Father of Western Medicine took a distinctly different direction, placing great value on experiential knowledge,

ABOVE: The flag of the WHO features the rod of Asclepius, the symbol commonly used outside North America to signify the medical profession. LEFT: Mercurius/Hermes is often portrayed carrying a Caduceus with entwined double snakes. BELOW: In 1902, the US Army Medical Corps adopted the Caduceus as its symbol.

he continued to honour his roots as an Asclepian. The Hippocratic oath makes this clear: “I swear by Apollo the physician, and Asklepios, and Hygea and Panacea [Asclepius’s daughters], and all the gods and goddesses…”

UNFAIR SWAP? Many historians are indignant at the thought that the venerable rod of Asclepius, with its origins in medicine and healing, might be swapped for the Caduceus, symbol of the god Hermes. Hermes, they say, is a rogue, a thief, a protector of perjurers and fraudulence. Possibly a fitting symbol after all, they sigh with irony, for a profession that has been plagued by lawsuits and demeaned for its commercial interests. But how exactly did the Caduceus find its way into modern medical iconography? Printers are to blame, say some. They took a liking to the Caduceus in the 16th century, adopting it as a printer’s mark, perhaps regarding themselves as messengers of the printed word and diffusers of knowledge. The Caduceus does in fact resemble one of the oldest and best-known printer’s marks, the dolphin and anchor, used in 1502 by the Venetian printer Aldus Manutius. A proliferation of the

Caduceus in books, some of them medical texts, may have given people an incorrect association. The conflation of the rod of Asclepius and the Caduceus in people’s minds was much more likely to have occurred some time in the 1800s though, when the Caduceus was adopted by ambulance drivers and other medical workers for use on the battlefield. This purpose is derived from a myth that describes Hermes using his own winged staff to break up a fight between two serpents, thereby lending the symbol the connotations of peacemaking or neutrality. Ambulance drivers made their way through the battlefield without getting shot at by brandishing flags bearing Hermes’ staff. Until 1902, most medical establishments used the rod of Asclepius to represent themselves. But that year, on the insistence of a single officer, the US Army Medical Corps adopted the Caduceus as its symbol, thereby cementing the image in the minds of many Americans and prompting its use in popular culture as a medical symbol. It is estimated that 76 percent of commercial healthcare organizations use the Caduceus symbol, while 62 percent of professional healthcare associations — the Canadian Medical Association and the World APRIL 2016 • Doctor’s

Review

Hippocrates himself is thought to have been trained as a priest at one of 500 Asclepius temples Health Organization, to name two — use the rod of Asclepius as their symbol. So who was that insistent American officer, one might ask. No one can be sure, but there are two suspects. The first is Charles Ransom Reynolds, who graduated with an MD degree from the University of Pennsylvania in 1890. He entered the army as a contract surgeon in 1899. He would later go on to become the surgeon general in 1902. Perhaps, having been on the battlefield himself as a medical officer and used the Caduceus as a trustworthy form of protection, he felt a certain attachment to the symbol. The other suspect is a Colonel John Van Rensselaer Hoff, who served 40 years in the United States Army Medical Corps. In 1887, the colonel took a “conspicuous part” in the formation of a hospital corps for the army and became the creator of the United States Field Hospital. This was a man who took his duties as a medical officer seriously. Speaking of his response to a battle at Wounded Knee in 1890, a fellow soldier says of then Captain Hoff and Lieutenant Glennan: “they did everything they could to alleviate the sufferings of the men, and exposed themselves to a storm of bullets while looking over the battlefield for the wounded. I have been in many a hard fight, but never saw doctors who performed their duties with so much zeal as these two did.” Of this same battle, it was said, “The Red Cross flag, held sacred in ordinary warfare, was shot full of holes, and the hospital corps were picked off as they kneeled over the wounded.” Little wonder, then, that Hoff would be particularly interested in a symbol that explicitly declared that the medical corps came in peace. There may be more to this story, an intriguing subplot buried beneath the surface. In addition to his association with thieves and con artists, Hermes is

the patron saint of yet another group whose credibility is sometimes questioned: alchemists. Hermeticism, a religious, philosophical and esoteric tradition affiliated with the ancient philosopher Hermes Trismegistus (“Thrice Great”) as well as with the god Hermes, often employs the Caduceus as its symbol. Hermetical concepts abound in Rosicrucianism, a secret society founded in late medieval Germany built on esoteric truths of the ancient past. Brothers of the Fraternity of the Rose Cross presented themselves as “mystic-philosopher-doctors” and were sent in mission throughout the world. Their top priority was, it is said, to cure the sick free of charge. Colonel Van R. Hoff lived a long and varied life distinguished by a series of monumental acts of life-saving and disease prevention. He was one of the first Europeans to walk through the sacred buildings in China’s Forbidden City, and he witnessed the building of the Trans-Siberian Railway. Could it be that somewhere in his travels he learned of the Caduceus’s esoteric roots in Hermeticism, and grasping the true nature of the symbol, wished to bring it to the new world? If so, it can be said that he met with a certain degree of success. Just ask anyone, “What’s the symbol of medicine?” and that will be clear.

MEDICAL QUIPS Patient during colonscopy “Now I know how a Muppet feels!”

Indications and clinical use: BYDUREON is indicated for use as monotherapy as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus for whom metformin is inappropriate due to contraindications or intolerance. BYDUREON is also indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin, a sulfonylurea, or metformin and a sulfonylurea (dual therapy), when the existing therapy, along with diet and exercise, does not provide adequate glycemic control. Use with caution in the elderly. Should not be used in pediatric patients. Contraindications: Personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) End-stage renal disease or severe renal impairment (creatinine clearance <30 mL/min), including patients on dialysis Most serious warnings and precautions: Thyroid C-cell tumours: Exenatide extended-release causes an increased incidence of thyroid C-cell tumours at clinically relevant exposures in rats compared to controls. It is unknown whether BYDUREON causes thyroid C-cell tumours, including MTC, in humans. Patients should be counselled regarding the potential risk for MTC and informed of symptoms of thyroid tumours. Routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with BYDUREON. Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis: patients should be observed carefully for signs and symptoms of pancreatitis; if suspected, discontinue and initiate appropriate management; if confirmed, BYDUREON should not be restarted. Other relevant warnings and precautions: Not for use in type 1 diabetes or for the treatment of diabetic ketoacidosis Should not be used in combination with PrBYETTA® (exenatide), other glucagon-like peptide-1 (GLP-1) agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors Not studied with warfarin; frequent INR monitoring recommended in patients taking warfarin Plasma levels decline over 10 weeks after discontinuation; choice of other medicinal products and dose selection should be considered accordingly Must not be administered by intravenous or intramuscular injection Heart rate increase; caution in patients with a history of ischemic heart disease or tachyarrhythmias Prolongation of heart rate-corrected PR interval of the electrocardiogram; caution in patients with underlying structural heart disease, pre-existing conduction system abnormalities, ischemic heart disease, cardiomyopathies and history of atrial fibrillation Increased risk of hypoglycemia in combination with sulfonylureas Not recommended in patients with severe gastrointestinal disease Serious hypersensitivity reactions, including anaphylaxis and angioedema; discontinue if a reaction is suspected, assess for other potential causes and institute alternative treatment for diabetes Potential for antibody development; discontinue if there is worsening glycemic control or failure to achieve targeted glycemic control and alternative antidiabetic therapy should be considered Serious injection site reactions Caution in patients with moderate renal impairment and in renal transplant patients; assess renal function prior to initiation and periodically thereafter, as appropriate Not for use in pregnant or nursing women; women of childbearing potential should use contraception during treatment For more information: Please consult the Product Monograph at www.azinfo.ca/bydureon/pm293 for important information relating to adverse reactions, drug interactions and dosing information that has not been discussed in this piece. The Product Monograph is also available by calling 1-800-668-6000. References: 1. BYDUREON Product Monograph. AstraZeneca Canada Inc., October 30, 2015. 2. Diamant M et al. Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial. Lancet Diabetes Endocrinol 2014;2:464-73.

BYDUREON® is a registered trademark of Amylin Pharmaceuticals LLC, used under license by AstraZeneca Canada. The AstraZeneca logo is a registered trademark of AstraZeneca AB, used under license by AstraZeneca Canada Inc.

01/17

Doctor’s Review • APRIL 2016 Notes supplémentaires

Introducing

Sam does it on Sunday, and only on Sunday

BYDUREON® A new once-weekly GLP-1 receptor agonist for the treatment of type 2 diabetes

Powerful and sustained A1c reductions from baseline shown vs titrated insulin glargine at 3 years • Demonstrated signiﬁcantly greater mean A1c reduction from baseline vs titrated insulin glargine at week 261* • A1c reductions were sustained at 3 years (-1.01% vs -0.81%, respectively; p=0.03)2

BYDUREON

Titrated insulin glargine

-1.48%

-1.32%

p=0.047

• BYDUREON was associated with fewer hypoglycemic events1*†

* 26-week, 2-arm, open-label, comparator-controlled study, followed by a 130-week open-label, comparator-controlled assessment period, plus a 10-week off-treatment follow-up period. 456 patients with type 2 diabetes were randomized to BYDUREON 2 mg QW SC (n=233) or titrated insulin glargine OD (n=223) and continued their usual diabetes treatment throughout the 26-week treatment period and the open-ended assessment period. After Week 48, addition of oral antidiabetes drugs or change to the dose of metformin or sulfonylurea was permitted as needed. † When BYDUREON is added to sulfonylurea therapy, a decrease in the dose of the sulfonylurea may be considered to reduce the risk of hypoglycemia. ‡ Please see Product Monograph for complete dosing and administration information. BYDUREON® is a registered trademark of Amylin Pharmaceuticals LLC, used under license by AstraZeneca Canada.

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One injection, ONCE A WEEK

1‡

2 mg once a week May be administered at any time of day, with or without meals

01/17

Count on

for powerful symptom relief

PRISTIQ is indicated for the symptomatic relief of major depressive disorder.

In major depressive disorder, her doctor calls it

“demonstrated improved functional outcomes” She calls it “helping her at work”*

Choose PRISTIQ:

demonstrated improvements in functional outcomes: work, family life and social life (secondary endpoints).

PRISTIQ 50 mg demonstrated signiﬁcant improvements in functional outcomes from baseline vs. placebo, as measured by the Sheehan Disability Scale (SDS).1* Work score: PRISTIQ -2.9 (n=156), placebo -2.2 (n=148), p=0.01. Family life score: PRISTIQ -3.0 (n=163), placebo -2.2 (n=160), p=0.002. Social life score: PRISTIQ -3.2 (n=163), placebo -2.3 (n=160), p=0.003. *The SDS measures the functional impairment that depressive symptoms have on a patient’s family life, social life and work.1 A decrease in SDS score represents improved functional outcomes.2

References: 1. Boyer P, et al. Efficacy, safety, and tolerability of fixed-dose desvenlafaxine 50 and 100 mg/day for major depressive disorder in a placebo-controlled trial. Int Clin Psychopharm 2008;23:243–253. 2. Sheehan DV, Rush AJ, et al., editors. Handbook of psychiatric measures. 2000.

• Interstitial lung disease and eosinophilic pneumonia with venlafaxine • Seizures • Narrow angle glaucoma • Mania/hypomania • Serotonin syndrome or neuroleptic malignant syndrome-like reactions For More Information: Please consult the product monograph at http://pfizer.ca/ en/our_products/products/monograph/226 for important information relating to adverse reactions, drug interactions and dosing information which have not been discussed in this piece. The product monograph is also available by calling 1-800-463-6001.

CA0115PRI005E

Clinical Use: − Severe agitation-type adverse events coupled with self-harm or harm to others • PRISTIQ is not indicated for use in children under the age of 18 − Suicidal ideation and behavior; rigorous monitoring • The short-term efficacy of PRISTIQ has been demonstrated in placebo-controlled trials of up to 8 weeks • The efficacy of PRISTIQ in maintaining an antidepressant • Discontinuation symptoms: should not be discontinued abruptly. Gradual dose reduction is response for up to 26 weeks, following response during recommended 20 weeks of acute, open-label treatment, was demonstrated in a placebo-controlled trial Other Relevant Warnings and Precautions: Contraindications: • Concomitant use with venlafaxine not recommended • Concomitant use with monoamine oxidase inhibitors • Allergic reactions such as rash, hives or a related (MAOIs) allergic phenomenon or within the preceeding 14 days • Bone fracture risk with SSRI/SNRI • Hypersensitivity to venlafaxine hydrochloride • Increases in blood pressure and heart rate (measurement prior to and regularly during treatment) Most Serious Warnings and Precautions: • Increases cholesterol and triglycerides • Behavioural and emotional changes, (consider measurement during treatment) including self-harm: SSRIs and other newer • Hyponatremia or Syndrome of Inappropriate antidepressants may be associated with: Antidiuretic Hormone (SIADH) with SSRI/SNRI − Behavioural and emotional changes including an • Potential for GI obstruction increased risk of suicidal ideation and behaviour • Abnormal bleeding SSRI/SNRI

D E P R E S S I O N K E Y P OI N T S by

Mairi MacKinnon

Issues in compliance Why people stop taking antidepressants… and ways to improve adherence Reviewed by Michael B. Rosenbluth, MD, FRCPC, Chief, Department of Psychiatry, University of Toronto

M .

ajor depressive disorder (MDD) is an extremely common and serious condition, but with early diagnosis and timely, effective intervention, it can be successfully treated.1 In fact, however, only 20% to 40% of patients achieve remission (full functional recovery with no residual symptoms) on initial treatment.2 MDD is increasingly recognized as a chronic disease that can benefit from long-term (even lifetime) treatment. Yet many patients stop taking their medications before the recommended minimum treatment duration of six to 12 months. Early discontinuation rates are high: 30% after 30 days, and 40% after three months.3 Nonadherence is a major factor in undertreatment. Since some features of MDD, such as low motivation/energy, lack of focus, negative thinking patterns, guilt/self-blame, can in themselves be deterrents to adherence, raising awareness about depression and the benefits of treatment can help patients overcome their resistance and improve outcomes.1,4

Top reasons people stop taking their meds

PHOTOGRAPHEE.EU / SHUTTERSTOCK.COM

Among the myriad of causes that contribute to nonadherence, here are some of the patient-related factors that are worth exploring. • Stigma attached to having a “mental illness” and/or being treated for depression: some people may view depression as a character flaw rather than a real illness, and blame themselves; others believe they should be able to deal with it on their own if they only “try harder.”3,4,5 • Misconceptions about medications, for example that they are addictive; they will not resolve personal issues; they will alter personality.4-6 • Misinterpreting an initial response for a “cure” and thinking that medications are no longer needed; not recognizing the severity of depression or the significance of residual symptoms.1,2

• Poor experiences of family members/friends with medications, which negatively affect their view of the value of medications. • Perception that the antidepressant is not working for them; not giving it time to act.3,4,6 • Tolerability issues: emergence of (or fear of) side effects such as weight gain, sexual difficulties, etc.3,4,6 • High cost of medications; personal preferences, e.g. interest in alternative therapies.4,6

Personalized care enhances adherence Optimal management relies on a collaborative approach tailored to individual patient profiles. This involves educating patients about depression, working together to set realistic goals, offering support and encouraging patients to stick with their management plan. It is important to establish confidence early and maintain a strong therapeutic alliance throughout the journey, monitoring regularly (using validated assessment scales) for treatment adherence, progress and adverse effects.1,4,6 Patients who feel that their concerns are heard are more likely to form positive therapeutic alliances. It can help to clarify that depression is a “real” medical condition that can benefit from early and ongoing pharmacologic treatment.1,4 Psychotherapies — such as cognitive behavioural therapy (CBT) and mindfulness-based CBT — are also highly recommended for initial and maintenance therapy and to address issues related to compliance.7 Explain that antidepressants have a delayed onset of action and that symptom improvement can take up to eight weeks; also advise patients why they may need to continue antidepressants long-term (if they are at high risk of relapse), and of the risks of stopping them abruptly (discontinuation syndrome).1,3,4 Manage side effects: these can involve gastrointestinal problems (e.g. nausea, vomiting, diarrhea), central nervous system symptoms (headache, insomnia, sedation), weight gain, sexual dysfunction or increase in suicidal thoughts. While most are mild and resolve with time, more serious and persistent effects may require intervention. Options include reducing the drug dosage, switching to a different antidepressant or prescribing a pharmacologic antidote.3 In addition, talk to your patients about the value of social support to increase their mental well-being as well as their ability to cope with depression and adhere to treatment as recommended.8,9 CBT and mindfulness websites are useful supplements to treatment. Exercise should be encouraged.10 REFERENCES ON PAGE 55

APRIL 2016 • Doctor’s

Review

Contraindications: • Patients with severe hypersensitivity to milk proteins. • In the primary treatment of status asthmaticus or other acute episodes of asthma. Most Serious Warnings and Precautions: • ASTHMA-RELATED DEATH: Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, increase the risk of asthma-related death. Physicians should only prescribe BREO® ELLIPTA® for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid, or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and do not use BREO® ELLIPTA® for patients whose asthma can be adequately controlled on low- or medium-dose inhaled corticosteroids. Other Relevant Warnings and Precautions: • BREO® ELLIPTA® should not be used for the relief of acute symptoms of asthma (i.e., as rescue therapy for the treatment of acute episodes of bronchospasm). • Patients who have been taking a rapid onset, short duration, inhaled bronchodilator on a regular basis (e.g., q.i.d) should be instructed to discontinue the regular use of these drugs and use them only for symptomatic relief if they develop acute symptoms while taking BREO® ELLIPTA®. • BREO® ELLIPTA® should not be initiated in patients with acutely deteriorating asthma, which may be a life-threatening condition. • Exacerbations may occur during treatment. Patients should be advised to continue treatment and seek medical advice if symptoms remain uncontrolled or worsen after initiation of therapy. • BREO® ELLIPTA® should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing a LABA, as an overdose may result. • Caution in patients with cardiovascular disease: vilanterol can produce clinically significant cardiovascular effects in some patients as measured by an increase in pulse rate, systolic or diastolic blood pressure, or cardiac arrhythmias such as supraventricular tachycardia and extrasystoles. In healthy subjects receiving steady-state treatment of up to 4 times the recommended dose of vilanterol (representing a 10-fold higher systemic exposure than seen in patients with asthma) inhaled fluticasone furoate/vilanterol was associated with dose-dependent increases in heart rate and QTcF prolongation. Use with caution in patients with severe cardiovascular disease, especially coronary insufficiency, cardiac arrhythmias (including tachyarrhythmias), hypertension, a known history of QTc prolongation, risk factors for torsade de pointes (e.g., hypokalemia), or patients taking medications known to prolong the QTc interval. • Effects on Ear/Nose/Throat: localized infections of the mouth and pharynx with Candida albicans have occurred. • Endocrine and Metabolic effects: possible systemic effects include Cushing’s syndrome; Cushingoid features; HPA axis suppression; growth retardation in children and adolescents; decrease in bone mineral density. • Hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients who are sensitive to these effects. • Adrenal insufficiency: particular care should be taken in patients transferred from systemically active corticosteroids because deaths due to adrenal insufficiency have occurred during and after transfer to less systemically available inhaled corticosteroids. • Bone Effects: decreases in BMD have been observed with long-term administration of products containing inhaled corticosteroids. • Effect on Growth: orally inhaled corticosteroids may cause a reduction in growth velocity when administered to children and adolescents. • Monitoring recommendations: serum potassium levels should be monitored in patients predisposed to low levels of serum potassium. Due to the hyperglycemic effect observed with other beta-agonists, additional blood glucose monitoring is recommended in diabetic patients. Monitoring of bone and ocular effects (cataract and glaucoma) should be considered in patients receiving maintenance therapy. Patients with hepatic impairment should be monitored for corticosteroid effects due to potentially increased systemic exposure of fluticasone furoate. • Use with caution in patients with convulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines. • Hematologic effects: may present with systemic eosinophilic conditions, with some patients presenting clinical features of vasculitis consistent with Churg-Strauss syndrome. Physicians should be alerted to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. • Hypersensitivity effects: immediate hypersensitivity reactions have occurred after administration, and patients should not be re-challenged with BREO® ELLIPTA® if it is identified as the cause of the reaction. There have been reports of anaphylactic reactions in patients with severe milk protein allergy with other inhaled dry powder drug products containing lactose.

• Immune effects: greater susceptibility to infections. Administer with caution and only if necessary in patients with active or quiescent tuberculosis infections of the respiratory tract; chronic or untreated infections such as systemic fungal, bacterial, viral, or parasitic; or ocular herpes simplex. Chickenpox and measles can have a more serious or even fatal course in susceptible patients using corticosteroids. In such patients who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. • Ophthalmologic effects: glaucoma, increased intraocular pressure, and cataracts. Close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts. • Respiratory effects: paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with a rapid onset, short duration inhaled bronchodilator. BREO® ELLIPTA® should also be discontinued immediately, the patient assessed, and alternative therapy instituted if necessary. The incidence of pneumonia in patients with asthma was uncommon. Patients with asthma taking BREO® ELLIPTA® 200/25 mcg may be at an increased risk of pneumonia compared with those receiving BREO® ELLIPTA® 100/25 mcg or placebo. • Drug interactions: caution should be exercised when considering coadministration with inhibitors of cytochrome P450 3A4; inhibitors of P-glycoprotein (P-gp); sympathomimetic agents; beta-adrenergic receptor blocking agents; non-potassium sparing diuretics (i.e., loop or thiazide diuretics); drugs that prolong the QTc interval (e.g., monoamine oxidase inhibitors and tricyclic antidepressants); xanthine derivatives; and acetylsalicylic acid. Adverse Events: Adverse reactions reported at a frequency of ≥1% and more common than placebo in one clinical study of BREO® ELLIPTA® 100/25 mcg included: nasopharyngitis, oral candidiasis, upper respiratory tract infection, headache, dysphonia, oropharyngeal pain, epistaxis. Adverse reactions reported at a frequency of ≥1% in another clinical study of BREO® ELLIPTA® 200/25 mcg and BREO® ELLIPTA® 100/25 mcg also included the following additional adverse reactions: influenza, bronchitis, sinusitis, respiratory tract infection, pharyngitis, cough, rhinitis allergic, abdominal pain upper, diarrhea, toothache, back pain, pyrexia, muscle strain. Dosage and Method of Administration: The recommended dose of BREO® ELLIPTA® 100/25 mcg or 200/25 mcg is one oral inhalation once daily, administered at the same time every day (morning or evening). Do not use more than once every 24 hours. The starting dose is based on patients’ asthma severity. For patients previously treated with low- to mid-dose corticosteroid-containing treatment, BREO® ELLIPTA® 100/25 mcg should be considered. For patients previously treated with mid- to high-dose corticosteroid-containing treatment, BREO® ELLIPTA® 200/25 mcg should be considered. After inhalation, patients should rinse their mouth with water (without swallowing). If a dose is missed, the patient should be instructed not to take an extra dose, and to take the next dose when it is due. Dosing Considerations: • For optimum benefit, advise patients that BREO® ELLIPTA® must be used regularly, even when asymptomatic. • Once asthma control is achieved and maintained, assess the patient at regular intervals and do not use BREO® ELLIPTA® for patients whose asthma can be adequately controlled on low-or medium-dose inhaled corticosteroids. • No dosage adjustment is required in patients over 65 years of age, or in patients with renal or mild hepatic impairment. • Caution should be exercised when dosing patients with hepatic impairment as they may be more at risk of systemic adverse reactions associated with corticosteroids. Patients should be monitored for corticosteroid-related side effect. For patients with moderate to severe hepatic impairment, the maximum daily dose is 100/25 mcg. For More Information: Please consult the Product Monograph at http://gsk.ca/breo/en for important information relating to adverse reactions, drug interactions, and dosing information, which have not been discussed in this piece. The Product Monograph is also available by calling 1-800-387-7374. To report an adverse event, please call 1-800-387-7374. References: 1. BREO® ELLIPTA® Product Monograph, GlaxoSmithKline Inc., August 26, 2015. 2. Data on file HZA106827. 3. Data on file HZA106829.

Member of Innovative Medicines Canada BREO and ELLIPTA are registered trademarks of Glaxo Group Limited, used under license by GlaxoSmithKline Inc. BREO® ELLIPTA® was developed in collaboration with Theravance, Inc. © 2016 GlaxoSmithKline Inc. All rights reserved.

01258 01/16

AN ICS/LABA COMBINATION

INTRODUCING AN ASTHMA TREATMENT SHOWN TO IMPROVE LUNG FUNCTION (FEV1)

DAY & NIGHT

BREO® ELLIPTA® 100/25 mcg provided improvements in FEV1 vs. placebo that were sustained over 24 hours at week 12, as demonstrated by serial FEV1 measurements taken at 5, 15, and 30 minutes and 1, 2, 3, 4, 5, 12, 16, 20, 23, and 24 hours.1,2*†

BREO® ELLIPTA® 200/25 mcg demonstrated improvements in FEV1 vs. an ICS (fluticasone furoate 200 mcg) that were sustained over 24 hours at week 24, as demonstrated by serial FEV1 measurements taken at 5, 15, and 30 minutes and 1, 2, 3, 4, 5, 12, 16, 20, 23, and 24 hours.1,3‡§

BREO® ELLIPTA® (fluticasone furoate/vilanterol) 100/25 mcg and BREO® ELLIPTA® 200/25 mcg are indicated for the once-daily maintenance treatment of asthma in patients aged 18 years and older with reversible obstructive airways disease. BREO® ELLIPTA® is not indicated for patients whose asthma can be managed by occasional use of a rapid onset, short duration, inhaled beta2-agonist or for patients whose asthma can be successfully managed by inhaled corticosteroids along with occasional use of a rapid onset, short duration, inhaled beta2-agonist. BREO® ELLIPTA® is not indicated for the relief of acute bronchospasm. BREO® ELLIPTA® 200/25 mcg is not indicated for COPD. ICS=inhaled corticosteroid; LABA=long-acting beta2-adrenergic agonist * A 12-week treatment, multicenter, randomized, double-blind, placebo-controlled, parallel group study to compare the efficacy and safety of BREO® ELLIPTA® 100/25 mcg, fluticasone furoate (FF) 100 mcg, and placebo administered once daily in the evening in subjects with persistent bronchial asthma (N=609). † ITT population, FEV1 data (mL) of BREO® ELLIPTA® vs. placebo, respectively: 5min: 495 vs. 224, 15min: 516 vs. 267, 30min: 530 vs. 252, 1hr: 546 vs. 271, 2hr: 561 vs. 264, 3hr: 538 vs. 216, 4hr: 537 vs. 212, 5hr: 536 vs. 222, 12hr: 494 vs. 126, 16hr: 502 vs. 245, 20hr: 525 vs. 228, 23hr: 517 vs. 237, 24hr: 508 vs. 260. ‡ A 24-week treatment, multicenter, randomized, double-blind, parallel group study to compare the efficacy and safety of BREO® ELLIPTA® 200/25 mcg administered once daily each evening with FF 200 mcg administered once daily each evening and fluticasone propionate (FP) 500 mcg administered twice daily in subjects with persistent asthma (N=586). § ITT population, FEV1 data (mL) of BREO® ELLIPTA® vs. FF 200 mcg, respectively: 5min: 465 vs. 326, 15min: 466 vs. 338, 30min: 472 vs. 348, 1hr: 478 vs. 343, 2hr: 505 vs. 343, 3hr: 483 vs. 340, 4hr: 478 vs. 343, 5hr: 487 vs. 351, 12hr: 441 vs. 274, 16hr: 470 vs. 322, 20hr: 454 vs. 335, 23hr: 431 vs. 371, 24hr: 446 vs. 372.

Safari Picture this: a large, luxurious villa, a private game reserve and your own wildlife guide at an affordable price by Anita Draycott

The Lion Rock River Lodge is located on the banks of the Crocodile River and features an upper-deck viewing platform with plunge pool.

extraordinaire ALL PHOTOS ANITA DRAYCOTT UNLESS OTHERWISE NOTED

hree lion cubs have just crawled out of the rib cage of a recently killed buffalo. Their noses are smudged in blood and they are

so stuffed they can barely walk. Nearby a vulture waits its turn on a tree branch.If you have never witnessed the majesty of wild animals on their own turf, it’s difficult to explain why a safari can be a life changing experience. Most of us are so accustomed to living in our manufactured concrete jungles that being exposed to nature in its rawest state in an environment that we don’t control reminds us that we are part of a much bigger picture. My recent South African safari was indeed life changing, but it was also a bargain. Fodor’s: The Complete African Safari Planner estimates that the cost per person per night in a luxury lodge can range from $500 to $2200. Our group of five recently returned from a week in a fivebedroom house located in the Mjejane Game Reserve (mjejanelifestyle.co.za) bordering on Kruger Park in northeast

APRIL 2016 • Doctor’s

Review

T. KALTENBRUNN PHOTOGRAPHY

Lions seem lazy because they rest most of the day, but they’re active during the cooler hours and can sprint fast.

South Africa and it cost approximately $600 per person for seven nights total (see Safari Smarts sidebar). Ideally located on the Crocodile River, our abode, called Lion Rock, had all the comforts of home and more. Each bedroom had both an indoor and outdoor shower, fine linens and modern fixtures. The kitchen was outfitted with stainless appliances, granite counters and more pots, pans and dishes than a professional chef could want. Outside, the huge deck and plunge pool overlooked the river where wildlife sightings were in constant supply. Our package included daily housekeeping, a gardener and our

The group’s guide, Johan, poses with the author’s four friends with whom she shared the Lion Rock Lodge.

own game ranger who took us on two drives per day at times of our convenience. The difference between Lion Rock and a luxury safari lodge is that it is a self-catering property, meaning we had to supply and cook our food. This was actually preferable for my group as we were able to prepare what and eat when we wanted. Every morning Santa, the cheery maid, took care of our dirty dishes and cleaned the house thoroughly. She even offered to wash and iron our clothes.

ut we really came to see the animals and we were never disappointed. South Africa is literally teeming with wildlife and boasts a staggering 870 bird species, approximately 160 species of mammal, 115 species of snake, and some 5000 spider and scorpion species. Mjejane is also home to the Big Five and because it’s a private game reserve, the sightings are much more intimate than at Kruger Park. There are fewer people and rangers limit the number of vehicles so as not to disturb the animals. The rangers also communicate amongst themselves via radios to share their sighting information. The true credit for our memorable experiences with the animal kingdom goes to Johan Rademeyer, the game ranger who works exclusively for the Lion Rock owners. The man was not only a veritable font of information with eyes like a hawk, but his passion and respect for nature and wildlife were genuine and infectious.

The group’s game ranger shared lots of informational tidbits such as an elephant’s trunk contains 100,000 muscles.

SAFARI SMARTS Fly to Nelspruit Airport (kmiairport.co.za) and rent a car. Make bookings for Lion Rock or other properties through the Winchester Group (winchestermarketing. com/mjejaneriverlodges). During off-peak periods, the per-night base rate for the lodge is $390 for the first four people. Thereafter, the rate is $61 per person per night up to a maximum of 10 people. During peak periods, the base rate is $435 for four and $65 per additional person. Children under 12 are half price. In addition to five en-suite bedrooms, a fully equipped kitchen, living and dining rooms, Lion Rock consists of a game room with pool table, a small gym, a furnished deck with plunge pool, barbecues, a boma (fire pit) and Wi-Fi. If you don’t want to go shopping, prepare a grocery list and the Winchester Group can arrange to have your food delivered from the Spar grocery store in nearby Malelane. Bring covered shoes, long pants, binoculars, sunscreen, sunglasses and a camera with a good zoom lens. Don’t forget your sense of adventure! Johan Rademeyer, a game ranger who works exclusively for the Lion Rock owners, introduces his chameleon friend.

Zebra stripes are the subject of many theories: to confuse predators, to keep them cool, as a â&#x20AC;&#x153;bar codeâ&#x20AC;? to help foals identify their moms.

The air-conditioned lodge features a spacious open-plan lounge, dining room and kitchen area.

Mjejane is home to the Big Five and because it’s a private game reserve, the sightings are intimate On our first evening drive, we spotted the Big Five: Cape buffalo, lion, leopard, rhino, elephant. Johan regaled us with all sorts of trivia and facts. Did we know that Big Five was originally a hunting term for the animals that posed the greatest risk to hunters on foot? Have we heard that giraffes are born two metres tall? Or that there are 100,000 muscles in an elephant’s trunk? Rhinos are near-sighted, which makes them vulnerable prey for poachers whose key market is Vietnam. Powder from the rhino horn has been used in traditional Chinese medicine and more recently some believe it can cure cancer and hangovers. Each zebra has a unique stripe pattern on its shoulder. When a baby is born, its mother turns it around clockwise and anti-clockwise to teach it her pattern. Dainty impalas have “M” markings on their rumps, hence they are known as the McDonald’s “fast food” of the bush. Some peculiar collective nouns include: a bloat of hippos, a zeal or dazzle of zebras, a murder of crows, a crash of rhinos. The Cape buffalo is considered to be the most dangerous of the Big Five due to its unpredictability and speed. Old buffalo bulls that the herd has deserted are called dagha boys because they love to wallow in mud (dagha means mud in

Zulu). They may be old, but you don’t want to mess with them. For seven days, our routine went something like this: 5:00: Up and under the outdoor shower where I watched the hippos and waterbucks perform their morning ablutions in the Crocodile River. 5:30: Load the cooler with a thermos of hot water, French press coffee pot, coffee and Amarula (an African liquor made of marula fruit —, the “Baileys” of the bush). 6:00: Off in the Toyota Land Cruiser with Johan for morning game watch. 8:00: Coffee break while watching frolicking hippos. 9:30: Return to Lion Rock. Download photos. Work out in the small gym. Take a dip in the plunge pool. Noon: Lunch on the deck, binoculars at the ready. 14:30: Siesta time. 16:00: Prepare cooler for sundowners and off with Johan for more surprise sightings. 17:30: Sundowners in the bush. 19:00: Return to Lion Rock for dinner. 21:00: Bonfire under a sky studded with stars.

Don’t forget to pack sunscreen, sunglasses, binoculars and a camera with a good zoom lens.

Thanks to the “M” on their rumps, impalas are known as the MacDonald’s fast food of the bush.

“It clicked when my doctor and I discussed Trulicity .” ™

• • •

Once-weekly dosing Ready-to-use pen† Preattached, hidden needle†

*Fictitious patient. May not be representative of all patients.

Trulicity 1.5 mg demonstrated A1c reduction comparable to liraglutide in a non-inferiority, open-label study. ‡§

Change from baseline in A1c at 26 weeks: Trulicity 1.5 mg + metformin, -1.4, liraglutide + metformin, -1.4; p<0.001 for non-inferiority. Trulicity is indicated for the once-weekly treatment of patients with type 2 diabetes mellitus to improve glycemic control, in combination with: • diet and exercise in patients for whom metformin is inappropriate due to contraindication or intolerance. • metformin, when diet and exercise plus maximal tolerated dose of metformin do not achieve adequate glycemic control. • metformin and a sulfonylurea, when diet and exercise plus dual therapy with metformin and a sulfonylurea do not achieve adequate glycemic control. • prandial insulin with metformin, when diet and exercise plus basal or basal-bolus insulin therapy (up to two injections of basal or basal plus prandial insulin per day) with or without oral antihyperglycemic medications, do not achieve adequate glycemic control.

CADUA00013

Clinical use: Trulicity has not been studied in combination with basal insulin. Trulicity is not a substitute for insulin. Trulicity should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Contraindications: Patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) • Pregnant and nursing women

Ernest Hemingway is credited with introducing “safari,” a Swahili word meaning journey, into the English language in the 1930s

•

Most serious warnings and precautions:

Risk of thyroid C-cell tumours: In male and female rats, dulaglutide causes dose-dependent and treatment duration-dependent thyroid C-cell tumors after lifetime exposure. Patients should be counseled regarding the risk and symptoms of thyroid tumors. Other relevant warnings and precautions: • Heart rate increase • Prolongation of PR interval • Hypoglycemia (in combination with a secretagogue or prandial insulin) • Severe gastrointestinal disease • Pancreatitis • Systematic hypersensitivity • Not studied in pediatric patients • No dose adjustment required in patients over 65 years of age • Hepatic or renal impairment • Recent myocardial infarction, unstable angina and congestive heart failure For more information: Please consult the product monograph at www.lilly.ca/TrulicityPM/en for important information relating to adverse reactions, drug interactions, and dosing information which have not been discussed in this piece. The product monograph is also available by calling us at 1-888-545-5972. Reference: 1. Trulicity Product Monograph. Eli Lilly Canada Inc., November 10, 2015. †

Clinical significance has not been established.

‡

The recommended starting dose for Trulicity is 0.75 mg once-weekly.

26-week, randomized, open-label, parallel group, multicentre, active-controlled, phase III non-inferiority study. Patients received either 1.5 mg Trulicity once weekly (n=299; baseline A1c 8.1%) or 1.8 mg liraglutide once daily (n=300; baseline A1c 8.1%). Treatment was added to background therapy with metformin (≥1500 mg/day). All n-values refer to intent-to-treat population. Primary endpoint was change in A1c from baseline to week 26 between once-weekly Trulicity and once-daily liraglutide.

ctually, there was never a “typical” day on safari at Mjejane. One afternoon we came very close to some flirting rhinos and Johan explained how the feisty female lays down the rules for this dating game. Another day, we got so close to an elephant I could almost reach out of the Toyota and touch its trunk. I learned that giraffes have to contort their long legs into a tripod base in order to bend and drink from the river. Perhaps most dramatic was that pride of lions that took down a buffalo. For three days afterwards, we watched mom and the cubs devour the carcass. Johan pointed out creatures great and small, including all sorts of beautiful birds, tiny crabs and chameleons, and plants used for medicinal purposes. He explained some of the multi-faceted aspects contributing to the balance of nature in the bush from the hunting rituals of lions to the secrets one can learn from a dung beetle’s dung. There were a few startling encounters. One night while we were out at a barbecue on the deck, a tree frog jumped into my wine glass. I came face to face with a hedgehog outside my bedroom door one morning and remembered Johan’s comment that the electric fence was to keep we humans in rather than the animals out. We had to shoo some frisky monkeys away from the pool. My group did not encounter any black mambas or scorpions, but those are two good reasons to keep the doors shut at all times. Never was there a dull moment at Lion Rock. When we weren’t out on game drives, we had a never ending parade of elephants, giraffes, various antelope and more coming to the Crocodile River for a drink or a bath. A particularly handsome kudu bull with spiraled horns enjoyed nibbling on bushes right beside our pool. Acclaimed writer Ernest Hemingway is usually credited with introducing “safari,” a Swahili word meaning journey, into the English language after his adventures in Africa in the 1930s. Once you’ve been on safari, you realize that the “journey” of understanding the balance of nature has just begun. Consider this African proverb: Every morning in Africa, a gazelle wakes up. It knows it must run faster than the fastest lion or it will be killed. Every morning a lion wakes up. It knows it must outrun the slowest gazelle or it will starve to death. It doesn’t matter whether you are a lion or a gazelle. When the sun comes up, you better start running. APRIL 2016 • Doctor’s

Review

Spain to Italy Life and luxury along ancient Mediterranean trading routes by John and Sandra Nowlan

The Wind Surf yacht can accommodate 310 guests in 122 staterooms and 31 suites.

by sailing ship don’t want to go on vacation with 2000 other people.” That was the view of one American guest on the Wind Surf, a five-masted, 310-passenger luxury yacht. Most of those on board were of a like mind. They preferred the intimacy of smaller craft and the ability to enter harbours that large ships couldn’t. “Cruise ships are getting too big,” Don and Nancy Williams of Ottawa told us. “We’ve been to the Caribbean and Alaska on them, but this is our type of sailing, especially in the Mediterranean with its character and history.” The itinerary — Barcelona to Rome with stops in France, Monaco and Italy — was another key reason we chose the Wind Surf, the largest in the Windstar (windstarcruises.com/yachts) six-ship fleet. Barcelona is a delightful city to start a Mediterranean adventure so we arrived a day early last April and stayed near the University of Barcelona at the Fairmont Rey Juan Carlos I, which features free shuttle service to the centre of the city. As much as we enjoyed our overnight, it was a thrill to slip out of the harbour the next day to watch

APRIL 2016 • Doctor’s

Review

We enjoyed our walk around the harbour on the hunt for a bowl of bouillabaisse

SANDRA NOWLAN

The French seaside village of Collioure boasts pretty pastel houses and only 3000 inhabitants.

SANDRA NOWLAN

The weeklong cruise package includes all meals and all non-alcoholic beverages.

WIND SURF

The authors enjoying champagne in front of Monaco’s Casino.

Doctor’s Review • APRIL 2016

Wind Surf’s seven computer-operated sails rising on 50-metre masts to meet the breeze. The staterooms, with two portholes, are commodious and come complete with many luxury touches like great lighting, a Bose audio dock, a DVD player and movie choices, a good selection of TV channels and a generous-sized bathroom with L’Occitane toiletries. Wind Surf is not all-inclusive, but provides complimentary bottled water, soft drinks and specialty coffees. Our first stop, after an overnight sail, was Collioure, France, a fortified town established in 673 CE during the Visigoths’ ascendancy as an important port. Now with just 3000 largely Catalan residents, it’s known for its many art galleries and as the birthplace of the colourful Fauvism art movement after Matisse, Derain and other painters established an art colony there in the early 1900s. The next morning, after some rough seas, nicely handled by the 185-metre ship, we docked in Marseille in the midst of a mistral, the cold northwest wind that blows from the Rhone Valley into the Camargue region. They say gusts are especially strong between seasons. In spite of a full day of powerful winds, we enjoyed our walk around the sheltered harbour on the hunt for a bowl of bouillabaisse. The stew made from at least four different kinds of fish cooked in a broth with onions, tomatoes, garlic, herbs and spices originated in Marseille. The Miramar, a famous waterfront restaurant, offered the dish at €63 ($90). We moved on and soon found a more modest establishment with an excellent fish stew for €28 which, even then, made it an $80 lunch between us.

ind Surf trips often include a special “private event.” At the layover in Monaco’s Monte Carlo, we were treated to something called “Lifestyles of Glitterati.” After a hop-on, hop-off tour of the glamorous principality, we returned to the ship for an excellent canard à l’orange, then it was off to the Café de Paris for dessert, champagne and a magic show. We closed the evening with a visit to the casino where travellers, but not locals, are encouraged to gamble as much as they wish at roulette and other such pastimes. (For more on Monaco, visit doctorsreview.com/features/makemost-monaco.) More glamour was in store the next day with a stop in Cannes on the French Riviera, site of the famous film festival. We didn’t rub shoulders with any movie stars, but we did take a culinary tour that was the highlight of the cruise.

Help relieve her menopausal symptoms.

Mary Seguin BACKGROUND: Mary has a husband, 3 boys and works as a top advertising executive downtown. She is experiencing frequent hot flashes and has not had a period for 12 months. TREATMENT GOALS: To help reduce the frequency of hot flashes she experiences on a daily basis. TREATMENT: Mary’s doctor prescribed Premarin oral tablets at the lowest effective dose once daily with a concomitant progestin. A one-month follow-up was suggested to evaluate treatment.

DEMONSTRATED REDUCTION OF

HOT FLASHES.1* Premarin (0.625 mg) with MPA (2.5 mg) showed a 90% decrease from baseline in the mean daily number of hot flashes vs 50% for placebo at 12 weeks (p<0.05)1,2

EFFECTIVE RELIEF OF MENOPAUSAL AND POSTMENOPAUSAL SYMPTOMS, INCLUDING HOT FLASHES, VULVAR AND VAGINAL ATROPHY AND THE PREVENTION OF POSTMENOPAUSAL OSTEOPOROSIS WERE DEMONSTRATED.1 Indications and clinical use: Premarin (conjugated estrogens sustained release tablets) is indicated for the following: • Relief of menopausal and postmenopausal symptoms occurring in naturally or surgically induced estrogen deficiency states including vulvar and vaginal atrophy • Prevention of osteoporosis in naturally occurring or surgically induced estrogen-deficiency states - When prescribing solely for the prevention of post menopausal osteoporosis, Premarin should be considered in light of other available therapies and should only be considered for women at significant risk of osteoporosis. Non-estrogen medications should be carefully considered - For older women who are not experiencing any more acute symptoms of menopause, use in combination with a progestin should only be considered for women who failed on, or were intolerant of, non-estrogen medication • Hypoestrogenism due to hypogonadism, castration, or primary ovarian failure • Atrophic vaginitis • Vulvar atrophy (with or without pruritis) - When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered • Not indicated for use in pediatric patients (< 16 years of age) In patients with an intact uterus, Premarin should be prescribed with an appropriate dosage of a progestin for women with intact uteri, in order to prevent endometrial hyperplasia/carcinoma. Contraindications: • Liver dysfunction or disease • Known or suspected estrogen-dependent malignant neoplasia

• Endometrial hyperplasia • Known, suspected, or past history of breast cancer • Undiagnosed abnormal genital bleeding • Known or suspected pregnancy • Active or past history of confirmed venous thromboembolism or active thrombophlebitis • Active or past history of arterial thromboembolic disease • Partial or complete loss of vision due to ophthalmic vascular disease • Known thrombophilic disorders • Migraine with or without aura Most serious warnings and precautions: Risk of stroke and deep vein thrombosis: estrogen-alone therapy (mean age 63.6 years). Risk of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli and deep vein thrombosis: estrogen plus progestin therapy (mean age 63.3 years). Therefore, estrogens with or without progestins: • Should not be prescribed for primary or secondary prevention of cardiovascular diseases • Should be prescribed at the lowest effective dose and for the shortest period possible for the approved indication Other relevant warnings and precautions: • Possible risk of ovarian cancer • Monitor blood pressure with hormone replacement therapy use • Caution in women with pre-existing endocrine and metabolic disorders • May exacerbate endometriosis • May increase pre-existing uterine leiomyomata • Abnormal vaginal bleeding

*This randomized, double-blind, placebo-controlled trial evaluated the safety and efficacy of lower doses of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) to relieve vasomotor symptoms (VMS) in postmenopausal women. A total of 2,673 healthy postmenopausal women 40 to 65 years of age with an intact uterus (mean age 53.3 years), including a VMS efficacy-evaluable population (n=241 at baseline), participated. Efficacy measures were frequency and severity of daily hot flashes. The baseline mean daily number of hot flashes was 10 for both groups.Eight treatment arms were evaluated for 13 cycles over a period of 1 year: CEE 0.625 mg/day; CEE 0.625 mg/MPA 2.5 mg/ day; CEE 0.45 mg/day; CEE 0.45 mg/MPA 2.5 mg/day; CEE 0.45 mg/MPA 1.5 mg/day; CEE 0.3 mg/day; CEE 0.3 mg/MPA 1.5 mg/day; or placebo. © 2015 Pfizer Canada Inc. Kirkland, Quebec ® Pfizer Inc., used under license H9J 2M5 PREMARIN ® Pfizer Canada Inc.

CA0115PRE003E

• Risk of gallbladder diseases • May exacerbate systemic lupus erythematosus • May induce or exacerbate anaphylactic reaction and angioedema symptoms • Risk of developing probable dementia (women >65 years) • May exacerbate epilepsy • Caution in patients with otosclerosis • May cause fluid retention • Risk of estrogen-induced hypocalcemia: Caution in individuals with hypoparathyroidism For more information: Please consult the product monograph at www.pfizer.ca/en/our_products/products/monograph/278 for important information relating to adverse reactions, drug interactions and dosing information which have not been discussed in this piece. The product monograph is also available by calling 1-800-463-6001. References: 1. Premarin Product Monograph, Wyeth Canada, December 1, 2014. 2. Utian W et al. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertility and Sterility 2001;75(6):1065-1079.

0.3 mg

0.625 mg

1.25 mg

Wind Surf’s seven sails rose on 50 metre masts to meet the breeze A dozen of us were bussed through the delightful French countryside to the village of Grasse, known for its perfume works. We then visited an olive grove, Domaine de la Royrie, where the owners took us for a stroll among the 500-year-old olive trees originally planted by monks; gave us a blind taste test of their early and late harvest olive oil; and, in the garden, served a delicious eight-course lunch, each plate of local food prepared with olive oil. This being France, we were also offered an excellent rosé and red wine.

SANDRA NOWLAN

JOHN NOWLAN

Elba is 10 kilometres from Italy’s mainland and a charming port stop for small ships.

The coquilles Saint-Jacques at restaurant Stella was “the best meal of the trip.”

Doctor’s Review • APRIL 2016

SANDRA NOWLAN

Napoleon spent 300 exiled days in Elba at the Villa dei Mulini and the Villa di San Martino (pictured).

ore heavy winds the next morning prevented our arrival at Portofino, Italy, but the captain, John Clark, an amiable Englishman, arranged instead for a stop at the UNESCO World Heritage Village of Porto Venere. With its ancient castle, church and narrow streets filled with cafés and craft shops, the town of 4000 was a delightful alternative. Our final stop, before disembarkation in Rome, was on the island of Elba, the location of Napoleon Bonaparte’s exile. In 1814, the emperor spent 300 days here and both his country residence, the Villa di San Martino, and his town house, Villa dei Mulini, in Portoferraio, are open to the public. Each is blessed with expansive views of the Mediterranean and although it’s said the emperor preferred to sleep on his camp cot, it’s clear he did not lack for luxury. As we left Elba heading towards Rome on a delightfully warm Mediterranean evening, the sails were unfurled to the stirring music of Vangelis’ “1492: Conquest of Paradise” and the guests enjoyed a last chance to visit with the ship’s officers. Windstar Cruises has an open bridge policy, a rarity these days. For our final meal, we chose to dine outdoors on the teak deck at Candles, a specialty restaurant that’s set up each evening. Earlier at Stella, a similar “pop-up,” we enjoyed an extraordinary coquilles Saint-Jacques and an imaginative mille-feuille, the best meal of the trip. Peggy and Roy Pollard, a British couple on their 10th Wind Surf cruise, were as enthusiastic as we were. “Back 15 years ago, we never ever wanted to go on a cruise,” Peggy said. “But a friend invited us aboard the Wind Surf in Barbados… and we were hooked.” This exclusive loyalty to a single ship is quite rare, but the Pollards love the mix of guests albeit usually middle age and above, the excellent food, the informal, laid-back atmosphere and the great ports. “We’ll be back,” Roy affirmed.

Help her treat painful intercourse.

Natalia Pottier BACKGROUND: Natalia is a wife, mother and grandmother. She is experiencing vaginal dryness as well as painful intercourse. TREATMENT GOALS: To alleviate the atrophic vaginitis and dyspareunia she has been experiencing. TREATMENT: Natalia’s doctor prescribed Premarin Vaginal Cream at the lowest effective dose. A threemonth follow-up was suggested to evaluate treatment response.

THE ONLY CE CREAM INDICATED TO TREAT PAINFUL INTERCOURSE (DYSPAREUNIA)1* *Comparative clinical significance is unknown. CE=Conjugated Estrogen

TREATMENT OF DYSPAREUNIA, ATROPHIC VAGINITIS AND KRAUROSIS VULVAE.

Indications and clinical use: Premarin Vaginal Cream (conjugated estrogens, CSD) is indicated for the treatment of atrophic vaginitis, dyspareunia, and kraurosis vulvae. It has not been shown to be effective for any purpose during pregnancy and its use may cause severe harm to the fetus. It should be prescribed with an appropriate dose of a progestin for women with intact uteri in order to prevent endometrial hyperplasia/carcinoma. • Not indicated for use in pediatric patients (<16 years of age) Contraindications: • Liver dysfunction or disease • Known or suspected estrogen-dependent malignant neoplasia • Endometrial hyperplasia • Known, suspected, or past history of breast cancer • Undiagnosed abnormal genital bleeding • Known or suspected pregnancy • Active or past history of confirmed venous thromboembolism or active thrombophlebitis • Active or past history of arterial thromboembolic disease • Partial or complete loss of vision due to ophthalmic vascular disease • Known thrombophilic disorders • Migraine with or without aura

For more information: Please consult the product monograph at www.pfizer.ca/en/our_products/products/monograph/276 for important information relating to adverse reactions, drug interactions, and dosing information which have not been discussed in this piece. The product monograph is also available by calling 1-800-463-6001.

Most serious warnings and precautions: Risk of stroke and deep vein thrombosis: estrogen-alone therapy (mean age 63.6 years). Risk of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis: estrogen plus progestin therapy (mean age 63.3 years). Therefore, estrogens with or without progestins: • Should not be prescribed for primary or secondary prevention of cardiovascular diseases • Should be prescribed at the lowest effective dose and for the shortest period possible for the approved indication

Other relevant warnings and precautions: • Possible risk of ovarian cancer • May weaken and contribute to the failure of condoms, diaphragms, or cervical caps • Monitor blood pressure with hormone replacement therapy use • Caution in women with pre-existing endocrine and metabolic disorders • May exacerbate endometriosis • May increase pre-existing uterine leiomyomata • Abnormal vaginal bleeding • Risk of gallbladder diseases • May exacerbate systemic lupus erythematosus • May induce or exacerbate angioedema symptoms • Risk of developing probable dementia (women >65 years) • May exacerbate epilepsy • Caution in patients with otosclerosis • May cause fluid retention

References: 1. Premarin Vaginal Cream Product Monograph, Wyeth Canada, December 11, 2014.

CA0115PRE004E

Silk Road rising

10 wonders along the fabled trade route that’s being resurrected in the Sichuan and Shanxi provinces text and photos by Gary Crallé

Pingyao is China’s best-preserved ancient town complete with imposing town walls and courtyard architecture.

Datong Beijing

Shanxi Pingyao

Sichuan Chengdu Yibin

CHINA Shanghai

Hong Kong

arco Polo wouldn’t recognize the place. Development is overwhelming. Old China and New China collide and coexist as the latter displaces the former at a

relentless, dizzying pace. And now China is resurrecting the Silk Road. The very name conjures up visions of plodding camel caravans laden with chests of pressed tea, aromatic spices, gold, jade, porcelain and silk brocade. To visitors it’s exotic; to China it’s pragmatic. The Western Han Dynasty initiated the ancient route in 139 BCE and the born-again Asian dragon boldly sees it as a proven path to economic growth. It’s part of a national strategy to develop the interior, similar to North America’s Westward Ho! pursuit in the 19th century. The fabled road will be the project’s grande allée with China pushing to weave loose threads into an economic belt linking Europe and Asia — and not in a small way. Tourism is a primary component of the plan, and promotion of many World Heritage locations has already begun. Laying the groundwork, a 5000-kilometre section of the central Asian route was declared a UNESCO site in 2014, largely at China’s urging. When the world’s longest route was a corridor for traders, pilgrims, monks and invaders, a journey from either end could take years. Traversing it was dangerous business, subject to brutal terrain, harsh climates, disease and murderous bandits. For nearly 1600 years, the tenuous path linked eastern and western empires before shipping by sea rendered it obsolete. The Venetian Marco Polo famously travelled (or claimed he did, depending on which historians you believe) a central Asian route through Persia (Iran) and the Takla Makan Desert to what is now Beijing. Surprisingly, the Silk Road didn’t get its name until German geographer Ferdinand von Richthofen bestowed the title in 1877. No single road existed. Instead, there were rough trade corridors that split into Northern and Southern Silk Roads plus a maritime route. Centuries of trade brought commercial, cultural and religious influences to the entire country. China’s portion of the Silk Road stretches eastward from the westernmost and largest province of Xinjiang to the very heart of the Middle Kingdom. In the beginning, Sichuan — “Land of Abundance” — produced the silk that gave the road its name. A hop and a skip to the north, Shanxi province is a cultural gem of architectural and religious wonders, without even mentioning the Terra Cotta Warriors. It also sits on enough coal to fuel the country for the next 500 years. On my recent trip along the southern road, I discovered that these central regions have unrolled the red carpet for visitors.

APRIL 2016 • Doctor’s

Review

Shanxi DATONG CITY WALLS Datong is the second largest city in Shanxi with a population of about three million. Together with the Old Town, the Ming-era city walls have been levelled and rebuilt presumably to enhance their appeal to visitors. Ambitiously begun by the previous mayor, the project is the largest of its kind in China. It’s nearly finished, but controversial. At least one expert has dismissed it as a “fake relic,” maybe so, still, the result, with its guard towers illuminated at night, is undeniably photogenic. The Huayan Monastery in the city centre is itself a walled temple complex of restored and rebuilt architecture marking the Liao Dynasty (907-1125). Buddhist sculpture, an 18,000-volume library and paintings from the later Ming and Qing Dynasties are meticulously maintained within its structures. The tallest pavilion features a fine view of the surrounding city, including a residential patch of what Datong once looked like.

The new walls and Ming-style homes in Datong are photogenic, but reconstruction has resettled thousands of locals and critics have described the results as “fake.”

The Yungang Grottoes consist of 252 caves and more than 51,000 Buddhist statues from the 5th and 6th centuries.

YUNGANG GROTTOES This UNESCO site near the city of Datong is one of the best examples of Buddhist cave art in China, displaying cultural and religious influences imported along the Silk Road, literally carved in stone. The caves were dug in a kilometre-long row and now have a wide paved walkway in front. They vary in age, condition and complexity, but each is dug out of the pockmarked sandstone base of Wuzhou Mountain. Some of the 51,000 statues suffered environmental or Cultural Revolution damage, but many are intact. The largest, number 20, a 14-metre-tall seated Buddha, faces the elements in a stoic pose outside the caves.

SAKYAMUNI PAGODA Yuan, Ming and Qing emperors have climbed this pagoda, but, unfortunately, you can’t because it’s now considered too fragile. At 67 metres, the Sakyamuni Pagoda of the Fogong Temple in Yingxian is the world’s tallest and oldest wooden tower. The structure is exemplary in other regards as well: it ranks in the first tier of the nation’s protected historic sites, provides a rare glimpse of what are said to be Buddha’s remaining teeth, discovered hidden in a statue on the pagoda’s fourth level, and is earthquake-proof. Built without iron nails, Sakyamuni is proudly paired with the leaning tower in Pisa and Eiffel tower in Paris as a trio of outstanding towers.

Doctor’s Review • APRIL 2016

Built in 1056, the 67-metre-high Sakyamuni Pagoda is the oldest wooden multi-storey structure in the world and also the tallest.

The most holy land of Chinese Buddhism, Wutai Shan is home to about 50 remaining temples, including the Great White Pagoda.

XUANKONG SI

Xuankong Si, or the Hanging Monastery, is an architectural wonder having survived winds and storms for over 1500 years.

One might be forgiven for thinking a large petrified insect was clinging to the side of a cliff. The “Hanging Temple” Buddhist monastery that began as the genius of a single monk some 1500 years ago is now a crowded, one-way pedestrian circuit of appreciative tourists. Original oak stilts (reinforced, I’m sure) hold it in place. Built at the foot of Mount Heng above a river gorge protected from floods, it was designed as a way station for pilgrims. The temple eventually included Buddhist, Confucian and Taoist sculptures within its 40 rooms as a hedge against any single religion falling out of favour with the authorities thereby triggering demolition.

WUTAI SHAN With an enclave scattered through a mountain forest of evergreens, the 53 monasteries atop Mount Wutai include some of China’s oldest wooden buildings. Wutai is one of four sacred mountains in Chinese Buddhism and home to the Bodhisattva (Buddhist seeker) of Wisdom. This is an active monastery with Chinese and Tibetan monks dressed respectively in brown and red robes going about their chores as visitors observe activities that range from prayers to house cleaning. There used to be 200 temples, but many were destroyed in the ninth century when the reigning emperor felt religion held too much sway. The Great White Stupa, built in 1301, is an unmistakable landmark visible from any of the hillsides, including the road northward over the peaks toward Datong.

PINGYAO Pingyao is one of China’s “ancient cities.” At an age of 2700 years that’s not surprising. Guidebooks gush for good reason: it’s authentic. People live and work here. The town centre is a charming mix of restaurants and shops catering to tourists; the outer streets with services for locals are quiet and less flashy, even drab. Pingyao is enclosed by its original city walls and small enough to be walkable. Viewing the historic south gatehouse by moonlight is to step back into the Middle Ages. The tempo increases on the main East-West and North-South Streets, illuminated at night by restaurants, shops and hanging lanterns. Everywhere there’s a muted cacophony of sound: the purr of electric scooters, the tinkle of bicycle bells, children’s laughter, conversations and music. APRIL 2016 • Doctor’s

Review

Sichuan CHENGDU PANDA BASE The Sichuan, Shanxi and Gansu provinces are home to pandas, but their ecosystems are fragile. The Chengdu Panda Base is actively involved in conservation and an international breeding program to put bears back into the wild and ensure survival of the species. China places great importance on the goodwill engendered through these programs. Visitors can wander footpaths while observing the bears in open pens and nose-smudged nursery windows.

LUZHOU WULIANGYE Wuliangye is a sprawling state-owned distillery in a suburb of Yibin. With 60,000 employees, the company is the town. From contemporary headquarters worthy of the world’s largest distillery, the company directs global sales of Wuliangye baijiu, a potent five-grain liquor that’s 40 to 60 percent alcohol by volume (vodka averages about 25 percent). It’s made with water from the Min River at the source of the mighty Yangtze using the only living natural treasure of China: pit mud, a microbial mass that produces the liquor’s characteristic aroma. Consuming baijiu in shots at banquet tables has doubtless put many a diner under them.

The Bamboo Sea can be dark with slender trunks of just one type of plant reaching up 10 metres or more.

TIANQUAN CAVE

BAMBOO SEA

Popularly known as the Stone Sea or Stone Forest, the limestone karst formation of rocks and caves in The subtropical monsoon climate of southern Sichuan Xingwen in southwest Sichuan marks the area as an has created a forest of bamboo in Yibin covering an outstanding global geo park. The timeless rock show area of about 120 square kilometres. The region is boasts the world’s largest sinkhole, various unusual popular for hiking and boating. stone formations including a Needless to say, umbrellas or few that bear a striking rewet weather gear are a must. semblance to people and aniRain, streams, lakes and wamals, plus the spacious Tianterfalls generate a high conquan Cave with its walkways, centration of oxygen anions, dazzling lights, laser show which are said to produce a and underground river ride. positive outlook. The soothA rock luge run is an optional “The patient is married, ing sea of green doesn’t hurt way to enter the cave. Asian active.” vegetable noodle soup. but sexually either. A legend says the sea was once a jade garment woFor more info on travel to ven by fairies. That’s much the region, visit the China more interesting than any National Tourism Office scientific explanation. (tourismchina-ca.com).

MEDICAL QUIPS Chart notes

MORE ONLINE

Chengdu’s pandas and UNESCO parks. doctorsreview.com/features/capital-wealth.

Doctor’s Review • APRIL 2016

The Chengdu Panda Base is one of the largest giant panda breeding centres in the world.

One of the most popular caves in the Xinwen Geo Park is Tianquan, which features a laser show and river ride.

Wuliangye is a state-owned distillery and its headquarters in Yibin employs 60,000 people.

The catch grilled cheese.

Commanders in

CHEESE

Brunch and lunch sandwiches that will make you melt recipes by

Heidi Gibson

with

Nate Pollak

photos by

Antonis Achilleos

ave you ever wondered what makes a great grilled cheese? Restaurant owners Heidi Gibson and Nate Pollak think it’s the bread. Their go-to

is from Pinkie’s Bakery in San Francisco, a pain au levain that’s a country-style French bread made with partial wholewheat flour and natural fermentation. The bakery is a few blocks from their first American Grilled Cheese Kitchen restaurant, which opened in 2010; another larger facility opened in 2013, a third in 2015. In addition to the restaurants, Heidi has seven trophies from national

Doctor’s Review • APRIL 2016

grilled cheese competitions solidifying the couple as an authority on cheese. Their new cookbook, Grilled Cheese Kitchen, published by Chronicle Books, features 39 grilled cheese recipes, and an additional 40 for accompaniments and sides. It also includes tips on the best cheeses for sandwiches — semisoft and semihard — and grilling techniques. Our favourite sandwiches follow.

SUNDAY BRUNCH GRILLED CHEESE The magnificent Monte Cristo is a hamand-cheese sandwich that’s battered, fried, dusted with powdered sugar and served with maple syrup or jam. Here’s a meatless version that marries slightly dry slices of brioche loaf with a thick batter enriched with butter, vanilla and flour which yields a nice crisp and dry finish on the outside and a perfect custardy consistency on the inside. one 1-lb (455-g) brioche or challah loaf, cut into 8 thick slices ¾ c. (180 ml) whole milk 1 egg, lightly beaten 4 tbsp. (60 g) salted butter; 2 tbsp. (30 ml) melted, 2 tbsp. (30 g) at room temperature 2 tsp. (10 ml) vanilla extract 2 tsp. (10 ml) granulated sugar ½ c. (125 ml) all-purpose flour ¼ tsp. (1.25 ml) salt 4 oz. (115 g) Brie or triple crème cheese, thinly sliced 8 ripe strawberries, hulled and thinly sliced confectioners’ sugar for dusting brown sugar bourbon sauce for drizzling (recipe follows)

Arrange the bread slices on a large baking sheet and let dry while preparing the other ingredients. In a medium bowl, whisk together the milk, egg, melted butter and vanilla. Add the granulated sugar, flour and salt, and whisk to combine. Scrape the batter into a shallow pan, such as a pie dish or cake pan. Set aside. Heat a stove-top griddle pan or a large cast-iron skillet over medium-low heat or heat an electric griddle to 350°F (180°C). When the griddle is hot, nestle two slices of the bread in the batter and let soak for 5 seconds, then carefully flip and soak on the second side for another 5 seconds. Transfer the soaked breads to a clean plate. Melt ½ tablespoon (7.5 g) of the room-temperature butter on the hot griddle and add both pieces of the soaked bread. Cook until the first sides are nicely browned and completely dry

to the touch, about 3 minutes. Using a wide spatula, carefully turn the breads. While the second sides are cooking, arrange one-fourth of the Brie and onefourth of the strawberries on top of one piece of bread. When the second sides are nicely browned and the Brie is just softened, use the spatula to transfer the bread with the cheese and strawberries to a platter, and gently place the other cooked bread on top. Cover loosely with aluminum foil and place in a low oven to keep warm. Repeat to cook and assemble the remaining sandwiches. Place each sandwich on a plate and cut in half, if desired. Dust with confectioners’ sugar, drizzle with the bourbon sauce and serve immediately. Serves 4.

Variations Chèvre and fig chutney: substitute 6 tablespoons (90 g) room-temperature goat cheese for the Brie and ½ cup (125 ml) fig chutney for the strawberries. Sunday brunch grilled cheese.

Cristo Hispanico: substitute 3 ounces (85 g) thinly sliced Manchego cheese for the Brie and pile 3 ounces (85 g) shaved or thinly sliced Jamón Serrano, prosciutto or speck on top; substitute ¼ cup (60 ml) pumpkin-orange marmalade for the strawberries. Garnish with fresh raspberries. Honey pot: substitute ¼ cup (55 g) room-temperature chèvre and 3 ounces (85 g) shaved or thinly sliced Carmody cheese for the Brie and top with 3 ounces (85 g) thinly sliced French-style ham. Substitute ¼ cup (60 ml) tomato jam for the strawberries. There is no honey in this sandwich; the name “honey pot” refers to the category in a grilled cheese competition that this sandwich won.

Brown sugar-bourbon sauce Drizzle this sauce over bread pudding, ice cream, cheese cake, pancakes or

waffles. Instead of bourbon, feel free to substitute rum, rye, amaretto, orange brandy or applejack (apple brandy) for different flavours. 1 c. (250 ml) packed dark brown sugar ½ c. (125 g) salted butter at room temperature ½ c. (125 ml) heavy cream 2 tbsp. (30 ml) bourbon 2 tsp. (10 ml) vanilla extract

In a small saucepan over medium-low heat, melt the brown sugar and butter together, whisking constantly until smooth. Turn the heat to low and carefully add the cream, bourbon and vanilla (the mixture may boil up, so add the liquids slowly and keep whisking constantly). Bring the sauce to a simmer and cook for 5 minutes, whisking occasionally or until slightly thickened. Remove from the heat and let the sauce cool for 5 to 10 minutes before using. Store in an airtight container in the refrigerator for up to 1 month. Reheat in a microwave when you’re ready to serve. Makes about 1½ cups (375 ml).

THE CATCH GRILLED CHEESE For the tuna one 6-oz (170-g) can oil-packed tuna, drained 2 tbsp. (30 ml) mayonnaise ¼ Granny Smith apple, minced ½ celery stalk, minced 1 tbsp. (15 ml) minced fresh flat-leaf parsley ½ shallot, minced 1 garlic clove, minced ½ tsp. (5 ml) salt ½ tsp. (5 ml) freshly ground black pepper For the sandwich 2 pretzel buns (hamburger size), split in half horizontally 4 tsp. (20 ml) stone-ground mustard 8 slices ripe plum tomato (about ¼-inch / 6-mm thick) 8 to 12 bread ’n’ butter pickles (recipe follows) 4 slices double-cream Gouda cheese

Doctor’s Review • APRIL 2016

Roast beef and blue cheese grilled cheese.

Preheat the oven to 450°F (230°C), with the convection option on, if you have it. In a medium bowl, combine the tuna, mayon naise, apple, celery, parsley, shallot, garlic, salt and pepper, and stir until well mixed. Set aside. Place the pretzel bun halves on a baking sheet, cut-side up. Spread 1 teaspoon (5 ml) mustard on each bun half. Layer two tomato slices, two or three pickle chips, one-fourth of the tuna mixture and one slice of the Gouda on top of each bun half. Bake the open-faced sandwiches for about 3 minutes or until the cheese is melted. Cut each sandwich in half, if desired, and serve immediately. Serves 2 to 4.

Bread ’n’ butter pickles Once you realize how easy it is to make your own pickles (not to mention how much tastier they are), you’ll never buy supermarket pickles again. 1 lb. (455 g) pickling cucumbers, scrubbed and cut into ¼‑in(6‑mm-) thick rounds

1 tbsp. (15 ml) prepared horseradish (not cream-style) 1 tbsp. (15 ml) dried dill 1 c. (250 ml) white vinegar 1 c. (250 ml) sugar 4 garlic cloves, peeled 2 tbsp. (30 ml) pickling spice 1 tbsp. (15 ml) ground turmeric 1 tbsp. (15 ml) salt 1 tsp. (5 ml) black peppercorns

Pack the cucumber rounds into a 4-cup (1-L) glass canning jar with a secure lid. Add the horseradish and dill, screw on the lid and shake gently to distribute. In a small saucepan over high heat, combine the vinegar, sugar, garlic, pickling spice, turmeric, salt and peppercorns, and stir thoroughly. Bring to boil and immediately remove from the heat. Open the jar and pour the hot brine over the cucumbers. Add cold water to fill the container, leaving ¼-inch (6‑mm) headspace and stir gently. Let cool at room temperature for 20 minutes then replace the lid tightly and gently shake the jar to ensure the pickles are covered in the brine, and the horseradish and dill are evenly dispersed.

Refrigerate for 6 hours before serving. Consume within 4 weeks. Makes about 4 cups (1 L).

Balsamic onion marmalade

ROAST BEEF AND BLUE CHEESE GRILLED CHEESE

This sweet and piquant onion marmalade is delightful in a simple grilled cheese with mild cheddar and a few crumbles of your favourite blue cheese or just on a cracker with a sliver of good cheese.

Warm savoury roast beef and salty pungent blue cheese give this grilled cheese its name; the purple-black, sweet and acidic balsamic onion marmalade ties everything together. If you don’t have time to make the marmalade, you can substitute store-bought onion jam, but don’t skip it altogether — it takes this sandwich over the top. 1½ tsp. (7.5 g) salted butter at room temperature 2 slices white country bread 2 tbsp. (30 ml) balsamic onion marmalade (recipe follows) 2 slices Muenster cheese 3 oz. (85 g) thinly sliced roast beef 1½ tbsp. (22.5 ml) crumbled blue cheese (like King Island Dairy’s Roaring Forties Blue from Australia and New Zealand; see note)

Heat a cast-iron or nonstick skillet over medium-low heat. Spread the butter on one side of each bread slice, dividing it evenly. Place one slice, buttered-side down, on a clean cutting board. Spread with the onion marmalade. Layer one slice of the Muenster, the roast beef, blue cheese and the second slice of Muenster on top. Finish with the second slice of bread, buttered-side up. Using a wide spatula, place the sandwich in the pan, cover and cook until the bottom is nicely browned, 3 to 4 minutes. Turn and cook until the second side is browned and the cheese is melted, about 3 minutes longer. Cut the sandwich in half, if desired, and serve immediately. Serves 1. Note: the sharpness of blue cheeses can vary considerably. Some are creamy and mild, others so sharp you can smell them across the room the minute they’re unwrapped. Adjust the amount you add to this sandwich depending on the strength of the cheese as well as your own tastes.

2 tsp. (10 ml) vegetable oil 2 medium red onions, cut into ¼‑in (6‑mm) dice 1 tsp. (5 ml) salt ½ tsp. (2.5 ml) freshly ground black pepper ¼ c. (60 ml) sugar 3 oz. (85 ml) balsamic vinegar

In a small saucepan over medium heat, warm the vegetable oil. Add the onions, salt and pepper, and stir to combine. Cook, stirring every couple of minutes, until the onions are soft and translucent, about 8 minutes. Stir in the sugar and continue to cook, stirring occasionally, until the liquid from the onions and melted sugar is reduced, but the mixture is not yet sticking to the pot, about 8 minutes longer. Turn the

heat to medium-low, stir in the vinegar and cook, stirring often to prevent scorching, until the liquid is reduced to a thick syrup and the mixture is starting to stick to the pan, about 30 minutes. Remove from the heat and let cool to room temperature. Store in an airtight container in the refrigerator for up to 2 weeks. Makes about 1½ cups (375 ml). Recipes and photos from Grilled Cheese Kitchen: Bread and Cheese and Everything in Between (Chronicle Books, 2016).

MEDICAL QUIPS Take two Man to pharmacist: “Give me Asian vegetable noodle soup. some prepared tablets of acetylsalicylic acid.” Pharmacist: “Do you mean aspirin?” Man slaps his forehead: “That’s it! I can never remember the name.”

DEPRESSION KEYPOINTS CONTINUED FROM PAGE 29

References 1. Patten SB, Kennedy SH, Lam RW et al. CANMAT Clinical guidelines for the management of major depressive disorder in adults. I. Classification, burden and principles of management. J Aff Disord 2009;117(Suppl 1):S5–S14. 2. Van Rhoads R, Gelenberg AJ. Treating depression to remission: Target recovery, and give patients back their lives. Current Psychiatry 2005;4:14-28. 3. Lam RW, Kennedy SH, Grigoriadis S et al. CANMAT Clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Aff Disord 2009;117(Suppl 1):S26–S43. 4. CANMAT CME. Depression. Treating depressive disorder.Tips to get depressed patients well. www.canmat.org/ cme-depression-tips-to-get-depressed-patients-well.php. Accessed March 11, 2016. 5. Allen A. What’s so hard about taking a pill? People with depression know: Staying with your treatment plan. Depression Health Center. WebMD. www.webmd.com/depression/features/depression-staying-with-your-treatmentplan. Accessed March 11, 2016. 6. Sansone RA, Sansone LA. Antidepressant adherence: Are patients taking their medications? Innov Clin Neurosci 2012;9:41-6. 7. Parikh SV, Segal ZV, Grigoriadis S et al. CANMAT Clinical guidelines for the management of major depressive disorder in adults. II. Psychotherapy alone or in combination with antidepressant medication. J Aff Disord 2009; 117(Suppl 1):S15–S25. 8. Government of Canada. The human face of mental health and mental illness in Canada 2006. Ottawa: Minister of Public Works and Government Services Canada, 2006. 9. Mood Disorders Society of Canada. What is depression? Fact sheet. www.mooddisorderscanada.ca/page/ resources Accessed March 14, 2016. 10. Ravindran AV, Lam RW, Filteau MJ et al. CANMAT Clinical guidelines for the management of major depressive disorder in adults. V. Complementary and alternative medicine treatments. J Affect Disord 2009;117(Suppl 1): S54-S64. APRIL 2016 • Doctor’s

Review

P H OT O FI NI S H by

Dr Er r o l B i lli n k of f

A slippery slope

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INTRODUCING INCRUSE ELLIPTA ™

A LAMA* for the treatment of COPD†

Indications and Clinical Use: INCRUSE™ ELLIPTA (umeclidinium) is indicated for the long-term once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. INCRUSE™ ELLIPTA is not indicated for the relief of acute deterioration of COPD. ®

Member of Innovative Medicines Canada

INCRUSE™ ELLIPTA should not be used in patients under 18 years of age. For More Information: Please consult the Product Monograph http://gsk.ca/incruse/en for important information relating to contraindications, warnings, precautions, adverse reactions, drug interactions, and dosing information, which have not been discussed in this piece. ®

The Product Monograph is also available by calling 1-800-387-7374. To report an adverse event, please call 1-800-387-7374. * LAMA=Long-acting muscarinic antagonist, also known as a long-acting anticholinergic (LAAC) † COPD=Chronic obstructive pulmonary disease INCRUSE and ELLIPTA are trademarks of Glaxo Group Limited, used under license by GlaxoSmithKline Inc. © 2016 GlaxoSmithKline Inc. All rights reserved.

00969 02/16

She’s a busy working mom who tries to manage her type 2 diabetes the best she can.

A type 2 diabetes add-on you and your

may agree on. New once-daily JARDIANCE™ is an oral SGLT2 inhibitor to improve glycemic control. Visit Jardiance.ca to learn more.

Indication and Clinical Use: Monotherapy: JARDIANCE™ (empagliﬂozin) is indicated for use as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus for whom metformin is inappropriate due to contraindications or intolerance. Add-on combination: JARDIANCE™ is indicated in adult patients with type 2 diabetes mellitus to improve glycemic control, when metformin used alone does not provide adequate glycemic control, in combination with: • metformin, • metformin and a sulfonylurea, • pioglitazone (alone or with metformin), • basal or prandial insulin (alone or with metformin), when the existing therapy, along with diet and exercise, does not provide adequate glycemic control. Important Limitation of Use: In combination therapy, use of JARDIANCE™ with insulin mix (regular or analogue mix) has not been studied. Therefore, JARDIANCE™ should not be used with insulin mix. Contraindications: • Patients with a history of hypersensitivity reaction to the active substance or to any of the excipients • Renally impaired patients with eGFR less than 45 mL/min/1.73m2, severe renal impairment, end-stage renal disease and patients on dialysis Relevant warnings and precautions: • Not indicated for use in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis

• Patients should be assessed for diabetic ketoacidosis (DKA) immediately if non-speciﬁc symptoms of DKA occur (nausea, vomiting, anorexia, abdominal pain, excessive thirst, difﬁculty breathing, confusion, unusual fatigue, or sleepiness), regardless of blood glucose level. Discontinuation or temporary interruption of JARDIANCE™ should be considered. Caution should be taken when reducing a patient’s insulin dose • Not recommended for use in patients who are volume depleted • Use with caution in patients for whom a drop in blood pressure could pose a risk or in case of intercurrent conditions that may lead to volume depletion. Careful monitoring of volume status and electrolytes is recommended. Temporary interruption of JARDIANCE™ should be considered for patients who develop volume depletion until the depletion is corrected • The use of JARDIANCE™ in combination with a secretagogue or insulin was associated with a higher rate of hypoglycemia • Dose-related increases in LDL-C can occur with JARDIANCE™. LDL-C levels should be measured at baseline and monitored • JARDIANCE™ increases the risk of genital mycotic infections, particularly for patients with a history of genital mycotic infections • JARDIANCE™ increases the risk of urinary tract infections • Use with caution in patients with an elevated hematocrit • Not recommended in patients with severe hepatic impairment • Assessment of renal function is recommended prior to JARDIANCE™ initiation and regularly during treatment. Do not initiate JARDIANCE™ in patients with an eGFR <60 mL/ min/1.73m2

* Fictitious patient. May not be representative of all cases. CA/EMP/00019 | BI/EMP/00019 JARDIANCE™ is a trademark of Boehringer Ingelheim International GmbH, used under license.

• Monitoring of renal function is recommended prior to and following initiation of any concomitant drug which might have an impact on renal function • JARDIANCE™ must not be used during pregnancy or breastfeeding • Should not be used in patients <18 years of age • Use with caution in patients ≥65 years of age due to a greater increase in risk of adverse events, and because diminished efﬁcacy is expected in this population as older patients are more likely to have impaired renal function • Patients ≥75 years of age are at a higher risk of volume depletion. Prescribe with caution • Initiation of therapy in patients ≥85 years of age is not recommended • Patients receiving JARDIANCE™ will test positive for glucose in their urine For more information: Please refer to the product monograph at www.JardiancePM.ca for important information relating to adverse events, drug interactions, dosing, and conditions of clinical use. The product monograph is also available by calling 1-800-263-5103 ext. 84633.

Introducing