April 2017 by Doctor's Review

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MEDICINE ON THE MOVE

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So many flowers!

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Vancouver’s Asian banquet

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A PAIR OF TURN SIGNAL BIKE GLOVES PAGE 14

Basque delicacies

UK’s glorious footpaths

Stroll

intospring

Innovative antidepression medicine Dialogues in low-dose COCs Death by sugar – yes or no?

Indications and clinical use: 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. 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 beta2adrenergic 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 betaagonists, 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

Find out if it’s a fit for your asthma patients.

Covered by all provincial formularies (special authorization)*

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 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. *Quebec Code RE41: For treatment of asthma and other reversible obstructive diseases of the respiratory tract, in persons whose control of the disease is insufficient despite the use of an inhaled corticosteroid (ramq.gouv.qc.ca/en/regie/ legal-publications/Pages/list-medications.aspx)

02012 02/17

Spring is what you make it “O, to be in England now that April’s there…” — Robert Browning My own first visit to England took place in the spring of, well, that’s not important, let’s just say that it was considerably after Queen Elizabeth II ascended to the throne. I flew into Glasgow — lowest airfare from Canada at the time. I rented a car, an Anglia, a Lilliputian, and started south along roads so narrow you could almost reach out and touch the stone walls on the opposite side. And what scenery! Spectacular, stunning, soaring. And so bloody tidy. I imagined a platoon of Scottish fairies came out every night with their tiny rakes and clippers and made every landscape look as though it had been copied from a storybook. I loved it. In the Lake District, the green trimmed hills rose dramatically from the road and the fields were alive with clouds of Wordsworth’s famous daffodils. Perfect sheep grazed in pastures where lambs frolicked. The grass was greener and thicker than any I’d ever seen. I just had to stop and get out and have a roll in it. Which I did. And in which paddock, as the British call them, I lost my car keys. After a good hour of pawing through the nearly foot deep grass, I gave up, and flagged down a passing car that took me to a garage one town over. The mechanic was a gem. He came out immediately and spent a very long time trying to hotwire the Anglia. In the end, he couldn’t. Not to worry. He wired in a starter button under the hood. To start the car, you merely had to push it and you were in business. One small catch. I was driving on the left side of the road, there were a plethora of roundabouts, the standard shift was finicky and given to stalling unless you treated it nicely. I stalled many, many times on my way to London. The most challenging was, I would say, that time on Trafalgar Square circa 5pm on a Friday. Out of the car, up with the hood, a push of the magic button, get back in and I was off again — until I stalled seconds later trying to get across four lanes of swirling traffic to my preferred exit. I stalled again and while leaning over the engine to restart, got a very colourful English lesson from the driver of the truck (sorry, lorry) behind me. Dr Heather Wrigley describes her adventures in “Paths to happiness,” page 30. Don’t miss it. And I’d be remiss if I didn’t recommend Cinda Chavich’s mouthwatering tour of Asian food in Vancouver, page 34.

Indications 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, • pioglitazone (alone or with metformin), • metformin and a sulfonylurea, • basal or prandial insulin (alone or with metformin), when the existing therapy, along with diet and exercise, does not provide adequate glycemic control. Add-on combination in patients with established cardiovascular disease: JARDIANCE® is indicated as an adjunct to diet, exercise and standard care therapy to reduce the incidence of cardiovascular death in patients with type 2 diabetes mellitus and established cardiovascular disease who have inadequate glycemic control. Important Limitation of Use: 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, endstage renal disease and patients on dialysis Most Serious Warnings and Precautions: Diabetic Ketoacidosis: Clinical trial and post-market cases of diabetic ketoacidosis (DKA), a serious, life-threatening condition requiring urgent hospitalization, have been reported in patients on JARDIANCE® and other sodium-glucose co-transporter 2 (SGLT2) inhibitors. Some cases of DKA have been fatal. A number of these cases have been atypical with blood glucose values below 13.9 mmol/L (250 mg/dL) • Patients should be assessed for DKA immediately if non-specific symptoms of DKA occur (difficulty breathing, nausea, vomiting, abdominal pain, confusion, anorexia, excessive thirst, unusual fatigue, or sleepiness), regardless of blood glucose level, and JARDIANCE® should be discontinued immediately • JARDIANCE® should not be used for the treatment of DKA or in patients with a history of DKA • Not indicated, and should not be used, in patients with type 1 diabetes Other Relevant Warnings and Precautions: • 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 • Caution should be observed in patients at high risk for cerebrovascular accidents • In clinical situations known to predispose to ketoacidosis (e.g., major surgical procedures, serious infections and acute serious medical illness), consider temporarily discontinuing JARDIANCE® • Use caution in patients at higher risk of DKA • Use caution when reducing the insulin dose in patients requiring insulin • 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 • 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 be discontinued if eGFR falls below 45 mL/min/1.73m2 • 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. For important safety information on SGLT2 inhibitors and the risk of DKA, please refer to http:// www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/58404a-eng.php. References: 1. JARDIANCE Product Monograph. Boehringer Ingelheim, September 12, 2016. 2. Boehringer Ingelheim (Canada) Ltd. Data on File. Medical Letter. September 6, 2016.

David Elkins, publisher and editor delkins@parkpub.com

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APRIL 2017

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JARDIANCE® is a registered trademark of Boehringer Ingelheim International GmbH, used under license.

CA/EMP/00086 BI/EMP/00086

NEW INDICATION

In type 2 diabetes patients with inadequate glycemic control and established CV disease…

CV DEATH HAS A NEW OPPONENT. JARDIANCE® is the only T2D agent indicated as an adjunct to diet, exercise and standard care therapy to reduce the incidence of cardiovascular death in patients with T2D and established CV disease who have inadequate glycemic control.1,2*

JARDIANCE® is not recommended for use in patients who are volume depleted. Due to its mechanism of action, JARDIANCE® causes diuresis that may be associated with decreases in blood pressure. Caution should be exercised in patients for whom an empagliflozin induced drop in blood pressure could pose a risk, such as patients with known cardiovascular disease, patients on antihypertensive therapy (particularly loop diuretics), elderly patients, patients with low systolic blood pressure, or in case of intercurrent conditions that may lead to volume depletion (such as gastrointestinal illness). Careful monitoring of volume status is recommended. Temporary interruption of JARDIANCE® should be considered for patients who develop volume depletion until the depletion is corrected. CV=cardiovascular; T2D=type 2 diabetes. *Comparative clinical significance is unknown.

SE ED F U ND O PA N EX TIO RA

FIBRISTAL® FOR THE MEDICAL MANAGEMENT OF UTERINE FIBROIDS FIBRISTAL® is the only medication indicated in uterine fibroids.

Indication: FIBRISTAL is indicated for the intermittent treatment of moderate to severe signs and symptoms of uterine fibroids in adult women of reproductive age. The duration of each treatment course is three months. ®

Contraindications: • Use during pregnancy and in women who are breastfeeding • Women with genital bleeding of unknown etiology or for reasons other than uterine fibroids • Women with uterine, cervical, ovarian or breast cancer Relevant warnings and precautions:

• Concomitant use of hormonal contraceptives not recommended • Use in patients with severe hepatic impairment unless the patient is

closely monitored

• Use in patients with moderate or severe renal impairment • Use in severe asthmatics insufficiently controlled by oral glucocorticoids • Changes in the histology of the endometrium may be observed in patients.

• Concomitant use with moderate or potent CYP3A4 inhibitors, CYP3A4

inducers, and potent enzyme inducers

• Should excessive bleeding persist beyond the first 10 days of treatment,

patient should notify physician

• If altered, persistent or unexpected bleeding pattern occurs during treatment,

investigation of the endometrium including endometrial biopsy should be performed to exclude other underlying conditions

For more information: For additional information relating to adverse reactions, drug interactions, and dosing information, please consult the product monograph at http://fibristal. ca/docs/Fibristal_Product_Monograph_E.pdf. The product monograph is also available by calling us at 1-800-668-6424. REFERENCES: 1. FIBRISTAL Product Monograph, Allergan Pharma Co., November 2016. 2. Data on File, Allergan Inc., November 2016. ®

These changes are denoted as “Progesterone Receptor Modulator Associated Endometrial Changes” (PAEC) and are reversible after treatment cessation. Investigate persistent endometrial thickening beyond 3 months following end of treatment. Studied in up to 4 intermittent treatment courses. FIBRISTAL and its design are registered trademarks of Allergan Sales, LLC, used under license by Allergan Pharma Co. ALLERGAN and its design are trademarks of Allergan Inc. © 2017 Allergan. All rights reserved. ®

contents APRIL 2017

30 COVER: SHUTTERSTOCK

features

England’s paths to happiness An Alberta FP extends her London layover to explore the country’s footpaths by Dr Heather Wrigley

34 Vancouver’s stunning Asian banquet The best Chinese food in the world from elegant halls to hip new concepts by young Asian-Canadian chefs by Cinda Chavich

The joys of spring Frolic all over the globe among wild bluebells, poppies, desert sunflowers and more by Camille Chin

Basque in its glory Stuffed onions and salt cod tortilla from the region that straddles France and Spain by José Pizarro

a new contest! Win a seven-day “CME Away” holiday at Sandals Barbados! Turn to the inside back cover for details.

44 34

APRIL 2017 • Doctor’s

Review

NOW AVAILABLE WITHOUT A PRESCRIPTION!

FLONASE® Allergy Relief is the same intranasal corticosteroid (INS) that has been trusted by doctors and pharmacists for nearly 20 years.1 FLONASE® Allergy Relief is the first and only over-the-counter (OTC) INS indicated to treat nasal and ocular symptoms of seasonal and perennial allergic rhinitis, without a prescription.1-3 It is available for OTC* use in adults 18 years of age and older.2

VISIT FLONASEPROFESSIONAL.CA FOR MORE INFORMATION. FLONASE® Allergy Relief (fluticasone propionate aqueous nasal spray 50 mcg) is indicated for the treatment of the symptoms associated with seasonal allergic rhinitis including hay fever, and perennial rhinitis; and the management of sinus pain and pressure symptoms associated with allergic rhinitis.

References: 1. Data on file. GSK group of companies. 2016. 2. FLONASE® Allergy Relief Product Monograph. GlaxoSmithKline Consumer Healthcare Inc. August 23, 2016. 3. Nasacort Allergy 24HR/Nasacort AQ Product Monograph. Sanofi-Aventis Canada Inc. December 11, 2013.

Please consult the product monograph at flonaseprofessional.ca or by calling 1-866-994-7444 for information relating to adverse reactions, drug interactions, and dosing information.

* BTC in Quebec, Schedule II.

contents APRIL 2017

regulars

LETTERS

MDs sound off on 3D reality

PRACTICAL TRAVELLER Air Canada’s new look, a major Georgia O’Keeffe retrospective in Toronto, bike from Denmark to Sweden this summer and more! by Camille Chin

GADGETS Lighted turn-signal gloves and a teeny tiny GPS system for your bike by David Elkins

HISTORY OF MEDICINE Death by sugar — fact or fiction? by Tilke Elkins

PHOTO FINISH Birds of a feather… by Dr H.M. Robinson

TOP 25 The best conferences scheduled for September

CONVERSATIONS IN WOMEN’S HEALTH Low-dose combined oral contraceptives (COCs) by Alison Palkhivala

DEPRESSION KEYPOINTS Innovative medicine’s brightening future by Dr David Desjardins with David Elkins

Coming in

May

Japan undercover An inspiring visit to little-known Oki Islands Free as a bird in Nepal Let a vulture be your guide to paragliding This land (of trains) is our land Ride the rails from coast to coast — the thrill of it!

Finland turns 100 Helsinki’s all season secrets worth waiting for

APRIL 2017 • Doctor’s

Review

LETTERS

MDs sound off on 3D reality

EDITOR

David Elkins

MANAGING EDITOR

Camille Chin

CONTRIBUTING EDITOR

Katherine Tompkins

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

BORDEAUX AND BEYOND A beautiful region. Bordeaux is like a miniature Paris [Aquitaine and the art of living, February 2017, page 32]. The Dordogne (Périgord to the French) has spectacular scenery, great food and fascinating pre-historic troglodyte sites. Sarlat makes an excellent centre from which to explore. Dr Ian Hammond Via DoctorsReview.com

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

A NEW TOOL OF THE TRADE? Here are a few of the online comments we received about the VR KiX Virtual Reality Headset [Gadgets, February 2017, page 12]: Technology is unstoppable, we have to learn and move forward, and this device is proof. Dr Oksana Yatsina

MONTREAL HEAD OFFICE

Parkhurst Publishing Ltd. 3 Place Ville Marie, 4th floor Montreal, QC H3B 2E3 Tel: (514) 397-8833 Email: editors@doctorsreview.com www.doctorsreview.com

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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, Parkhurst Publishing Ltd., 3 Place Ville Marie, 4th floor, Montreal, QC H3B 2E3. 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.

Winning this would make me seem so cool with the younger folk. Dr Aileen Comerton

I have experienced this very cool technology and would love to own this. In fact, if I don’t win it, I will likely purchase. Dr Greg Patey

HEADS UP I love the idea of paper bike helmets [“Made from recycled paper,” Practical Traveller, February 2017, page 9]. I’d much rather purchase a clean, recyclable helmet for $5 than one that’s been worn by dozens if not hundreds of people and then rinsed quickly (if at all!) before being tossed back in a bin for more people to rent and use. I’m very impressed by the student designer who invented this and so pleased that it was a woman. I look forward to more bright ideas from her and other women inventors. Bridgette Song Via email

Doctor’s Review • APRIL 2017

BREAKFAST IN THE BOWL I saw your article on breakfast bowls [Spoon feed, January 2017, page 44]. They were very unusual. It reminded me of a breakfast that I used to make called Budwig. A doctor invented it in the ’50s as an anti-cancer recipe. It was made with flaxseed oil and cottage cheese and all kinds of other really good, healthy ingredients. I would whip up a batch at night and eat it a few times during the week. Margaret L. Via email

LEAN, PLEASE Thanks for the great photo of the smoked meat sandwich, dill pickle and fries [Cover, March 2017]. I think I recognized the Schwartz’s placemat. Never realized quite how famous the sandwiches are until I visited Santa Fe last summer and saw a big restaurant sign advertising “Montreal smoked meat.” I went in and had one, of course. In case you’re wondering, it didn’t come close to the real thing. Enjoyed the article [Montreal turns 375, March 2017, page 38] too. It’s a party I don’t want to miss. Ex-Montrealer (name withheld) Toronto, ON

Editor’s note: You got that right. The placemat is indeed from Schwartz’s Montreal Hebrew Delicatessen.

We want to hear from you! Send your comments and questions to: Doctor’s Review, Parkhurst Publishing Ltd., 3 Place Ville Marie, 4th Floor, Montreal, QC H3B 2E3. Or email us at editors@doctorsreview.com.

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

Georgia O’Keeffe’s Music Pink and Blue No. I, 1918. BELOW: Georgia O’Keeffe, An American Place, by Arnold Newman, 1944.

C a mi lle C hi n

COLLECTION OF BARNEY A. EBSWORTH. PARTIAL AND PROMISED GIFT TO SEATTLE ART MUSEUM

Meet the Mother of American Modernism Georgia O’Keeffe at Toronto’s Art Gallery of Ontario, April 22 to July 30, will be a major retrospective featuring over 100 works by the 20th-century modernist. “This partnership with Tate Modern adds to the slate of major collaborations we have established with some of the best art institutions in the world,” says Stephanie Smith, AGO Chief Curator. “Due to its depth, scope and focus on dispelling persistent clichés surrounding the work of this great artist, this will be one of the most significant exhibitions of O’Keeffe’s art ever presented in Canada.” Often hailed as the “Mother of American Modernism,” O’Keeffe (1887-1986) was born in a farmhouse in Wisconsin. She worked as a teacher in Virginia and Texas for several years, before moving to New York and later the Southwest. Nature, landscapes and still life were important themes in her work. A selection of photos by her art dealer/ photographer husband, Alfred Stieglitz, will also be on view, including portraits and nudes of O’Keeffe. Closed Mondays. Adults $19.50. ago.net. APRIL 2017 • Doctor’s

Review

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

Your personal art curator? The Shazam app has been around for decades. Available on both iPhones and Androids, the mobile app can instantly tell you the name of the song that’s playing on your car radio or in your favourite coffee shop. Now, a new app called Smartify will allow users to scan artwork at museums to get art commentary on the piece. The app’s co-founder, Thanos Kokkiniotis, has himself likened the platform to Shazam. Only four museums were covered by the app when we checked at the end of March and reviews weren’t particularly favourable, but Smartify is set to launch across more major institutions including the Louvre in Paris and The Met in NYC. Some museums have their own apps, of course, with commentary from artists and curators.

Denmark to Sweden by bike (and boat)

WILLIAM PERUGINI / SHUTTERSTOCK.COM

Christiansborg Palace in Copenhagen, Denmark.

Doctor’s Review • APRIL 2017

The Øresund Bridge that connects Copenhagen in Denmark to Malmö in Sweden is beautiful, but when the 16-kilometre-long road and rail link opened in 2000, cyclists felt left behind. Commuters can take their bikes across the bridge by train, but they have to pay the price of a child’s ticket for their wheels. As a DIY alternative, four people tried to ride across the bridge last summer, which led to a temporary closure. This season, a converted shipping boat called the M/S Elefanten will ferry up to 36 cyclists at a time across the Øresund Strait in a trial project beginning in June until August. It’ll depart Dragør near Copenhagen and arrive in Limhamn, west of Malmö, an hour later. Fees are TBD.

AC’s new look

plus bidding for an upgrade Air Canada is being redesigned. The inside and outside of its airplanes will soon have a whole new look as will employee uniforms. AC’s fleet of 300 mainline and regional aircraft (currently baby blue in colour) are being repainted in a black and white design with a red, maple leaf-encircled ensign on the tails. A black mask will surround the cockpit’s windshield to give the planes the facial markings of a bird, a nod to Canada’s wildlife and First Nations heritage. The blue decor of cabin interiors will be replaced with cream, grey and black. Employee uniforms will be updated too. Canadian-designer Christopher Bates created charcoal-coloured wool uniforms for flight attendants and black suits for pilots, both with red accents, to replace the current navy uniforms. In more news, Air Canada announced last month that customers with seats in economy or premium economy can now bid for upgrades in premium economy or business class. Passengers can offer a bid between a set minimum and maximum on AC’s Bid Upgrade website (upgrade.plusgrade.com/ offer/AirCanada) any time up until 96 hours before their flight. Forty-eight hours before their flight, AC will send an email to let passengers know if their offer was accepted. Note: not all flights are eligible.

APRIL 2017 • Doctor’s

Review

P R AC T I C AL T R A V E L L E R National Aeronautics and Space Administration

TOTAL SOLAR ECLIPSE ON AUGUST 21, 2017

This unique map shows the path of the moon’s umbral shadow – in which the sun will be completely obscured by the moon – during the total solar eclipse of August 21, 2017, as well as the fraction of the sun’s area covered by the moon outside the path of totality. The lunar shadow enters the United States near Lincoln City, Oregon, at 9:05 a.m. PDT. Totality begins in the United States in Lincoln City, Oregon, at 10:16 a.m. PDT. The total eclipse will end in Charleston, South Carolina, at 2:48 p.m. EDT. The lunar shadow leaves the United States at 4:09 p.m. EDT. A partial eclipse will be visible throughout the United States.

Lunar topography data from NASA’s Lunar Reconnaissance Orbiter and the Japan Aerospace Exploration Agency’s SELENE lunar orbiter were used to precisely calculate the location of the moon’s shadow. Land shading is based on a global mosaic of images from NASA’s Moderate Resolution Imaging Spectroradiometer, and elevations are based on data from NASA’s Shuttle Radar Topography Mission. Planetary positions are from NASA’s Jet Propulsion Laboratory Development Ephemeris 421. Credit: NASA’s Scientific Visualization Studio

EXPERIENCE

THE

2017 ECLIPSE ACROSS AMERICA

THROUGH THE EYES OF NASA http://eclipse2017.nasa.gov

NP-2016-11-525-GSFC

www.nasa.gov

The dark times ahead A lot of people are thinking twice about travelling to the US these days, but there’s one big event that hasn’t happened south of the border since 1776 that will draw some people this August 21: the total solar eclipse. Total solar eclipses occur when the new moon comes between the sun and earth, casting the darkest part of its shadow, the umbra, on our humble planet. Scientists and historians have dubbed 2017’s eclipse the “Great American Eclipse” because its path of totality will lie completely within the continental US and no other country. The eclipse will begin in Oregon at 10:15am and then move diagonally through 12 states before ending in South Carolina at 2:49pm (see the map above for details). Cities and towns in the path of the moon’s umbra will have their summer day turn dark, cool, even eerie. Still, never look directly at the sun, eclipsed or otherwise, without protective eyewear. Another thing you might need? The Vistabule campervan (from US$18,000). Hotel rooms within the eclipse’s path of totality are already selling out. The Vistabule features a huge overhead window perfect for skygazing. eclipse2017.nasa.gov.

Doctor’s Review • APRIL 2017

VYVANSE®*

The 1 & only medication in Canada indicated for the treatment of moderate to severe Binge Eating Disorder in adults1,2† Limitation of Use for Binge Eating Disorder (BED): Serious cardiovascular (CV) events have been reported with this class of sympathomimetic medications. The BED clinical trials were not designed to assess CV safety. Given the higher CV risk associated with obesity, the BED population may be at a higher risk. The safety and effectiveness of VYVANSE for the treatment of obesity have not been established. VYVANSE is not indicated or recommended for weight loss.

Consider a conversation with your patients who you believe may be suffering with Binge Eating Disorder. In addition to your clinical assessment, ask: • • • • •

Have you eaten an abnormally large amount of food in a short period of time? Did you have a sense of lack of control over eating during the episode? Are you distressed about the binge eating? Do you feel disgusted or guilty? Do you eat alone because you are embarrassed?

VYVANSE (lisdexamfetamine dimesylate capsules) is indicated for the treatment of Moderate to Severe Binge Eating Disorder (BED) in adults.3 Recurrent episodes of binge-eating are characterised by: • consuming an abnormally large amount of food in a short period of time and sense of lack of control over eating during the episode • marked distress about the behavior • feeling disgusted or guilty, or eating alone because of embarrassment.

Limitation of Use for BED: Prescribers should consider that serious cardiovascular (CV) events have been reported with this class of sympathomimetic medications. The BED clinical trials were not designed to assess CV safety. While there is an accumulation of safety data with VYVANSE use in the Attention Deficit Hyperactivity Disorder (ADHD) population, this is of limited relevance regarding CV risk in the BED population. Given the higher CV risk associated with obesity, the BED population may be at a higher risk.

The safety and effectiveness of VYVANSE for the treatment of obesity have not been established. VYVANSE is not indicated or recommended for weight loss. Use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events. Consult the product monograph at www.shirecanada.com/vyvpm/en for important information on conditions of clinical use, contraindications, warnings, precautions, adverse reactions, interactions, and dosing. The product monograph is also available by calling Shire Pharma Canada ULC at 1-800-268-2772.

References: 1. Shire Pharma Canada ULC. Data on file. 2. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA, American Psychiatric Association, 2013. 3. VYVANSE Product Monograph. Shire Pharma Canada ULC, September 30, 2016. † Moderate BED is defined as 4-7 binge-eating episodes per week. Severe BED is defined as 8-13 binge-eating episodes per week.

G AD G E T S A N D GE A R by

D a v i d Elk i n s

Light up your (bike) life

In case you missed it, 2017 is the 200th anniversary of the invention of the twowheeled bike. German inventor Baron Karl Drais put the first contraption together in 1817. It looked remarkably like bikes today, but there were some significant differences. Most notably, it didn’t have a drive chain or brakes. You straddled the seat and propelled yourself forward with your feet, as you would today’s bikes — if you don’t use the pedals. The baron called it a running machine. You could move at up to 15 kilometres an hour on it and it was Drais’s intention

that it would help the poor who could not afford a horse to get around. Instead, it was adopted by wealthy young men and enjoyed a short-lived craze in Europe where it became known as the “dandy” or “hobby horse.” The concept never died completely. In 2005, Austrian Walter Werner rode one the entire 3400 kilometre length of the Danube in five months and, more recently, a similar device has been marketed in Germany as a kids “glide bike.”

Win your choice of either a pair of gloves or the Garmin bike computer by entering the Gadget of the Month contest at doctorsreview.com Clearly the bicycle has come a long way since then. In some urban centres it has begun to challenge the car as a favourite mode of transportation. It’s a trend that is likely to continue and, coupled with the current movement toward shared city transport, may come to alter the way inner cities are designed. We’re not there yet, however, and these days cars and bikes too often challenge one another for the right of way with unpleasant consequences. Enter a small step forward for the cyclist: the Zackees Turn Signal Cycling Gloves which incorporate bright red LED lights. Activated by touching two metal rivets that sit between the thumb and the side of your palm along your index finger, the lights are a godsend to night bikers and are bright enough that

hand signals are seen even in daylight. An ambient light sensor increases the brightness. The well-designed bike gloves have a breathable mesh back and a foam-padded palm to absorb shocks. Winter models are also on offer. US$75. zackees.com/product/zackees-turnsignal-gloves. The gloves are listed on Amazon.ca, but were unavailable at the time of writing. Also consider adding the Garmin Edge 20 GPS Cycling Computer to your arsenal. This, the smallest of cycle GPS systems, will track your speed and distance, and point the way home if you get lost on the trail. There are even preset courses you can download if that’s your fancy. $148. Available at bike and sports stores, and at Amazon.ca.

CONGRATULATIONS! The winner of a VR headset is Dr Radu Puscas, an FP from Laval, QC. 14

Doctor’s Review • APRIL 2017

SALINE

XLEAR

THERE IS A DIFFERENCE BETWEEN

RINSING AND CLEANING Stop recommending an incomplete solution for nasal and sinus issues. Recommend something that works better than saline. Simple saline solutions alone do little more than rinse out

shown to significantly reduce bacterial adhesion.

2.5%

M. catarrhalis

H. influenzae

S. pneumoniae

M. catarrhalis

those suffering from acute rhinitis.* Xylitol has also been

H. influenzae

S. pneumoniae

has shown that xylitol increases airflow by up to 35% in

M. catarrhalis

reduce inflammation without the use of steroids. A study

H. influenzae

xylitol to safely and effectively alleviate congestion and

S. pneumoniae

does more. Xlear nasal and sinus care products have

Bacteria per epithelial cell

your patientsâ&#x20AC;&#x2122; nose. Start recommending something that

Concentration of xylitol S. pneumoniae, H. influenzae, and M. catarrhalis have a reduced ability to adhere to nasal epithelial cells *

Bellanti, J.A., Nsouli, T.M. â&#x20AC;&#x153;Xylitol Nasal Irrigation: A

Possible Alternative Strategy for the Management of Chronic Rhinosinusitis, Oral Abstract #46. ACAAI Conference: 9 Nov. 2015.

Try it with your patients

GET 30 FREE PATIENT SAMPLES at xlear.com/sample-canada

To order contact one of these fine distributors: AC Distributors Ltd. - Kelly Walden Office: 604.278.7442

Axel Kraft International - Stewart Selina Office: 905.841.6840

Purity Life Health Products Office: 1.800.265.2615

Enjoy more good mornings.

One daily spoonful of ULTIMATE GLUCOSAMINE helps relieve the pain of osteoarthritis.

A recent study published in the Annals of the Rheumatic Diseases demonstrated that glucosamine type molecules have comparable efficacy to celecoxib in reducing pain and stiffness after 6 months of treatment.† • ULTIMATE GLUCOSAMINE powder can be added to any beverage as a mild sweetener, sprinkled over cereal or added to a yoghurt smoothie. • It consists of 100% pure N-Acetylglucosamine, a natural substance, extracted from the shell of crustaceans. It is also found in healthy human cartilage. N-Acetylglucosamine has no known interactions with prescription medications. • The ULTIMATE GLUCOSAMINE formulation contains no additives, salts, preservatives, colouring agents, gluten, lactose or yeast. For more information on Ultimate Glucosamine see the 2016 CPS monograph.

Wellesley Therapeutics Inc. UltimateGlucosamine.com 1.800.449.1130

† Hochberg, M. C., J. Martel-Pelletier, et al. (2016). “Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib.” Ann Rheum Dis 75:37

® ULTIMATE GLUCOSAMINE and ULTIMATE GLUCOSAMINE logo are registered trademarks. All are used under license.

THE TOP 25 MEDICAL MEETINGS compiled by Camille Chin

Access 2500+ conferences at doctorsreview.com/meetings Code: drcme Canada Calgary, AB September 9-11 Canadian Stroke Congress strokecongress.ca

2017 Annual Conference of the Canadian Psychiatric Association cpa-apc.org

September 15-17 2017 Annual General Meeting and Educational Sessions of the Federation of Medical Women of Canada fmwc.ca/2017agm

September 17-19 37th Annual Conference of the Canadian Academy of Child and Adolescent Psychiatry cacap-acpea.org

September 20-23 2017 Canadian Hospice Palliative Care Conference conference.chpca.net

Quebec City, QC August 20-23 150th Annual Meeting of the Canadian Medical Association cma.ca/En/pages/upcoming-annual-meetings.aspx

TRABANTOS / SHUTTERSTOCK.COM

Ottawa, ON September 14-16

Bilboa’s La Salve Bridge.

Vancouver, BC September 7-10 18th Congress of the International Headache Society ihc2017.com

September 14-16 63rd Annual Meeting of the Canadian Fertility and Andrology Society cfas.ca/annual-meeting/future-meetings

Victoria, BC September 14-16 4th Annual Congress of the Canadian Hernia Society canadianherniasociety.ca

To register and to search 2500+ conferences, visit doctorsreview.com/meetings

Around the world Barcelona, Spain September 21-23 7th Congress of the European Society for Swallowing Disorders and the World Dysphagia Summit essd2017.com

Belgrade, Serbia September 9-12 40th Annual Meeting of the European Thyroid Association eta2017.com

ANDROVER / SHUTTERSTOCK.COM

Berlin, Germany September 20-22 12th Scientific and Annual Meeting of the European Society of Coloproctology escp.eu.com/conference-and-events/escp-2017

The Inner Harbour in Victoria, BC.

Bilbao, Spain September 8-11 47th European Brain and Behavior Society Meeting ebbs-meeting.com APRIL 2017 • Doctor’s

Review

New LIXIANA®:

Helping patients along the journey of stroke prevention in AF LIXIANA® (edoxaban) is indicated for: › Prevention of stroke and systemic embolic events in patients with atrial fibrillation (AF), in whom anticoagulation is appropriate. › Treatment of venous thromboembolism (VTE) (deep vein thrombosis [DVT], pulmonary embolism [PE]) and the prevention of recurrent DVT and PE.

In the prevention of stroke and systemic embolic events in AF (primary composite endpoint), LIXIANA® 60 mg (30 mg dose-reduced):* • Demonstrated NON-INFERIORITY vs. warfarin

› Event rate of 1.18% vs. 1.50% per year seen with LIXIANA® 60 mg (30 mg dose-reduced*) vs. warfarin (mITT – on-treatment†)‡,1,2 HR (97.5% CI): 0.79 (0.632, 0.985); p<0.0001 for non-inferiority§

• Component scores (% per year) seen with LIXIANA® 60 mg (30 mg dose-reduced*) vs. warfarin‡ › First ischemic stroke: 0.87 vs. 0.93 HR (95% CI): 0.94 (0.75, 1.19)

› First hemorrhagic stroke: 0.26 vs. 0.49 HR (95% CI): 0.53 (0.36, 0.78)

› First systemic embolic events: 0.05 vs. 0.08 HR (95% CI): 0.62 (0.26,1.50)

• Significantly LOWER rates of MAJOR BLEEDING events demonstrated vs. warfarin

› Adjudicated event rate of 2.75% vs. 3.43% per year seen with LIXIANA® 60 mg (30 mg dose-reduced*) vs. warfarin (mITT – on-treatment†)‡,¶,1,2 HR (95% CI): 0.80 (0.71, 0.91); p=0.0009

Bleeding: LIXIANA® increases the risk of bleeding and can cause serious, potentially fatal bleeding. LIXIANA®, like other anticoagulants, must be used with caution in patients with increased risk of bleeding. Patients at high risk of bleeding should not be prescribed LIXIANA®. Should severe bleeding occur, treatment with LIXIANA® must be discontinued and the source of bleeding investigated promptly. Close clinical surveillance is recommended throughout the treatment period, especially in the presence of multiple risk factors for bleeding. ASA: acetylsalicylic acid; CI: confidence interval; CrCL: creatinine clearance; HR: hazard ratio; mITT: modified intent-to-treat; NSAID: nonsteroidal anti-inflammatory *In the study, patients receiving verapamil, quinidine, or dronedarone concomitantly with LIXIANA® had their dosing regimens halved. The recommended dose of LIXIANA® is 30 mg once daily in patients with concomitant use of P-gp inhibitors other than amiodarone and verapamil. †mITT population included only subjects who received at least one dose of study drug; the on-treatment period was the period during which the subject took study drug unless the patient had early drug discontinuation(s), in which case the on-treatment period included the 3 days following drug discontinuation(s). ‡Event rate (%/yr) is calculated as number of events/subject-year exposure. §The two-sided p-value is based on the non-inferiority margin of 1.38. ¶A major bleeding event (the primary safety endpoint), as defined by ISTH (International Society of Thrombosis and Haemostasis), was a clinically overt bleeding event that met one of the following criteria: fatal bleeding; symptomatic bleeding in a critical site such as retroperitoneal, intracranial, intraocular, intraspinal, intra-articular, pericardial, or intramuscular with compartment syndrome; a clinically overt bleeding event that caused a fall in hemoglobin of at least 2.0 g/dL (or a fall in hematocrit of at least 6.0% in the absence of hemoglobin data), when adjusted for transfusions (1 unit of transfusion = 1.0 g/dL drop in hemoglobin). **Please see Product Monograph for complete dosing and administration information.

® Registered trademark of Daiichi Sankyo Co., Ltd. Used under license.

DAILY

Convenient one pill, once-daily dosing, taken with or without food**

Clinical use Not recommended for use in children < 18 years. Contraindications › Clinically significant active bleeding, including gastrointestinal bleeding › Lesions or conditions at increased risk of clinically significant bleeding, e.g., recent cerebral infarction (hemorrhagic or ischemic), active peptic ulcer disease with recent bleeding, patients with spontaneous or acquired impairment of hemostasis › Hepatic disease associated with coagulopathy and clinically relevant bleeding risk › Concomitant treatment with any other anticoagulant, including: » unfractionated heparin (UFH), except at doses used to maintain a patent central venous or arterial catheter; » low molecular weight heparins (LMWH), such as enoxaparin and dalteparin; » heparin derivatives, such as fondaparinux; and » oral anticoagulants, such as warfarin, dabigatran, apixaban, rivaroxaban except under circumstances of switching therapy to or from LIXIANA® › Pregnancy › Nursing women Most serious warnings and precautions Premature discontinuation: PREMATURE DISCONTINUATION OF ANY ORAL ANTICOAGULANT, INCLUDING LIXIANA®, INCREASES THE RISK OF THROMBOTIC EVENTS. To reduce this risk, consider coverage with another anticoagulant if LIXIANA® is discontinued for a reason other than pathological bleeding or completion of a course of therapy. INR: Although LIXIANA® therapy will lead to an elevated INR, INR is not a valid measure to assess anticoagulant activity of LIXIANA®. INR is only calibrated and validated for vitamin K antagonists (VKA) and should not be used for any other anticoagulant, including LIXIANA®. Peri-operative spinal/epidural anesthesia, lumbar puncture: Risk of epidural or spinal hematoma is increased by use of indwelling catheters or concomitant use of drugs affecting hemostasis. Indwelling epidural or intrathecal catheters must be removed ≥ 5 hours prior to the first dose of LIXIANA®. Risk may also be increased by traumatic or repeated epidural or spinal puncture. If traumatic puncture occurs, administration of LIXIANA® should be delayed for 24 hours.

Other relevant warnings and precautions › Concomitant use of drugs affecting hemostasis may increase the risk of bleeding, such as aspirin, P2Y12 platelet inhibitors (i.e. clopidogrel, prasugrel, and ticagrelor), other antithrombotic agents, fibrinolytic therapy and chronic NSAIDs; long-term concomitant use is not recommended › Concomitant use with UFH is not recommended except at doses used to maintain a patent central venous or arterial catheter › Concomitant use of low dose (≤ 100 mg/day) ASA or thienopyridines (clopidogrel) and NSAIDs increased rates of clinically relevant bleeding › Not recommended in patients with prosthetic (mechanical or biological) heart valves or those with hemodynamically significant rheumatic heart disease, especially mitral stenosis › Not recommended in patients with severe hepatic impairment; caution in patients with mild to moderate hepatic impairment › A specific anticoagulant reversal agent for LIXIANA® is not commercially available › Not recommended in patients with severe renal impairment (CrCL ≤ 30 mL/min). Patients who develop acute renal failure while on LIXIANA® should discontinue treatment. › Peri-operative/procedural considerations › Following an invasive procedure or surgical intervention, restart LIXIANA® as soon as adequate hemostasis has been established and the clinical situation allows › Not recommended for prevention of VTE in patients who have undergone elective total knee or hip surgery › Not recommended as an alternative to UFH in patients with PE who are hemodynamically unstable or may receive thrombolysis or pulmonary embolectomy › Not recommended for treatment and/or prevention of VTE in patients with active cancer For more information Please consult the Product Monograph at https:// health-products.canada.ca/dpd-bdpp/index-eng. jsp 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 1-800-363-6093. Please visit www.servier.ca/references/ LIXIANA_EN.pdf to access the study parameters and reference list.

Servier Canada Inc. 235, boulevard Armand-Frappier, Laval, QC H7V 4A7 www.servier.ca | 1-888-902-9700

Servier Canada Inc. 235, boulevard Armand-Frappier, Laval, QC H7V 4A7

LIPR0117E

edoxaban tosylate monohydrate tablets

THE TOP 25 MEDICAL MEETINGS

Access 2500+ conferences at doctorsreview.com/meetings Code: drcme Chicago, IL September 16-19

Lisbon’s Museum of Art, Architecture and Technology.

2017 National Conference and Exhibition of the American Academy of Pediatrics aapexperience.org

Copenhagen, Denmark September 6-9 10th Congress of the European Pain Federation, EFIC efic2017.kenes.com

Dallas, TX September 16-19 21st Annual Scientific Meeting of the Heart Failure Society of North America meeting.hfsa.org

Edinburgh, Scotland September 11-14 RIBEIROANTONIO / SHUTTERSTOCK.COM

2017 Annual Meeting of the European Society for Immunodeficiencies esid2017.kenes.com

Geneva, Switzerland September 2-5 14th World Conference of the World Organization for Specialized Studies on Diseases of the Esophagus oeso.org

Glasgow, Scotland September 6-9 50th Anniversary Meeting of the European Society for Paediatric Nephrology espn2017.org

MEDICAL QUIPS Pun #1 Statistically… 9 out of 10 injections are in vein.

Lisbon, Portugal September 11-15 53rd Annual Meeting of the European Association for the Study of Diabetes easd.org

13th International Congress of the European Union Geriatric Medicine Society eugms.org/2017.html

Liverpool, England August 30-September 3

Vienna, Austria September 23-27

20th International Congress of the International Society for Psychological and Social Approaches to Psychosis isps2017uk.org

Milan, Italy September 9-13 27th International Congress of the European Respiratory Society erscongress.org

Doctor’s Review • APRIL 2017

Nice, France September 20-22

30th Annual Conference of the European Society of Intensive Care Medicine esicm.org/events

Washington, DC September 14-17 10th International Meeting of Pediatric Endocrinology internationalmeeting2017.org

Lolo A low-dose combined oral contraceptive with 10 mcg of ethinyl estradiol * ®

*Any beneﬁts from the lower estrogen exposure provided by Lolo have not been evaluated. ®

Lolo offers the lowest ethinyl estradiol dose of any combined oral contraceptive in Canada * ®

Want to know more? Visit lolocanada.ca. Indication and clinical use: Lolo® is indicated for the prevention of pregnancy. The safety and efﬁcacy of Lolo® have not been evaluated in women with a body mass index >35 kg/m2 or in women <18 years of age. Lolo® is not indicated for use before menarche or postmenopause. Any beneﬁts from the lower estrogen exposure provided by Lolo® have not been evaluated. Contraindications: Women with: • History of (or actual) thrombophlebitis or thromboembolic disorders • History of (or actual) cerebrovascular disorders • History of (or actual) myocardial infarction or coronary artery disease • Valvular heart disease with complications • History of (or actual) prodromi of a thrombosis • Active liver disease, or history of (or actual) benign or malignant liver tumours • Known or suspected carcinoma of the breast • Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia • Undiagnosed abnormal vaginal bleeding • Steroid-dependent jaundice, cholestatic jaundice, history of jaundice of pregnancy • Any ocular lesion arising from ophthalmic vascular disease • Known or suspected pregnancy • Current (or history of) migraine with focal aura • History of (or actual) pancreatitis if associated with severe hypertriglyceridaemia • Presence of severe/multiple risk factor(s) for arterial or venous thrombosis

Most serious warnings and precautions: Smoking: Cigarette smoking increases the risk of serious cardiovascular events associated with the use of hormonal contraceptives. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, Lolo® should not be used by women over the age of 35 who smoke. Sexually Transmitted Infections (STIs): Patients should be counselled that birth control pills DO NOT PROTECT against sexually transmitted infections (STIs) including HIV/AIDS. For protection against STIs, it is advisable to use latex or polyurethane condoms IN COMBINATION WITH birth control pills. General: Patients should discontinue medication at the earliest manifestation of thromboembolic and cardiovascular disorders, conditions which predispose to venous stasis and vascular thrombosis, visual defects (partial or complete), papilledema or ophthalmic vascular lesions, severe headache of unknown etiology or worsening of pre-existing migraine headache, or increase in epileptic seizures. Other relevant warnings and precautions: • Potential increased risk of breast cancer, cervical cancer, hepatocellular carcinoma • Predisposing factors for coronary artery disease • Hypertension • Diabetes • Adverse lipid changes • Crohn’s disease, ulcerative colitis • Vaginal bleeding • Fibroids • Increased risk of arterial and venous thrombotic and thromboembolic diseases • Jaundice, gallbladder disease, hepatic nodules

LOLO® and its design are registered trademarks of Allergan Pharmaceuticals International Limited, used under license by Allergan Pharma Co. Allergan® and its design are trademarks of Allergan Inc., used under license by Allergan Pharma Co. © 2017 Allergan. All rights reserved.

• Angioedema, fluid retention • Risk of thromboembolic complications after major surgery • History of emotional disturbances • Amenorrhea • Reduced efficacy (due to missed dose, gastrointestinal disturbances or concomitant medication) • Chloasma • Pregnant or nursing women • Physical examination and follow-up For more information: Consult the Product Monograph at www.lolocanada.ca/lolo/pm for important information regarding adverse reactions, drug interactions and dosing information (particularly in regards to dose intervals not exceeding 24 hours) not discussed in this piece. The Product Monograph is also available by calling 1-855-892-8766. References: 1. Lolo® Product Monograph. Warner Chilcott Canada Co. December 10, 2013. 2. Data on file. 2012 Hormonal Contraception Available in Canada. The Society of Obstetricians and Gynaecologists of Canada.

ethinyl estradiol 10 mcg/ norethindrone acetate 1 mg and ethinyl estradiol 10 mcg

CONVE RSA T I ON S I N WO M E N ’S H E A L T H by

Alison Palkhivala

Low-dose combined oral contrac

C .

anadian women enjoy more choice than ever with regard to hormone-based contraception. Among the latest developments is a low-dose combined oral contraceptive pill. These new agents have been produced with the goal of maintaining excellent pregnancy prevention while minimizing the adverse events, whether life-threatening or simply inconvenient, that have traditionally been associated with hormone-based contraception. Combined oral contraceptives are available in a variety of formulations, but all contain a form of estrogen, usually ethinyl estradiol, and a progestin, such as norethindrone acetate, levonorgestrel, or drospirenone. They all work by preventing ovulation through suppression of release of follicle-stimulating hormone (FSH) by the pituitary gland. This in turn prevents development of a dominant follicle in the early days of the menstrual cycle and the resulting surge in luteinizing hormone (LH) that triggers ovulation.1

In the decades since combined oral contraceptives were first introduced in the 1960s, doses and types of estrogens and progestins have been modulated in an effort to achieve the highest level of efficacy with the lowest risk of serious adverse events and troublesome side effects. Important changes include the development of third- and fourth-generation progestins, such as norgestimate and norelgestromin,2 as well as reductions in estrogen dose, since estrogen has been shown to drive the risk of serious thrombotic events3,4,5 in a dose-dependent manner.6

Thus, an additional strategy for improving the risk/benefit balance of combined oral contraceptives is to reduce the hormonefree interval, either by shortening the monthly duration of the interval or by having fewer intervals overall. Not only can this limit the troublesome side effects that lead women to discontinue therapy, such as bloating, breast tenderness, headaches, and nausea, but it has the added benefit of reducing or even eliminating cyclic bleeding.8 In a key trial of a COC of 10 mg EE with NETA in a 24/2/2 schedule (24 days active hormonal treatment, 2 days EE only, 2 days placebo) women reported only light periods of withdrawal bleeding of less than two days in a cycle.10 Fully 32% of women in the study reported a complete absence of all bleeding in the first cycle, rising to 49% by cycle 13. That rate is higher than those reported by users of other COCs but the data is sparse and no direct comparisons exist. It does suggest, however, that this dosing schedule does provide a reasonable alternative to the common off label practice in which some women attempt to achieve amenorrhea by skipping the placebo pills of a standard monthly-cycle COC and proceed directly to the next active cycle without an HFI.11 Importantly, this reduction in withdrawal bleeding does not occur at the expense of efficacy. On the contrary, there is evidence that a shorter hormone-free interval contributes to follicular suppression,8,9 potentially allowing for even lower doses of estrogen to be used without sacrificing efficacy. There is also evidence that the increased follicular suppression reduces the risk of contraceptive failure (i.e., an escape ovulation) when pills are missed.12

Shortening the hormone-free interval

References

Traditionally, combined oral contraceptives have been prescribed in a 28-day cycle consisting of 21 days of active hormone therapy followed by a 7-day hormone-free interval, during which time patients may discontinue therapy altogether or take a placebo pill. During the hormone-free interval, bleeding triggered by hormone withdrawal mimics a natural menstrual period, and one of the primary benefits of the 21/7 cycle was perceived to be that it closely resembles women’s natural menstrual cycle. But another consequence of this interval is the emergence of hormone-withdrawal-associated symptoms. In fact, many of the adverse events associated with combined oral contraceptives are not direct effects of the hormone treatment itself but of hormone withdrawal.7

1. Baerwald AR, Pierson RA. Ovarian follicular development during the use of oral contraception: a review. J Obstet Gynaecol Canada 2004;26:19-24. 2. Davtyan C. Four generations of progestins in oral contraceptives. Proc UCLA Healthcare 2012;16:1-3. 3. Lidegaard O, Edstrom B, Kreiner S. Oral contraceptives and venous thromboembolism: a five-year national case–control study. Contraception 2002;65:187-96. 4. Lidegaard O, Lokkegaard E, Jensen A, et al. Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med 2012;366:2257-66. 5. Lidegaard O, Nielsen LH, Skovlund CW, et al. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ 2011;343:d6423. 6. de Bastos M, Stegeman BH, Rosendaal FR, et al. Combined oral contraceptives: venous thrombosis. Cochrane Database Syst Rev 2014;3:CD010813. 7. Sulak PJ, Scow RD, Preece C, et al. Hormone withdrawal symptoms in oral contraceptive users. Obstet Gynecol 2000;95:261-6.

Lowering the dose

Doctor’s Review • APRIL 2017

SRTOCK-ASSO / SHUTTERSTOCK.COM

Alterations in hormone formulations, doses, and administration protocols all work together to maintain efficacy while minimising side effects and risks

aceptives

8. Edelman A, Micks E, Gallo MF, et al. Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception. Cochrane Database Syst Rev 2014;7:CD004695. 9. Willis SA, Kuehl TJ, Spiekerman AM, et al. Greater inhibition of the pituitary – ovarian axis in oral contraceptive regimens with a shortened hormone-free interval. Contraception 2006;74:100-3. 10. Archer DF, Nakajima ST, Sawyer AT, et al. Norethindrone acetate 1.0 milligram and ethinyl estradiol 10 micrograms as an ultra low-dose oral contraceptive. Obstet Gynecol 2013;122:601-7. 11. Brian A. Hauck & Vivien Brown (2015) A primer on the hormone-free interval for combined oral contraceptives, Current Medical Research and Opinion, 31:10. 1941-48. 12. Sullivan H, Furniss H, Spona J, et al. Effect of 21-day and 24-day oral contraceptive regimens containing gestodene (60 microg) and ethinyl estradiol (15 microg) on ovarian activity. Fertil Steril 1999;72:115-20. 13. Klipping C, Duijkers I, Trummer D, et al. Suppression of ovarian activity with a drospirenone-containing oral contraceptive in a 24/4 regimen. Contraception 2008;78:16-25. 14. Guilbert E, Boroditsky R, Black A, et al. Canadian Consensus Guideline on Continuous and Extended Hormonal Contraception, 2007. J Obstet Gynaecol Canada 2007;29:S1-32. 15. Vessey M, Yeates D. Oral contraceptive use and cancer: final report from the Oxford-Family Planning Association contraceptive study. Contraception 2013;88:678-83 16. Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives and the risk of breast cancer. N Engl J Med 2002;346:2025-32. 17. Beaber EF, Buist DS, Barlow WE, et al. Recent oral contraceptive use by formulation and breast cancer risk among women 20 to 49 years of age. Cancer Res 2014; 74:4078-89. 18. Beral V, Doll R, et al. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet 2008;371:303-14. 19. Gierisch JM, Coeytaux RR, Urrutia RP, et al. Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: a systematic review. Canc Epidemiol Biomarkers Prev 2013;22:1931-43. 20. Reid R, Leyland L, Wolfman W, et al. SOGC clinical practice guideline. No. 252, December 2010. Oral contraceptives and the risk of venous thromboembolism: an update. J Obstet Gynaecol Canada 2010;32:1192-204.

Talking to your patients about hormone-free interval (HFI) in low-dose COCs The first step in a discussion with patients about contraceptive use involves a thorough examination of relevant lifestyle and health issues including age, marital status, number of sexual partners, plans to become pregnant, smoking status etc. When a lowdose combined oral contraceptive appears to be a good option, it is often necessary to dispel myths and address concerns about their use. Ask patients if they have any misgivings about using hormone-based contraception. It can also be helpful to specifically address the following common concerns: 1. Effects of compliance on efficacy: Stress the importance of taking an oral contraceptive without fail every day but also explain how to address errors. Typically, one missed pill can be compensated for by doubling up the next day, but two missed pills means an additional form of contraception should be used. Point out that all forms of contraception require proper use to be effective and that shortening the hormone-free interval may reduce the impact of forgetting a pill. 2. Effects on cancer risk: Data on breast cancer risk and use of combined oral contraceptives have been equivocal.15,16,17 Patients can thus be reassured that the potential increased risk is far outweighed by the benefits of low-dose combined oral contraception, particularly given evidence that it may slightly diminish the risk of ovarian18 and endometrial19 cancers. 3. Effect on thrombotic events: Overall, the absolute risk of thrombotic complications associated with combined oral contraceptive use has been calculated to be 9 to 10 events per 10,000 womanyears of use. This is about 3- to 40-fold lower than it is during pregnancy and the immediate postpartum period.20 Explain that selecting a lowdose option can help minimize this risk.6 Next, discuss with patients the possibility of adjusting the hormone-free interval to suit their needs and preferences. Asking the following questions can be helpful in making this determination: 1. Do you suffer from uncomfortable or heavy periods? 2. Have you experienced troublesome side effects (bloating, constipation, diarrhea, headaches etc.) with withdrawal bleeding in COC use? 3. Do you feel your quality of life is suffering during your period due to symptoms and side effects? APRIL 2017 • Doctor’s

Review

Count on

for powerful symptom relief

PRISTIQ is indicated for the symptomatic relief of major depressive disorder.1

In major depressive disorder, her doctor calls it

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

Choose PRISTIQ:

Demonstrated improvements in functional outcomes: work, family life and social life (secondary endpoints)2*

PRISTIQ 50 mg demonstrated signiﬁcant improvements in functional outcomes from baseline vs. placebo, as measured by the Sheehan Disability Scale (SDS).2† 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 Clinical use: • PRISTIQ is not indicated for use in children under the age of 18 • 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 response for up to 26 weeks, following response during 20 weeks of acute, open-label treatment, was demonstrated in a placebo-controlled trial Contraindications: • Concomitant use with monoamine oxidase inhibitors (MAOIs) or within the preceding 14 days • Hypersensitivity to venlafaxine hydrochloride Most serious warnings and precautions: Behavioural and emotional changes, including self-harm: SSRIs and other newer antidepressants may be associated with:

•

− Behavioural and emotional changes including an increased risk of suicidal ideation and behaviour − Severe agitation-type adverse events coupled with self-harm or harm to others − Suicidal ideation and behavior; rigorous monitoring • Discontinuation symptoms: should not be discontinued abruptly. Gradual dose reduction is recommended Other relevant warnings and precautions: Concomitant use with venlafaxine not recommended • Allergic reactions such as rash, hives or a related allergic phenomenon • Bone fracture risk with SSRI/SNRI • Increases in blood pressure and heart rate (measurement prior to and regularly during treatment) • Increases cholesterol and triglycerides (consider measurement during treatment) • Hyponatremia or Syndrome of Inappropriate Antidiuretic Hormone (SIADH) with SSRI/SNRI •

Potential for GI obstruction Abnormal bleeding SSRI/SNRI • Interstitial lung disease and eosinophilic pneumonia with venlafaxine • Seizures • Angle-Closure Glaucoma • Mania/hypomania • Bipolar Disorder • Serotonin syndrome or neuroleptic malignant syndrome-like reactions • •

For more information: Please consult the Product Monograph at http://pfizer.ca/ pm/en/Pristiq.pdf 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.

* A randomized, double-blind, parallel-group, placebo-controlled, multicentre trial involving 485 patients with MDD and a 17-item Hamilton Rating Scale for Depression (HAM-D17 ) total score ≥20, a HAM-D17 item 1 score ≥2, and a Clinical Global Impression-Severity (CGI-S) scale score ≥4. Patients were randomized to receive fixed-dose PRISTIQ 50 mg/day, PRISTIQ 100 mg/day, or placebo for 8 weeks. Primary endpoint was change from baseline to last observation carried forward (LOCF) in HAM-D17 total score. Secondary endpoints included change from baseline to LOCF in SDS individual domain scores.2

References: 1. PRISTIQ Product Monograph, Pfizer Canada Inc., October 26, 2016. 2. 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 Psychopharmacol 2008;23:243-253. 3. Sheehan DV. Sheehan Disability Scale in: Rush AJ, Pincus HA, First MB, et al. eds. Handbook of psychiatric measures. Washington, DC: American Psychiatric Association; 2000:113-115.

CA0116PRI017E

† The SDS measures the functional impairment that depressive symptoms have on a patient’s work, family life and social life.2 A decrease in SDS score represents improved functional outcomes.3

DEPRESSI ON K EY PO I NT S by

David Desjardins, PhD

with

David Elkins

Innovative medicine in depression The history, challenges — and progress

P .

sychotropic science began with the discovery of lithium as a chemical element in 1817. By the mid-1800s, there was great interest in “urate imbalances,” which were thought to explain a variety of diseases, including mania and depression. But it wasn’t until 1948 that Australian psychiatrist John Cade began treating patients with mania using lithium. Cade initially also believed that urate was responsible for his positive results and only later realized that the calming effect came from lithium.1

The discovery of antidepressants Soon after, scientists working at the Munsterlingen asylum in Switzerland searching for a medication-based treatment for schizophrenia stumbled across a drug that altered the balance of neurotransmitters in the brain. It had little effect on schizophrenics but researchers found it was effective in treating people suffering from depression. In 1958, imipramine, a mood-altering drug, called a tricyclic because of its triple-ring molecular structure, was marketed under the name Tofranil and was followed by a host of similar products. For the next 25 years tricyclics became the drugs of choice for depressed patients despite some of their less attractive side effects. By the 1980s it was clear that a new, more selective product with fewer disruptions of the brain’s chemistry was needed. Researchers working with Eli Lilly & Co discovered fluoxetine hydrochloride, the first agent of the class of antidepressants known as selective serotonin-reuptake inhibitors (SSRIs). They worked by blocking the delivery of serotonin produced in the brain to another nerve cell, allowing it to remain active for longer periods. It was marketed as Prozac and was followed by dozens of similar but slightly different formulations offered by a variety of pharmaceutical firms. More recently, serotonin and norepinephrine reuptake inhibitors (SNRIs) were developed which act on norepinephrine as well as serotonin using the same mechanism.

Fresh needs for innovation Effective as these products are, it’s been 30 years since the advent of these inhibitors. Continued research to find new and innovative psychotropic products continues. In the broader picture, mental disorders remain the world’s single greatest health problem.2 The annual economic cost of major depressive disorder alone is estimated to be upward of $51 billion in this country alone.3 By reducing the need for hospitalization and returning patients more quickly to their

normal lives, novel medicines developed to alleviate chronic mental illnesses have an important role to play in the future physical and fiscal health of Canadians. Yet another reason for ongoing research is that each new development that moves the science ahead, even by small increments, paves the way to more significant discoveries to follow. “Discovering truth by building on previous discoveries” has always been the foundation of the scientific method. Developing innovative medicine, particularly in mental health, is costly and this can put pressure on prices.4 The federal government recognizes this through the Patented Medicine Prices Review Board (PMPRB), which alleviates some of the price concern by ensuring that new drug prices remain similar to those in comparable countries.5

Spotlight on innovative anti-depressives There are significant challenges to finding innovative depression medication. Research continues into better understanding how existing treatments function within the brain. There is also a need for more qualified biomarkers to diagnose genetic causes, measure disease progression and assess the effectiveness of treatments. The search, however, is well underway. • There are more than 135 biopharmaceuticals either in clinical trials or waiting FDA approval. Of these 29 are for depression.6 • The identification of risk-associated genes in patients with a family history of mental illness continues, accelerated by the decreasing cost of whole genome sequencing.7 Excitingly, some of these risk-associated genes are shared across several common mental illnesses. SSRIs and SNRIs continue to offer significant relief to millions of Canadians suffering from depression. The savings to the country in reduced hospital stays and in returning citizens to productive lives are equally significant. The medical profession, sufferers of mental illness and their families look forward to future innovative medications confident that research will continue to offer ever better cures. References: 1. Cade J. Lithium salts in the treatment of psychotic excitement. Med J Aust. 1949; 2(36):349-352. 2. World Health Organization. Depression Fact Sheet. Updated February, 2017. 3. Lim KL, Jacobs P, Ohinmaa A, et al. A new population-based measure of the economic burden of mental illness in Canada. Chronic Dis Can. 2008;28:92-98. 4. Hyman SE. Psychiatric drug development: diagnosing a crisis. Cerebrum. 2013; 2013:5. 5. Patented Medicine Prices Review Board. Annual Report 2015. 6. From hope to cures. Medicine in development for mental illness. 2016 Update. 7. MIT Technology Review. Rotman D. Shining Light on Madness. June 17, 2014. APRIL 2017 • Doctor’s

Review

H I S T O R Y O F M E D I CI N E by

T i lk e Elk i n s

Does sugar kill? The history is long and tortured, but perhaps not fatal

ugar was not always regarded as the dubious foodstuff it has come to be seen as today. For thousands of years, on the island of New Guinea

where it originated, it was considered a magic elixir of health. In its raw form, the cane requires vigorous chewing to extract a pleasantly sweet juice — virtually impossible to eat too much of before exhausting one’s jaw muscles. But, in the spirit of Mae West’s decree that “too much of a good thing can be wonderful,” inventors in India figured out how to distill the sugar cane juice into an irresistible powder by 500BCE. Mosques made entirely of marzipan expressed the Muslim love for sugar, discovered by Arabs while conquering Persia. British and French crusaders travelling east to wrench the holy land from the infidel were similarly smitten, and by 1500 demands for the “sweet salt,” as it was known, turned refinement into an industry whose work was so brutal it was considered

suitable only for the lowest of labourers. Later, in 1791, when the horrors of slave work on the plantations became evident in England, Quaker leader William Fox would declare that, “In every pound of sugar used we may be considered as consuming two ounces of human flesh.” A little later, when slavery was on the verge of abolition, poet Robert Southey spoke of tea as “the blood-sweetened beverage.” Early on, European fondness for sugar spawned the search for tropical places to colonize which were favourable to the cane, as well as locals to enslave, in what came to be known as the “age of exploration.” Madeira, a Portuguese archipelago in the north Atlantic Ocean southwest of Portugal, was one of the earliest islands to be colonized, cleared and planted with sugar cane in 1425 or so, soon to be followed by The Cape Verde Islands, the Canaries, Hispaniola, Brazil and eventually, Barbados, Jamaica, Cuba, Puerto Rico, and Trinidad. Initially a luxury “spice” available only to the rich, sugar steadily sifted down to the lower classes as availability rose, eventually becoming a staple. In 1700, the average Englishman consumed four pounds of sugar a year. A hundred years later the figure rose to 18 pounds and, by 1870, commoners consumed 47 pounds annually. A mere 30 years later, in 1900, they were gobbling up 100 pounds of the sweet every 12 months. Did all this sugar cause the English to rocket into a collective state of obesity? No, it doesn’t seem to have. For

An illustration of slaves cutting sugar cane in Antigua, by William Clark, 1823.

centuries, obesity rates in the UK were stable at a mere six percent. But then in 1980, in Canada and the United States as well as in the UK, the rates began a steady upward climb, doubling in children and tripling in adults by 2015. What could possibly be to blame for this sudden increase? A quick glance at the news today seems to name sugar as the culprit in the health crime against humanity that is obesity. While sugar has played a role, it is not the only villain that many would like to believe it is. Sugar has had accomplices.

SUGAR SHOCK Truth be told, nutritionists may have been responsible for what happened in 1980 and thereafter. One currently popular theory, suggested by journalist Nina Teicholz in her painstakingly researched 2015 book The Big Fat Surprise, is that an establishment of senior nutrition scientists whose research was abundantly backed by the sugar industry maligned research that showed sugar to be harmful and exaggerated the case for low-fat diets. The low-fat diet, promoted by nutritionist Ancel Keys at the University of Minnesota, was first suggested to the public in 1955, right after US President Dwight Eisenhower suffered a heart attack. The “fat hypothesis” as-

By 1500 demands for the “sweet salt” turned refinement into an industry suitable only for the lowest of labourers serted that an excess of saturated fats in the blood from the consumption of meat and dairy products caused heart disease by raising blood cholesterol levels and hardening arteries. Eisenhower himself cut saturated fats from his diet completely — he died from heart disease in 1969. Concurrent with Keys’ research was the work of John Yudkin, a British professor of nutrition who became convinced that excess sugar, not fat, was responsible for heart disease. “If only a small fraction of what we know about the effects of sugar were to be revealed in relation to any other material used as a food additive,” Yudkin wrote in his 1972 book, Pure, White and Deadly, “that material would promptly be banned.” In fact, the Food and Drug Administration (FDA) was in the process of considering changes to its sugar recommendations some time in the 1960s, but after what is now an extensively documented aggressive campaign by Big Sugar to cover up negative research

on its product, the agency settled on the conclusion that sugar was “generally considered safe.” By the early 1980s, the “fat-causes-heart-disease” theory made it into the national food guides in Canada, the US and the UK, and obesity rates began their rapid ascension. People were cautioned to avoid saturated fats like the devil and eat moderate amounts of unsaturated vegetable oils, which are now known to produce oxidation by-products and are recognized as potentially harmful. To replace the loss of calories caused by the dramatic reduction in fat, dietary guides upped the number of daily recommended calories, and gave carbohydrates the biggest slice of the pie out of the four primary food groups. This calorie increase, combined with the increased consumption of carbs, is now widely recognized as signaling the start of the obesity epidemic. An attempt to steer the public away from an awareness of the dangers of sugar resulted in APRIL 2017 • Doctor’s

Review

“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 adult 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.

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

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., August 4, 2016. †

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 EDFNJURXQG WKHUDS\ ZLWK PHWIRUPLQ Ű PJ GD\ $OO 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.

PP-DG-CA-0016

The senate committee reported that 62 percent of the Canadian diet is comprised of prepackaged, processed foods what some have called a major global health catastrophe. A report on the obesity crisis in Canada in 2014 by the Standing Senate Committee on Social Affairs, Science and Technology is in agreement with this theory. The report reads: “Health Canada, for the past 25 years has advised a low fat diet, primarily of unsaturated fats and oils from vegetables and fish, with minimized saturated fat consumption. Review of the scientific evidence, suggesting that saturated fats are unhealthy, indicates a misinterpretation of the data.”

SUGAR AND THE HEART OF IT The link between heavy sugar consumption and heart disease is now readily acknowledged by the American Heart Association, and has been confirmed by a multitude of recent studies. The World Health Organization recommends that adults and children reduce their daily intake of added or “free” sugars to less than 10 percent of their total energy intake — this is about 50 grams or 12 teaspoons a day. However, they stress that half that amount — just six teaspoons daily — would provide additional health benefits. Last year, the FDA echoed the WHO’s daily sugar intake recommendation, in addition to announcing a new Nutrition Facts label for packaged foods. The label reflects “new scientific information, including the link between diet and chronic diseases such as obesity and heart disease,” says the agency. “Added sugars” in grams and as percent of “Daily Value” is included on the new label, as a reflection of research that shows that consuming more than 10 percent of one’s total daily calories in added sugar makes it difficult to meet dietary needs.

Health Canada has yet to chime in on a daily recommended amount of sugar for Canadians. New labelling laws put in place in December 2016 (with a five-year transition period) indicate a percentage value for total sugars, but do not make a distinction for added sugars. The ingredients listing is required to group all sugars together in brackets, making those sugars with obscure names (there are 52 different names for sugar!) easier to identify. The imposition of a 20 percent tax on all sugary beverages is the subject of a heated debate in Ottawa. Places like Mexico and Berkeley, California where sugar taxes have been put in place have shown significant reduction in sugary drink consumption, with a 7.9 percent reduction in Mexico and 21 percent in Berkeley over a two year period. Many other cities and countries are planning to impose some form of tax in the hopes of reducing the fiscal impact of obesity. Sugar has been proven to elevate the risk for cardiovascular disease and diabetes, but its causal relationship to obesity is not quite as clear. The senate committee reported that 62 percent of the Canadian diet is comprised of prepackaged, processed foods, most of which contain sugar, together with refined, genetically modified carbohydrates and a host of chemically formulated emulsifiers and preservatives. Among northern First Nations populations, which in an absence of fresh foods rely on processed foods for most of their nutrition, obesity and overweight rates are at a shocking 70 percent and higher. While the world is focused on the evils of sugar, the white stuff may be little more than a scapegoat for the deeper, and harder-to-face truth: that it isn’t a single ingredient but the entire food landscape we have created for ourselves in the last 30 years that is to blame. APRIL 2017 • Doctor’s

Review

I PRES CR I B E A TRIP TO... ENGLAND

Paths to happiness An FP extends her layover in London to walk the surrounding countryside and discovers it’s every bit as charming as she imagined text and photos by Dr Heather Wrigley

like to travel, and due to the vagaries of international flight itineraries from Canada, I often find myself passing through London. If I have time to leave the airport for a few hours, I poke around London

Many of the footpaths in England’s countryside are hundreds, if not thousands, of years old.

Dr Heather Wrigley is a family physician in Calgary, AB. She is ashamed to confess that she typed most of this article on her phone while walking in rural England. She already regrets the scenery she missed.

Doctor’s Review • APRIL 2017

or one of its nearby towns. Invariably I find myself enchanted with the place and I regret having to return to the airport to board my ongoing flight. The last time this happened, I started to wonder why I was wasting time elsewhere, when I could be spending it in England. On a recent trip through London, en route home from somewhere else, I had the good sense to arrange a layover of nearly a week to do some walking in the English countryside. There are wonderfulsounding walks in every part of the country that range in length from a few hours to a few weeks. I hardly knew where to begin, but I knew that I wanted to sample the available options and I didn’t have much time to accomplish it. In the end, I chose to walk a greenway (rail trail) called the Nickey Line (nickeyline.org) in Hertfordshire, spent two days doing part of a longer-distance trail (the Saffron Trail in Essex) and took in various unnamed rural footpaths in nearby areas. All of these were accessible using easy, fast and inexpensive passenger rail connections from London. I stayed in 16th-century inns in small towns and ate dinner in 650-year-old pubs. It was every bit as lovely as it sounds. Compared to North America, and most other places I’ve been, England seems so civilized to me. It has been under human habitation and cultivation for such a long time that every bit of it has been touched by human hands and yet somehow most of our meddling, at least in the rural areas, seems to have been benign, even beneficial. Verdant rolling

There are several long distance walking routes in England that combine footpaths and roads to link green spaces.

fields bounded by hedgerows and falling-down stone walls are the norm. For the price of a few pounds, a convenient passenger train will drop you in your choice of quaint tiny village of tidy cottages, each house with its own name, and some with actual thatched roofs. In these towns, flocks of uniformed schoolchildren on the sidewalks charmed me with their posh-sounding accents. Outside the towns, there are rabbits, foxes, quail and so many ancient castles and medieval cottages that British people scarcely seem to give them a glance. Old stone parish churches leave their doors unlocked so that curious passersby can enter, inhale the intoxicating scents of old wood, candles and paper, and envision a Thomas Hardy damsel, having just made some shocking and terrible discovery, weeping inconsolably in a pew.

The Cross Keys Restaurant and Hotel in Saffron Walden dates back 850 years.

YOU CAN GET THERE FROM HERE British footpaths are a walkerâ&#x20AC;&#x2122;s dream. Because many of them predate automobiles, they are a genuinely practical means of getting from one place to another. Towns are frequent enough that all you need to carry with you is your clothing, toothbrush and passport; meals, shops and inns always seem to be around the next corner when you want them. There are dozens of books and websites listing British walks, and they invariably direct you to the trail starting and ending The Nickey Line footpath and cycle way in Hertfordshire is a former railway line.

You’ll cut through plenty of woodland along the 115-kilometre-long Saffron Trail in Essex, but also unspoiled villages with tidy cottages.

points by referencing a nearby pub, which ensures that you will never lack nourishment. To a Canadian, these footpaths are almost bizarrely numerous. At one point, I was walking near a town called Newport in Essex. Newport is just a short distance by train from London’s Stansted Airport, but it feels a world apart from the city: it’s tiny, sleepy and completely quaint. I was in real danger of never starting my walk because I was taking so many photos of the pretty town itself. The directions from my walking book had me stymied: I did indeed start “behind The White Horse” (Public House, of course) — but the first path I tried veered off in what was clearly the wrong direction and the next was so overgrown with stinging nettles as to be completely impassable, even after I tried wearing my rain jacket for protection. I retraced my steps to the street. I must have appeared baffled because a 60ish fellow who was unloading groceries from his car asked whether I needed help. I explained that I was looking for the footpath to Saffron Walden (visitsaffronwalden.gov.uk), two towns away.

Doctor’s Review • APRIL 2017

The man inquired, “You want to walk to Saffron Walden?” “Yes,” I replied. “Here it comes,” I thought, certain that he was going to tell me that it was much too far to walk and that I should take the bus or a taxi as almost certainly would have been the reply in Canada. But I was wrong. Instead, the man turned to his wife and they began to discuss the relative merits of two alternative footpaths to my destination. I listened to this exchange in happy astonishment, but was even more amazed by what he said next. “She can probably tell you better than I can. She was the local Footpaths Officer for years.” The local Footpaths Officer? How marvellous to find a country that believes so strongly in the concept of footpaths, that they appoint public officials in miniscule villages to manage them! In the end, I happily followed the friendly couple’s advice. Neither of the paths they suggested was in fact the one I’d originally been seeking. It turned out that there were at least three distinct pedestrian routes from that one tiny Essex town to another small town nearby. The Canadian walker’s mind boggles.

Newport is just a few minutes by train from London’s Stansted Airport, but it feels a world apart.

Brits are finding innovative ways to repurpose the UK’s iconic phone booths.

British footpaths are a walker’s dream because they predate cars and are genuine means of getting from one place to another WALKS IN A BOOK If you are a reader as well as a walker, you will find as you traverse England on foot that much of the countryside already seems familiar. For me it mostly evoked Hardy’s Wessex, but I also had frequent visions of James Herriot rambling the Yorkshire Dales with his border terrier. Things from those books that never seemed plausible to me — like the ubiquity of ancient and mysterious ruins, the presence of an inn at every crossroads, and the ability for characters to simply walk across miles of neighbours’ fields to the next town — suddenly made a lot more sense after I had experienced them. England really was, and is, like that. Walkers are given right-of-way across rural lands, and once you discover the elegant simplicity and inherent friendliness of stiles, you will mourn that they cannot be found everywhere. Of course, my praise of England’s rural footpaths is idealized. They certainly have their flaws. There are nettles and brambles in abundance. (I suggest long pants.) Stepping into a drainage ditch or foxhole can easily sprain your ankle or worse. As everywhere, there

is the usual litter of discarded trash, though I can sometimes find a queer British charm even in that. Every time I picked up a potato chip bag in England, my brain insisted on labelling it a “crisp packet,” which sounds less distasteful somehow. And British litter is just different. Sure, there are McDonald’s cups and cigarette packages, but I also found a discarded tin that had once contained “Earl’s Meaty Chunks with Jelly.” Yum. Probably because the footpaths are so terrific, England’s roads are not ideal for walking. Occasionally an idyllic rural path would eject me onto a narrow strip of vergeless asphalt where tiny cars hurtled along at absurdly fast speeds. (My sense of their recklessness was almost certainly enhanced by the fact that, to me, they all seemed to be driving on the wrong side of the road.) Nevertheless, before long I would always be rescued from the din by yet another lichen-encrusted stone or wooden signpost bearing an arrow and that sacred inscription: “Public Footpath.” And, smiling, onward I would go. For more info on Hertfordshire and Essex, go to Visit Herts (visitherts.co.uk) and Visit Essex (visitessex.com). APRIL 2017 • Doctor’s

Review

BOULEVARD KITCHEN & OYSTER BAR

One of Alex Chen’s elaborate creations at the Boulevard Kitchen & Oyster Bar in the Sutton Place Hotel.

A truly authentic Chinese culinary adventure awaits, no passport required by Cinda Chavich

Doctor’s Review • APRIL 2017

It’s exciting to encounter a perfectly soupy xiao long bao (soup dumpling) so far from its origins in Shanghai.

he fat dumpling sags seductively at the end of my outstretched chopsticks, proof of its delicate wrapper and perfectly soupy interior. As instructed, I’ve lifted it carefully by the nub that sits at the apex

of its 18 perfect folds, sliding the base through a saucer of inky black vinegar sauce. When the soup dumpling bursts in my mouth, revealing all of the hot, porky perfection within, I mumble my best multilingual culinary compliment: “Mmmmmm.” Though it’s a simple food, the skillful execution of this Chinese specialty, xiao long bao, is what makes it so special. The fact that I’m eating it half a planet away from its origins in Shanghai makes it even more remarkable. But this is just one of the many remarkable — and authentic — Chinese food experiences you can have in Metro Vancouver, now considered “the most Asian city” outside of Asia, with 45 percent of its residents of Asian descent. Whether it’s the great ramen shops along Robson Street, the elegant Chinese dining rooms for dim sum, or hip new Asian concepts serving up small plates and sake cocktails, it’s easy to eat something exotic at every meal. It’s like a trip to Hong Kong — via Tokyo and Seoul — without the jet lag.

— fresh, seasonal and overlaid with influences of the Orient. Chen has watched Vancouver’s Asian food scene blossom like a pot of flowering tea especially “after we started to see the Michelin star chefs arriving from Hong Kong.” “I go to New York, I go to San Francisco, I hit all the Chinatowns,” he says, “but it’s here I find that perfect har gow, the skin strong enough to encase the sweet prawns, but so thin and delicate it almost melts in your mouth.” It’s access to fresh ingredients, from local ling cod and Dungeness crab, to big geoduck clams and pristine greens, that makes Vancouver’s Chinese food unique, he says. But traditional technique is key, too, and Chen points me to his favourite haunts for Chinese baking and barbecue meats. In search of the latter, we head to an unassuming shop, behind a supermarket parking garage in suburban Richmond.

The first wave of Chinese immigrants arrived in Vancouver in the late 1800s, but it wasn’t until the 1980s and ’90s that Vancouver saw a large influx of immigrants and capital from Hong Kong and Mainland China, including some of the country’s top master chefs. Alex Chen, one of the young Asian-Canadian chefs making their mark in Vancouver restaurants today, takes his inspiration from those pioneers. A child of Chinese immigrants, Chen built his impressive culinary career in top kitchens across North America, competed for Canada at the prestigious Bocuse d’Or, and now runs Boulevard Kitchen & Oyster Bar at the Sutton Place Hotel. His upscale menu, like many in Vancouver, represents that confluence of cultures

Celebrity Chef Clement Chan oversees his team at Torafuku, artfully plating his modern Asian cuisine in a busy open kitchen.

PHOTOS BY CINDA CHAVICH, UNLESS OTHERWISE NOTED

CHINESE MASTER CHEFS

AUTHENTIC ASIAN There’s a row of mahogany glazed ducks hanging in the window next to the busy take-out counter at Hong Kong B.B.Q. Master. Anson Leung, barbecue master Eric Leung’s son, brings us plates piled with duck and soy chicken but it’s the roasted pork, with its crisp layer of golden crackling, that brings me back. “It’s a traditional way of cooking food, all done by hand and by eye,” explains this second-generation, chef-in-training. “It’s pure fire, and how you move the meat around, a lost art.” Almost lost, but thankfully not quite. In this sprawling city of new immigrants, with its traditional tea shops, ginseng merchants and designer knock-offs, it’s easy to imagine you’ve fallen through a rabbit hole and arrived in the Middle Kingdom. But it’s only a 20-minute ride on The Canada Line from downtown Vancouver, and just 10 from the airport. Richmond has a colourful history as a fishing village and boats still unload their catch of fresh salmon and prawns at the dock in Steveston. But food has become a big draw for visitors, says Colin Wong, guiding me through the city’s 400-plus Asian eateries. “We can eat all regions of China in Richmond, Hunan, Szechuan, even authentic Muslim Chinese cuisine,” says Wong as we sample the Shanghainese specialties at Su Hang Restaurant. “It’s gotta be authentic, because there are a lot of new immigrants, and they demand it.” In fact, there’s so much that’s authentic here, it’s hard to know where to start. Whether you’re snacking on the ethereal “shaved ice” at Frappé Bliss in the uberAsian Aberdeen mall or a crispy bubble waffle doled out by the elderly Cantonese couple at the Rainbow Café, eating your way through Richmond is a culinary adventure. Where else will you find authentic “dragon beard candy” pulled by hand on the street, flaky wife cakes (lao po bing) filled with winter melon and sesame paste, or snowy balls of coconut-crusted mochi? The array of sweets and savouries at the lovely Kam Do Bakery is stunning. We select buttery egg tarts, golden “pineapple” buns with crackled sugar tops, and coconut-filled buns for noshing while we continue to explore.

RESTAURANT ROW Alexandra Road (a.k.a. “Food Street”) with its clusters of strip malls and signage bristling with Chinese and Korean characters, can be a navigational nightmare, even for a savvy explorer with a Google map. Thankfully, the clever tourism types at Visit Richmond understand this cultural conundrum. So they’ve created a Dumpling Trail pamphlet and smartphone app, to lead diners to a dozen local restaurants, all carefully curated for cleanliness, English-speaking staff and, of course, delicious dumplings.

Doctor’s Review • APRIL 2017

The Dr. Sun Yat-Sen Classical Chinese Garden in downtown Vancouver remains a peaceful sanctuary.

At Chef Tony Seafood Restaurant, traditional pork and shrimp sui mai are elevated with black truffles.

Cantonese dishes like slippery rolls of bean curd filled with mushrooms are the specialty of Hoi Tong’s master chef Leung Yiu Tong.

Richmond’s Kam Do Bakery offers stunning sweets and savouries.

The fluffy, deep-fried taro dumplings (wu gok) arrive with a sliver of abalone perched on top at Chef Tony in Richmond.

Metro Vancouver is now considered “the most Asian city” outside of Asia, with 45 percent of its residents of Asian descent It’s a great place to start, as many of the stops on their trail are known for other specialties, too, from hand-pulled noodles to hot pots and, that popular daily ritual, dim sum. We dig into the latter at Chef Tony Seafood Restaurant, a bright space swathed in glossy white enamel, with the double bling of neon and crystal chandeliers. Tony He opened his first Sea Harbour restaurant in China, expanded to Richmond and Los Angeles, then created the eponymous Chef Tony here in 2014. The big dim sum menu is illustrated and easy to navigate. The fluffy, fried taro dumplings (wu gok) arrive with a sliver of abalone perched on top, the translucent har gow has matusake in the sweet shrimp filling, and steamy egg buns ooze golden custard. Like the pork and shrimp sui mai topped with black truffles, it’s all about elevating the traditional, in both quality and price. As much as Chef Tony is about dazzle, Hoi Tong Seafood Restaurant celebrates subtlety. Tucked into one of the ubiquitous strip malls along Westminster Highway, Hoi Tong is small and unassuming, but Chef Leung Yiu Tong is known for his precision with delicate Cantonese dishes. We start with fish maw soup, then sample his crisp, salt-baked chicken, an ethereal cloud of dai lang fried milk with quenelles of tofu, slippery bean curd rolls filled with mushrooms, and taro-crusted layers of tender pressed duck. It’s clear why this friendly septuagenarian is a local legend, a master chef true to classical Chinese cooking.

INNOVATIVE ASIAN

In Richmond’s authentic dim sum restaurants you can watch the chefs as they fold every dumpling by hand.

Office workers line up at the counter at Heritage Asian Eatery in the downtown financial district for morning Peking Duck Benny Bowls, congee, and fluffy bao with pork belly, daikon kimchi and shiitake mushrooms. Chinese-born Chef Felix Zhou and his partners (with Chinese and Japanese/Spanish roots) designed the menu to reflect their shared heritage. They’re on APRIL 2017 • Doctor’s

Review

At Hong Kong B.B.Q., Eric Leung piles plates high with duck and soy chicken.

“I go to New York, I go to San Francisco, I hit all the Chinatowns,” chef Chen says, “but it’s here I find that perfect har gow” WHERE TO DINE Hong Kong B.B.Q. Master 4651 No 3 Rd, Richmond, BC; (604) 272-6568 BBQ duck, BBQ pork, roast pork with crackling — take-out or eat in Su Hang Restaurant 100-8291 Ackroyd Road, Richmond, BC; (604) 278-7787; suhang.ca Shanghainese menu including soup dumplings (xia long bao), steamed or pan fried, hand-pulled noodles and ma lan, a cold dish of bean curd and sautéed greens Aberdeen Centre Food Court 4151 Hazelbridge Way, Richmond, BC; (604) 270-1234; aberdeencentre.com/en/home.php Mall food court with 20 stalls featuring fast food, from shaved ice and hot pots to bubble waffles, sushi and Taiwanese fried chicken Kam Do Bakery 6211 No 3 Rd #135, Richmond, BC; (604) 284-5611 Flakey egg tarts, pineapple buns, coconut buns, wife cakes in Chinese bakery next to Richmond Centre Chef Tony Seafood Restaurant Empire Centre Mall, 600 No 3 Rd #101, Richmond, BC; (604) 279-0083; cheftonycanada.com/en/ Busy, modern dining room for dim sum or dinner, with specialties like sui mai with black truffles Hoi Tong Chinese Seafood Restaurant 8191 Westminster Hwy., Richmond, BC; (604) 276-9229 Traditional, high-end, Cantonese cuisine from Hong Kong master chef in small, private setting; reservations required Heritage Asian Eatery 108 W Pender St, Vancouver, BC; (778) 737-1108; eatheritage.ca Counter service for creative bao, congee, breakfast bowls in downtown Financial District Bao Bei Chinese Brasserie 163 Keefer St, Vancouver, BC; (604) 688-0876; bao-bei.ca Compact, stylish Chinatown space for Asian-inspired cocktails and shared plates Torafuku 958 Main St, Vancouver, BC; (778) 903-2006; torafuku.ca Playful Asian fusion menu, bold flavours and cocktail scene, on edge of Chinatown

Doctor’s Review • APRIL 2017

a trajectory that mirrors the evolution of Asian immigration and food trends in Vancouver, mashing up old and new ideas, family comfort foods and fresh ingredients, with classical chef training. “This is the Chinese food we know,” says Zhou. “When we go to Asia, we don’t think the food is as good as Vancouver.” The rice bowl is simple, but the confit duck, like the pork char siu, is all made in house, and the udon is topped with a perfect sous vide egg. Zhou’s Lunar New Year dinner — “the most traditional menu you will ever see me cook” — is a feast of updated flavours, from the pork consommé with a brunoise of vegetables and Chinese ham, to steamed oysters with puffed vermicelli, and eggplant dumplings, another of this young star chef’s popular creations. Old Chinatown is no longer the city’s Chinese food hub. It’s crumbling around the edges and seems an aberration among the luxury brand boutiques and posh hotels of downtown Vancouver. But we wander through the peaceful Dr. Sun Yat-Sen Classical Chinese Garden and stop at trendy Bao Bei for a rum cocktail flavoured with plum juice and Sichuan uu CONTINUED ON PAGE 47

WHERE TO STAY Four Points by Sheraton Vancouver Airport, 8368 Alexandra Rd, Richmond, BC; (604) 214-0888 Located in the heart of Richmond’s restaurant row, right along Alexandra Road (a.k.a. Food Street), with 200-plus restaurants in a three-block stretch, and free shuttle service to the airport. From $124. The Listel Hotel 1300 Robson St., Vancouver, BC; (604) 684-8461; thelistelhotel.com A downtown boutique hotel with two notable local restaurants, Forage and Timber. Centrally located. From $145. Opus Hotel 322 Davie St, Vancouver, BC; (604) 642-6787; vancouver.opushotel.com Stylish boutique hotel in trendy Yaletown, conveniently located next to the Canada Line station for travels to Richmond and airport. From $249.

The

joys of spring MARGO DUBBELDAM / SHUTTERSTOCK.COM

From wild bluebells in Belgium to candy-coloured tulip fields in Holland, six places to see the season’s best flowers by Camille Chin

LOWE LLAGUNO / SHUTTERSTOCK.COM

CALIFORNIA

Doctor’s Review • APRIL 2017

The Goldilocks Principle applies to desert wildflowers: the conditions have to be “just right” for them to appear in spring. Heat (ideally mild) and moisture (wet) are the big players. The Anza-Borrego Desert State Park, California’s largest, a 90-minute drive south of Palm Springs, got downpours this winter so brilliant flowers were coerced out of the dry landscape that is generally devoid of flora the rest of the year. March heralded purple sand verbena, yellow desert sunflowers, white spectacle pod and more. The Wildflower Hotline (tel: 760-767-4684) is a very real thing that is updated regularly. The Antelope Valley Poppy Reserve (hotline: 661-724-1180) in LA county is covered in orange poppies this time of year. But they’re sooo temperamental. They only unfurl when conditions are sunny and warm. visitcalifornia.com/ ca/attraction/spring-wildflowers.

BELGIUM Every April, a fairy tale comes true. Delicate bell-shaped perennials blanket the Halle Forest and when the soft spring light stretches through the bright green canopy of young beech leaves to reach the purple-blue flowers, the effect is magical. Throw in some mist and even a skeptic like me might look out for a beat up pumpkin and an old lady with a wand. Bluebells seed freely and spread quickly, but the abundance suggests they’ve been there for centuries. Many of the beech trees were replanted after the First World War. The forest is near where the northern Flanders and southern Wallonia regions meet, about 30 minutes south of Brussels. There are three marked trails, including a four-kilometre walk that follows blue poles to giant sequoia trees. hallerbos.be/en.

CHINA

GUITAR PHOTOGRAPHER / SHUTTERSTOCK.COM

Luoping is a small county in eastern Yunnan near the Guizhou and Guangxi borders that was long overlooked by travellers. Yuanyang’s rice-covered hills and Shaxi’s wooden houses received a lot of the attention. But bright yellow rapeseed flowers are impossible to ignore, particularly when its farms are terraced. Rapeseed is grown, of course, to produce cooking oil and also animal feed. The rapeseed farms in Luoping are among the largest in China and when its flowers bloom they create a sort of golden sea in spring. Karst (limestone) peaks only add to the surrealism. It’s become a mecca for photographers and also busy bees — literally. Luoping is also a hub for raising bees and producing honey. The honey is an amber gold and is available in spring everywhere in the valley. For more on China: cnto.org.

PHURINEE CHINAKATHUM / SHUTTERSTOCK.COM

VALI LUNG / SHUTTERSTOCK.COM

THE NETHERLANDS National Geographic once named the Tulip Route in Noordoostpolder one of the world’s most beautiful road trips. Located northeast of Amsterdam, it stretches for about 100 kilometres past thousands of hectares of candy-coloured tulip fields in Flevoland, Holland’s flower-growing province. The tulips generally bloom for about three weeks, but are at their best around mid-April. Keukenhof (adults €16) in the town of Lisse is the other place to see the bulbous perennials. Seven million flower bulbs are planted in the world’s largest garden every year, including 800 varieties of tulips. Alternatively, cycle the Flower Strip from Haarlem to Leiden (32 kilometres, 90 minutes) through Bollenstreek, the Bulb Region, for a classic Dutch experience on two wheels. holland.com/global/ tourism/article/tulip-festival.htm

GRISCHA GEORGIEW / SHUTTERSTOCK.COM

ITALY People travel to the areas around Montepulciano and Pienza in the province of Siena in southern Tuscany just to draw and photograph its poppies. The fields, groves and vineyards of the hilltop towns are literally painted with them in April and May. Even roadsides and train tracks are dotted with red. Poppies are delicate little things, with featherlight petals, but their seeds are tough. They adapt to most climates and many soil types, including alkaline/clay (the soil of Tuscany) and even sand. Disturbed soil isn’t a problem and the flowers still sprout, as if by magic, when neglected. After you’ve frolicked among the wildflowers, amble about the towns. Their ancient churches, Renaissance palaces and charming squares are as picturesque as the poppies. For more on Italy: turismo.intoscana.it.

JAPAN You can’t tell where the flowers end and the sky begins in Hitachi Seaside Park (adults $5) in spring. Millions of blooming nemophila with transparent baby blue petals erupt on Miharashi Hill, the park’s highest point, mid-April through mid-May every year. Crowds flood the hill’s gentle slopes and meandering pedestrian paths to snap photographs and also marvel at the Pacific Ocean view. Located in the Ibaraki Prefecture less than two hours northeast of Tokyo, the park is magnificent in other seasons too. About 30,000 kochia plants huddle on the hillside in summer and fall. The quirky little bush has soft, hair-like foliage that’s bright green July through midSeptember, dark red through mid-October. en.hitachikaihin.jp. APRIL 2017 • Doctor’s

Review

Tortilla de bacalao / cod.

Basque in its glory Small plates from the region that straddles the border between France and Spain recipes by

José Pizarro

photos by

Laura Edwards

hen chef José Pizarro completed his studies to be a dental technician, he realized he’d ignored his true calling. Originally from Extremadura,

the Spanish region bordering Portugal known for its inland specialties like roasted meats, creamy Torta del Casar cheese and the finest Monesterio jamón (ham), Pizarro followed up with a year at the hotel school of Cáceres.

Doctor’s Review • APRIL 2017

After moving to the UK and working at Spanish restaurants in London for 15 years, Pizarro opened José in 2011 and a year later Pizarro. In 2014, he was voted one of the world’s “100 Españoles.” The award honours Spaniards who

exemplify success internationally; recipients include actor Antonio Banderas and shoe designer Manolo Blahnik. Not bad for a dental technician! Basque: Spanish Recipes from San Sebastián and Beyond, published by Hardie Grant Books, is Pizarro’s third cookbook. It’s filled with pintxos (small tapas) and main courses from the Northern Spanish region that straddles France. The town of San Sebastián, on the north coast, has more three-star Michelin restaurants than anywhere else in Europe. Here are our favourite pintxos from the book.

ROASTED ONIONS STUFFED WITH PARSLEY AND GARLIC MIGAS Onions never feature very often on menus or in books as a dish in their own right, which is a great shame as they are so versatile. You can stuff onions with fried beef or lamb mince, or cheese and walnuts and then roast them. This particular recipe is really good to make as a pintxo (small snack), and it’s something that people probably wouldn’t expect so you will impress them. Migas are small fried breadcrumbs that you add to dishes for some texture, normally made with plenty of olive oil, garlic and peppers.

Heat a little oil in a pan and fry the chopped onion hearts with the garlic for a few minutes. Add the bread, apricots and toasted pine nuts, and fry together for a few minutes. Season and add the parsley. Stuff the mixture into the onions and place on a baking tray. Drizzle with oil and roast for 20 to 25 minutes until the onions are tender and golden. Scatter with sea salt and serve. Serves 4.

TORTILLA DE BACALAO / COD Tortilla de Bacalao is a must-have dish when you are in a sidreria (cider house). Caramelizing the onions brings more sweetness to the tortilla and the bacalao (cod) is not cooked. When you caramelize the onions, make plenty as you can keep them in the fridge for at least a week. They make a great addition to any sandwich or just on toast with some goat’s cheese. Heaven.

14 oz. (400 g) salt cod ½ c. (125 ml) olive oil 3 large white onions, finely sliced handful of thyme, leaves stripped 6 free-range eggs freshly ground black pepper handful of finely chopped flat-leaf parsley

Soak the salt cod in cold water, skin side up, for 24 hours, changing the water a couple of times. Heat the oil in a large pan and gently fry the onions for a few minutes. Cover with a lid and cook over a low heat for 25 minutes until really soft. Remove the lid, add the thyme and cook for a further 20 to 25 minutes until really caramelized and sticky. Scoop out with a slotted spoon, keeping some of the oil, and cool. Remove the skin from the cod and flake into large pieces. Beat the eggs with plenty of black pepper and gently fold in the onion, cod and parsley. In a large (23 cm/9 in.) non-stick pan, heat 2 to 3 tablespoons (30 to 45 ml) of

8 small onions olive oil 2 garlic cloves, finely chopped 2 oz. (50 g) stale bread, cut into small cubes (about 1½ slices) 1 oz. (25 g) dried apricots, chopped (about ¹⁄8 c. / 30 ml) 2 oz. (50 g) toasted pine nuts (about ¹⁄³ c. / 80 ml) sea salt and freshly ground black pepper small handful of chopped parsley

Cut the base and top off the onions, blanch them for 20 minutes in simmering water to soften them, then peel off the skins. Use a small knife to remove the heart of each of the onions and finely chop. Preheat the oven to 170°C (340°F/ Gas 3).

Roasted onions stuffed with parsley and garlic migas.

APRIL 2017 • Doctor’s

Review

the reserved oil and pour in the egg mixture. Swirl the pan over a high heat until the mixture starts to set around the edges, then reduce the heat and cook for 4 to 5 minutes until it just starts to set, so that the bottom and sides are golden, but it is still quite loose in the middle. Cover the pan with a flat lid or board, turn the tortilla carefully onto it, then put the pan back on a low heat. Return the tortilla to the pan, cooked side up, and use a spatula to tuck the edges of the tortilla under to give its characteristic curved look. Cook for a couple of minutes, then turn onto a board and serve. It should still be lovely and juicy when you cut into it. Serves 4 to 6.

GRIDDLED QUAIL WITH PICKLED SHALLOTS If you go to A Fuego Negro, a pintxo place in San Sebastián, something you musn’t miss is pajarito frito (little fried bird) — it’s just amazing. They marinate the bird with vermouth, roasted garlic and honey then leave it for 24 hours so the flavours really infuse into the meat. Here we marinate the quail for the same amount of time, but with lemon, garlic and thyme instead. The pickled shallot garnish is the same as it’s a perfect combination. Happy days.

Griddled quail with pickled shallots.

6 quail, spatchcocked juice of 2 lemons 1 banana shallot (echalion), finely chopped 2 garlic cloves, finely chopped 4-5 sprigs of thyme olive oil For the shallots ¹⁄³ c. (75 ml) cider vinegar ¹⁄³ c. (75 ml) raspberry vinegar 2 oz. (50 g) caster (superfine) sugar (about ¼ c. / 60 ml) 6 black peppercorns 4 banana shallots (echalions), finely sliced sea salt and freshly ground black pepper extra-virgin olive oil

Put the quail into a dish. Mix the lemon juice with the shallot, garlic, thyme and a good amount of olive oil. Pour the mixture over the quail and marinate overnight. The next day heat the vinegars with the caster sugar and peppercorns until the sugar has dissolved. Pour the hot vinegar over the shallots and set aside. Heat a barbecue or chargrill pan. Once the pan is hot, remove the quail from the marinade and griddle for 15 minutes, turning, until cooked. Set aside to rest. Drain the shallots from the vinegar, season with a little salt and pepper, and add some extra-virgin olive oil. Serve with the griddled quail. Serves 6. Recipes and photos from Basque: Spanish Recipes from San Sebastián and Beyond (Hardie Grant Books, 2016).

MEDICAL QUIPS Pun #2 “Did you hear about the guy whose whole left side was cut off?” “He’s all right now.”

Doctor’s Review • APRIL 2017

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VANCOUVER'S STUNNING ASIAN BANQUET uu CONTINUED FROM PAGE 38

peppercorns, and bar “schnacks” of house-made Taiwanese sausage and Chinese pickles. Dinner is at another modern Asian eatery, Chef Clement Chan and partner Steve Kuan’s award-winning Torafuku. Chan is at the pass in the busy open kitchen, and we sit at the polished concrete bar and watch our artfully-plated order emerge: Dy-No-Mite prawn tempura roll, Humboldt squid in yam flour batter with crispy Brussels sprouts and compressed apples, seafood laksa in a miso and red curry sauce, creamy Panna Cotta with yuzu gelée and a sliver of black sesame shortbread for dessert. The room is sleek and minimalist, a buzz of hip diners enjoying cocktails, the soft grey and blue upholstery along the walls dampening the clatter and chatter in this narrow space. Chan was born in Vancouver, his grandmother owner of a popular Shanghainese restaurant, and went from culinary school to cooking alongside top city chefs. With his Le Tigre food truck, pop-up dinners, and Food Network appearances,

this celebrity chef is a poster child for the evolution of modern Asian food in Vancouver, where cultures fuse, even as traditions endure. “In Vancouver, it’s all about diversity, especially in Asian places,” says Chan. “But better Asian or Chinese cooking here is mainly about better ingredients. We can have anything you can think of.” There’s a creative hot pot of far eastern flavours to explore on Canada’s west coast, no passport required.

IF YOU GO There are 20 restaurants listed on Visit Richmond’s Dumpling Trail (visitrichmondbc.com/365days-of-dining/dumpling-trail) map. Visit the website to download a copy and learn more. Explore Tourism Vancouver’s website (tourismvancouver.com) for dining guides including their Dim Sum Tasting Tour.

INDICATION: ASMANEX® Twisthaler®, a preventative agent, is indicated for the prophylactic management of steroid-responsive bronchial asthma in patients 4 years of age and older.2 CONTRAINDICATIONS:2 • Hypersensitivity to this drug, milk proteins (from the excipient lactose), or any component of the container • Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required • Untreated systemic fungal, bacterial, viral or parasitic infections, active or quiet tuberculous infection of the respiratory tract, or ocular herpes simplex RELEVANT WARNINGS AND PRECAUTIONS:2 • Should not be stopped abruptly • Risk of adrenal insufficiency in patients transferred from systemically active corticosteroids • Oropharyngeal candidiasis • Risk of systemic effects of inhaled corticosteroids • Hypercorticism, adrenal suppression, growth retardation in children/adolescents, reduced bone mineral density, osteoporosis, fracture, cataracts, glaucoma • Risk of dose-dependent bone loss • Enhanced effect of corticosteroids in patients with cirrhosis or hypothyroidism • Do not exceed recommended dose • Rare systemic eosinophilic conditions

ACTAVIS SPECIALTY PHARMACEUTICALS Lolo.............................................................21 ALLERGAN INC. Fibristal..........................................................4 BOEHRINGER INGELHEIM (CANADA) LTD Jardiance........................................................3 ELI LILLY Trulicity........................................................28 GLAXOSMITHKLINE Breo Asthma .........................................IFC, 1 Flonase...........................................................6 MERCK CANADA INC. Asmanex..................................................OBC PFIZER CANADA INC. Pristiq...........................................................24 SEA COURSES INC. Corporate.....................................................11 SERVIER CANADA INC. Lixiana................................................... 18, 19 SHIRE CANADA INC. Vyvanse........................................................13 VALEANT CANADA INC. Jublia............................................................39 WELLESLEY THERAPEUTICS Ultimate Glucosamine.................................16 XLEAR INC. Xlear nasal spray..........................................15

FAIR BALANCE INFORMATION Asmanex......................................................47 Jardiance....................................................... 2 Trulicity.......................................................29

• Caution when used with acetylsalicylic acid

in hypoprothrombinemia

• Risk of immunosuppression • Not for rapid relief of bronchospasm • Possible inhalation induced bronchospasm • No adequate studies in pregnant/nursing women • Risk of hypoadrenalism in infants born to women

receiving corticosteroids

• Monitoring of: HPA axis function and haematological status

periodically during long term therapy, use of short-acting inhaled bronchodilators, bone and ocular effects, height of children and adolescents

For more information: Please consult the Product Monograph at http://www.merck.ca/ assets/en/pdf/products/ASMANEX_Twisthaler-PM_E.pdf for important information relating to adverse reactions, drug interactions, and dosing/administration information (particularly dose reduction to the lowest possible dose required to maintain asthma control) which have not been discussed in this advertisement. The Product Monograph is also available by calling us at 1-800-567-2594. References: 1. Bousquet J et al. Comparison of the efficacy and safety of mometasone furoate dry powder inhaler to budesonide Turbuhaler®. Eur Respir J. 2000;16:808-816. 2. ASMANEX® Twisthaler® Product Monograph. Merck Canada Inc., March 18, 2015.

APRIL 2017 • Doctor’s

Review

PHOTO FINISH by

D r H .M . R ob i n s on

Birds of a feather...

Visiting Peche Island along the Detroit River, this family of swans caught my eye. Mute swans are monogamous, I have come to learn, and you will see whole families out looking for food. This family had five cygnets. The mother was carrying some of her young on her back. They are very territorial so I will be venturing back to hopefully catch a glimpse of them again and watch the cygnets grow.

MDs, submit a photo! Please send a high-resolution photo along with a 150- to 300-word article to:

editors@doctorsreview.com

Doctorâ&#x20AC;&#x2122;s Review â&#x20AC;˘ APRIL 2017

co ne nt w es t!

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Wondering if ASMANEX® Twisthaler® (mometasone furoate) can help your asthmatic patients? Compared to PULMICORT* Turbuhaler* (budesonide) 400 mcg BID, ASMANEX® Twisthaler® 200 mcg BID demonstrated a: Statistically significant greater improvement in FEV1 in patients ≥12 years of age (p <0.05†)1‡ Change in FEV1 from Baseline to Endpoint

2.6x

Change from baseline (L)

0.25

greater improvement

in FEV1 at endpoint (p <0.05)

0.20

0.15

ASMANEX® Twisthaler® (mometasone furoate) 200 mcg BID (n=176); baseline 2.52 L

0.10

0.05

0.00 0

6 Time (weeks)

PULMICORT* Turbuhaler* (budesonide) 400 mcg BID (n=181); baseline 2.47 L

Adapted from Bousquet et al., 2000.1

ASMANEX® Twisthaler®: The flexibility of three dosage strengths with the convenience of once-daily dosing in many patients.2§

ASMANEX® Twisthaler®, a preventative agent, is indicated for the prophylactic management of steroid-responsive bronchial asthma in patients 4 years of age and older.2 Refer to the page in the bottom-right hand icon for additional safety information and a web link to the product monograph discussing: • Contraindications in patients hypersensitive to this drug, milk proteins (from the excipient lactose), or any component of the container; in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required; in untreated systemic fungal, bacterial, viral or parasitic infections, active or quiet tuberculous infection of the respiratory tract, or ocular herpes simplex.2 • Other relevant warnings and precautions regarding abrupt discontinuation, risk of adrenal insufficiency in patients transferred from systemically active corticosteroids, oropharyngeal candidiasis, risk of systemic effects of inhaled corticosteroids, risk of dose-dependent bone loss, enhanced effect of corticosteroids in patients with cirrhosis or hypothyroidism, exceeding the recommended dose, rare systemic eosinophilic conditions, use with acetylsalicylic acid in hypoprothrombinemia, risk of immunosuppression, relief of acute asthma episodes, possible inhalation induced bronchospasm, pregnant/nursing women, hypoadrenalism in infants born to women receiving corticosteroids, monitoring of HPA axis function and haematological status, use of short-acting inhaled bronchodilators, bone and ocular effects, height of children and adolescents.2 • Conditions of clinical use, adverse reactions, drug interactions and dosing/administration instructions.2 The Product Monograph is also available by calling us at 1-800-567-2594. *All trademarks are properties of their respective owner(s). † p<0.05 for the 200 mcg BID ASMANEX® Twisthaler® vs. PULMICORT* Turbuhaler* (budesonide) 400 mcg BID at Week 12 (endpoint). ‡ This was a 12-week, randomized, active-controlled, evaluator blind, international study of 730 patients from 57 centres, which included researchers from multiple Canadian institutions. All patients were ≥12 years of age and previously maintained on daily inhaled corticosteroids for treatment of moderate persistent asthma. Patients were randomized with no inhaled corticosteroid wash-out period to BID treatment with ASMANEX® Twisthaler® (mometasone furoate) 200 mcg or PULMICORT* Turbuhaler* (budesonide) 400 mcg. The mean change from baseline to endpoint in FEV1 was the primary efficacy endpoint. All study medications were taken as one inhalation, twice daily.1 § ASMANEX® Twisthaler® should be taken regularly, even when the patient is asymptomatic. Improvement in asthma control following inhaled administration of ASMANEX® Twisthaler® can occur within 24 hours of beginning treatment, although maximum benefit may not be achieved for 1 to 2 weeks or longer. The lowest dose required to maintain good asthma control should be used. Attempt at dose reduction should be carried out on a regular basis. For patients ≥12 years of age, the recommended dose is 200 mcg or 400 mcg administered by oral inhalation once daily in the evening. In some patients ≥12 years of age, such as those previously on high doses of inhaled corticosteroids, 200 mcg given twice daily may provide more adequate asthma control. For patients ≥12 years of age who require systemic corticosteroids, the recommended starting dose is 400 mcg twice daily (maximum dose). Once reduction of the oral steroid dose is complete, titrate ASMANEX® Twisthaler® to the lowest effective dose. In pediatric patients 4 to 11 years of age, the recommended dose is 100 mcg administered by oral inhalation once daily in the evening.2 BID=twice daily. FEV1=forced expiratory volume in 1 second. ® MSD International Holdings GmbH. Used under license. © 2017 Merck Canada Inc. All rights reserved. RESP-1206327-0000

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