October 2016 by Doctor's Review

CANADIAN PUBLICATIONS MAIL SALES PRODUCT AGREEMENT No. 40063504

OCTOBER 2016

Nature by Burchfield Elegance by Relais & Châteaux Rentals by Frank Lloyd Wright BC brewpubs by the sea

MEDICINE ON THE MOVE

WIN

THIS MONTH’S

GADGET PAGE 17

THINGStoDO PLACEStoGO A case of natural knee repair Antidepressants: brand name versus generic Wireless headsets

Type 2 diabetes can be heartbreaking.

According to the Canadian Diabetes Association (CDA):1, 2 Patients with type 2 diabetes are at increased risk for cardiovascular mortality. Diabetes can reduce life expectancy by about 12 years. The BI and Lilly Diabetes Alliance is committed to the heart health of your type 2 diabetes patients.

References: 1. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Vascular protection in people with diabetes. Can J Diabetes. 2013;37 Suppl 1:S100-4. 2. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Screening for the presence of coronary artery disease. Can J Diabetes. 2013;37 Suppl 1:S105-9. Member of Innovative Medicines Canada

Visions of delight Steve Martin, the comedian, actor, banjo player and writer, over the summer, curated an exhibition at the AGO titled The Idea of North: The Paintings of Lawren Harris. It was also the first solo show of Harris’s work in the US with stops at galleries in Los Angeles and Boston. The Toronto exhibition closed late last month, but you can admire the artist’s work and that of other members of the Group of Seven at the excellent website, arthistoryarchive.com/arthistory/canadian/the-group-of-seven.html. I urge you to have a look. Our precious seven produced many, many paintings of eye-popping power and beauty. Mr. Martin recognized that years ago, but few other collectors had his eye. Until recently. A Harris canvas, Mountain and Glacier, sold at Heffel’s Toronto auction last fall for a record-breaking $4.6 million. I expect Steve has a few Group of Seven’s hanging around here and there. He’s a man who knows a great deal about art on the walls and behind the scene. I’ve just read his charming, informative and faintly disturbing novel, An Object of Beauty. It tells of how the lovely, young Lacey Yeager storms the New York art scene between 1993 and 2011 starting with modern masters at Sotheby’s uptown and shifting downtown to Chelsea and Soho galleries where emergent artists light up and flame out in a matter of months. Beauty and greed duke it out on every page, many of which contain colour illustrations of the work being bought, inflated and sold. There’s more art in this issue. “Burchfield’s Transcendent Vision,” Medicine and the Arts, is all about American artist Charles Burchfield. Ohio-born, he moved to Buffalo, NY and switched to industrial subjects in his late 20s in order to feed his wife and kids, then, later in life, he went back to painting nature as he had in his youth with works whose vibrancy is now compared to those of Van Gogh and Emily Carr. He sought to incorporate sound and movement into his pictures — you’ll find some remarkable examples starting on page 30. To see the originals, visit the Burchfield Penney Art Center (burchfieldpenney.org) on the University of Buffalo campus. Other places you might add to your fall agenda are a stay at a Relais & Châteaux inn, page 40. Somewhat old-fashioned in the most comfortable possible way, association members strive to uphold the highest standards of food and accommodation. Don’t be surprised to find a few classic French dishes on menus which — in case you missed it — is once again the food of choice in New York. The three most highly rated restaurants in Gotham City — Le Bernardin, Bouley and Daniel — are French. And there’s more. Don’t miss Sails and Ales with Cinda Chavich who takes you on a very special cruise around BC’s Salish Sea, page 34. Happy autumn days,

Mountain and Glacier by Lawren Harris.

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David Elkins, publisher and editor delkins@parkpub.com

@doctorsreview

OCTOBER 2016 • Doctor’s

Review

Covered in 8 out of 10 provinces with special authorization*

Help your OAB patients fight the urge Proven efficacy in OAB with symptoms of urgency, urgency incontinence and urinary frequency.2

Consider MYRBETRIQ (mirabegron): A potent and selective β-3 adrenoceptor agonist for OAB ®

2‡

Indication and clinical use: MYRBETRIQ® (mirabegron) is indicated for the treatment of overactive bladder (OAB) with symptoms of urgency, urgency incontinence and urinary frequency • Safety and efficacy in pediatric patients have not been established •

Contraindications: Severe uncontrolled hypertension (SBP ≥180 mm Hg and/or DBP ≥110 mm Hg) • Pregnancy •

Relevant warnings and precautions: Serious adverse events of neoplasm • Serum ALT/AST increase with/without bilirubin increase and Stevens-Johnson syndrome • Dose dependent QTc prolongation, elevated blood pressure, elevated heart rate •

Caution in patients with risk factors for torsade de pointes or patients taking medications known to prolong the QT interval • Interaction with CYP2D6 substrates • Caution in patients with clinically significant bladder outlet obstruction or taking antimuscarinics for OAB • Caution in patients with moderate hepatic impairment; not recommended in severe hepatic impairment • In patients with glaucoma, ophthalmological examinations should be performed regularly • Angioedema of the face, lips, tongue and/or larynx has been reported. If involvement of tongue, hypopharynx or larynx occurs, discontinue MYRBETRIQ® and initiate appropriate therapy and/or measures • Caution in patients with severe renal impairment; not recommended in end stage renal disease • Should not be used during nursing •

M Y R BE T R IQ is the ®

dispensed OA B medication prescribed by Canadian urologists

For more information: Please consult the Product Monograph at http://www.cmsastellas.ca/uploads/pdf/2015-12-17%20 Myrbetriq%20English.pdf for more 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 1-888-338-1824. References: 1. IMS Health (April 2016). Canadian CompuScript (April 2015 – March 2016). 2. Astellas Pharma Canada, Inc. MYRBETRIQ® Product Monograph, 2015.

MYR B ETR IQ ® is a trademark of Astellas Pharma Canada, Inc.

1†

* MYRBETRIQ® is eligible for formulary coverage with special authorization in Alberta, Saskatchewan, Manitoba, Ontario, Quebec (http://www.ramq.gouv.qc.ca/en/regie/legalpublications/Pages/list-medications.aspx)§, New Brunswick, Newfoundland and Labrador, and Nova Scotia. Please refer to the respective formularies for coverage information. † Comparative clinical significance is unknown. ‡ Clinical significance is unknown. §For treatment, as monotherapy, of vesical hyperactivity in persons for whom oxybutynin is poorly tolerated, contraindicated or ineffective.

TrintellixÂŽ is indicated for the treatment of major depressive disorder (MDD) in adults. Pr

Consult the product monograph at www.trintellixmonograph.ca for important information about contraindications, warnings and precautions, adverse reactions, interactions, dosing instructions, and conditions of clinical use. The product monograph is also available by calling 1-800-586-2325. TRINTELLIXÂŽ is a registered trademark of Lundbeck Canada Inc.

contents OCTOBER 2016

COVER: DARIA MINAEVA / SHUTTERSTOCK.COM

features

Rent a Frank Lloyd Wright gem The Palmer House in Ann Arbor, Michigan is a small masterpiece of American architecture — and you can have it all to yourself by Gerald Fitzpatrick

Weeknight winners Gnocchi with squash, kale and cheese, plus more 30-minute meals from one of Canada’s experts on nutrition by Rose Reisman

Sails and ales Five-days aboard a hand-built schooner exploring food and beer pairings at craft breweries around BC’s Salish Sea by Cinda Chavich

Gracious spaces

Charming Relais & Châteaux properties in Canada, Europe and the US to elevate your fall getaway experience by Lin Stranberg

Treating chronic pain, our shared responsibility.

CLIENT: Purdue

OCTOBER 2016 • Doctor’s

DOCKET NUMBER: PQ9818

Review

COLOURS

PRODUCER

DATE

Choose Alvesco first. Demonstrated effective symptom control with an excellent safety profile. ®

1,2

Indications and clinical use: Alvesco is indicated for the prophylactic management of steroid-responsive bronchial asthma in adults, adolescents, and children 6 years of age and older.

• Immunosuppressant drugs • May cause eosinophilic conditions • May cause candidiasis • As with other inhalation therapy, paradoxical bronchospasm may occur Contraindications: • Caution in systemic steroid replacement by inhaled steroid • Untreated fungal, bacterial or tuberculosis • Patients with hypoprothrombinemia in infections of the respiratory tract conjunction with acetylsalicyclic acid • Primary treatment of status asthmaticus or other acute episodes of asthma or in patients • Systemic effects of inhaled corticosteroids may occur, particularly at high doses for with moderate to severe bronchiectasis prolonged periods Relevant warnings and precautions: • Monitor HPA axis function and effects • Patients with hypothyroidism on the eye • Patients with cirrhosis and/or severe hepatic impairment ®

ALVESCO is a registered trademark of Takeda GmbH, used under licence. The AstraZeneca logo is a registered trademark of AstraZeneca AB, used under license. © AstraZeneca Canada Inc. 2016. ®

For more information: For important information on conditions of clinical use, contraindications, warnings, precautions, adverse reactions, drug interactions and dosing, please consult the product monograph at http://www.azinfo.ca/alvesco/pm258/. The product monograph is available by calling AstraZeneca Canada at 1-800-668-6000. REFERENCES: 1. Alvesco (ciclesonide inhalation aerosol) Product Monograph. Takeda Canada Inc. December 17, 2012. 2. Lougheed MD et al. Canadian Thoracic Society 2012 guideline update: Diagnosis and management of asthma in preschoolers, children and adults. Can Respir J 2012;19(2):127-164. ®

contents OCTOBER 2016

regulars 9

LETTERS Medical musings

Canada’s most liveable cities, new weekday flights between Toronto and Niagara, tours for architecture aficionados and more by Camille Chin

PRACTICAL TRAVELLER

The best medical meetings scheduled for next March

GADGETS Three wireless headsets that connect to any cell phone — except iPhone 7! by David Elkins

TOP 25

CROSS CURRENTS IN OSTEOARTHRITIS The case of the knee that predicted rain by Dr Gordon Ko

DEPRESSION KEYPOINTS Antidepressants: brand name versus generic by Eva Chanda

MEDICINE AND THE ARTS The healing power of nature glows in the art of American painter Charles Burchfield by Tilke Elkins

Coming in

November

• (Nearly) everything old is new again at Victoria’s fabled Empress Hotel • Stroll through Northern Europe’s traditional Christmas markets • Bask in the art, architecture, food, wine and multi-layered history of Southern Spain • Canada turns 150 next year — Ottawa is all dressed up and ready to party! PUR15TA007_bootlug_1E_E1.indd 1

OCTOBER 2016 • Doctor’s

Review

2016-01-25 4:56 PM

C MING SOON 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 will be approved and 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. 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. 1. GSK data on file. 2013. 2. FLONASE® Allergy Relief Product Monograph. GlaxoSmithKline Consumer Healthcare Inc. August 2016. 3. FLONASE® Product Monograph. GlaxoSmithKline Inc. Dec. 10, 2015. *Provincial exclusions may apply.

LETTERS

EDITOR

David Elkins

Medical musings

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

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

MONTREAL HEAD OFFICE

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

THE HISTORY OF MASTECTOMIES In July 2013, Jackie Rosenhek wrote a fine article on the history of mastectomy [doctorsreview.com/history/breastcancer-history-medicine]. Family lore tells that my great grandmother was diagnosed with breast cancer and had a mastectomy sometime in the 1870s or ’80s. Rare, but not impossible until we find that she lived in very rural Eastern Nebraska. The nearest real hospitals were in Sioux City, Omaha, Minneapolis, etc. But everything I read says that mastectomies were performed at that time only in New York City, Philadelphia and perhaps Chicago. The family story is related by my great grandma’s sister, so pretty hard evidence. But how likely is it, really, that anything like this could actually have happened? Grandma bore and nursed 12 kids (on one breast) and lived 76 years — again against all (19th-century) odds. I wonder if anyone might be able to lend me a hand with information or advice.

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

Mariam Hume Via email

DRILL ENVY Here are a few of the online comments we received about the Black + Decker LDX112C Lithium Drill/Driver [Gadgets, September 2016, page 16]: If it is light, powerful and holds its charge, it would be great for most household tasks. Dr Barry Lamont

Rol Morris Ladysmith, BC

This would make a great Christmas gift.

TORONTO SALES OFFICE

553 Prestwick Oshawa, ON L1J 7P4 Tel: (905) 571-7667 Fax: (905) 571-9051

isn’t that something. You’d think that wanting to write all the time would be wonderful. All those ideas.

Gilda

THE WRITE STUFF The article on hypergraphia was really great [“Hypergraphia: a two-sided affliction,” Medicine and the Arts, September 2016, page 23]. I had no clue that a disease like that existed, but

Great looking drill. My hubby needs one like this for the screened in porch at the cottage. I enjoy Doctor’s Review magazine every month! H. Dixon

COVERED BY MOST PRIVATE INSURANCE PLANS

TRINTELLIX® is a registered trademark of Lundbeck Canada Inc.

OCTOBER 2016 • Doctor’s

Review

Notes supplémentaires

ÉPREUVE

03F

Gdansk, Poland.

P R AC T I C AL T R A V E L L E R C a mi lle C hi n

Architectural KAMIRA / SHUTTERSTOCK.COM

plans

Doctor’s Review • OCTOBER 2016

The American Institute of Architects just launched a new travel program that offers group tours led by building and design experts. Called Architectural Adventures, the program has 11 trips scheduled for 2017. Havana Revealed, March 10 to 15, US$5295 per person, is expected to be popular. It’ll include visits to the 16th-century stone El Morro Castle, the Instituto Superior de Arte commissioned by Fidel Castro and Che Guevara in the 1960s, the University of Havana to meet with architecture professors and students, and of course plenty of neighbourhoods to see restored mansions and prefab Soviet-style architecture. A trip to Northern Italy is happening in May, Cities of the Baltic Sea in June, Portugal and Northern Spain as well as China in October. Twenty to 30 people per tour. Prices include accommodations, some meals and ground transportation; airfare is extra. Havana, Cuba. architecturaladventures.org.

WAJ / SHUTTERSTOCK.COM

Avoiding TO traffic:

GTA

priceless

Greater Toronto Airways launched weekday flight service between Niagara and Toronto on September 15. The trip takes only 15 minutes and costs $85 one way, $159 round trip. Carry-ons are an additional $10; a suitcase $25. For some, avoiding the two or three hours of Toronto traffic is worth every penny. The six-passenger executive and eight-passenger commuter plane leaves the Niagara District Airport in Niagara-on-the-Lake at 8:30am and the Billy Bishop Toronto City Airport at 4:30pm for the return; the reverse trip leaves Toronto at 7:15am and Niagara at 6pm. To book: flygta.com.

TV come true

Last month, Game of Thrones broke the record for the highest number of Emmy Awards won by any fictional series. The show’s seventh season is rumoured to air mid-2017, but to tide viewers over until then, the Game of Thrones Live Concert Experience will tour North America February through March 2017, with stops in Montreal on March 3 and Toronto on March 4. The performances will feature music by the show’s composer, Ramin Djawadi, an orchestra with a choir and musical soloists, as well as footage from the show and imagery created specifically for the concerts. For tickets: livenation.com/artists/162474/ game-of-thrones.

OCTOBER 2016 • Doctor’s

Review

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

BIKEWORLDTRAVEL / SHUTTERSTOCK.COM

Night riders in the UK London recently launched 24-hour weekend service on three of its Underground Tube lines. The Night Tube currently operates Fridays and Saturdays on the Central, Victoria and Jubilee lines; night service on the Northern and Piccadilly lines will follow later this season and include Heathrow Airport. More than 100 British transport police officers will eventually patrol the 144 stations that will be open throughout the night. For details: tfl.gov.uk/modes/tube.

The countryside in Sin

City

The Bellagio Gallery of Fine Art in Las Vegas is hosting an exhibit dedicated to the exact opposite of big city lights. Organized in partnership with Boston’s Museum of Fine Arts, Town and Country: From Degas to Picasso, on now until February 20, 2017, features 47 works inspired by the growing urbanization in Europe and the US during the 19th and 20th centuries. Paintings, prints, drawings and photographs by Degas, Monet, Picasso, Renoir, Van Gogh and more are on view. “Town and Country reveals each artist’s interpretation of growth, expansion and development,” says Tarissa Tiberti, the gallery’s executive director. “The artworks will provide a dazzling recount of cities and the countryside during the Industrial Revolution.” Admission US$16; kids 12 and under free. bellagio.com/bgfa.

Doctor’s Review • OCTOBER 2016

STYVE REINECK / SHUTTERSTOCK.COM

St. Anton, Arlberg, Austria.

One pass, six countries

Vail Resorts’s Epic Pass is committed to living up to its name. For the first time ever, skiers and snowboarders will be able to use the multi-resort pass in France, Italy, Austria and Switzerland this 2016-17 winter season. The pass already includes unlimited, unrestricted access and lift tickets to 13 ski areas in the US — from Beaver Creek and Vail in Colorado, Park City in Utah, Heavenly and Kirkwood at Lake Tahoe — as well as Perisher in Australia. The Epic Pass was available for US$809 for a limited time through September 5; when we checked at the end of September it was priced at US$854. Access is limited in Europe (six days in France, three days in Italy, three in Austria and five in Switzerland), but covers some mighty places: 3 Vallées, Paradiski and Tignes-Val d’Isère in France; Skirama Dolomiti Adamello Brenta in Italy, Arlberg in Austria, 4 Vallées in Switzerland. For more details: snow.com/ epic-pass/info/europe-is-epic.aspx.

OCTOBER 2016 • Doctor’s

Review

NEW

VIACORAM

EN ROUTE TOWARDS BP CONTROL The only combination antihypertensive medication with an ACEi (perindopril arginine) and a dihydropyridine CCB (amlodipine besylate)*

Contraindications Patients who are hypersensitive to the active ingredients of this drug, to any ingredient in the formulation or component of the container, to any other angiotensin converting enzyme inhibitor (ACE-inhibitor), or to any other dihydropyridine derivatives • Patients with renal impairment (creatinine clearance < 60 ml/min) • Patients with a history of hereditary/ idiopathic angioedema, or angioedema related to previous treatment with an ACE-inhibitor • Pregnant women or planning to become pregnant • Nursing women • Patients with mitral valve stenosis and left ventricular outflow tract obstruction (e.g. aortic stenosis, hypertrophic cardiomyopathy) • Patients with heart failure • Concomitant use of angiotensin converting enzyme (ACE) inhibitors, including VIACORAM®, with aliskiren-containing drugs in patients with diabetes mellitus (type 1 or 2) or moderate to severe renal impairment (GFR < 60 ml/min/1.73 m2) • Patients with hereditary problems of galactose intolerance, glucose-galactose malabsorption, or the Lapp lactase deficiency as VIACORAM® contains lactose • Patients with extracorporeal treatments leading to contact of blood with negatively charged surfaces • Patients with bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney •

Most serious warnings and precautions sulphate): May lead to life-threatening anaphylactoid reactions. Pregnancy: When used in pregnancy, angiotensin converting enzyme (ACE) Other relevant warnings and precautions inhibitors can cause injury or even death • Caution in driving a vehicle or performing of the developing fetus. When pregnancy other hazardous tasks is detected, VIACORAM® should be • Co-administration of ACE inhibitors, discontinued as soon as possible. including the perindopril component of Hyperkalemia (serum VIACORAM®, with other agents blocking the potassium > 5.5 mEq/L): Can cause serious, RAS, such as ARBs or aliskiren-containing sometimes fatal arrhythmias; serum potassium drugs, is generally not recommended in must be monitored periodically in patients patients other than patients with diabetes ® receiving VIACORAM . Concomitant use with mellitus (type 1 or type 2) and/or potassium supplements, potassium-sparing moderate to severe renal impairment diuretics, or potassium-containing salt (GFR < 60 ml/min/1.73 m2) as it is substitutes is not recommended. contraindicated in these patients Collagen vascular disease, • Risk of hypotension; closely monitor immunosuppressant therapy, treatment patients at high risk of symptomatic with allopurinol or procainamide, or a hypotension. Similarly monitor patients combination of these complicating with ischaemic heart or cerebrovascular factors (especially if there is pre-existing disease; an excessive fall in blood pressure impaired renal function): May lead to could result in a myocardial infarction or serious infections, which may not respond to cerebrovascular accident ® intensive antibiotic therapy. If VIACORAM is • Risk of mild to moderate peripheral edema used in such patients, periodic monitoring of • Safety and efficacy of VIACORAM® in white blood cell counts is advised and patients hypertensive crisis have not been established should be instructed to report any sign of • Risk of angina worsening/acute myocardial infection to their physician. infarction after starting therapy or dose increases Angioedema: May be life-threatening and occur at any time during therapy. Where there • Risk of hyperkalemia; monitor serum potassium periodically is involvement of the tongue, glottis or larynx • Risk of neutropenia/agranulocytosis, likely to cause airway obstruction, it may be thrombocytopenia and anemia fatal. Emergency therapy should be • Increases in serum transaminase and/or administered promptly. bilirubin levels, cholestatic jaundice, Syndrome starting with cholestatic cases of hepatocellular injury with or jaundice with progress to fulminant without cholestasis hepatic necrosis: May lead to death. • Not recommended in patients with impaired Use during low-density lipoproteins liver function (LDL) apheresis (with dextran • Angioedema

•

• •

• • •

•

Risk of anaphylactoid reactions during desensitization or membrane exposure (hemodialysis patients) Risk of nitritoid reactions in patients on therapy with injectable gold Patients undergoing major surgery or during anesthesia with agents that produce hypotension Black patients vs. non-black patients Not recommended in patients with a recent kidney transplantation Risk of changes to renal function in susceptible patients; potassium and creatinine should be monitored in these patients Risk of cough Dermatological reactions Not indicated for the initiation of treatment in the elderly (> 65 years) patients; not recommended in pediatrics (children < 18 years of age) Patients with diabetes treated with oral antidiabetic agents or insulin, glycemic control should be closely monitored during the first month of treatment with VIACORAM® Patients with unilateral or bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney Sexual function/reproduction

For more information Please consult the Product Monograph at http://webprod5.hc-sc.gc.ca/dpd-bdpp/indexeng.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.

P R AC T I C AL T R A V E L L E R A new option in the treatment of mild to moderate essential hypertension in initial therapy

Jericho Beach, Kitsilano, Vancouver.

CTC

VIACORAM® (perindopril arginine/amlodipine) is indicated for the treatment of mild to moderate essential hypertension in patients for whom combination therapy is appropriate. VIACORAM® 3.5 mg/2.5 mg is indicated for initial therapy in patients with mild to moderate essential hypertension. VIACORAM® is not indicated for switching therapy from the individual drugs currently on the market (perindopril as erbumine or arginine salt, amlodipine). VIACORAM® is not indicated for the initiation of treatment in elderly patients (> 65 years of age). There is not sufficient clinical experience to justify the use in these patients. VIACORAM® is not indicated in pediatric patients < 18 years of age. The efficacy and safety have not been studied in this population.

Canada’s most liveable cities INDICATED IN INITIAL THERAPY

3.5 mg Perindopril arginine / 2.5 mg Amlodipine

*Comparative clinical significance unknown. Reference: VIACORAM® Product Monograph. Servier Canada Inc. February 17, 2016. VIACORAM® is a registered trademark of Servier Canada Inc.

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

It’s probably not surprising that Melbourne has been recognized as the most liveable city in the world; it’s an honour the city has held for six consecutive years in the Economist Intelligence Unit’s Global Liveability Ranking. A pleasant surprise might be that Vancouver, Toronto and Calgary have made the top five this year. The index, measured out of 100, considers 30 factors related to safety, health care, educational resources, infrastructure and the environment — that is, quality of living, not cost of living — to calculate scores for 140 cities. Terrorist attacks and civil unrest have caused nearly a fifth of the cities surveyed to drop in position — Sydney, Brussels, Paris, Chicago, Atlanta among them. Damascus, the capital of Syria, is understandably the lowest-ranked with a rating of 30.2 out of 100. THE 10 MOST LIVEABLE CITIES: 1. Melbourne, Australia (97.5 out of 100) 2. Vienna, Austria (97.4) 3. Vancouver, BC (97.3) 4. Toronto, ON (97.2) 5. Calgary, AB (96.6) 6. Adelaide, Australia (96.6) 7. Perth, Australia (95.9) 8. Auckland, New Zealand (95.7) 9. Helsinki, Finland (95.6) 10. Hamburg, Germany (95) OCTOBER 2016 • Doctor’s

Review

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

• Abdominal pain

• Bloating • Constipation2

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

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

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

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

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

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

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

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

linaclotide capsules

GA DGE T S by

D a v i d Elk i n s

Headsets without wires The headphone jack is gone from the iPhone 7 and 7 Plus. The only way you can use the new devices is with wireless earbuds or an extra connector. Apple is clearly setting a new standard for all cell phones. Expect to see the rest of the cell phone pack follow. A host of new wireless devices are on the market with more coming on every week. Before you toss your wired headset into that drawer full of obsolete devices and their myriad of connectors, it’s worth pausing to consider the pluses and minuses of headsets generally. The wired variety is so ubiquitous, so many people wear them, so much of the time, they can almost be considered a fashion accessory. The technology took a leap forward around the time the iPhone 4 was launched. The sound quality of the earbuds was good enough to listen to your favourite music without having to wince. Apple headsets have come a long way, but the sound they reproduce is still not as good as that of many other headsets. Also, the connected microphones worked well enough to use them even on sensitive calls. These days you can’t tell if passersby are listening to Drake or Debussy or getting lab results on their latest urine test. And the wires do dangle. They get caught in hair and clothing and they tangle, oh how they can tangle! So doubtless Apple is on the right track going wireless as they have been with many previous innovations. With technological upgrades, there’s usually a downside. Bluetooth headsets

Win your choice of one of three wireless headsets by entering the Win the Gadget of the Month contest at doctorsreview.com

whether in-ear or over-ear do not deliver quite the same sound quality as their wired counterparts. The difference is small particularly in higher quality devices, but here’s the real zinger: Bluetooth sets have to be charged to operate, some of them overnight, every night. An insufficient remaining charge would be a major annoyance if they cut out when you’re on an important call. Pairing to most devices and to Apple products with IOS is straightforward, except, possibly, to the iPhone 7 which has a new chip that makes it very easy to connect to Apple devices, but more difficult for non-Apple products to connect (Apple says they’re working on a solution.) Choosing a wireless headset that’s right for you is highly personal. For all their benefits, they can also be finicky and prone to wear out. Most earbuds are intended to be used during exercise and by far the majority of the hundreds on the market are in-ear. Prices range

from about $15 to well into the hundreds. Here are three with decent reviews — price does not always mean better when it comes to wireless headphones. Bluetooth earbuds by E Tronic Good fit, lightweight, clear sound, strong bass, eight hours on a charge. $39.97. amzn.to/2dxw8M0. Sony SBH-80 Solid sound, older, proven Bluetooth 3.0 technology, five hours on a charge. $79.99. ebay.to/2dtzjix. JBL Synchros S400BT Good to very good sound, 15 hours on a charge, carrying case. $139.99. bit.ly/2dBUQdN.

CONGRATULATIONS! The winner of the Pentax Zoom Binoculars is Dr Aline Levi, a general pediatrician from Dollard-des-Ormeaux, QC. OCTOBER 2016 • Doctor’s

Review

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

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

THE TOP 25 MEDICAL MEETINGS compiled by Camille Chin

Access 2500+ conferences at doctorsreview.com/meetings Code: drcme Canada Banff, AB March 3-5, 2017 62nd Annual Scientific Assembly of the Alberta College of Family Physicians acfp.ca/what-we-do/annual-scientific-assembly

March 3-6, 2017 March 16-18, 2017 2017 Society of Obstetricians and Gynecologists West/Central CME sogc.org/continuing-medical-education-cme/ events/index.html

Vancouver, BC March 1-4, 2017

PAUL ZIZKA / BANFF LAKE LOUISE TOURISM

Canadian Digestive Diseases Week cag-acg.org/cddw/overview

7th International Conference on Fetal Alcohol Spectrum Disorder interprofessional.ubc.ca/fasd2017/default.asp

Banff National Park.

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

March 31-April 1, 2017 Sexual Health 2017 ubccpd.ca/course/SexualHealth2017

Barcelona, Spain March 8-12, 2017

Around the world

9th International DIP Symposium on Diabetes, Hypertension, Metabolic Syndrome and Pregnancy comtecmed.com/dip/2017/welcome.aspx

Amsterdam, Netherlands March 2-4, 2017 4th International Conference on Nutrition and Growth 2017.nutrition-growth.kenes.com

Bologna, Italy.

March 30-April 1, 2017

Atlanta, GA February 23-26, 2017

2017 Annual Meeting of American Academy of Allergy, Asthma and Immunology annualmeeting.aaaai.org

Buenos Aires, Argentina March 16-18, 2017 4th Latin America Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension codhy.com/la/2017/default.aspx

Cannes, France March 2-5, 2017

Cape Town, South Africa February 28-March 4, 2017 AGATA DOROBEK / SHUTTERSTOCK.COM

March 3-6, 2017

4th International Congress on Controversies in Rheumatology and Autoimmunity cora2017.kenes.com

7th International Conference on Fixed Combination in the Treatment of Hypertension, Dyslipidemia and Diabetes Mellitus 2017.fixedcombination.com

4th World Congress on Controversies in Pediatrics congressmed.com/copedia

2017 Annual Meeting of the International Society for the Study of Women’s Sexual Health isswshmeeting.org

Bologna, Italy March 9-11, 2017

31st International Papillomavirus Conference hpv2017.org

March 20-22, 2017 2017 World Congress of the Royal College of Obstetricians and Gynecologists rcog2017.com

OCTOBER 2016 • Doctor’s

Review

THE TOP 25 MEDICAL MEETINGS

Access 2500+ conferences at doctorsreview.com/meetings Code: drcme To register and to search 2500+ conferences, visit doctorsreview.com/meetings

Street performers in New Orleans’ French Quarter district.

Dublin, Ireland March 6-9, 2017 7th World Congress on Women’s Mental Health iawmh2017.org

QUINTANILLA / SHUTTERSTOCK.COM

Florence, Italy March 23-26, 2017 2017 World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases wco-iof-esceo.org

Houston, TX February 22-24, 2017 International Stroke Conference 2017 professional.heart.org/professional/index.jsp

Madrid, Spain March 23-26, 2017 5th International Congress on Dual Disorders icdd-congress.com

Melbourne, Australia March 26-29, 2017 12th International Congress on SLE and the 7th Asian Congress on Autoimmunity lupus2017.org

Miami Beach, FL March 29-April 2, 2017 2017 Annual Meeting of Americas HepatoPancreato-Biliary Association ahpba.org/meeting/annual-meeting-registration. phtml

Matadero Bridge, Madrid, Spain.

New Orleans, LA March 8-11, 2017

Vienna, Austria March 29-April 2, 2017

2017 Annual Meeting of the Society for Adolescent Health and Medicine adolescenthealth.org/meetings.aspx

13th International Conference on Alzheimer’s and Parkinson’s Diseases adpd2017.kenes.com

Orlando, FL March 3-7, 2017 2017 Annual Meeting of the American Academy of Dermatology aad.org/meetings/annual-meeting

Paris, France March 30-April 1, 2017 11e Congrès de la Médecine Générale – France 2017 congresmg.fr/index.php/en

MEDICAL QUIPS Alternate medical definitions Colic: A sheep dog. Dilate: To live long. Enema: Not a friend.

Amsterdam, Brasilia, Florence, Hamburg, Honolulu, Istanbul, Madrid, Milan, Paris, Quebec City, San Diego, Seoul, Shanghai, Sydney, Toronto

Go to doctorsreview.com/meetings for conferences in these cities... and many more!

Doctor’s Review • OCTOBER 2016

TARGET THEIR RELAPSED OR REFRACTORY APL WITH

TRISENOX

For induction of remission and consolidation of APL refractory to or relapsed from retinoid and anthracycline therapy, and where APL shows the presence of the t(15;17) translocation or PML-RAR gene expression.

PART OF THE LUNDBECK ONCOLOGY PORTFOLIO Overall 87% CR* rate demonstrated (n=52) (combined results of 2 open-label, single-arm studies)† TRISENOX (arsenic trioxide) is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL), which is refractory to or has relapsed from retinoid and anthracycline therapy, and whose APL is characterized by the presence of the t(15;17) translocation or promyelocytic leukemia-retinoicacid-receptor alpha (PML-RAR ) gene expression. Refer to the page in the bottom-right icon for additional safety information and a web link to the Product Monograph discussing: • Contraindications in pregnancy and nursing mothers • Most serious warnings and precautions regarding APL differentiation syndrome, acute cardiac toxicities (rhythm disturbance) and avoiding concomitant use of drugs that prolong the QT interval or disrupt electrolyte levels • Other relevant warnings and precautions regarding tumor lysis syndrome, carcinogenesis of arsenic trioxide, increased heart rate, hyperleukocytosis, elevated transaminases, peripheral neuropathy, fertility, embryotoxicity, teratogenicity, presence of arsenic in semen (use condom during treatment and for 3 months after stopping treatment), patients with renal or hepatic impairment, and monitoring of electrocardiograms, laboratory parameters (potassium, calcium, magnesium, glucose, hematologic, hepatic, renal, coagulation), serious arsenic toxicity in the obese, and for hypoxia and development of pulmonary infiltrates and pleural effusion in all patients • Conditions of clinical use, adverse reactions, drug interactions and dosing instructions In addition, the page contains the reference list and study parameters relating to this advertisement. *CR (complete remission) was defined as cellular bone marrow aspirate with 5% blasts, peripheral blood leukocyte count 3,000/mm3 or absolute neutrophil count 1,500/mm3, and platelet count 100,000/mm3. APL=acute promyelocytic leukemia; PML-RAR =promyelocytic leukemia-retinoic-acid-receptor alpha

We have created an animated video aimed at helping children better understand cancer in the family and help them cope with the situation. If you think that this video could be helpful for your patient, it is located at http://www.lundbeck.com/ca/en/therapeutic-areas/oncology.

® Trisenox is a registered trademark.

See additional safety information on page 53 xx

CR OSS CUR R E N T S I N O S T E OA R T H R I T I S by

D r Gordon Ko

The case of the knee that predicted rain

W .

illiam, a 53-year-old anesthetist, presented at a physiatry clinic for worsening chronic left knee pain over the past five years, with occasional buckling, swelling and stiffness. Pain was typically worse with weight-bearing activities. He joked that he could predict rain, since barometric changes caused throbbing pain that would even awaken him at night.

Physical Physical examination revealed a male of healthy weight, normal vitals, no systemic signs of gout or of seronegative arthritides. He had no hypermobile joints, but had findings of 1+ laxity in the right sacroiliac joint, with mild restriction in the right hip internal rotation due to a previous acetabular fracture in a motor vehicle accident. Standing alignment revealed moderate genu varum with left knee mild effusion (bulge sign), positive Lachman’s and pivot shift tests, and 1+ laxity on anterior drawer testing. McMurray’s test was painful on loading the left lateral compartment. Stressing the collateral ligaments showed no laxity; patellofemoral inhibition tests were negative, and no extension lag was noted. Hamstrings were much tighter on the affected side, with visible atrophy of the left thigh, especially the vastus medialis. The foot showed moderate hyperpronation on weightbearing, with preserved longitudinal arches on tiptoeing, but shoe wear wasn’t grossly uneven. Neurologic exam was otherwise normal. Gait assessment revealed reduced left knee extension on heel strike, with more difficulty going down stairs. No walking aids or braces were used. X-rays revealed grade 1–2 osteoarthritis (OA) with lateral joint space narrowing and spurring of the tibial prominences. Ultrasound study revealed a small effusion without Baker’s cyst or ligament tears.

History Significant medical history included a partial tear of the left anterior cruciate ligament (ACL) from ball hockey 30 years earlier, aggravated by playing touch football 15 years ago, when the knee swelled up considerably. Subsequent surgery revealed a completely torn, retracted ACL, with loss of the lateral compartment cartilage. An abrasion arthroplasty was carried out, but ACL repair wasn’t recommended due to chronicity and degeneration. Gordon D. Ko, MD, CCFP(EM), FCFP, FRCPC, DABPMR, DABPM is medical director of interventional physiatry clinics, Sunnybrook Health Sciences Centre, Toronto, and of the Canadian Centre for Integrative Medicine (www.DrKoPRP.com), and is adjunct lecturer, University of Toronto.

Doctor’s Review • OCTOBER 2016

William’s postoperative rehabilitation was long and included physiotherapy with ultrasound, interferential current therapy and aquatic exercise. Despite this, he still had pain, feelings of instability and swelling. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) were not an option, due to a history of peptic ulcer disease, so he tried topical diclofenac solution and gel. William also took supplements of omega 3-6-9 fatty acids and glucosamine sulfate (500 mg TID), which he found difficult to take consistently and eventually stopped due to lack of efficacy. He wore a knee brace for prolonged upright activities, and customized foot orthotics for hyperpronated feet. In 2011, symptoms worsened after a fall, with fracture dislocation of the contralateral right ankle requiring urgent open reduction and internal fixation. Postoperative pain medications included oxycodone/acetaminophen, codeine/acetaminophen and pregabalin. During the postsurgical period, increased weightbearing on the left leg worsened left knee pain, for which he took duloxetine briefly.

Treatment William hoped he could return to his active lifestyle without relying on medications, so his doctor suggested a trial of N-acetyl glucosamine (NAG) 2 g daily, combined with supervised graduated exercise. After one month, he reported significant pain relief. He continued with 1 g NAG daily, optimal nutrition (avoiding sugar and refined carbs) and further rehabilitation. For activity-related flare-ups, he took devil’s claw herbal supplements and used a topical compounded dimethyl sulfoxide (DMSO) gel. One year later, he was able to participate in a 30-minute charity run and won 2nd place for his age category. The following year, he completed a 5k run in 36 minutes. Prior to these runs, he underwent platelet-rich plasma injections to his left knee. He continues taking NAG about 3 times/week with his workouts, which include kickboxing and floorball. Best of all, William reports, he can’t predict rain anymore.

Before and after stats Pretreatment ratings: NRS (numeric rating scale) for pain, 6/10 (range 3–8/10); KOOS (Knee disability and Osteoarthritis Outcome Score), 105/168; WOMAC (Western Ontario and McMaster Universities Arthritis Index) subscales for pain, 9/20, stiffness, 3/8, and function difficulty, 25/68; and Lequesne index for knee OA, 14/25. Posttreatment ratings: NRS pain, 1/10 (range 0–3/10); KOOS, 23/168; WOMAC pain, 1/20, stiffness, 0/8, function difficulty, 3/68; and Lequesne index, 4/25.

Standing by you and your patients with a variety of treatments

With the Pﬁzer Strive card, your patients can receive savings* on their Pﬁzer brand medication such as:

• Tell your patients to visit www.pfizeroriginal.ca and download the Pfizer Strive card • You can also order Pfizer Strive cards for your patients at www.physiciansonline.ca/ physician or by calling 1-866-794-3574

Encourage your patients to ask for original Pﬁzer brands at the pharmacy. *Payment assistance is available for patients taking LIPITOR, NORVASC, CADUET, ACCUPRIL and ACCURETIC. Amount will vary by province. Pﬁzer Strive is available in all provinces except Quebec.

Inderal-LA remember to specify

If you want your patients to receive the INDERAL-LA brand.

CA016LI003E

For patients taking

Count on

for powerful symptom relief

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

In major depressive disorder, her doctor calls it

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

Choose PRISTIQ:

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

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

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

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

CA0115PRI005E

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

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

Eva Chanda, MSc

Generic antidepressants How do they compare to brand name?

T .

o control the rising costs of prescription medications, cash-strapped provincial drug plans and cost-conscious insurance companies are turning to mandatory generic substitution. Could these rules affect the safety, efficacy and availability of prescription drugs your patients rely on?

Bioequivalence ambivalence Generic drugs have the same chemical structure, strength, dosage form and route of administration as their brand-name counterparts. However, they may have different non-medicinal ingredients, such as fillers, colouring agents and preservatives, as well as different shapes, colours or markings, from the originals. For physicians, of course, the key issues are safety and efficacy. These properties are gauged through bioequivalence: if a generic product shows the same rate and extent of absorption in the body, or bioavailability, as the innovator drug, there probably won’t be any clinically significant differences. To be accepted as bioequivalent, a generic product must meet both of the following criteria:1 • maximum blood concentration (Cmax): 80%–125% of reference • area under the curve (AUC; a measure of total drug exposure over time): 90% confidence interval (CI) 80%–125% of reference This means an absolute variance of less than 5% between products — not the 45% difference between 80% and 125%, as some claim.1 In over 2000 generic drugs approved by the US Food and Drug Administration (FDA), average differences were 4.35% for Cmax and 3.56% for AUC.2 That’s well within the 5% batch-to-batch variation permitted for individual products.3 However, even relatively small variations in dose or concentration can have serious consequences for a small group of drugs that are highly toxic or have a narrow therapeutic range. Known as critical dose drugs, Health Canada has stricter bioequivalence standards for their generic versions.4 The only critical dose drug used in depression is lithium,1 an add-on option for resistant depression.5 Another concern is patients with allergies or intolerances to fillers, such as lactose, gluten, sulfites and tartrazine, but drug excipients can be checked in the Compendium of Pharmaceuticals and Specialties.6 Some patients — and physicians — may still have doubts about the clinical equivalence of generic drugs. Case reports and observational studies have suggested adverse outcomes from generic substitution of various drugs, including psychotropics,7 but high-quality, well-controlled studies in many therapeutic classes generally haven’t found any differences.8

Quality questions Generic drug manufacturers have to follow the same strict federal manufacturing guidelines — enforced by regular inspections

— as innovator companies. Violations posing a risk to safety are subject to immediate corrective measures: recalls, public advisories, border restrictions, even license suspension or termination.9 And since about 80% of medications used in Canada are imports, these regulations apply equally to foreign manufacturers. Recently, Health Canada stopped imports of drugs and drug ingredients from several factories in China and India due to “data integrity concerns,” from sloppy record-keeping to outright fraud,10 but companies in other countries, including the US, UK and Italy, have also been flagged for problems.11 Drug recalls and warnings in Canada tripled during 2005–13 (from 42 to 143), mainly due to stability and contamination issues. The majority involved generic manufacturers, but innovator companies were also affected.12 Drug bans and recalls can cause or worsen drug shortages, which in turn may force pharmacies to switch patients from one generic to another, or even from brand name to generic versions. If a brand-name medication has a generic equivalent, most provincial and private drug plans will usually only cover the generic cost. Pharmacists aren’t legally required to inform patients or doctors of a generic substitution, but they’re generally encouraged to tell patients, who may keep the brand-name version if they’re willing to pay the difference. Insurers are also cracking down on “No substitution” prescriptions, requiring them to be handwritten and documented as medically necessary.13 To avoid misunderstandings, nonadherence, and unexpected adverse events or treatment failures, prepare patients for the possibility of generic substitution, and encourage them to tell you if they’ve been switched. If you can confidently reassure them that generic drugs work just as well as brand-name ones, you’re far more likely to achieve successful treatment. References 1. Canadian Agency for Drugs and Technologies in Health. cadth.ca/sites/default/files/ pdf/What_Are_Bioavailability_and_Bioequivalence_e.pdf. Accessed Sept. 30, 2016. 2. Davit BM, Nwakama PE, Buehler GJ, et al. Ann Pharmacother. 2009;43:1583-97. 3. Health Canada. hc-sc.gc.ca/dhp-mps/alt_formats/pdf/compli-conform/info-prod/ drugs-drogues/actingre-gui-0104-eng.pdf. Accessed Sept. 30, 2016. 4. Health Canada. hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/bio/ gd_standards_ld_normes-eng.php. Accessed Sept. 30, 2016. 5. Patten SB. Can J Psychiatry. 2016;61(9):504-505. 6. Canadian Agency for Drugs and Technologies in Health. cadth.ca/generic-drugs/ similarities-and-differences-between-brand-name-and-generic-drugs. Accessed Sept. 30, 2016. 7. Desmarais JE, Beauclair L, Margolese HC. CNS Neurosci Ther. 2011;17(6):750-760. 8. Kesselheim AS. CMAJ. 2011;183(12):1350-1351. 9. Health Canada. healthycanadians.gc.ca/drugs-products-medicaments-produits/ inspecting-monitoring-inspection-controle/inspections/about-au-sujet-eng.php. Accessed Oct. 3, 2016. 10. CBC News. cbc.ca/news/health/drug-companies-caught-faking-data-1.3620483. 11. Health Canada. hc-sc.gc.ca/dhp-mps/pubs/compli-conform/tracker-suivi-eng.php. Accessed Sept. 30, 2016. 12. Almuzaini T, Sammons H, Choonara I. BMJ Open. 2014;4(10):e006088. 13. Glauser W. canadianhealthcarenetwork.ca/physicians/your-practice/practice-tips/ how-to-navigate-no-subs-rules-36118. Accessed Sept. 30, 2016. OCTOBER 2016 • Doctor’s

Review

Trust in a name that has been available for 16 years: PrEFFEXOR® XR EFFEXOR XR (venlafaxine hydrochloride) is indicated for the symptomatic relief of:1 Major Depressive Disorder, Anxiety causing clinically significant distress in patients with Generalized Anxiety Disorder, Social Anxiety Disorder (Social Phobia), Panic Disorder, with or without agoraphobia, as defined in DSM-IV

Recommended as a first-line agent for:2-3* •

Depression

•

General Anxiety Disorder

•

Social Anxiety Disorder

•

Panic Disorder

Help your patients taking EFFEXOR XR by offering payment assistance with Pfizer Strive Payment Assistance† * See respective guidelines for complete recommendations. † Pfizer Strive Payment Assistance is available in all provinces except Quebec. Availability and coverage vary by province.

Clinical use: Depression: Short-term efficacy has been demonstrated in placebo-controlled trials of up to 12 weeks. Efficacy in maintaining an antidepressant response for up to 26 weeks, following response to 8 weeks of acute treatment, was demonstrated in a placebo-controlled trial. Generalized Anxiety Disorder: Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. The effectiveness in long-term use has been evaluated for up to six months in controlled clinical trials. Social Anxiety Disorder (Social Phobia): Efficacy was demonstrated in four 12-week, multi-centre, placebo-controlled, flexible-dose studies and one 6-month, fixed/flexible-dose study in adult outpatients. Panic Disorder: Efficacy was established in two 12-week, placebo-controlled trials in adult outpatients. The efficacy in prolonging time to relapse for up to six months, in responders of a 12-week acute treatment, was demonstrated in a placebo-controlled trial. The physician who elects to use EFFEXOR XR for extended periods should periodically re-evaluate the long-term usefulness of the drug. Caution should be exercised in the elderly.

• Caution in patients operating machinery or engaging in tasks requiring alertness. • Caution in patients with a history of myocardial infarction or unstable heart disease. • Increases in heart rate may occur; caution in patients whose underlying conditions may be compromised. • Risk of QTc prolongation, Torsade de Pointes (TdP). – Caution in patients with cardiovascular disease or family history of QT prolongation, or in patients taking medicines known to increase QT interval, especially for patients with increased risk of QT prolongation. • Caution in patients with diseases or conditions that could affect hemodynamic responses or metabolism. • Risk of serum cholesterol elevations; monitor levels, especially during long-term treatment. • Potential for changes in appetite and weight. • Risk of hyponatremia and syndrome of inappropriate antidiuretic hormone (SIADH) secretion, usually in volume-depleted or dehydrated patients. • Risk of bleeding; concomitant use with NSAIDs, ASA or other drugs affecting coagulation may add to the risk; caution in patients with a history of bleeding disorder or predisposing conditions.

Not indicated for use in children under 18 years of age. Contraindications: • In combination with Monoamine Oxidase Inhibitors (MAOIs) or within two weeks of terminating treatment with MAOIs. Most serious warnings and precautions: • Risk of potential association with behavioural and emotional changes, including self-harm: – Rigorous clinical monitoring for suicidal ideation or other indicator of potential for suicidal behaviour is advised in patients of all ages. This includes monitoring for agitation-type emotional and behavioural changes. – Patients, families, and caregivers should watch for the emergence of unusual behavioural changes, depression worsening and suicidal ideation, especially during treatment initiation or change in dose/dose regimen. • Discontinuation symptoms: dosage should be tapered gradually and the patient monitored. • Bone fractures: increased risk of bone fractures have been shown with some antidepressants, including selective serotonin reuptake inhibitors/serotonin norepinephrine reuptake inhibitors (SSRIs/SNRIs). • Hepatic and renal impairment: dosage adjustments required.

• Caution in patients with a history of seizures; promptly discontinue if seizure develops. • Risk of serotonin syndrome or neuroleptic malignant syndrome (NMS). – Careful observation if concomitant treatment with other agents affecting serotonergic and/or dopaminergic neurotransmitter systems is clinically warranted. – Concomitant use with serotonin precursors is not recommended. • Can cause mydriasis which may trigger an angle-closure glaucoma attack. • Treatment-emergent insomnia and nervousness. • Mania/hypomania: caution in patients with a history or family history of bipolar disorder. • Lactating women should not nurse their infants. For more information: Please consult the Product Monograph at www.pfizer.ca/pm/en/Effexor.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.

Other relevant warnings and precautions: • Risk of allergic reaction. • Risk of hypertension, including acute severe and sustained hypertension; monitor blood pressure regularly in all patients. • Caution in the treatment of pregnant women, especially during the third trimester.

References: 1. EFFEXOR XR Product Monograph, Pfizer Canada Inc., July 2016. 2. Lam R, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical Guidelines for the management of major depressive disorder in adults. J Affec Disord 2009;117:S26-S43. 3. Swinson R, et al. Clinical Practice Guidelines Management of Anxiety Disorders.Can J Psychiatry 2006;51(suppl 2):S1-92S.

® Pfizer Inc, used under license Effexor ® Wyeth LLC., owner/ Pfizer Canada Inc., Licensee

CA0116EFX004

– Exposure late in the third trimester may result in discontinuation symptoms and complications requiring prolonged hospitalization, respiratory support and tube feeding.

M EDICINE AND T H E AR T S by

Ti lke Elki ns

Burchfield’s transcendent vision Discover a great, yet too often overlooked, 20th-century painter

Charles E. Burchfield in his studio, Gardenville, NY, 1963.

Doctor’s Review • OCTOBER 2016

clouds and illuminations of the land strike deep chords in the soul of a person newly-arrived to this earth. This ability to feel into the emotions of a place, as we do the fleeting expressions on the faces of our early caregivers, is what sensitizes us to that place, and binds us to it at our very core. Here are the seeds of a relationship so inherent to our cominginto-being, and so powerful, that if we leave the place where we grew up, are we destined to carry its absence as an impression of longing for the rest of our lives, whether we know it or not? American painter Charles Burchfield thought so. He was never far from the land that raised him. One of six children of a school teacher and a tailor, he fell deeply in love with the woods and fields around his rural hometown, Salem, Ohio. At age 14, he suffered from exhaustion after a manic episode during which he attempted to draw all the flowering plants and fruit trees he could find close to home. By age 25, his love affair with the land was fullblown. After a brief two-month stint in New York City, he took to the fields day after day impassioned by streams and hillocks, creating what he called “all-day sketches” that chronicled the variances of weather and light. That year, 1917, became what he would later refer to as his “Golden Year,” a period of extreme artistic proliferation when he painted more than 200 works in a bold

CHARLES E. BURCHFIELD FOUNDATION

CHARLES E. BURCHFIELD ARCHIVES, BURCHFIELD PENNEY ART CENTER

oes the child know best how to read a landscape for its moods? Empty of factual information, the curves and hollows, brightness and shadows,

The Insect Chorus, 1917; watercolor with ink, graphite and crayon on paper.

style merging a nexus of influences including Fauvism and Chinese landscapes. These watercolours would be discovered by a New York art dealer 13 years later and passed on to the curator of the then new Museum of Modern Art (MOMA) who featured them in its first-ever solo show: Charles Burchfield: Early Watercolours 1916-1918. The paintings in the MOMA show presented moments pregnant with atmosphere and have titles like Yellow Afterglow, Autumnal Wind and Rain, Moon Through Young Sunflowers, Noontide in Late May and The Insect Chorus. Writing of the latter, Burchfield explains: “It is

CHARLES E. BURCHFIELD FOUNDATION

Early Spring, 1966-67; watercolor and charcoal on paper.

At age 14, Burchfield suffered from exhaustion after a manic episode during which he attempted to draw all the flowering plants he could find late Sunday afternoon in August. A child stands alone in the garden, listening to the metallic sounds of insects. They are all his world, so, to his mind, things become saturated with their presence — crickets lurk in the depths of the grass, the shadows of the trees conceal fantastic creatures, and the boy looks with fear at the black interior of the arbor, not knowing what terrible thing might be there.” Believing that memory was the vehicle through which the impressions of a place became coherent, he sought to recreate his boyhood memories in these paintings.

Burchfield knew, even as a student attending the Cleveland School of Art between 1912 and 1916, that his urgency to capture and communicate the deep bond he felt with nature was at the centre of his creative impulse — instead of, say, a passion for art in and of itself. In fact, writing felt as near vital a craft to him as painting, and he agonized over which he should pursue, feeling that each captures elements of the landscape that the other cannot. After a winter of painting indoors, he heard the first call of a red-bird and was cast into doubt: how to capture sound in painting? Which do I love more, he wrote in his journal, painting or writing?

He ended up seeking a hybrid of the two, a place where the seen and the unseen intersect, where sound and movement are conveyed through a vocabulary of radiating wavy lines that would be familiar to cartoonists as well as to admirers of painter Vincent van Gogh’s pen and ink sketches. Burchfield’s images from this time are radiant with blurgits and agitrons, the tongue-in-cheek terms that comic artists use to refer to lines indicating movement. Though there is no evidence of the influence of comics on the artist, he probably read the Sunday funnies like everyone else. He took the impulse for visual shorthand OCTOBER 2016 • 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 patients with type 2 diabetes mellitus to improve glycemic control, in combination with: • diet and exercise in patients for whom metformin is inappropriate due to contraindication or intolerance. • metformin, when diet and exercise plus maximal tolerated dose of metformin do not achieve adequate glycemic control. • metformin and a sulfonylurea, when diet and exercise plus dual therapy with metformin and a sulfonylurea do not achieve adequate glycemic control. • prandial insulin with metformin, when diet and exercise plus basal or basal-bolus insulin therapy (up to two injections of basal or basal plus prandial insulin per day) with or without oral antihyperglycemic medications, do not achieve adequate glycemic control.

CADUA00013

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

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.

For more information: Please consult the product monograph at www.lilly.ca/TrulicityPM/en for important information relating to adverse reactions, drug interactions, and dosing information which have not been discussed in this piece. The product monograph is also available by calling us at 1-888-545-5972. Reference: 1. Trulicity Product Monograph. Eli Lilly Canada Inc., November 10, 2015. †

Clinical significance has not been established.

‡

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

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

CHARLES E. BURCHFIELD FOUNDATION

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 Noontide in Late May, 1917; watercolor, gouache and graphite on paper.

a step further, recording a vocabulary of shapes that, when incorporated into a picture, would indicate moods, such as brooding, fear of loneliness and morbidity. He built these shapes into cloud forms and doorways, tree branches and mine shafts. In 1918, his pastoral rompings came to an end when he was inducted into the U.S. Army. His skills as an artist were put to use designing camouflage for artillery. To his great relief, he was honourably discharged the following January, and threw himself back into painting. This time, though, his subject matter changed. After being moved by descriptions of the quiet and often desperate lives of country folk described in Winesburg, Ohio — a short-story collection by Sherwood Anderson — he turned to what he called “the hardness of human lives,” choosing to paint dilapi-

dated row houses and brooding industrial scenes. In 1921, Burchfield married Bertha Kenreich, the daughter of a farming family, and realized he would need to make a reliable living if they hoped to raise a family. They moved to Buffalo and “Chaz,” as Bertha called him, got a job designing wallpaper at M.H. Birge & Sons. His production of paintings slowed to one or two a month if he was lucky. Over the following two decades, he slowly honed his skills as a painter, moving away from his symbolic, gestural style to a realist depiction of architecture and light, empty winter streets and luminous oil slicks. Though he continued to paint scenes of weather and nature, he gained recognition as a painter for his somber industrial images. The stark uu CONTINUED ON PAGE 54 OCTOBER 2016 • Doctor’s

Review

Maple Leaf Adventures has two hand-built vessels in their fleet: the MV Swell tugboat and the Maple Leaf schooner (pictured).

Sails

and ales A five-day culinary adventure cruise exploring the best craft breweries around BC’s Salish Sea text and photos by Cinda Chavich

t’s traditional to launch a sailing vessel with something bubbly, so starting our journey on the historic Maple Leaf schooner with a beer tasting seems fitting. It certainly sets the stage for what’s brewing

for our five days at sea, the Maple Leaf Adventures’ annual Sails and Ales tour — now called the Craft Beer and Culinary Cruise (mapleleafadventures.com; from $2654 per person) — along the coast of Vancouver Island. Not only do I have a glass of Spinnaker’s special Maple Leaf brew in hand, I have the Victoria brewery’s founder sitting next to me, describing how each of his distinctive craft beers, lined up on the mahogany and brass-fitted deck, came to be. “The beer we make for the Maple Leaf is a rye saison, barrel-aged in rye whisky barrels,” says Paul Hadfield, holding the sparkling ale up against the low angle of the afternoon sun. “We got to make this whole thing up, and changed what pubs were,” he continues, casting his mind back to 1984 when Spinnakers became the first pub in the country to brew and sell its own beer on site. “We’re now three generations in, with more than 100 craft breweries in BC and more opening all of the time.” Which is exactly why we’re here on a late fall exploration of the “wet” coast, a corner of Canada known for both its warm, rainy winters and now for the country’s largest concentration of craft brewers. Hadfield is the granddaddy of the craft-brewing

scene, but there are dozens of other brewers and unique bottles to discover. And so, like sailors of yore, we head out in search of treasure, our ports of call determined by what’s in the glass. We set sail from the pretty Sidney Marina and motor up through the sheltered side of the Strait of Georgia to coastal communities where beer has long been the tipple of choice.

The five-day trip began with a tasting led by the founder of Spinnakers, Paul Hadfield (far left), and guide and beer expert Greg Evans (far right).

OCTOBER 2016 • Doctor’s

Review

his is not a booze cruise, but rather a floating classroom for a dozen ale aficionados, a chance to learn about BC’s burgeoning world of craft brewing with tastings, food pairings and visits to out-of-the-way island enclaves of suds. Our guide to it all is beer historian and all-round beer geek Greg Evans. Evans, who is now writing the official history of brewing in BC, seems to be on a first name basis with every brewer in the province. He has an encyclopedic brain filled with tasting notes, brewing science and random beer history, gossip and lore. “Gary Lohin is one of BC’s best brewers. He got a home brewing kit at 13,” says Evans as we sip a glass of Central City’s Red Racer Pale Ale paired with a spicy crab cake, anchored next to Prevost Island for our first night at sea. “He’s a self-described hop head and he’s into antique bikes hence the name Red Racer, a hugely successful brand.” The characters and tales of this small, but burgeoning BC beer revolution overlap and intertwine, and Evans explains it all in a nonstop, running commentary as we travel between ports of call. Sean Hoyne first brewed beer at Swans in 1988, moved on to be the brewer at Canoe Brewpub and finally opened his namesake Hoyne Brewing in 2011. Matt Phillips raised the initial capital for his

Many of the dishes served onboard were infused with beer including the pecan pie, which contained Cannery Maple Stout.

Meals for all 10 travellers and crew were served at the tiny table in the galley kitchen / dining room.

successful brewing empire with a fistful of credit cards. His Blue Buck Ale is now one of the industry’s wildest success stories. There’s the pioneer brewer, William Steinberger, a German who came to Victoria in search of gold and instead struck it rich with Victoria Brewery in 1858, “the first commercial brewery west of the Great Lakes.” Then came the war, Prohibition and the rum runners who used this same cluster of remote islands and coves as drop points for sacks of illegal booze. Evans has a tale for every beer with every course for every meal: the story of Bomber Brewing’s Extra Special Bitter that’s added to the dressing for our spinach salad; the Flemish Beer Stew made with Beaver Brown Ale from Canoe Brewpub; the Swans Coconut Porter to match molten chocolate lava cakes, served alongside a yarn about the late Michael Williams, the Shropshire shepherd turned publican who renovated an old “ugly duckling” feed store into Swans hotel and brewpub more than 25 years ago, still a downtown Victoria landmark. Evans even explains the First Nations’ myths around Bigfoot — and the continuing hunt for the creature on Vancouver Island — while we dig into tender lamb marinated in award-winning Sasquatch Stout. It’s a launching point for a discussion about these dark ales, from dry Dublin-style to sweet English or cream stouts and the Imperial stouts of the Baltics. We learn the history of hops and that BC’s Fraser Valley was once “the largest area growing hops in the Commonwealth.” Evans teaches us how to sip and evaluate beer (“morning taste buds are best” and “never taste beer after coffee”), and what’s meant by the IBU number (international bitterness units) listed on labels.

or craft-brewing scholars, this is the perfect five-day immersion course, but for me, it’s about the beer and the food designed to match it, pairings created by chef James McKerricher at every meal. A memorable lunch starts with Japanese-style shrimp and egg drop soup infused with the coriander and orange flavours of Driftwood White Bark Wheat Ale. “Wheat beer is sweet and great for steaming seafood, whether it’s shrimp, mussels or crab,” explains McKerricher as he works his magic in the cramped galley kitchen below deck, where the 10 of us, both travellers and crew, squeeze around the table for every meal. Sweet onion soup starts with Riley’s Scottish Ale. Chicken is braised in Hoyne’s Dark Matter. There’s beer-infused syrup with our breakfast pancakes, Cannery Maple Stout in the pecan pie, fruity dessert beers and after-dinner wild blackberry porter to sip in the cozy wheelhouse, before we crawl into our big berths below deck, anchored in another secluded bay.

The Maple Leaf schooner is made of Douglas fir, yellow cedar and mahogany, and is 92 feet long.

All of the beer and food pairings were created by Chef James McKerricher in the shipâ&#x20AC;&#x2122;s galley kitchen.

The onboard team included beer expert Greg Evans (left), first mate Nick Sinclair (centre) and Captain Greg Shea (right).

In addition to humpback whales, travellers were treated to wildlife sightings that included sea lions.

Our journey is both extremely civilized and outdoorsy, a blend of culinary-tourism and soft adventure. We’ve barely been on deck an hour when, sailing off into the sunset, a humpback rolls deep, lifting its graceful tail, like a welcome into this west coast wilderness. The tall ship winds through the scenic Gulf Islands, through Sansum Narrows, and past Thetis and Valdes Islands, to the shores of Gabriola. We motor into a pretty cove on a tiny, uninhabited Tumbo Island and hike past an old farmstead before settling down on a grassy bank for a lunch of chili and beer in the sunshine. When the wind finally comes up, we take turns helping to hoist the main sail then zoom out in the zodiac for an up-close look at a colony of sea lions. There are whales, seals and eagles spotted daily, our adventure tied to the tides and changeable west coast weather.

Murray Hunter uses his own spring water, locally-grown hops and other island botanicals to craft beer at Salt Spring Island Ales.

The Crow and Gate Pub received BC’s first neighbourhood pub license more than 40 years ago, but it’s still a favourite with locals.

As we go ashore in Nanaimo, “the second largest brewing centre on the island,” according to Evans, a major gale blows in from the west. The Maple Leaf stays secure at the marina, bobbing in the chop, while we head off through the storm to learn more about the process of beer making with tours at Wolf Brewing and Longwood Brewpub, the latter renowned for its Belgian-style framboise, fermented with 90 kilograms of fresh raspberries in every tank. Before sailing off the next day we stop at the Crow and Gate Pub, another bit of BC publican history. Opened more than 40 years ago, it received the province’s first “neighbourhood pub” license and the rural watering hole, with its old English atmosphere, remains a favourite. After a traditional pub lunch — Stilton and leek quiche, pan-fried local oysters and Scotch eggs — we dutifully sample the selection of local brews on tap.

he Maple Leaf is the other important craft in our craft beer tour and travelling in this historic ship adds much to our adventure. Built for a wealthy Vancouver businessman in 1904, the yellow cedar and Douglas fir schooner was billed as “the most expensive pleasure craft on the Pacific Coast,” and once ferried high society guests. Converted to a halibut fishing vessel after the First World War, the ship was finally refitted in the 1980s for both tourism and the Tall Ship Program for Royal Canadian Sea Cadets learning to sail. Today, restored to its original glory by Maple Leaf Adventures’ owner Kevin Smith, the ship is a museumquality vessel, its mahogany woodwork gleaming. Our sleeping compartment has the air of an elegant

luxury train, the gentle sway and creak of the ship at anchor is reminiscent of the rhythm of rails. Tucked into a cozy berth with fluffy duvets and brass reading lamps, it’s hard to imagine this was once the ship’s hold, slithering with a cargo of freshly caught fish. Like this historic ship, BC’s beer-making history is fascinating, but it’s changing constantly, with new pubs and craft breweries popping up every year, some 130 and counting. At the tiny Salt Spring Island Ales, the final stop on our island-hopping journey, brewer Murray Hunter tells us about the beer he crafts with his own spring water, locally-grown hops and other island botanicals, like the traditional Heather Ale made with flowers from Butchart Gardens. “It tastes like home,” says Hunter, adding the ale is so popular, you need to come to the island to taste it. “We can’t even make enough to get it to Vancouver.” There’s a race to make the hoppiest beer — and apparently the craziest name and most memorable label, too. Today it’s Spinnaker’s Jolly Hopper Imperial IPA with 100 IBUs — “surrender thy taste buds” trumpets the small print — but we also try Kelp Ale (literally brewed with local seaweed) from Tofino Brewing Co. and A Wee Angry Scotch Ale from Russell Brewery with its smoky, peated malts. “People will actually walk out of the pub with an armload of these things,” says Hadfield, describing a hoppy Northwest Ale with 85 IBUs brewed by his

daughter Kala, one of the second generation of local craft brewers among the brewery’s eclectic lineup. “We’ve doubled our fermentation capacity and we still can’t keep up.” Spinnakers remains an innovator in the craft brewing business, the historic brewpub offering farm-to-table cuisine alongside 20 ever-changing taps, their own beer-infused breads, truffles and malt vinegars for sale. Spinnakers also runs a pair of city liquor stores, stocked with rare beer, wine and spirits from every corner of the island, and has entered the business of beer tourism, with its own guest houses for rent. “The drinking experience has changed dramatically,” says Hadfield. “Craft beer is tied to tourism. People travel to drink beer.” Note: While Maple Leaf Adventures continues to sail its historic Maple Leaf schooner for several itineraries along the BC coast, they now take beer lovers on their fall Craft Beer and Culinary Cruise in the newly refurbished tugboat, the MV Swell. An 80-foot former working vessel (originally built in 1912), the classic wooden tug was refitted and relaunched in 2015, offering more privacy and space for guests, with six private staterooms, each with its own ensuite “head” (bathroom with shower), two decks for wildlife spotting, and spacious lounges. With the same experts on board, Swell cruises the Gulf Island to ports from Salt Spring Island to Nanaimo to explore the world of BC craft brews.

The Pharmaceutical Advertising Advisory Board (PAAB) provides independent, third

www.paab.ca

party review of all promotional materials targeted at healthcare professionals, including prescription, biologics and non-prescription products. PAAB preclearance ensures the materials you see present evidence-based and balanced risk/benefit information. So look for the PAAB logo on promotional materials. It’s your assurance of information you can trust.

1/2 PAGE WHAT MEDICAL ADVERTISING SHOULD BE WEARING.

EVIDENCE SPEAKS FOR ITSELF.

OCTOBER 2016 • Doctor’s

Review

Gracious spa

The sunlit reception room at the Hotel FauchĂ¨re welcomes guests who are staying in one of the 16 rooms.

by Lin Stranberg

ith that long, hot summer now behind us, there’s no time like the present to get up

and get going under the bright skies and crisp, clear air of autumn. The chillier weather and friendlier off-season rates are an invitation to hit the open road for an overnighter or cozy weekend somewhere lovely. Pack a small bag, jump in the car and head for the hills — or the coast, or simply the nearest countryside. If you like your comforts — eating well, sleeping well and being surrounded by beauty (and who doesn’t?) — then the gracious spaces of the nearest Relais & Châteaux small hotel or restaurant would be a logical destination. I forget all about urban bigbox hotels and trendy hotspots whenever I check into one. Each property is different and has its own individual allure. They are the polar opposite of gimmicky or flashy. Think local flavour with a transatlantic accent. Relais & Châteaux, a global association of independently owned and operated hotels and restaurants, dates back to 1954. It was the brainchild of Marcel and Nelly Tilloy, a French music-hall couple who owned a 17th-century farmhouse hotel in the Rhône Valley. The Tilloys decided to link together eight entirely different, out-of-the-way historical properties from Paris to the Côte d’Azur. They named it La Route du Bonheur, “the road to happiness.” It was a hit with travellers, so the group of eight combined forces and began to market themselves under the Relais & Châteaux fleur-de-lis.

HOTELFAUCHERE.COM

ces

From an inn in Pennsylvania to a medieval castle in France, Relais & Châteaux properties promise character and haute cuisine

OCTOBER 2016 • Doctor’s

Review

One of the most memorable places I visited last spring (or ever, for that matter) was the glorious Château de la Chèvre d’Or (chevredor.com; from €310 a night), one of the original Route du Bonheur locations, dramatically perched on a sheer rock mountaintop in the ancient walled village of Èze in southeastern France. I had a spectacular lunch at the Michelin two-starred main restaurant, served against a magnificent view of the Mediterranean stretching to Cap Ferrat, Nice and beyond. After lunch, I strolled through a fanciful sculpture garden and past an Iron Age battlement, both part of the hotel. Seriously. It was entirely enchanting. I came away with a handsome little book that informed me that there are now more than 500 Relais & Châteaux properties all over the world, including more than a dozen in Canada and many more within driving distance of the US border. This inspired me to add a night at a Relais & Châteaux to an otherwise boring road trip from Toronto to New England last summer. The Hotel Fauchère (hotelfauchere.com; from US$245 a night), a small, historic hotel tucked into the Pocono Mountains in picturesque Milford, Pennsylvania, delivered the joie de vivre I was hankering for. What makes a Relais & Châteaux worth checking into? “At a Relais & Châteaux there’s a better chance of everything falling into place,” said Michael Gantz, executive chef at the Fauchère. “Service is key.” Rightly so. I was greeted like a friend, dined on Chef Michael’s sushi pizza (hands-down the best ever), perused the collection of Hudson River paintings in the hallways, had a long, hot shower in the Pennsylvania blue stone-and-marble bathroom, and slept like a baby. Boring-trip problem solved. Built in 1852 by Swiss-born chef Louis Fauchère, the hotel was restored a decade ago by its current owner, Sean Strub, to be as faithful as possible to the original. It is luxuriously and elegantly understated. Guests have included President Roosevelt to Iggy Pop. I had the sense I was staying somewhere noteworthy. “The hotel was the cornerstone of the town,” explained maître d’hôtel Xavier Morales. “And it still is.”

Doctor’s Review • OCTOBER 2016

HOTELFAUCHERE.COM

y stay was a classic taste of the Relais & Châteaux experience, which is about more than hospitality, style and a great kitchen. Every establishment must reflect its owner’s dedication to the art — and joy — of living, or else it’s out. The soul of the proprietor is central to a member’s status because “each property beats to the innkeeper’s heart.” The membership process is long and exacting, requiring candidates to meet hundreds of different criteria before they pass muster. Then, to make sure the membership criteria are rigorously upheld, Relais & Châteaux properties are visited regularly by one

The Barlow Suite at La Chèvre d’Or is a tribute to the American composer who visited the hilltop village of Eze regularly over 30 years.

La Chèvre d’Or in the village of Eze sits 500 metres above the Mediterranean Sea between Nice and Monaco.

PASCAL LATTES

Built in 1880, the Hotel Fauchère is housed in an Italianate-style building, which reopened in 2006 after extensive renovations.

HOTELFAUCHERE.COM

All Relais & Châteaux properties feature excellent restaurants like the Delmonico Room at the Hotel Fauchère.

T:2.125” S:1.875” Refer to the page in the bottom icon for additional safety information and a web link to the Product Monograph discussing:

A prominent Nova Scotia businessman built the Kingsbrae Arms in 1897 as a summer cottage for his family.

of the association’s inspectors on a 10-member “mystery shopper” audit team. The overarching criteria for membership are five principal attributes that differentiate properties from chain hotels. Known as the “five Cs,” they are: character, courtesy, calm, charm and cuisine. Properties must be four-stars or equivalent with no more than a hundred rooms plus a high-quality restaurant. Relais & Châteaux members have a total of more than 300 Michelin stars. Here’s a stellar sampling of Relais & Châteaux hotel/restaurant locations in Canada:

KINGSBRAE ARMS, ST. ANDREWS, NB Built in 1897, a romantic country house hotel overlooking the harbour, right next door to the famous Kingsbrae Garden. kingsbrae.com.

A stately country house hotel in a turn-of-the-century Federal Revival mansion outside Cambridge, ON. langdonhall.ca.

WICKANINNISH INN, TOFINO, BC An artistic inn on a rocky outcrop on Vancouver Island’s west coast that’s surrounded by the Pacific, the beach and the rainforest. wickinn.com. If you simply can’t get away, you can still have a very Relais & Châteaux kind of time in city hotels and restaurants. City hotels include Auberge St-Antoine (saintantoine.com) in Quebec City, Calgary’s Kensington Riverside Inn (kensingtonriversideinn.com) and Vancouver’s Wedgewood Hotel & Spa (wedgewoodhotel.com). You can also dine out at a Relais & Châteaux restaurant owned and operated by Grand Chefs in Montreal and Quebec. In Montreal, there’s Normand Laprise’s Restaurant Toqué! (restaurant-toque.com) and Jérôme Ferrer’s Restaurant Europea (europea.ca). In Quebec, try Yvan Lebrun’s Restaurant Initiale (restaurantinitiale.com).

Doctor’s Review • OCTOBER 2016

• Conditions of clinical use, adverse reactions, drug interactions, patient counselling information, dosing instructions and storage under lock and key The additional safety information page contains the reference list relating to this advertisement. *Multicentre, randomized, 8-week, double-blind, placebo-controlled, double-dummy, cross-over study in adults (N=83) with chronic low back pain of moderate or greater intensity (a score of ≥2 on a 5-point ordinal scale). At enrolment, patients were taking opioids or had not previously responded to non-opioid therapy (nonsteroidal anti-inflammatory drugs or muscle relaxants). These patients, requiring around-the-clock opioid therapy, were randomized to receive 10/5 mg TARGIN® or placebo q12h. Patients were titrated weekly according to efficacy and tolerability to 20/10, 30/15, and 40/20 mg or placebo q12h. All patients were provided with codeine/acetaminophen PRN as rescue medication. Baseline mean (±SD) VAS pain scores: 61.4±16.3 mm and 61.4±16.3 mm; and final week: 48.6±23.1 mm and 55.9±25.4 mm for TARGIN® and placebo, respectively.1,3 The studies included both subjective (i.e. drug liking VAS) and objective (i.e. pupillometry) measures. Collectively for these studies, the subjective results that were produced were supported by similar results in objective measures. Solutions contained a 2:1 ratio by weight of oxycodone HCl to naloxone HCl.1

‡

Comparative clinical significance has not been established. Naloxone is for the relief of opioid-induced constipation (OIC).

See page xxx 55 for additional safety information.

B:10”

LANGDON HALL, CAMBRIDGE, ON

• Other relevant warnings and precautions regarding use of 5/2.5 mg tablets for titration and dose adjustment; do not consume alcohol; dose reduction or change in opioid may be required in hyperalgesia; peritoneal carcinomatosis; potential diarrhea; marked withdrawal symptoms if abused; withdrawal symptoms after abrupt discontinuation; dependence/ tolerance; not approved for managing addictive disorders; use cautiously in patients receiving other CNS depressants; increased respiratory depression in patients with head injuries; use cautiously in patients with pre-existing cardiovascular conditions; psychomotor impairment; administer with caution and at reduced dosage to debilitated patients, and patients with Addison’s disease, cholelithiasis, hypotension, hypothyroidism, mild hepatic impairment, myxoedema, renal impairment, toxic psychosis, prostatic hypertrophy or urethral stricture; disposal of TARGIN®

T:10”

A turn-of-the-century manor house modelled on George Washington’s home on Mount Vernon located on scenic Lake Massawippi in the Eastern Townships. manoirhovey.com.

• The most serious warnings and precautions regarding limitations of use; addiction, abuse, and misuse; life-threatening respiratory depression; accidental exposure; neonatal opioid withdrawal syndrome; administration including must be swallowed whole; 40/20 mg tablets for opioid-tolerant patients only; use by patient only; not for patients with constipation not related to opioid use; patients currently taking oral oxycodone; conversion from other opioids/opioid preparations; maximum dosage

S:9.75”

MANOIR HOVEY, NORTH HATLEY, QC

• Contraindications in patients with known or suspected mechanical gastrointestinal obstruction or any known condition that affects bowel transit; rectal administration; suspected surgical abdomen; mild, intermittent or short duration pain that can be managed with other pain medications; management of acute pain; management of perioperative pain; acute asthma or other obstructive airway, and status asthmaticus; acute respiratory depression, elevated carbon dioxide levels in the blood, and cor pulmonale; acute alcoholism, delirium tremens, and convulsive disorders; severe CNS depression, increased cerebrospinal or intracranial pressure, and head injury; MAO inhibitor use; pregnancy, labour and delivery, breastfeeding; opioid-dependent patients and for narcotic withdrawal treatment; moderate to severe hepatic impairment

Assessing a chronic pain patient can be complex. TARGIN® offers three features: Provided reduction in pain intensity compared to placebo.1* TARGIN® provided significantly greater reductions in pain intensity compared to placebo (reduction in mean 100-mm VAS scores from baseline after 4 weeks of treatment: TARGIN® -12.8 from 61.4; placebo -5.5 from 61.4; p =0.0296)

Demonstrated safety and tolerability profile.1 The most frequently reported adverse events (>5%; % of patients, N=520) were nausea (12.3%), constipation (6.5%), hyperhidrosis (6.5%), diarrhea (6.2%), headache (6.2%), vomiting (5.4%), and fatigue (5.4%)1

Demonstrated reduced drug liking relative to oxycodone, when administered intranasally or intravenously.1†‡ Demonstrated in a series of clinical studies designed to explore the abuse/misuse potential of TARGIN® in recreational drug users †

The clinical significance of these results has not yet been established.1

The first and only analgesic that combines the efficacy of oxycodone and the benefits of oral naloxone in one tablet.1,2§¶ Adults: TARGIN® (oxycodone hydrochloride/naloxone hydrochloride) is a controlled release tablet having a dual therapeutic effect. The oxycodone component in TARGIN® is indicated for the management of pain severe enough to require daily, continuous, long-term opioid treatment, and that is opioid-responsive and for which alternative treatment options are inadequate. The naloxone component in TARGIN® is indicated for the relief of opioid-induced constipation (OIC).

The soaring triangles on the house’s exterior create a great room on the interior, which appears much larger than it really is: three cypress-clad triangles that come together to form the peaked ceiling.

Rent a

Frank Lloyd Immerse yourself in the great architect’s vision text and photos by Gerald Fitzpatrick

ven the local wildlife knows this place is special. A deer munches contentedly by the Teahouse. Suddenly a fox appears and as quickly vanishes down a garden path. As for the scampering chipmunks

on the terrace, they are oblivious to the serenity of this stunning house, tucked into a grassy knoll in the leafy woods of Ann Arbor, Michigan. A small masterpiece of American architecture, the perfection of the Palmer House was created by the coming together of an architectural genius and clients who stuck to their guns to get what they wanted. Considering the architect was Frank Lloyd Wright, who had a Donald Trump-sized ego, that was no small accomplishment. Today you can stay in this remarkable house (for a minimum of two nights) and have it all to yourselves

Doctor’s Review • OCTOBER 2016

— after the owners have given you a brief tour and departed. In Wright homes, such as Falling Water in Pennsylvania or the Robie House in Chicago, touching the furniture, let alone sitting in a Wright-designed chair, is strictly verboten. But in this house you are invited to simply make yourself at home. You can even take a nap on the couch where Wright himself slept on one of his visits in 1957. For that, the present owners must be congratulated: they have placed inordinate trust in those who find their way here. In 1950 when Billy and Mary Palmer commissioned Wright to design a house for them, the great

Wright gem man was 83 years of age and at the peak of his abilities — which were soon to diminish. Only 186 square metres in size, it is said to be one of the last projects to which he gave his full attention. The house is a variant of Wright’s “Usonian” principle: small, single storey dwellings conceived in the 1930’s Depression era, and characterized by no attics or basements, not much storage, radiant floor heating and carports (a term originally coined by Wright who said “a car is not a horse and it doesn’t need a barn”). About 60 Usonian homes were built across the US over the next decades. Many of them have deteriorated over the years, due partly to the materials used, but the brick Palmer House was built to last. The house is also one of many that Wright based on the hexagon or equilateral triangle with absolute consistency: there is scarcely a 90-degree angle in the whole place.

Although rude and overbearing to many of his clients, Wright formed a close friendship with the Palmers, especially Mary whom he took to calling “Sister.” The architect usually resisted changes to his designs but his rapport with the Palmers even led him to agree to reorient the entire house so that the terrace led to the gently sloping lawn. In December 1952 they moved in and the house remained in the family for 57 years until March 2009 when it was purchased by the present owners, Jeffrey and Kathryn Schox. Jeffrey’s parents, Sue and Gary Cox, manage the property. “When we took possession,” said Sue Cox, “the house was a little tired but still well maintained, apart from the garden which needed a lot of work.” The house was essentially as Mary had left it, including her books and other personal items. OCTOBER 2016 • Doctor’s

Review

The house seems to emerge from a knoll, which slopes dramatically up to the roofline of the bedroom wing and a partly subterranean study.

Browsing through the library in Billy Palmer’s study, a letter from Mary falls out of a book about Wright. And that’s what makes the experience of staying here so unique. You reach The Palmer House by a twisting, narrow dirt road that curves around a small knoll. Just before a right-angled turn, a driveway leads up to the carport and a view of the entire house. The immediate impression is how the house seems to emerge from the knoll itself, which slopes dramatically up to the roofline of the bedroom wing and Billy’s partly subterranean study. From the driveway a walled entryway leads to the spatial compression of the partly concealed entrance — a typical Wright touch. Once inside, a dog-leg turn takes you up three steps to the narrow book-lined corridor which then gives onto the bedrooms and study. That jog means the bedrooms remain quiet from the main activity of the house. Turning left from the low-ceilinged entrance gives directly into the soaring great room that is a triumph of Wright’s art.

Doctor’s Review • OCTOBER 2016

The room is one magnificent triangle after another. Three sided with the corners cut off; one by the two piers flanking the entrance to the terrace, another by the large brick fireplace and a third by the hidden entrance to the kitchen. Around it all runs an alcove with concealed lighting. The concrete floor is Wright’s favourite Cherokee-Red colour and runs throughout the entire building. The room appears much larger than it really is because of the three cypress clad triangles that come together to form the peaked ceiling. Other than Mary’s grand piano, the room retains most of its original furniture, including the slightly tippy chairs around the dining table, the hexagonal occasional tables and stools, the “origami” chairs — even Mary’s pieces of driftwood. The Palmers challenged Wright to design a home in which music would be a unifying feature and this is the room that epitomised that vision. It became the stage for the Palmer’s lives and hosted a steady stream of recitals, celebrations and community events. As the Palmer’s daughter, Mary Louise, said of her mother: “She realized her nature in the house.”

IF YOU GO

Rooms retain much of the original furniture, including the hexagonal occasional tables and stools, and the “origami” chairs. The concrete floor is Wright’s favourite Cherokee-Red colour and runs throughout the entire building.

The Palmer House (flwpalmerhouse.com; average US$361 per night, weekends US$500 per night, cleaning fee US$100; minimum two-night stay) has three bedrooms and two bathrooms, one with a shower (hexagonal, of course). Not surprisingly, there is no telephone and no TV. Other Wright homes that offer short term rentals: Louis Penfield House (penfieldhouse.com), Willoughby Hills, Ohio; Emil Bach House (emilbachhouse.com), Chicago, Illinois; Elam House (theelamhouse.com), Austin, Minnesota; Seth Peterson Cottage (sethpeterson.org), Lake Delton, Wisconsin; Duncan House (polymathpark.com), Acme, Pennsylvania.

The house is a variant of Wright’s “Usonian” principle: small, single-storey dwellings conceived in the 1930’s Depression era.

O .

ne drawback of the house for the Palmer’s two young children was that there was nowhere for them to play or leave a mess — as kids always do. But they both later realized that, unlike their friends, they grew up in a piece of art and when, on a dark winter’s night, the fireplace threw dancing shadows on the brick and cypress interior they were clearly enchanted. Waking up in the room that had been Billy and Mary’s bedroom for more than five decades is a novel experience. Just to lie back in the hexagonal bed and admire how brick, glass and wood come together to form the ceiling while looking in vain for a right angle is not something that happens to you every morning. Then notice the design of the fireplace and how the wide roof overhang narrows the height of the windows — and you’re not even out of bed yet. The house is quiet. No one else is up. Walking into the great room the early sun throws dappled patterns on the red floor and Wright’s origami chairs. Just beyond the continuous floor-to-ceiling windows the

trees seem to form an integral extension of the house. Brew a cup of coffee, sit back in one of those chairs and just let your eyes wander over the details of this sublime space. It’s still quiet. Step onto the terrace and take the path down to the Teahouse, a place for contemplation and refuge designed in 1964 by John Howe, who had supervised the building of the Palmer House for Wright. The bricks Howe used had been weathering in a large pile left over from the main building, and what’s left of them are a few steps away — still weathering. The other special time of day is just after sundown. Stand on the terrace — both Palmer children were married here — and look back at the house, maple and locust trees towering protectively over it. With its cypress-lined surfaces lighted from the inside, the house exudes a sense of warmth and calmness; an almost primeval feeling of shelter and security enhanced by the dramatic cantilevered roof. No wonder the Palmers loved this place almost as though it were a living thing. OCTOBER 2016 • Doctor’s

Review

Gnocchi with squash, kale and Parmesan.

Weeknight winners

Healthy meals in 30 minutes from one of Canada’s experts on nutrition recipes by

Rose Reisman

photos by

Mike McColl

ose Reisman admits that she was motivated to write Rush Hour Meals for a very personal reason. She has two new identical granddaughters and her

daughter recently returned to work full time. Her daughter and son-in-law are committed to eating well, but running a household with two babies can be difficult. Enter the 115 recipes in Reisman’s

Doctor’s Review • OCTOBER 2016

latest cookbook (19 and counting!), most of which can be made in just 30 minutes. Reisman is a registered nutritional consultant and an adjunct professor in the department of health at York

University in Toronto so in addition to prep and cook times, nutritional details are featured for every dish. There are dairy-free, gluten-free and vegetarian options, and also ideas to make each recipe more kid friendly. One of Reisman’s favourite recipes is the gnocchi with squash, kale and Parmesan — it’s included here along with more dishes that are just right for fall.

CAULIFLOWER WITH SUN-DRIED TOMATO AND OLIVE SALSA GLUTEN FREE

VEGETARIAN

Prep time: 10 minutes Cook time: 21 minutes

This dish is inspired by an entrée that Rose Reisman’s daughter, who is a vegetarian, once ordered at a restaurant in Las Vegas. It was so delicious that Rose developed her own version. It’s a very elegant way to serve cauliflower, and it works equally well as a first course, side dish or main course. Once you have tasted roasted cauliflower, you’ll never want to boil it again.

steaks for about 3 minutes per side, just until browned. Transfer the steaks to the prepared baking sheet and bake in the preheated oven for 15 to 20 minutes, just until fork-tender. Meanwhile, in a small bowl, combine the olives, tomatoes, garlic, olive oil, lemon juice and basil. To serve, divide the cauliflower steaks among serving plates. Top with the olive mixture and sprinkle the feta over top. Makes 8 servings. NUTRITION TIP: Cauliflower is part of the cruciferous family of vegetables, which includes broccoli and Brussels sprouts. One serving (1 cup / 250 ml) contains over 77 percent of your daily vitamin C requirement, which acts as an antioxidant.

sprinkle them with shredded mozzarella cheese. NUTRITIONAL INFORMATION PER SERVING Calories Carbohydrates Fibre Protein Fat Saturated Fat Cholesterol Sodium

(1 steak) 166 14.4 g 4.9 g 6.2 g 11 g 1.7 g 2.1 mg 380 mg

GNOCCHI WITH SQUASH, KALE AND PARMESAN VEGETARIAN

FOR KIDS: If your children are apprehensive about cauliflower, roasting it, which brings out its sweet flavour, may change their minds. If desired, you can omit the olives. You can also try serving these steaks over a bed of tomato sauce and

Prep time: 10 minutes Cook time: 18 minutes

Gnocchi, which means “dumpling” in Italian, is made from a soft potato

1 large head cauliflower ½ c. (125 ml) thinly sliced pitted black olives 6 sun-dried tomatoes, rehydrated (in boiling water), thinly sliced 2 tbsp. (30 ml) olive oil 1 tsp. (5 ml) minced garlic 1 tsp. (5 ml) fresh lemon juice 2 tbsp. (30 ml) chopped fresh basil or flat-leaf parsley leaves 1 oz. (30 g) light feta cheese, crumbled

Preheat the oven to 400°F (200°C). Line a baking sheet with foil. Remove the leaves from the cauliflower, leaving the stem end intact. Cut the entire cauliflower in half crosswise, starting from the top. Then slice each half into four ½-inch (1-cm) to ¾-inch (2-cm) steaks. You should end up with 8 pieces; some florets will separate — reserve them for another recipe. Heat a large skillet over medium heat. Lightly spray the skillet with vegetable oil and sauté the cauliflower Cauliflower steak with sun-dried tomato and olive salsa.

FOR KIDS: Try making this with either baby kale or spinach, which tend to be sweeter and slightly more tender than large kale leaves. NUTRITIONAL INFORMATION PER SERVING Calories Carbohydrates Fibre Protein Fat Saturated Fat Cholesterol Sodium

234 41 g 4.1 g 10.2 g 4.5 g 2.1 g 12 mg 625 mg

ASIAN TURKEY BURGERS AND SLAW DAIRY FREE

Prep time: 15 minutes Cook time: 10 minutes

Asian turkey burgers and slaw.

dough. It’s true comfort food. Although it’s tasty in a simple tomato sauce, it’s paired in this recipe with cubes of butternut squash, kale and two cheeses to make it a heartier — and more nutritious — dish. The vegetables and cheese keep the gnocchi moist, so no sauce is needed. If you like a more flavourful cheese than Parmesan, try Romano, Asiago or Pecorino. 1 tsp. (5 ml) vegetable oil 1 c. (250 ml) diced onion 1½ tsp. (7.5 ml) minced garlic salt and pepper 1½ c. (375 ml) diced peeled butternut squash 1 c. (250 ml) diced red bell pepper 1 lb. (500 g) premade gnocchi (about 1¾ c. / 430 ml) 8 c. (2 L) lightly packed chopped trimmed kale leaves ¾ c. (180 ml) freshly grated Parmesan cheese ¹⁄³ c. (80 ml) shredded light mozzarella cheese

Preheat the oven to 425°F (220°C). Spray a 9- x 13-inch (23- x 33-cm) cas-

Doctor’s Review • OCTOBER 2016

serole dish with vegetable oil. In a large skillet over medium heat, heat the oil. Add the onion and cook for about 3 minutes, until softened. Add the garlic, salt, pepper, squash and red pepper and cook for 5 minutes, stirring often, until the squash is tender. Transfer to a large bowl. Meanwhile, bring a pot of water to a boil. Add the gnocchi and return the water to a boil. Boil for 4 or 5 minutes, just until the gnocchi rise to the surface and are tender. Stir in the kale during last 2 minutes of cooking. Drain well. Add the cooked gnocchi and kale to the squash mixture and gently toss to combine. Sprinkle with the Parmesan and gently toss again. Transfer the gnocchi mixture to the prepared baking dish. Top with the mozzarella. Bake for 5 minutes or just until the cheese has melted. Makes 6 servings. NUTRITION TIP: Butternut squash is filled with vitamins A and C, potassium and fibre. Kale is a cancer-fighting cruciferous vegetable that contains our daily amounts of vitamins K, C and A.

Asian flavours go well with turkey. For ease, you can use a pre-packaged coleslaw mix, or make your own by grating a selection of your favourite vegetables — try white, red or green cabbage, carrots and broccoli. This dish is quite satisfying without the bun, but it’s also delicious served on a whole-grain roll with sliced tomato and an extra dollop of hoisin sauce. For the burgers 1 lb. (500 g) ground turkey ¼ c. (60 ml) unseasoned panko or dry breadcrumbs 3 tbsp. (45 ml) hoisin sauce 1½ tsp. (7.5 ml) minced peeled fresh ginger 1 tsp. (5 ml) minced garlic ¼ c. (60 ml) finely diced onion 2 tsp. (10 ml) reduced sodium soy sauce 1 tsp. (5 ml) Sriracha or your favourite hot sauce 1 tsp. (5 ml) sesame oil For the slaw 2½ c. (625 ml) packed coleslaw (pre-packaged or homemade) 2 tbsp. (30 ml) chopped fresh cilantro leaves 1 tbsp. (15 ml) hoisin sauce 1 tsp. (5 ml) sesame oil

1 tsp. (5 ml) minced peeled fresh ginger 1 tsp. (5 ml) Sriracha or your favourite hot sauce 1 tsp. (5 ml) toasted sesame seeds

In a bowl, combine the turkey, panko, hoisin, ginger, garlic, onion, soy sauce, Sriracha and oil. Divide the mixture into 4 equal portions and, using your hands, form into 4 patties. Preheat a grill or heat a skillet to medium-high. If using a skillet, lightly spray with vegetable oil. Cook the burgers for about 5 minutes per side or until cooked through and temperature reaches 165°F (74°C) on a cooking thermometer. In a large bowl, toss together the coleslaw, cilantro, hoisin, oil, ginger, Sriracha and sesame seeds. To serve, divide the burgers among the serving plates. Top each burger with slaw. Makes 4 servings. NUTRITION TIP: Turkey is an excellent source of lean protein and contains the amino acid tryptophan, a building block of the brain compound serotonin, which induces better sleep and calmness. Plus, 4 ounces (120 g) of ground turkey contains only 163 calories, 8 grams of fat and 2 grams of saturated fat. Compare that with the same amount of ground beef, which contains 250 calories, 17 grams of fat and 7 grams of saturated fat. FOR KIDS: Turn this burger into mini sliders for kids. Turkey contains vitamin B12, important for a child’s brain function. If they don’t like a store-bought slaw, simply serve this with some grated carrots. Omit the Sriracha.

advertisers index ALLERGAN Constella.................................................. 16 ASTELLAS PHARMA CANADA INC. Myrbetriq............................................... 2, 3 ASTRAZENECA CANADA INC. Alvesco......................................................6 BOEHRINGER INGELHEIM (CANADA) LTD Corporate..............................................IFC Trajenta...............................................OBC ELI LILLY Trulicity............................................. 32, 33 GLAXOSMITHKLINE Breo Ellipta......................................56, IBC Flonase......................................................8 LUNDBECK Trintellix................................................ 4, 9 Trisenox............................................ 22, 23 PFIZER CANADA INC. CV Portfolio............................................ 25 Effexor............................................... 28, 29 Pristiq...................................................... 26 PURDUE PHARMA Analgesic Portfolio.............................. 5, 18 OxyNeo.....................................................7 Targin................................................ 44, 45 SEA COURSES INC. Corporate................................................ 13 SERVIER CANADA INC. Viacoram........................................... 14, 15 XLEAR INC. Xlear nasal spray...................................... 21

FAIR BALANCE INFORMATION Targin...................................................... 55 Trintellix.................................................. 53 Trulicity................................................... 33

NUTRITIONAL INFORMATION PER SERVING Calories Carbohydrates Fibre Protein Fat Saturated Fat Cholesterol Sodium

262 15.6 g 2g 24.1 g 11.7 g 2.6 g 75 mg 467 mg

Recipes and photos from Rush Hour Meals: Recipes for the Entire Family (Whitecap Books, 2016).

MEDICAL QUIPS Alternate medical definitions Fibula: A small lie. Morbid: A higher offer. Post-Operative: Letter carrier.

Indications & clinical use TRISENOX (arsenic trioxide) is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL), which is refractory to or has relapsed from retinoid and anthracycline therapy, and whose APL is characterized by the presence of the t(15;17) translocation or promyelocytic leukemia-retinoicacid-receptor alpha (PML-RARa) gene expression. The indication is based on complete response rate. The duration of remission has not been determined. The response rate of other acute myelogenous leukemia subtypes has not been examined. There is limited clinical data on use in geriatric patients. Caution is needed in these patients. Safety and effectiveness in patients l 5 years of age have not been studied. There is limited clinical data on use in patients L 5 and l 18 years of age. Caution is advised in pediatric patients, who should be closely monitored for toxicities due to expected higher exposure to TRISENOX than in adults. Dosage adjustments are necessary when administering in obese pediatric patients. Contraindications • Pregnancy and nursing mothers. Most serious warnings and precautions • APL Differentiation Syndrome: Can be fatal. At first signs or symptoms, high-dose steroids (dexamethasone 10 mg intravenously BID) should be immediately initiated. • Acute Cardiac Toxicities (Rhythm Disturbance): Can cause potentially fatal QT prolongation and complete atrioventricular block. Patients with syncope, rapid or irregular heartbeat should be hospitalized for monitoring. Serum electrolytes should be assessed and treatment interrupted. Special electrocardiogram and electrolyte monitoring is required. • Concomitant drug use: Avoid use of drugs that prolong the QT interval or disrupt electrolyte levels. Other relevant warnings and precautions • Tumor lysis syndrome • Carcinogenesis of arsenic trioxide • Increased heart rate • Hyperleukocytosis • Elevated transaminases • Peripheral neuropathy • Fertility, embryotoxicity and teratogenicity • Presence of arsenic in semen (use condom during treatment and for 3 months after stopping treatment) • Patients with renal or hepatic impairment • Monitoring of electrocardiograms, laboratory parameters (potassium, calcium, magnesium, glucose, hematologic, hepatic, renal, coagulation), serious arsenic toxicity in the obese, and for hypoxia and development of pulmonary infiltrates and pleural effusion in all patients. For more information Please consult the Product Monograph at http://www. lundbeck.com/upload/ca/en/files/pdf/pm/Trisenox.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 514-844-8515 or 1-800-586-2325. † Based on results from two open-label, single-arm trials, one multicentre (n=40) and one single-centre (n=12). Trisenox dose: multicentre trial: 0.15 mg/kg daily; single-centre trial: 5, 10, or 15 mg or 0.15 mg/kg daily (median dose of 0.16 mg/kg/day; the recommended daily dose is 0.15 mg/kg). Treatment continued until CR or for a maximum of 60 days for induction and 25 days for consolidation.

lundbeck.com/ca OCTOBER 2016 • Doctor’s

Review

Burchfield’s images are radiant with blurgits and agitrons, the tongue-in-cheek terms that refer to lines indicating movement MEDICINE AND THE ARTS images, executed in watercolor, as the world careened towards the Great Depression, became a source of income for the family when magazines like Fortune commissioned a series of the dreary depictions. He earned a reputation as a Regionalist, which for an artist who was essentially his own movement, was somewhat of a dowdy category. An epiphany came in 1943, when Burchfield realized he had gained enough stature as an artist that he could abandon industrial subject matter and return to the ecstatic fodder of his Golden Year. For Burchfield, the change was not as dramatic as it was for the general public, who had just gotten used to the idea of Burchfield as a competent though perhaps somewhat dull painter of train tracks and mine shafts. Burchfield had nourished his relationship with the land consistently, especially since 1925 when he and his family of five moved from Buffalo to the adjacent suburb of West Seneca spending the rest of his life in the rural neighborhood of Gardenville. He returned to some of the 1917 pieces, enlarging them by meticulously gluing strips of watercolor paper around the edges and elaborating on the images. These are considered by many to be among his best works, the gift of a rare occurrence: experimenta-

MEDICAL QUIPS Alternate medical definitions Artery: The study of paintings. Caesarean Section: A neighbourhood in Rome. Cauterize: Made eye contact with her.

Doctor’s Review • OCTOBER 2016

CHARLES E. BURCHFIELD FOUNDATION

uu CONTINUED FROM PAGE 33

Black Iron, 1935; watercolor on paper.

tion and dramatic artistic development later in life. The merging of his symbolic vocabulary from youth with all the subtleties of painterly form and technique that he refined throughout his lifetime resulted in images that are paradoxically seen as both realistic and fantastical. Heavy summer light cascades from the crowns of trees, an insect, leaf, flower and wind all seem to echo each other, as though they share an intrinsic mathematic that is felt rather than seen in the repeating structures that underlie individual difference. Burchfield’s later work is often called “visionary” — a reference to a transcendence of the physical world and a portrayal of spiritual or mystical themes. Still what Burchfield aches to convey is not a transcendence of the physical, but rather a total immersion in every sense: a divinity experienced through the senses. His amalgamation of sensory impressions through shape and line is a lush cornucopia that he invites his viewers to occupy. At age 21, he had already elucidated this desire in his journal:

“I hereby dedicate my life and soul to the study and love of nature, with the purpose to bring it before the mass of uninterested public, that they may see and become familiar with the endless number of nature’s beauties, wherein lies my greatest happiness. If I can bring only a few serious-minded people to see how vital nature is, besides being beautiful, I shall be content.” Early Spring, the painting on Burchfield’s easel when he died of a heart attack in 1967 at age 73, depicts a scene that glows with the lucent light of the season. Dandelions push up through snow and small high clouds are lit up by the reflected colour of the earth’s new leafing: the world described at its highest state of joy. In an inversion of the light-at-the-endof-the-tunnel trope, a tunnel of darkness under a grove of trees at the center of the panel describes the unknown, a hereafter which cannot possibly measure up to the majesty of the Now. Burchfield hoped to give us a portal to that joy, a reality more rich and fantastic than anything we could devise with our imaginations.

Indications And Clinical Use: Adults: TARGIN® (oxycodone hydrochloride/naloxone hydrochloride) is a controlled release tablet having a dual therapeutic effect. The oxycodone component in TARGIN® is indicated for the management of pain severe enough to require daily, continuous, long-term opioid treatment, and that is opioid-responsive and for which alternative treatment options are inadequate. The naloxone component in TARGIN® is indicated for the relief of opioid-induced constipation (OIC). TARGIN® is not indicated as an as-needed (prn) analgesic. Not recommended for use in patients <18 years of age. Select dose cautiously in elderly patients, usually starting at the low end of the dosing range. Contraindications: • Known or suspected mechanical gastrointestinal obstruction or any known condition that affects bowel transit • Rectal administration • Suspected surgical abdomen • Mild, intermittent or short duration pain that can be managed with other pain medications • Management of acute pain • Management of perioperative pain • Acute asthma or other obstructive airway, and status asthmaticus • Acute respiratory depression, elevated carbon dioxide levels in the blood, and cor pulmonale • Acute alcoholism, delirium tremens, and convulsive disorders • Severe CNS depression, increased cerebrospinal or intracranial pressure, and head injury • MAO inhibitor use • Pregnancy, labour and delivery, breast-feeding • Opioid-dependent patients and for narcotic withdrawal treatment • Moderate to severe hepatic impairment Most Serious Warnings And Precautions: Limitations of use: Should only be used in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide appropriate management of pain. Addiction, abuse, and misuse: Assess patient risk prior to prescribing; monitor all patients regularly; store TARGIN® securely. Life-threatening respiratory depression: May occur with TARGIN® use. Monitor patients for respiratory depression, especially during initiation or following dose increases. Must be swallowed whole. Cutting, breaking, crushing, chewing, or dissolving TARGIN® can lead to rapid release and absorption of a potentially fatal dose of oxycodone. Accidental exposure: Serious medical consequences, including death, may occur, especially in children. Neonatal opioid withdrawal syndrome: Can result from prolonged maternal use during pregnancy. Administration: Must be swallowed whole. Broken, chewed, dissolved, or crushed tablets could lead to rapid release and absorption of a potentially fatal dose of oxycodone. Do not administer rectally. 40/20 mg tablets: For opioid-tolerant patients only. Medication sharing: Patients for whom TARGIN® is prescribed should not give TARGIN® to anyone else. Constipation: Not for patients with constipation not related to opioid use. Patients currently taking oral oxycodone: Switch to TARGIN® based on an equivalent oxycodone dose. Conversion from other opioids/opioid preparations: Initiate at the lowest available strength, provide adequate rescue medication, with dose titration to achieve satisfactory pain relief with acceptable side effects. Maximum dosage: Single doses should not exceed 40/20 mg. Maximum daily dose is 80/40 mg. Other Relevant Warnings And Precautions: • 5/2.5 mg tablets are intended for titration and dose adjustment • Do not consume alcohol • An oxycodone dose reduction or change in opioid may be required in hyperalgesia • Use in peritoneal carcinomatosis • Potential diarrhea • Marked withdrawal symptoms if abused rectally, intravenously or intranasally • Withdrawal symptoms after abrupt discontinuation of therapy • Dependence/tolerance • Not approved for managing addictive disorders • Use cautiously in patients receiving other CNS depressants • Increased respiratory depression in patients with head injuries • Use cautiously in patients with pre-existing cardiovascular conditions • Psychomotor impairment: Advise patients that TARGIN® may impair mental and/or physical ability required for the performance of potentially hazardous tasks especially when starting TARGIN®, when dose has been adjusted, and receiving other CNS-active drugs. Patients should be advised not to drive a car or operate machinery unless they are tolerant to the effects of TARGIN® • Administer with caution and at reduced dosage to debilitated patients, and patients with Addison's disease, cholelithiasis, hypotension, hypothyroidism, mild hepatic impairment, myxoedema, renal impairment, toxic psychosis, prostatic hypertrophy or urethral stricture • Disposal and security: Unused or expired TARGIN® should never be thrown into household trash, where children and pets may find it. Return to pharmacy for proper disposal. Should be kept under lock and out of sight and reach of children and pets. Adverse Events: Adverse events often observed with other drugs with opioid-agonist activity were also seen with TARGIN®. The most frequently observed were nausea, which tends to reduce with time, as well as constipation, diarrhea, fatigue, headache and hyperhidrosis. For More Information: Please consult the Product Monograph at http://www.purdue.ca/files/2014-08-05_Targin-pm-mktg-eng.pdf for important information relating to adverse reactions, patient counselling, drug interactions, and dosing information which have not been discussed in this piece. The Product Monograph is also available by calling us at 1-800-387-5349. References: 1. TARGIN® Product Monograph, Purdue Pharma, August 2014. 2. Purdue Pharma, letter on file, September 25, 2014. 3. Cloutier C et al. Controlled-release oxycodone and naloxone in the treatment of chronic low back pain: A placebo-controlled, randomized study. Pain Res Manag. 2013;18(2):75-82.

OCTOBER 2016 • Doctor’s

Review

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

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

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

01258 01/16

AN ICS/LABA COMBINATION

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

DAY & NIGHT

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

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

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

For your adult patients with type 2 diabetes

Equipped for glycemic control. Trajenta® is indicated in adult patients with type 2 diabetes mellitus (T2DM) to improve glycemic control. • Monotherapy: In conjunction with diet and exercise in patients for whom metformin is inappropriate due to contraindications or intolerance. • Combination therapy: • With metformin when diet and exercise plus metformin alone do not provide adequate glycemic control. • With a sulfonylurea when diet and exercise plus a sulfonylurea alone do not provide adequate glycemic control. • With metformin and a sulfonylurea when diet and exercise plus metformin and a sulfonylurea do not provide adequate glycemic control. Please refer to the product monograph at www.TrajentaPM.ca for important information relating to contraindications, warnings, precautions, adverse events, drug interactions, dosing and conditions of clinical use. The product monograph is also available by calling 1-800-263-5103 ext. 84633. Jentadueto™ (linagliptin/metformin hydrochloride) is indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus when treatment with both linagliptin and metformin is appropriate, in patients inadequately controlled on metformin alone or in patients already being treated and well controlled with the free combination of linagliptin and metformin. Jentadueto™ is also indicated in combination with a sulfonylurea (i.e., triple combination therapy) as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus inadequately controlled on metformin and a sulfonylurea. Please refer to the product monograph at www.JentaduetoPM.ca for contraindications, warnings, precautions, adverse reactions, drug interactions, dosing and conditions of clinical use. The product monograph is also available by calling 1-800-263-5103 ext. 84633.

Trajenta® is a registered trademark used under license by Boehringer Ingelheim (Canada) Ltd. Jentadueto™ is a trademark used under license by Boehringer Ingelheim (Canada) Ltd.

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