September 2016 by Doctor's Review

SEPTEMBER 2016

Fun around the Fundy The power of French pharmacists Southern kitchen treats Long-life cordless drills

MEDICINE ON THE MOVE

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THIS MONTH’S

GADGET PAGE 16

Count on the proven experience of JANUMET ® The #1 dispensed FDC DPP-4 inhibitor in Canada2† Over 21.8 million prescriptions dispensed worldwide 6 years on the Canadian market

JANUMET® (sitagliptin/metformin) is indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus inadequately controlled on metformin or in patients already being treated with the combination of sitagliptin and metformin. Refer to the page in the bottom-right corner for additional safety information and for a web link to the product monograph discussing: • Contraindications regarding type 1 diabetes; metabolic acidosis; lactic acidosis; renal impairment; alcohol intake; hepatic dysfunction; cardiovascular collapse and hypoxemia; stress conditions; severe

dehydration; hypersensitivity; pregnancy and breastfeeding; radiologic studies (iodinated contrast material) and any surgical procedure. • Most serious warnings and precautions regarding lactic acidosis and excessive intake of alcohol. • Other relevant warnings and precautions regarding type 1 diabetes or diabetic ketoacidosis; patient selection and follow-up; pancreatitis, hypoglycemia; hypersensitivity reactions; congestive heart failure, hypoxic states; change in clinical status of previously controlled diabetes; loss of control of blood glucose; vitamin B12 levels; hepatic disease immunocompromised patients; peri-operative

consideration; renal disease; skin; caution in elderly patients; should not be used in patients <18 years of age; monitoring of glycemic and hematologic parameters and of renal function. • Conditions of clinical use, adverse reactions, drug interactions and dosing instructions.

FDC=fixed-dose combination; DPP-4=dipeptidyl peptidase-4. † Clinical significance is unknown.

Consider JANUMET® See additional safety information on page xx 54

The pleasures of eating well

FOTOTIP / SHUTTERSTOCK.COM

Over the summer I went to a sale to raise money for The Pumphouse, a community arts centre in Niagara-on-the-Lake, Ontario, and made a purchase that has changed my life — at least, the culinary part. For an embarrassingly low price, I purchased a cardboard box full of pastamaking equipment: rollers and cutters for almost any kind of pasta you can think of. There’s even one that produces neatly crimped ravioli ready for stuffing and folding. I’d tried my hand at making pasta years ago and remembered how delicious it was, how very unlike even the best of the dried stuff, better even than “fresh” pasta you find in coolers in most supermarkets. That very afternoon, I found an online recipe at ricardocuisine.com and by suppertime was rolling out my first dough. The ingredients are about as simple as you can get: 2½ c. (625 ml) of unbleached flour, four eggs, about a tablespoon (15 ml) of olive oil and salt. That’s it. Make a well in the flour, stir in the other ingredients with a fork and when they hold together, turn the dough out on a floured surface and knead it with your hands until it’s smooth and elastic. Let stand for half an hour then roll it out until it’s as thin as you can get it and cut it in strips. Unless you have a pasta machine, that is. Then the real fun begins. Pass the dough through the stainless-steel rollers until it’s the desired thinness and length. The thin dough will stretch out remarkably long — a couple of metres if you like. Next run it through the cutter for the width you want and you’re done. Have a pot of boiling water ready, pop it in and cook for two minutes, not a second more, for the very best pasta you’ll have ever eaten. Serve with a sauce made from local tomatoes and fresh basil, both so abundant at this time of year. It’s a meal that’s hard to beat — and kids love to help with it. For more in the same vein turn to Anita Draycott’s charming Flavours of the Veneto (page 38) where she learns a thing or two about cooking Italian-style and also about Prosecco, the Venetian wine of choice. Still hungry? How about the last of the season’s lobster? Darcy Rhyno leads us on a tour around the Bay of Fundy, Our finest bay (page 32), and dines on lobster tacos topped with caviar and candied lemon peel washed down with a glass of New Brunswick’s only appellation, Tidal Bay. Oh yes! Continuing with the food theme, should you ever find yourself dining in France and you come down with a touch of dyspepsia, don’t even think of self-diagnosing. Instead, do as the French do, look out for the nearest pharmacy where you are certain to be in good hands. To find out just how good, read Karen Burshtein’s In France, the pharmacist rules (page 47). This is Ms. Burshtein’s first appearance in the magazine. I think you’ll enjoy her light touch.

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SEPTEMBER 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.

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.

BITRJ00110 CATRJ00110

contents SEPTEMBER 2016

38 COVER: BRIAN D. LUSTER / FLICKR

features

Our finest bay

Lobster tacos and adventure trails along the Fundy fringe in Nova Scotia and New Brunswick by Darcy Rhyno

Flavours of the Veneto A culinary holiday with pasta and Prosecco at an Italian villa north of Venice by Anita Draycott

Coming in

In France, the pharmacist rules When the French feel under the weather, this is who they consult first by Karen Burshtein

The Southern table Fried okra and meatloaf with a twist from a South Carolina native and national pie champion by Francine Bryson with Ann Volkwein

October

• Palmer House: the Frank Lloyd Wright House in Ann Arbor, Michigan that you can rent by the night • Relais & Châteaux: feeling nostalgic for the gracious travel of yesteryear? Look no further, it never went away. • Botox on the Empress: Victoria, BC’s grand old dame gets a lift here and a tuck there and looks better for it — mostly • Sails and ales: the perfect fall cruise may well be around our own Salish Sea • Ancient and modern secrets and pleasures of Southern Spain

47 SEPTEMBER 2016 • Doctor’s

Review

Helping you support your patients on ALESSE.

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

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

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

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

CA0115ALS016E

Alesse makes sense

contents SEPTEMBER 2016

regulars 9

LETTERS A seeing machine and more

PRACTICAL TRAVELLER A new music museum in Calgary, a camper with a customizable interior, Star Trek celebrates 50 years and more! by Camille Chin

MEDICINE AND THE ARTS Hypergraphia: when writers just can’t stop writing by Tilke Elkins

DEPRESSION KEYPOINTS The mental illness in those with other serious medical conditions by Eva Chanda

APL THEN AND NOW Improved prospects for acute promyelocytic leukemia sufferers by Dr Francesco Lo-Coco

23 16

GADGETS

PHOTO FINISH Rare form by Dr Lourene Roode

A cordless drill and screwdriver for every home by David Elkins

TOP 25 The biggest medical meetings scheduled for the start of 2017

SEPTEMBER 2016 • Doctor’s

Review

Picture yourself in Edinburgh. Doctorâ&#x20AC;&#x2122;s Review makes planning your personal and professional travel easier.

Go to doctorsreview.com/meetings to search 2500+ top world conferences. Access code: drcme

LETTERS

EDITOR

David Elkins

MANAGING EDITOR

Camille Chin

CONTRIBUTING EDITOR

Katherine Tompkins

A seeing machine and more

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

DO IT WITH ZEST It was fun to see Sweet and Tart in your magazine. Lemon desserts are my absolute favourite and a girlfriend of mine gave me the cookbook for my birthday last year. My daughter and I made the lemon, yogurt and poppy seed cake and I’ve also made the one with caramelized plums on top. They both turned out wonderfully. It’s a fantastic little book. I look out for your recipes every month. Dr Denise Pacini Via email

Dr Rasheda Motala

READY FOR A CLOSE-UP Here are a few of the online comments we received about the Zoom Green Binoculars from Pentax [ Gadgets, July/August 2016, page 13]:

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Just the thing I need for the next safari: lightweight, instant focusing, wow.

I love the notion that the binoculars are lightweight yet don’t sacrifice clarity of vision. Dr Margaret Ibey

The 8-16x zoom gives the best of all worlds in a compact binocular. Dr Michael Golbey

Makes Swarovski’s very extravagant. Dr Tom Paton

If it gives a clear image, is not shaky and requires little adjustment, it would be great.

STYLE AND SUBSTANCE I was pleasantly surprised to read about the tattoo exhibit in Toronto [“Toronto Ink,” Practical Traveller, June 2016, page 9]. It reminded me of something I recently came across. A Facebook post written by a nurse with rainbowcoloured hair has gone viral. She said that a grocery store cashier had just berated her for her unprofessional look (she was wearing her scrubs). The nurse explained in the post that her personal style has never affected her ability to treat patients and that her hair matches her cheerful disposition. The same judgment is made of nurses and doctors with tattoos. It’s high time we stop focusing on look and instead concentrate on character. Roxanna Diza Via email

Dr Barry Lamont

Anything Hammacher endorses has to be great.

Schlemmer

We want to hear from you!

Dr Caroline Despard Send your comments and questions to:

Only 309 grams! Wow! I could fit them in my purse! Dr Gilda Bowdridge

Doctor’s Review, Letters, 400 McGill Street, 4th Floor, Montreal, QC H2Y 2G1. Or email us at editors@doctorsreview.com. SEPTEMBER 2016 • Doctor’s

Review

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. ®

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

C a mi lle C hi n

The new Studio Bell, which houses the National Music Centre (NMC), opened this summer in Calgary’s East Village. Part museum, part education centre, part concert venue, the multi-purpose facility consists of nine interlocking towers and cost $191 million to build. The Studio Bell portion features a 300-seat performance hall as well as broadcast facilities; the NMC features acoustic and electronic soundlabs, artifact conservation and restoration workshops, recording spaces (including the Rolling Stones Mobile Recording Studio) and, on the fifth floor, three Canadian music halls of fame. The Icons and Idols exhibit is also on the NMC’s top floor and includes Stompin’ Tom Connors’ wooden stompin’ boards, Corey Hart’s sunglassesat-night Ray Bans and Alanis Morissette’s harmonica. A lot of the exhibits are interactive: you can try out a guitar or drum kit or go into a studio and get a guitar-playing tutorial from a musician. Adults $18; students $14; kids three to 12 $11. studiobell.ca.

ARCHITECTURAL RENDERING COURTESY MIR

PHOTOS THIS PAGE LEBLOND STUDIO

Calgary takes centre stage

SEPTEMBER 2016 • Doctor’s

Review

Communicator from the 1966–1969 series.

Star Trek in Seattle The height of ambition British Airways i360 opened in August and it’s being described as the tallest moving observation tower in the world. (The “i” stands for intelligence, innovation and integrity, but the shape of the structure has encouraged locals to give it all kinds of nicknames.) Located on Brighton’s seafront near the West Pier, the tower’s fully-enclosed glass viewing pod reaches a height of 137 metres — the CN Tower’s observation pod sits a mere metre lower — and boasts 42-kilometre views. The climb takes 20 to 30 minutes. Conceived and designed by Marks Barfield Architects, creators of the London Eye, the glass pod is 10 times the size of a London Eye capsule and capable of carrying up to 200 passengers. The pod becomes the Nyetimber Sky Bar after 6pm. Online bookings made at least three days in advance: adults £13.50; students £11.25; kids four to 15 £6.75. britishairwaysi360.com.

Doctor’s Review • SEPTEMBER 2016

Star Trek aired its first-series episode 50 years ago on September 8, 1966. Called “The Man Trap,” the show featured a shapeshifting alien whose goal was to extract salt from human bodies. The show placed first in its 8:30pm time slot; reviewers criticized the level of violence, but praised the acting. The EMP Museum in Seattle is commemorating the event with Star Trek: Exploring New Worlds, on now through February 2017. More than 100 artifacts and props are on view, including set pieces from the original series: Captain Kirk’s command chair and the navigation console; one of only two phasers still in existence; costumes for Kirk, Spock, Uhura and McCoy. The exhibit also explores the show’s cultural impact and ethical themes: creator Gene Roddenberry used alien worlds, interspecies conflicts and sci-fi premises to make statements about war, racism and politics. Adults US$30 (US$27 online); students US$27; kids five to 17 US$21. empmuseum.org.

PAUL G. ALLEN FAMILY FOUNDATION / PHOTOS BRADY HARVEY

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

A camper that you can customize There are many reasons to want a Happier Camper. The retro-modern trailer is compact and light, can be towed by smaller cars, and fits in a single parking space and most garages. Hand built in California and made of fibreglass, it features an Adaptiv modular interior, which consists of cubes that can sleep up to five, or that can be configured to sleep four with kitchenette and dining table, or completely emptied to haul your motorcycle or watercraft. The cubes are made of weather resistant material so they can also be used outdoors for seating and even washed. The trailer has a huge rear hatch, wide entry door and big Jalousie windows. Possible add-ons include a 100-watt contoured solar panel, portable fridge/freezer, shelter and tailgate tent. Seven colours. From US$16,000 to US$24,000. Canadian distribution to come. happiercamper.com

SEPTEMBER 2016 â&#x20AC;˘ Doctorâ&#x20AC;&#x2122;s

Review

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

Fall for the Maritimes October 7 to 15 will mark the 20th edition of the Celtic Colours International Festival in Cape Breton. Artists from Scotland, Ireland, England and more have joined Cape Breton’s musicians, singers, dancers and storytellers for the annual autumn celebration in past years. Cape Breton’s music and culture was inspired by the island’s geography and the 19th-century settlers from Scotland and Ireland — and the French before them — and influenced by the Aboriginal Mi’kmaq people, and immigrants from other countries who arrived during industrialization. Communities around the island will host concerts and workshops in everything from church and fire halls to performance venues. Expect Gaelic singing, Cape Breton fiddling, bagpiping. The festival coincides with the island’s leaf peeping season for an even more scenic week. For events and tickets: celtic-colours.com.

PHOTOS COREY KATZ

Manitoba-born Loreena McKennitt was a performer in 2015; The Nordic Fiddlers Bloc on stage in 2013.

2016 World’s Top 100 Airlines 1. Emirates (5*) 2. Qatar Airways (1) 3. Singapore Airlines (2) 4. Cathay Pacific (3) 5. ANA All Nippon Airways (7) 6. Etihad Airways (6) 7. Turkish Airlines (4) 8. EVA Air (9) 9. Qantas Airways (10) 10. Lufthansa (12)

* 2015 rating

Doctor’s Review • SEPTEMBER 2016

Survey says… SORBIS / SHUTTERSTOCK.COM

Skytrax launched its first airline passenger satisfaction survey in 1999. Since then, it’s grown annually — 19.2 million entries from 104 nationalities were completed for the 2015-2016 edition. According to Skytrax, no outside sponsorship, payment or external influence is applied to any part of the survey, rather it is “independent, impartial and global.” Airlines from the Middle East and Asia dominate the world’s top 10 airlines. For more: worldairlineawards.com.

GADG ETS by

D a vid El kin s

A cordless drill that keeps on giving I’ve had a Black + Decker drill since I was 13. I remember it clearly because I still have it. It’s big and heavy with a cast metal body and a thick electrical cord. The unit came with a black steel chuck for loosening the head to change bits and a rubber band for affixing it to the cord. It’s still dangling there, always at the ready. I used it the other day when I attached a round disk sander which I used to sand just enough off the top of the bathroom door so it would close properly — company was coming and the door had warped over the summer so if you closed it tightly, you had to use your shoulder to open it again. But I digress. I used the old drill because it had more power — though I could be wrong — than the cordless, 12-volt, lithium-ion sweetheart I generally use nowadays. Still, the Black + Decker LDX112C 12V MAX Lithium Drill/Driver is the handiest, most-convenient tool I’ve ever used. It gets me through pretty much anything that needs to be done around the house, from hanging pictures to putting up curtain rods, assembling IKEA furniture — great for this one — to screwing in 2.5- x 15-cm replacement boards on the deck. It’s lightweight, feels good in the hand, and you change screwdriver and drill bits with an easy twist of the wrist. There’s even an LED light that shines on your work. And here’s the big one: it charges quickly

and holds a charge for up to 18 months. I’ve owned it for almost a year and have only had to charge it once. There are 20-volt models offered by many manufacturers, but the 12-volt LDX112C has more than enough oomph for any of the jobs I’ve run into so far. The 11 clutch settings let you adjust the

Win your choice of the driver/drill or the screwdriver by entering the Win the Gadget of the Month contest at doctorsreview.com torque to handle various bits and screw sizes with aplomb. You may think this is a guy thing — think again. The women in my circle are equally enamoured, especially my

daughter who takes great pride in her DIY abilities. On the other hand, if your main need is putting in screws, consider the WORX SD 4V Li-Ion Semi-Automatic Cordless Screwdriver. This little number comes with two nifty cartridges each loaded with six bits that easily slip in and out. No more hunting for the right bit! At only four volts, it doesn’t have the power of the B+D driver/drill, but delivers enough juice for most jobs around the house and also holds a charge for up to a year-and-a-half. Find the Black + Decker Drill/Driver at a local retailer or online from Amazon, $71.32, and the WORX Screwdriver at Canadian Tire, $49.95.

CONGRATULATIONS! The winner of the smartphone light control system is Dr Michael Bendall, an OB/GYN from Whitehorse, Yukon. 16

Doctor’s Review • SEPTEMBER 2016

Binge Eating Disorder is a cycle of

Binge. Distress. Repeat.

In a study of over 24,000 people across 14 countries, the lifetime prevalence of Binge Eating Disorder (BED) was estimated to be 1.9%, affecting about 1 in 52 adults.2* Though its exact cause is unknown, BED may have a neurobiological basis.3-6 Now recognized as a distinct disorder in the DSM-5, BED is defined as eating large amounts of food in short time periods with a perceived lack of control. During these episodes (occurring one or more times a week for 3 months), patients may eat extremely fast, to the point of physical discomfort, or with no physical hunger. They may eat alone due to shame, feel distress or self-disgust afterwards, and may hide these symptoms, even from you. BED is not associated with compensatory behaviour as in bulimia nervosa.1 Identifying and accurately diagnosing adults with BED is the first step to helping them.

Learn to recognize it. You can help. * Based on lifetime prevalence rates of BED among adults over the age of eighteen across 14 countries. Prevalence and correlates of eating disorders from nationally representative samples (or those representative of urbanized areas) via face-to-face surveys (n=24,124) were assessed using the WHO Composite International Diagnostic Interview. References: 1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013. 2. Kessler RC, et al. The prevalence and correlates of binge eating disorder in the WHO World Mental Health Surveys. Biol Psychiatry 2013;73(9):904–14. 3. Manwaring JL, et al. Discounting of various types of rewards by women with and without binge eating disorder: evidence for general rather than specific differences. Psychol Rec 2011;61(4):561-82. 4. Balodis IM, et al. Divergent neural substrates of inhibitory control in binge eating disorder relative to other manifestations of obesity. Obesity 2013;21(2):367-77. 5. Davis CA, et al. Dopamine for “wanting” and opioids for “liking”: a comparison of obese adults with and without binge eating. Obesity 2009;17(6):1220-5. 6. Wang GJ, et al. Enhanced striatal dopamine release during food stimulation in binge eating disorder. Obesity 2011;19(8):1601-8. © 2016 Shire Pharma Canada ULC. All rights reserved. CDA/NPRMCDA/NBU/16/0014 66653-05-2017-E

THE TOP 25 MEDICAL MEETINGS compiled by Camille Chin

Canada

Toronto’s Distillery District features a sculpture by Dennis Oppenheim called Still Dancing.

Banff, AB March 3-6, 2017 Canadian Digestive Diseases Week cag-acg.org/cddw/overview

25e Réunion Scientifique Annuelle de la Société Québécoise d’Hypertension Artérielle sqha.hypertension.qc.ca/congres-scientifique

Toronto, ON December 7 Challenging Cases in Opioid Use and Misuse cpd.utoronto.ca/opioidprescribing/developing-skills

December 9-10 Heart and Stroke Clinical Update 2016 heartandstroke.on.ca

Vancouver, BC March 31-April 1, 2017

KIEV.VICTOR / SHUTTERSTOCK.COM

Montreal, QC January 19-20, 2017

February 23-26, 2017 2017 Annual Meeting of the International Society for the Study of Women’s Sexual Health isswshmeeting.org

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

Beaver Creek, CO February 28-March 4, 2017

Bonita Springs, FL December 8-11

Around the world

17th Annual Winter Conference on Pediatric Emergencies symposiamedicus.org/conferences.aspx

2016 Annual Meeting of the American Academy of Addiction Psychiatry aaap.org/annual-meeting

Atlanta, GA December 2-4

Berlin, Germany November 30-December 1

Canberra, Australia February 24-27, 2017

2016 World Congress on Clinical Trials in Diabetes wctd2016.com

70th Annual Scientific Meeting of the Urological Society of Australia and New Zealand usanz2017.com

Sexual Health 2017 ubccpd.ca/course/SexualHealth2017

9th World Congress on Prevention of Diabetes and its Complications wcpd9.com

The Georgia State Capitol building in Atlanta is a National Historic Landmark.

Cape Town, South Africa February 28-March 4, 2017 31st International Papillomavirus Conference hpv2017.org

ROB HAINER / SHUTTERSTOCK.COM

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Florence, Italy March 23-26, 2017

Grand Bahama, Bahamas February 20-24, 2017 Mayo Clinic Update in Urology 2017 ce.mayo.edu/courses

Houston, TX February 22-24, 2017 International Stroke Conference 2017 professional.heart.org/professional/Education Meetings/Meetings/InternationalStrokeConference/ UCM_316901_International-Stroke-Conference.jsp

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Palm Desert, CA February 13-15, 2017

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MEDICAL QUIPS You know you’re a doctor when you’ve had to decide whether eating or going to the bathroom is more important because you don’t have time to do both.

58th Annual Meeting and Exposition of the American Society of Hematology hematology.org/annual-meeting

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“fine, fine, thanks.”

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

ZENHALE® is indicated for the treatment of asthma, in patients 12 years of age and older with reversible obstructive airway disease.1

in patients transferred from systemically active corticosteroids, risk of systemic effects of inhaled corticosteroids, risk of dose-dependent bone loss, use with another long-acting beta2-agonist, exceeding the recommended dose, small ZENHALE® is not indicated for patients whose asthma can be managed by occasional increases in QTc interval, caution with cardiovascular conditions, oropharyngeal use of a rapid-onset, short-duration, inhaled beta2-agonist, with or without inhaled candidiasis, potentially serious hypokalemia, diabetic patients, rare systemic ® corticosteroids. ZENHALE is not indicated for the relief of acute bronchospasm. eosinophilic conditions, enhanced effect of corticosteroids in patients with cirrhosis Refer to the page in the bottom-right hand icon for additional safety information and or hypothyroidism, risk of immunosuppression, immediate hypersensitivity reactions, a web link to the product monograph discussing: relief of acute asthma episodes, serious asthma-related adverse events and • Contraindications in the primary treatment of status asthmaticus or other acute exacerbations, paradoxical bronchospasm, pregnant and nursing women, risk of episodes of asthma where intensive measures are required in patients with untreated labour inhibition, and monitoring of: HPA axis function and haematological status systemic fungal, bacterial, viral or parasitic infections, active tuberculous infection periodically during long term therapy, use of short-acting inhaled bronchodilators, of the respiratory tract, or ocular herpes simplex and in patients with cardiac bone and ocular effects, height of children and adolescents tachyarrhythmias • Conditions of clinical use, adverse reactions, drug interactions and • The most serious warnings and precautions regarding the risk of asthma-related death dosing/administration instructions • Other relevant warnings and precautions regarding abrupt discontinuation, serious adverse event risk due to adrenal insufficiency and unmasking of pre-existing allergy The Product Monograph is also available by calling us at 1-800-567-2594.

Do you have patients you suspect are unsure about how to help manage their asthma? Talk to them about their treatment plan.

5 minutes post-dose on Day 1

Significant difference in serial FEV1 (0-1 h) was demonstrated for ZENHALE® vs. ADVAIR DISKUS† (FP/S-DPI)‡ (200 mL vs. 90 mL, respectively, p<0.001)

Adapted from Bernstein DI, et al. 2011.2

Consider ZENHALE® In a non-inferiority study comparing ZENHALE® 200/10 mcg and ADVAIR DISKUS† (FP/S-DPI) 250/50 mcg in patients (≥12 years) with uncontrolled persistent asthma,

ZENHALE® 100/5 (2 inhalations BID) demonstrated:2‡

• Statistically significant faster onset-of-action on Day 1 compared with ADVAIR DISKUS† (FP/S-DPI) 250/50 (1 inhalation BID) (secondary endpoint) - Least squares mean increase in FEV1 from baseline at 5 minutes post-dose on Day 1 = 200 mL vs. 90 mL, respectively, p<0.001 (baseline LS mean trough FEV1 values were 2.31 and 2.39 L in the MF/F-MDI and FP/S-DPI groups, respectively) • ZENHALE® 200/10 mcg demonstrated non-inferiority to ADVAIR DISKUS† (FP/S-DPI) 250/50 in FEV1 AUC0–12 h at Week 12 (LOCF): Mean change in FEV1 from baseline to Week 12 = 3.43 vs. 3.24 L X h, respectively (95% CI -0.40, 0.76)2

References: 1. ZENHALE® Product Monograph. Merck Canada Inc. October 21, 2014. 2. Bernstein DI, et al. Efficacy and onset of action of mometasone furoate/formoterol and fluticasone propionate/salmeterol combination treatment in subjects with persistent asthma. Allergy Asthma Clin Immunol. 2011; 7:21 LOCF = last observation carried forward. FEV1 = forced expiratory volume in 1 second. MDI = metered dose inhaler. FP/S = FLUTICASONE PROPIONATE/SALMETEROL. DPI = dry powder inhaler. MF/F = MOMETASONE FUROATE/ FORMOTEROL. ‡ This was a 12-week, multicentre, randomized, open-label, evaluator-blind, active-controlled, non-inferiority and safety study of patients 12 years of age and older with uncontrolled persistent asthma previously treated with medium-dose ICS with or without a LABA (n=722). The effects of ZENHALE® (MDI) and ADVAIR DISKUS† (FP/S-DPI) combination therapies were compared. The study was designed to assess the non-inferiority of ZENHALE® 200/10 compared with ADVAIR DISKUS† (FP/S-DPI) 250/50 in their effect on lung function as measured by the change from baseline (mean of 2 predose measurements on Day 1) to Week 12 (last observation carried forward [LOCF]) in area under the curve (AUC) in FEV1 measured serially over 0-12 hours postdose (FEV1 AUC0-12 h). As a key secondary assessment, the study was also powered to assess whether ZENHALE® was superior to ADVAIR DISKUS† (FP/S-DPI) in onset of action (ie, change from baseline in FEV1 at 5 minutes postdose on Day 1) if lung function non-inferiority was demonstrated. ZENHALE® was administered as 2 inhalations, twice daily. ADVAIR DISKUS† (FP/S-DPI) was administered as 1 inhalation, twice daily.2 †All trademarks are properties of their respective owner(s). ® MSD International Holdings GmbH. Used under license. © 2016 Merck Canada Inc. All rights reserved.

Printed in Canada

Member of Innovative Medicines Canada

See additional safety information on page 46 xx

Introducing

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

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

CODE

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

EN167

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

EN148

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

EN149

DPP-4 = Dipeptidyl peptidase-4

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

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

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

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

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

ME D I C I N E A N D T H E A R T S by

T i lk e Elk i n s

Hypergraphia: a two-sided affliction The joys and sorrows of the incurable writing disease

W Dr Alice Flaherty, author of The Midnight Disease, holds up an arm to illustrate the depth of her obsession.

Give me a condor’s quill! Give me Vesuvius’ crater for an inkstand! Friends, hold my arms! – Herman Melville, Moby Dick

I could not stop, and it sucked me away from family and friends. Sensations outside of language dried up: music became irritating discord, the visual world grew faint. – Alice W. Flaherty, The Midnight Disease:

The Drive to Write, Writer’s Block, and the Creative Brain

That’s not writing, that’s just typewriting. – Truman Capote, about the Beats

hat writer wouldn’t consider exchanging their soul for the ability to churn out page after page of brilliant prose at any time of the day or night? To be seized by inspiration so strong that not to write was impossible? Such an affliction seems like the ideal antidote to writer’s block but it is not without a dark side. Dostoyevsky, Flaubert, Stephen King, Joyce Carol Oates and other prolific writers are considered by many health experts to be not merely gifted, but also cursed with an illness. The diagnosis? Acute hypergraphia. The “incurable writing disease” was described as long ago as the first century by Roman poet Juvenal. Even before that, Hippocrates had labelled it the “sacred disease.” For Edgar Allan Poe, another of the afflicted, it was the “midnight disease.” Not until the 20th century did neurologists begin to explore the brain chemistry behind the compulsion to write. Biochemically speaking, the condition appears to arise from an abnormal interaction between the temporal lobes and frontal lobe of the brain, wherein activity in the temporal lobes is reduced, boosting activity in the frontal lobe, which regulates speech. The staunching of the writer’s inner critic results in a florid outpouring, which may or may not be pleasurable to read — not surprisingly, it depends on the quality of the writing before hypergraphia strikes. The term “hypergraphia” — not to be confused with hypergraphy, which refers to the combining of text with visual SEPTEMBER 2016 • Doctor’s

Review

Not until the 20th century did neurologists begin to explore the brain chemistry behind the compulsion to write

material — was first coined in the 1970s by behavioural neurologists Waxman and Geschwind. The team observed hypergraphia as part of a cluster of personality traits that are associated with some cases of temporal lobe epilepsy. The behaviours seen in Geschwind syndrome, as it’s known, include a deepened emotional life, sometimes described as hyper-philosophical or hyper-religious, emotional volatility which manifests as aggressive outbursts, and altered sexuality. Another trait is over-inclusiveness, the tendency to engage in extreme chatting with excessive attention paid to detail. One logical alternative to talking your loved-ones’ ears off, especially at night when everyone’s asleep, is, naturally, writing. Russian writer Dostoyevsky’s episodes of epilepsy began when he was 25. He was ruled by pronounced mood swings, compulsive gambling, and attacks of rage — all the while being deeply thoughtful and religious, often mystical. He was apparently asexual until his mid-30s, but then married twice and had extramarital affairs. Writing seemed to worsen his medical condition, but this didn’t stop him

Doctor’s Review • SEPTEMBER 2016

from churning out 19 novels and novellas as well as extensive notebooks, diaries and letters. In Notes From Underground, the unnamed main character voices Dostoyevsky’s own hypergraphic experience saying, “Again, what is my object precisely in writing? If it is not for the benefit of the public, why should I not simply recall these incidents in my own mind without putting them on paper? Quite so; but yet it is more imposing on paper… Besides, I shall perhaps obtain actual relief from writing.”

THE CATALYST OF GRIEF Indeed, many of those with hypergraphia describe the pleasure that writing gives them. Alice Flaherty, a Harvard medical school neurologist and author of The Midnight Disease: The Drive to Write, Writer’s Block, and the Creative Brain, first experienced hypergraphia after the death of her premature twin boys. She was swallowed by an ocean of grief, but 10 days after their birth, she awoke with an overwhelming desire to write and was unable to do much else for four months. The sequence repeated itself a year later, though in happier circumstances, when twin girls were born prematurely, but lived. A passionate reader and writer before the loss of the boys, her drive to write was possibly magnified and altered by her bipolar illness, but the act of writing, though abnormal in its excess, TOP: Vincent van Gogh’s creative drive spilled out in his need to write as well as paint. LEFT: Russian writer Fyodor Dostoyevsky’s hypergraphia, shown in this letter, was likely one manifestation of his epilepsy.

remained pleasurable unless she felt it blocked. “I feel joy when I’m writing well. I have my bad days, and I’m terrified of writer’s block. But in the end, the joy of finding even one good verb makes it all worthwhile,” she says. Dr Flaherty’s hypergraphia was triggered not by epilepsy, but by her depression and its ensuing mania. It seems that mood disorder-related hypergraphia may be more common than the research reflects. One blogger who is himself gripped by hypergraphia notes that contemporary psychiatrists seem disinterested in wan papers about the frenzied writing habits of their patients, while neurologists, who are more apt to study conditions like epilepsy, have shown greater interest in the subject. He points out that there are thousands of bipolar bloggers and Tweeters, many of whom incorporate the term “hypergraphia” into their blog titles, though as someone made miserable by his fits of compulsive writing, he takes umbrage at their tongue-in-cheek use of the term. Another similarly afflicted bipolar blogger sums up this frustration, writing, “I cannot see why anyone would want to have the condition. Everything else more or less ceased to exist during (the 20 days I was writing); friends and family became cardboard cutouts, chores got ignored.”

ALCOHOL AND THE CREATIVE PROCESS Statistically, there is a distinct correlation between bipolar illness and writers and poets. Is the disease part and parcel of being prolific? Perhaps not. Stephen King, author of 63 novels and nearly 200 short stories, has written in defense of prolific writers. As a child, he says he had “a thousand ideas, but only 10 fingers and one typewriter,” but this was, he thinks, a good thing. Though he struggled with alcoholism for years, and did experience depression briefly after he quit the drink, he has since written some of his best works, and his production has not slowed. Joyce Carol Oates, similarly prolific, disparages the idea that one can write “too much” and says “I assure you,

there is very little that is compulsive about my life, either in writing or otherwise. [One] is behaving normally and instinctively and healthily when one is creating […]. I am disturbed that a natural human inclination would, by some Freudian turn of phrase, be considered compulsive — perhaps even pathological. To me this is a complete misreading of the human enterprise.” Aside from illness or sheer inspiration, there is another way to invite the symptoms of hypergraphia, one that Truman Capote, the author of Breakfast at Tiffany’s and In Cold Blood may have had in mind when he referred to the writings of Jack Kerouac and his beatnik cohorts: intoxication. Kerouac famously typed On the Road onto a 37-metrelong scroll in 20 days, though it was hardly a sponAuthor Lewis Carroll was said to have had hypergraphia and taneous act — he had been often wrote in patterns as illustrated by the “The Mouse’s Tale.” preparing to write his version of the “Great American Novel” for years. Still, the compressed iments involving creativity and brain rush of words was brought on by Benstimulation at Harvard, is riveted by the zedrine, his drug of choice, and endless paradox of examining a phenomenon cups of coffee, cigarettes and bowls of as elusive and esteemed as creativity. pea soup supplied by his wife. She writes, “My belief that I write because Robert Louis Stevenson, author of I love to is not inconsistent with my belief Treasure Island and other classics, was a that I do it because my brain is in a parlifelong invalid whose sad state of ticular state. […] I went into science health inspired one doctor to prescribe because I thought it would help me solve cocaine for his afflictions. In a fit of the mind-body problem. Instead, it seems coke-fuelled inspiration, he wrote nonto have made me unable to forget it.” stop for three days, then asked for his wife Fanny’s opinion. When she suggested that his new work was “too allegorical,” he chucked it in the fire and began again, completing The Strange Case of Dr Jekyll and Mr Hyde just three days later. “That an invalid in my husYou know you’re a doctor when band’s condition of health should have you’re being charged twice what been able to perform the manual layour neighbour is for a brake job. bour alone of putting 60,000 words to paper in six days seems incredible,” remarked Fanny. Dr Flaherty, who, as a neurologist, continues to study the impact of exper-

MEDICAL QUIPS

SEPTEMBER 2016 • Doctor’s

Review

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

Depression and medical Negotiate the mean streets of comorbidities comorbidity for better outcomes

M .

edical comorbidity is common in patients with depression, and mounting evidence shows it’s a complex two-way relationship. Depression is a risk factor for onset, progression and worse outcomes of numerous medical conditions, including cardiovascular disease (CVD), stroke, type 2 diabetes, epilepsy and cancer. Medical illness, in turn, increases the risk of developing depression, through both biologic and psychosocial factors, and worsens prognosis. In addition, depression and chronic illness may have shared vulnerabilities, such as childhood adversity, stressful life experiences, isolation and genetic predispositions. Last but not least, comorbidities increase the risk of drug-drug interactions.1 For clinicians, medical comorbidities can make treating depression especially challenging. This article will highlight recommendations on managing depression with several common medical comorbidities from the Canadian Network for Mood and Anxiety Treatments (CANMAT) 2012 guidelines on managing patients with mood disorders and comorbid conditions.2 Metabolic syndrome, a cluster of risk factors for CVD, diabetes and premature mortality, is characterized clinically by obesity, hypertension, dysglycemia (insulin resistance and diabetes) and dyslipidemia. Rates of metabolic syndrome range from 20% to 65% in patients with depression and other mood disorders. Patients with depression should be comprehensively assessed and regularly monitored for factors associated with metabolic syndrome, including exercise, diet, smoking, thyroid function, weight, body mass index (BMI), serum glucose and lipids, and blood pressure. For patients who are already overweight/obese, it’s important to avoid further weight gain. Lifestyle changes such as increased exercise and healthier diet are general recommendations, and consider weight gain potential when choosing an antidepressant. Mirtazapine and paroxetine often lead to gradual, persistent weight gain, while bupropion is associated with weight loss. A weight-increasing drug may be replaced with a weight-neutral or -reducing one, but don’t switch if it provides optimal depression control. If lifestyle and antidepressant changes fail, consider bariatric medicine approaches. Metformin, topiramate, modafinil and orlistat are second-line choices, while liraglutide, amantadine and nizatidine are third-line options. When treating hypertensive patients for depression, keep in mind: SSRIs are considered “blood pressure-neutral;” serotoninnoradrenergic reuptake inhibitors (SNRIs) may cause dosedependent blood pressure elevation; bupropion, mirtazapine, nefazodone and trazodone have “minimal” blood pressure impact; tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) may cause orthostatic hypotension; and MAOIs and

moclobemide increase risk of malignant hypertension when given with other monoaminergic agents or tyramine-rich foods. Weight-gain-promoting antidepressants have clinically significant effects on lipid levels related mainly to their impact on weight. Behavioural approaches are encouraged as first-line weight management. Despite the prevalence of dyslipidemia, lipid-lowering therapies have yet to be tested in populations with depression. Diabetes mellitus affects about 8% of the population, and depression seems to be more common in those with diabetes or dysglycemia. Antidepressants, especially those promoting weight gain, are known to disrupt glucose homeostasis. Overall, antidepressants have a moderate effect on depression in patients with diabetes mellitus, compared to a large effect for psychotherapy combined with diabetes self-management. Thus, behavioural interventions and antidepressants are recommended first-line, while pioglitazone may be a third-line option.3 Patients with CVD should be routinely screened for depression. SSRIs, and noradrenergic and specific serotonergic antidepressants, are beneficial in treating depression after a cardiac event, with no evidence of harm. CVD patients being treated for depression should be monitored for treatment adherence, response to therapy, and safety (both cardiovascular and mental health). For mild to moderate depression, psychotherapy such as cognitive-behavioral therapy (CBT), interpersonal therapy (IPT) or problem-solving therapy, alone or in combination with medication, appears to be beneficial.4 The CANMAT recommendations for poststroke depression (PSD) list citalopram as the first-line choice due to its safety in cardiac and elderly patients, while nortriptyline, though efficacious, has a delirium risk and safety concerns in cardiac patients that relegate it to second-line status. Third-line options include amitriptyline and trazodone, but paroxetine and fluoxetine should be avoided, due to their potent inhibition of cytochrome P450 and interactions with cardiac medications. After the guidelines were released, Health Canada issued warnings for QT prolongation for citalopram, escitalopram and mirtazapine.5–7 References 1. Ramasubbu R, Beaulieu S, Taylor VH, Schaffer A, McIntyre RS, Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force. Ann Clin Psychiatry. 2012;24(1):82-90. 2. Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force. Ann Clin Psychiatry. 2012;24(1):2-109. 3. McIntyre RS, Alsuwaidan M, Goldstein BI, et al. Ann Clin Psychiatry. 2012;24(1):69-81. 4. Ramasubbu R, Taylor VH, Samaan Z, et al. Ann Clin Psychiatry. 2012;24(1):91-109. 5. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2012/14672a-eng. php. Published 2012. Accessed August 25, 2016. 6. http://www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2012/13674aeng.php. Published 2012. Accessed August 25, 2016. 7. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/38709a-eng.php. Published 2014. Accessed August 25, 2016. SEPTEMBER 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.

APL THEN AND NOW by

Dr Francesco Lo-Coco, Tor Vergata University, Rome, Italy

Improved prospects for acute promyelocytic leukemia sufferers Only a few thousand people worldwide are diagnosed each year with a rare tumour known as acute promyelocytic leukemia (APL), a subtype of acute myelogenous leukemia (AML). However, progress in the treatment of APL, leading to dramatic improvements in patient outcomes, provides a unique paradigm in the field of oncology. Once considered one of the most malignant and rapidly fatal AML subtypes, APL has been transformed over the past 2 decades into the most frequently curable. This article provides a timeline of advances in both biologic and clinical research that have enabled more precise diagnosis and highly effective treatment (Figure 1).

Unravelling the cause of APL In 1957, the Norwegian hematologist Leif Hillestad first identified APL as a distinct, highly aggressive subset of AML. The disease was described in more detail in 1959 by Jean Bernard, who reported on a series of 20 cases observed at St. Louis Hospital in Paris. However, it was only in 1977 that the unique translocation between chromosomes 15 and 17 (t[15;17]) that characterizes APL was described by Janet Rowley in Chicago.1 Then, in 1990, the altered genes involved (15;17) were identified. These were PML, a newly identified gene named after promyelocytic leukemia, and RARA (retinoic acid receptor alpha), which fuse as a consequence of the translocation to form the PML-RARA hybrid gene. Interestingly, the empirical use of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) preceded by a few years the notion that these 2 agents actually target the RARA and PML moieties, respectively, of the hybrid protein.1 Progress in pinpointing the molecular features of APL also paved the way for more precise diagnosis at the genetic level. The gold standard for diagnosis today is reverse transcriptasepolymerase chain reaction (RT-PCR) from either bone marrow or peripheral blood (when infiltrated by high blast numbers), although fluorescence in situ hybridization (FISH) may also be used.2 White blood cell (WBC) counts are an important prognostic factor and help to determine the need for aggressive early treatment, as well as the risk of early death and relapse following initial treatment. The presence of PML/RARA fusion protein drives the disease and is predictive of favourable response to targeted treatment with ATRA and ATO.2,3

APL treatment: past, present and future The first major breakthrough in the treatment of APL came in 1973, when the disease was found to be highly sensitive to daunorubicin. Clinical trials showed some durable responses with anthracycline chemotherapy, and this approach was adopted in Italy and Spain, where specifically tailored clinical studies were designed for APL long before the advent of ATRA.4

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FIGURE 1. Timeline of advances in APL treatment

ACUTE PROMYELOCYTIC LEUKEMIA: FROM HIGHLY FATAL TO HIGHLY CURABLE

Responses with anthracycline chemotherapy Responses to ATRA (vitamin A derivative)

1988

High cure rates with ATRA + chemotherapy

1993

Improved, risk-adapted ATRA + chemotherapy combination

1957

First description

1977

Specific chromosome lesion identified

1990

Altered genes identified

1997

Responses to ATO

1973

2004-10 2006-15

Chemotherapy-free (ATO + ATRA) results

ATO=arsenic trioxide; ATRA=all-trans retinoic acid.

Chinese scientists reported in 1988 that APL was highly sensitive to ATRA, which produced terminal differentiation of leukemic cells without inducing myelosuppression.5 This finding contradicted the dogma that malignant transformation was always an irreversible condition. In 1997, a group from Shanghai reported that APL was also highly responsive to arsenic trioxide (ATO), an old remedy used for many centuries in the treatment of various conditions, including cancer.6 The efficacy of ATO as a single agent in APL was first established in patients who relapsed after ATRA + chemotherapy.7 Studies published in the early 2000s showed improved overall and relapse-free survival with ATO + ATRA in both relapsed and newly diagnosed low-risk patients.8,9 The randomized APL0406 trial found that ATO + ATRA was noninferior to ATRA + chemo therapy in low-intermediate risk patients, with higher event-free and overall survival after 2 years, less hematologic toxicity and fewer infections.10,11 In 2015, another randomized trial reported significantly better outcomes and less hematologic toxicity for ATRA + ATO vs ATRA + chemotherapy.12 A chemotherapyfree treatment regimen also reduces the risk of developing secondary malignancies.4,13

Recognizing a medical emergency APL is a rare disease with early symptoms that may be attributed to other causes, increasing the risk of delayed or missed diagnosis. Comprising just 10% to 15% of all patients with newly diagnosed AML,14 only 399 cases of APL were diagnosed in

Canada between 1993 and 2007.15 Clearly, many physicians will never see a case of APL. The most common symptoms include easy bleeding or bruising, pallor, dyspnea, fatigue, fever and infection. Compared to other AMLs, APL affects a younger patient population: the median age at diagnosis for APL is 44, versus 67 for AML. Men and women are affected in almost equal numbers.16,17 Prompt diagnosis is crucial, as APL frequently develops abruptly, and patients are at high risk of mortality from cerebral or pulmonary hemorrhage, which may occur in up to 40% of untreated patients.18 Hence, the disease has to be considered and managed as a medical emergency.2 Initiating treatment quickly is essential in a patient suspected of having APL. Patients presenting with clinical symptoms suggestive of APL should have a blood and bone marrow smear done rapidly in conjunction with coagulation tests. Meanwhile, a sample should be sent to the reference laboratory for genetic analysis to identify the PML/RARA by RT-PCR or FISH. Simultaneously, and even before results of the RT-PCR are available, aggressive supportive care should be instituted with transfusion of platelets and fresh frozen plasma (or concentrates), and treatment with ATRA should be started.2,17,19 Risk stratification is important for determining appropriate treatment and assessing the risk of relapse: patients with WBC counts ≤10x109/L are considered as low-intermediate risk for relapse, while those with WBC counts >10x109/L are considered at high risk and are generally subjected to more intensive consolidation regimens.17

lant monitoring for signs of potentially fatal differentiation syndrome (DS), which include: dyspnea, fever, weight gain, peripheral edema, hypotension, acute renal failure, congestive heart failure and, especially, pulmonary infiltrates or pleuropericardial effusion, with or without leukocytosis. At early signs of DS, high-dose dexamethasone should be used immediately; in certain situations, such as patients with WBC counts >10x109/L, steroids may be provided prophylactically.17,21,22

Current recommendations

References 1. Lo-Coco F, Cicconi L. History of acute promyelocytic leukemia: a tale of endless revolution. Mediterr J Hematol Infect Dis. 2011;3(1):1-6. 2. Sanz MA, Grimwade D, Tallman MS, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113(9):1875-1891. 3. Testa U, Lo-Coco F. Prognostic factors in acute promyelocytic leukemia: strategies to define high-risk patients. Ann Hematol. February 2016:1-8. 4. Lo-Coco F, Cicconi L, Breccia M. Current standard treatment of adult acute promyelocytic leukaemia. Br J Haematol. 2016;172(6):841-854. 5. Huang ME, Ye YC, Chen SR, et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988;72(2):567-572. 6. Shen ZX, Chen GQ, Ni JH, et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (AFL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood. 1997;89(9):3354-3360. 7. Soignet SL, Frankel SR, Douer D, et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol. 2001;19(18): 3852-3860. 8. Shen Z-X, Shi Z-Z, Fang J, et al. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2004;101(15):53289. Estey E, Garcia-Manero G, Ferrajoli A, et al. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006;107(9):3469-3473. 10. Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia. N Engl J Med. 2013;369(2):111-121. doi:10.1056/NEJMoa1300874. 11. Platzbecker U, Avvisati G, Ehninger G, et al. Improved outcome with ATRAarsenic trioxide compared to ATRA-chemotherapy in non-high risk acute promyelocytic leukemia – updated results of the Italian-German APL0406 trial on the extended final series. Blood. 2014;124:12. 12. Burnett AK, Russell NH, Hills RK, et al. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): Results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015;16(13):1295-1305. 13. Eghtedar A, Rodriguez I, Kantarjian H, et al. Incidence of secondary neoplasms in patients with acute promyelocytic leukemia treated with all-trans retinoic acid plus chemotherapy or with all-trans retinoic acid plus arsenic trioxide. Leuk Lymphoma. 2015;56(5):1342-1345.

Until recently, ATRA + chemotherapy was the standard firstline therapy for APL, and it is still widely used in this setting.20 However, a chemotherapy-free approach has become the current standard of care for induction therapy in untreated low- to intermediate-risk APL patients.6,20 The U.S. National Comprehensive Cancer Network (NCCN) 2016 guidelines endorse the following options for newly diagnosed low-, intermediate- and high-risk patients: ATRA + ATO (+ idarubicin for high-risk patients); ATRA + daunorubicin + cytarabine; or ATRA + idarubicin.17 The panel advises using patient risk group, age and cardiovascular risk to guide regimen selection, and following the chosen trial protocol consistently for both induction and consolidation. NCCN notes that all 3 combinations “will yield excellent results,” but lists ATRA + ATO as the first choice based on the APL0406 study results.17 Canadian consensus guidelines released in 2014 recommend ATRA + ATO for both induction and consolidation in untreated low- to intermediate-risk APL patients and, for high-risk patients, induction with ATRA + ATO + idarubicin, followed by consolidation with ATRA + ATO.19 ATO has been approved for induction of remission and consolidation in patients with APL that 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 PML-RARA gene expression. Screening for cardiac arrhythmias is essential, along with monitoring for hemorrhage, liver function alterations and QTc prolongation.21 Patients on ATRA or ATO need to be managed with vigi-

Real-world outcomes Survival in APL has improved dramatically over the years: 5-year relative survival was only 18% in the 1975–1990 period, compared to 64% in 2000–2008.23 The early death rate (≤30 days after diagnosis) is low for patients enrolled in clinical trials (5%–10%) but remains high in the “real world” (17%–29% in registry studies).19 Older patients have still-poorer outcomes: population-based studies in Canada have shown an early death rate of 10.6% among <50-year-olds, but a significantly higher 35.5% in patients ≥50.15

Continuing challenges Despite impressive progress, APL still represents a challenging disease, with many patients dying early of severe hemorrhage. It is likely that misdiagnosis, late recognition and delayed referral to secondary/tertiary care centres contribute to this situation. In addition to educational efforts, further laboratory and clinical investigation is needed to predict and prevent severe hemorrhagic and thrombotic events.

REFERENCES CONTINUED ON PAGE 55 SEPTEMBER 2016 • Doctor’s

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Our ‘‘ Powerful Fundy tides have led to the creation of numerous sea caves as well as the famous Flowerpot Rocks.

I’m going to fall.

finest bay Frolics along Fundy’s famous fringe text and photos by Darcy Rhyno

I’ve never done this before and I’m going to die. This is what I want to shout down from my precarious perch to Alex Reid, the experienced rock climber and guide with Maritime DayTripping (daytrippingnb. com) in Saint John, New Brunswick. Instead, I muster a little dignity and yell, “I can’t go any further. What do I do?” “There’s a foothold just to your left,” Alex calmly calls back. My fingertips grip a harelip of rock exactly an arm’s length over my head. The edge of my right foot has just enough purchase on a tiny ledge in the 554-million-year-old exposed lava rock face beneath me here in Rockwood Park as I swing my left foot wildly in an attempt to catch a sizeable and safe shelf of stone that seems hopelessly out of reach. All week, I’ve been adventuring along the shores of the Bay of Fundy between Nova Scotia and New Brunswick. This place is like a playground for adults. At the start of the Fundy loop on Digby Neck, Nova Scotia — a thin peninsula and islands that runs parallel with the Fundy — and at the end in the old resort town of St. Andrews by-the-Sea in New Brunswick near the border with Maine, the whale watching is world class. As is the seafood. Digby is the self-proclaimed scallop capital of the world and Saint Andrews boasts far more than the usual mix of excellent restaurants for a small town, including the classy Algonquin Resort (algonquinresort. com) and the highly creative Rossmount Inn

’’

(rossmountinn.com). The latter is where chef Chris Aerni prepared a deliciously moist cut of halibut, which he served on a bed of goose grass he foraged himself from the Fundy shore.

Learn to rock climb at Rockwood Park with Maritime DayTripping guide Alex Reid.

SEPTEMBER 2016 • Doctor’s

Review

The bird life in Grand Manan is plentiful and varied, attracting the likes of J.J. Audubon

he Saint Andrews area is also the jumping off point for various Fundy island adventures south of Saint John. After a spin around the Deer Island, Campobello Island loop via a couple of tiny car ferries, I hopped onto a larger ship for an overnight stay on Grand Manan Island. There, I poked around historic Swallowtail Lighthouse near the ferry terminal and explored the coastline along cliff edge walking trails. The bird life in the bay is plentiful and varied, attracting the likes of J.J. Audubon himself in 1831. To the north, between Saint John and the Nova Scotia border, no less than four internationally significant coastal features caught my fancy. Less than an hour from the port city, the nearly unknown and unique Fundy Trail Parkway (fundytrailparkway. com) offers hiking and biking trails that parallel 11 kilometres of low-speed paved road showing off wild coves, isolated beaches and dramatic cliffs. Another hour north, there are endless hiking opportunities in Fundy National Park (pc.gc.ca/eng/pn-np/ nb/fundy/index.aspx), including the multi-day 48-kilometre Fundy Circuit. If rugged isn’t your idea of a vacation, the park has a heated saltwater pool, and Headquarters Campground is within walking distance of the sweet little town of Alma where fishing boats rest on the seabed at low tide.

The enormous red stone pinnacles at Hopewell Rocks are sculpted by 16-metre tides, the highest in the world.

Doctor’s Review • SEPTEMBER 2016

But for me, two other natural wonders outshine even this magnificent national park. At Cape Enrage (capeenrage.ca) the lighthouse is perched at the edge of a rocky promontory past which the Fundy tides rip. There’s a zipline and rock climbing here for bird’s eye views of the bay, but it’s the surprising creature comforts that I’ll remember just as much. The lobster tacos at Cape House Restaurant (capeenrage.ca/en/ plan-your-trip/cape-house-restaurant-at-cape-enrage) come three to a plate and topped with caviar and candied lemon peel. The star of New Brunswick’s Fundy coast, the red stone pinnacles at Hopewell Rocks were carved by the tides into shapes that resemble flowerpots — narrow necks hold heavy heads topped with trees and plants. At high tide, kayakers paddle among them. At low tide, I walked this natural sculpture garden, marveling at the power of the Fundy. The tides in the bay rise as much as 16 metres over a 12-hour period twice a day.

n the other side of the bay in Nova Scotia, I revisited a favourite site: Port-Royal (pc.gc.ca/eng/lhn-nhs/ns/ portroyal/index.aspx), the replica of Samuel de Champlain’s 1605 settlement and a National Historic Site. Champlain and company spent two years here until the King of France, Henry IV, revoked the colony’s monopoly on the fur trade and the colonists were forced to return home. In their last winter there, Champlain established the now famous Order of Good Cheer (l’Ordre du Bon Temps) to boost morale with frequent feasts, copious wine and theatrical entertainment. Champlain stayed behind and in 1608 went on to establish the settlement at Quebec City and took the idea of the Order with him. While I was in the area I also visited the Historic Gardens (historicgardens.com) — named Canada’s Garden of the Year in 2015 — in the nearby town of Annapolis to admire its collection of some 2000 rosebushes and walk the shady garden trails along the Fundy salt marsh. Further north, two UNESCO World Heritage Sites tell very different stories of the Fundy, one cultural and one natural. At Grand-Pré (pc.gc.ca/eng/ lhn-nhs/ns/grandpre/index.aspx), I strolled the lawns and visited the interpretation centre to learn about the French-speaking Acadians who claimed rich farm land from the bay with an ingenious system of dikes still in place today and about their violent deportation by the British in 1755. Today, this is wine

Grand Manan is tied to fishing and the sea, and fish sheds and boats dot the island’s shores.

Brightly painted shops along St. Andrews by-the-Sea’s main street offer some of the best retail therapy on the Bay.

Virtually every visitor stops in at the Algonquin Resort if not to stay then at least to say they’ve been there.

The lobster tacos at Cape House Restaurant are topped with caviar and candied lemon peel.

There are over 120 kilometres of walking and hiking trails in Fundy National Park.

Help protect your patients from invasive disease caused by Neisseria meningitidis serogroup B strains (MenB). BEXSERO® is indicated for active immunization of individuals from 2 months through 17 years old against invasive disease caused by N. meningitidis serogroup B strains. As with any vaccine, BEXSERO® may not protect all vaccine recipients. BEXSERO® is not expected to provide protection against all circulating meningococcal serogroup B strains.

BEXSERO

The first and only vaccine for active immunization against meningococcal disease caused by serogroup B strains

1,2*

For more information about BEXSERO ®, please contact GSK Medical Information at 1-800-387-7374. Indications and clinical use: • Protection against invasive meningococcal BEXSERO is indicated for active immunization disease caused by serogroups other than of individuals from 2 months through 17 years serogroup B should not be assumed old against invasive disease caused by • As with any vaccine, BEXSERO may not N. meningitidis serogroup B strains. fully protect all vaccine recipients • Anxiety-related reactions, including As the expression of antigens included in vasovagal reactions (syncope), the vaccine is epidemiologically variable hyperventilation, or stress-related reactions in circulating B strains, meningococci that may occur in association with vaccination as express them at sufficient levels are predicted a psychogenic response to the to be susceptible to killing by vaccine-elicited needle injection antibodies. • Administration of BEXSERO should be Contraindications: postponed in subjects suffering from an • BEXSERO should not be administered acute severe febrile illness to individuals with hypersensitivity to • Temperature elevation may occur following this vaccine or to any ingredient in the vaccination of infants and children (less than formulation or components of the 2 years of age). Antipyretic treatment can container closure. be initiated according to local Relevant warnings and precautions: treatment guidelines • The vaccine is not expected to provide • Availability of appropriate medical treatment protection against all circulating strains of and supervision in case of an anaphylactic meningococcal serogroup B strains event following administration of the vaccine ®

• Risk of apnea in premature infants; consider respiratory monitoring for 48-72 hours • Caution in subjects with known hypersensitivity to latex • Vaccine use in kanamycin-sensitive recipients has not been established • Individuals with thrombocytopenia, hemophilia or any coagulation disorder that would contraindicate intramuscular injection • The expected immune response may not be obtained after vaccination of immunosuppressed patients

Adverse events: The most frequent (these may affect more than 1 in 10 people) local and systemic adverse reactions after vaccination with BEXSERO observed in clinical trials were: ®

Infants and children (less than 2 years of age): • local reactions – tenderness, erythema, induration, pain, swelling • systemic reactions – change in eating habits, fever ≥38 °C, irritability, unusual crying, sleepiness, vomiting, diarrhea, rash Children (aged 2 years through 10 years): • local reactions – pain, tenderness, erythema, induration, swelling • systemic reactions – change in eating habits, sleepiness, diarrhea, irritability, unusual crying, arthralgia, vomiting, headache, rash, fever ≥38 °C Adolescents and adults (11 years or older): • local reactions – pain, erythema, induration • systemic reactions – malaise, headache, muscle and joint pain, nausea, myalgia Recommended dose and dosage adjustment: Infants aged 2 months through 5 months: The recommended immunization series consists of four doses, each of 0.5 mL. The primary infant series consists of three doses, given at 2, 4 and 6 months of age, followed by a fourth dose (booster). The primary series can also be given at 2, 3 and 4 months of age, but the immune response to the NHBA antigen is lower. With both schedules, a fourth dose (booster) is required in the second year of life between 12 and 23 months of age. It is preferred this dose be given early in the second year of life, whenever possible. Unvaccinated infants aged 6 months through 11 months: The vaccination schedule consists of three doses each of 0.5 mL with an interval of at least 2 months between the first and second dose. A third dose is required in the second year of life with an interval of at least 2 months between the second and third dose. The need for further booster doses has not been established. Unvaccinated children aged 12 months through 23 months: The vaccination schedule consists of two doses, each of 0.5 mL, with an interval of at least 2 months between doses. The need for a booster dose after this vaccination schedule has not been established. Children aged 2 years through 10 years: The vaccination schedule consists of two doses, each of 0.5 mL, with an interval of at least 2 months between doses. The need for a subsequent dose after this immunization schedule has not been established. Individuals aged 11 years through 17 years: The vaccination schedule consists of two doses, each of 0.5 mL, with an interval of at least 1 month between doses. The need for a subsequent dose after this vaccination schedule has not been established. Administration: BEXSERO should be given by deep intramuscular injection, preferably in the anterolateral aspect of the thigh in infants or in the non-dominant deltoid muscle region of the upper arm in older subjects. ®

Separate injection sites must be used if more than one vaccine is administered at the same time. The vaccine must not be injected intravenously, subcutaneously or intradermally and must not be mixed with other vaccines in the same syringe. BEXSERO must not be mixed with other medicinal products. ®

For more information: Please consult the Product Monograph at myg.sk/bexseroPM 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 Medical Information at 1-800-387-7374. To report an adverse event, please call 1-800-387-7374. *Comparative clinical significance is unknown. References: 1. BEXSERO Product Monograph. December 11, 2015. 2. An Advisory Committee Statement (ACS), National Advisory Committee on Immunization (NACI). Advice for the use of the Multicomponent Meningococcal Serogroup B (4CMenB) Vaccine. April 2014. ®

country, home to the East Coast’s only appellation, the crisp, fruity Tidal Bay, named for the Fundy, which many vineyards overlook. In Joggins, near the New Brunswick border, I walked the eroded shoreline to view huge fossils of tree trunks and 200 other species dating back some 300 million years. At the Joggins Fossil Centre (jogginsfossilcliffs.net) I learned that the fossil record here is so important, Charles Darwin described it in his book On the Origin of Species.

rom Joggins, it’s a short hop onto the Trans Canada Highway to fly out of Halifax or drive west, or to the US border at Calais, Maine. Whatever starting point you choose to explore the 275-kilometre coastline around the Bay of Fundy, the loop includes a crossing of the bay between Saint John and Digby via the MV Fundy Rose (ferries.ca/fundyrose), a 774-person car ferry from which to view fishing boats, seabirds and sometimes whales and dolphins. The ferry terminal in Saint John is where I’m heading to return home to Nova Scotia — that is, right after I get down from this cliff in Rockwood Park (rockwoodpark.ca). It’s one of Canada’s largest municipal parks at 890 hectares and one of 60 smaller geo-sites inside the much larger, 2500- squarekilometre Stonehammer Geopark in southern New Brunswick. Stonehammer — this continent’s first UNESCO geopark — is where the Atlantic Ocean and the Bay of Fundy began as the earth’s tectonic plates shifted. Instead of rock climbing, I could have chosen another of the many challenging Stonehammer activities like ziplining over the famous reversing rapids where the Saint John River meets the mighty tides of the bay causing the water flow to reverse twice daily. There’s also fossil hunting through a billion years of relatively continuous geologic history, bird and whale watching tours on the bay, geocaching, walking the ocean floor at low tide and kayaking in sea caves. “Now, plant your feet nice and wide,” Alex Reid calls from the bottom of the rock face as evenly as a parent might talk his two-year-old down a playground slide for the first time. “You gotta take some deep breaths right now. You’re nearly there. I’ve got you nice and tight down here.” And he does. A heavy rope runs from my harness to the top of the cliff back over my head down to Alex, my anchor. I take a breath and with a leap of faith reach that impossibly distant ledge. From there, it’s a quick scramble to the top. I feel elated with my accomplishment… until I remember I have to rappel back down. For more info on travel to the region, visit Bay of Fundy Tourism (bayoffundytourism.com) and Tourism New Brunswick (tourismnewbrunswick.ca).

01403 04/16

SEPTEMBER 2016 • Doctor’s

Review

COURTESY ANITA DRAYCOTT

The group made pasticcio, which involved kneading and rolling pasta as demonstrated by Vanessa (left) and the author (right).

Flavours of the I

t’s easy to be seduced by Italy’s la dolce vita. The laidback lifestyle where friends and family linger over sun-drenched meals, where the wine and conversation flow effortlessly. Haven’t we all harboured

a fantasy to take off and live in a villa? My fantasy has come true. I’m at the Susegana villa on the Borgoluce estate in the Veneto region about 50 kilometres from Venice and I’ve signed up for a stint with Flavours Holidays. A driver picked me up at the Marco Polo Airport

Doctor’s Review • SEPTEMBER 2016

and now I’m sitting on the terrace with my hostess for the week, Livia di Giovani, who pours me the first of many flutes of Prosecco to come. The orderly vines in the distance of this bucolic rolling countryside remind me that we are in the heart of Prosecco country. By early afternoon the rest of our small group

When the group’s chef and instructor had the night off, they dined at the Borgoluce Estate’s on-site osteria.

The osteria has three dining rooms as well as an outdoor terrace.

The 1200-hectare estate consists of woodlands, pastures, vineyards and grain fields.

Veneto arrives. We have David, Vanessa and Gloria from different parts of England; Corné from Cape Town, South Africa; Rob and Mary who live near Toulouse, France. Lorne Blyth, Flavours’ director and founder, has dropped by as part of her whirlwind trip through Italy to visit other venues in Tuscany and Puglia. Borgoluce is an agro-tourism estate that consists of 1200 hectares of woodlands, pastures, vineyards and grain fields in the province of Treviso. For a few weeks in spring and autumn, Flavours rents its Susegana villa for cooking holidays. Borgoluce raises its own

Learn to cook like a local during a hands-on holiday at an agro-tourism estate in the historic area of Venice by Anita Draycott buffalo, cattle and pigs. They produce buffalo milk products and charcuterie, plus wine, grains, olive oil and honey, all sold at the estate’s store. Having attended Flavours Holidays in other parts of Italy, I can vouch that this is no sterile cooking school experience. It’s more like being part of an intimate Italian house party where you’re welcome to raid the fridge for leftovers or brew a pot of tea. Now that everyone has arrived, Livia invites us into the dining room where we have more bubbles and a light lunch of Buffalo mozzarella, cold meats SEPTEMBER 2016 • Doctor’s

Review

You can buy meat, wine, olive oil, honey and more at the store.

The estate raises its own buffalo, cattle and pigs to produce cheese and charcuterie.

A daytrip to Venice included a stop at Al Merca, which serves small snack sandwiches, and wine and spritzes.

and salads. Livia explains how our week will unfold, and distributes recipes and aprons to everyone. “A Flavours holiday is not about teaching you knife skills,” she says. “We want to give you a taste of the authentic flavours of the region.” Gabriella Salvador, our chef for the week, lives on the estate and bakes all the bread sold in its store and Osteria. Her husband is the estate butcher. Gabriella doesn’t speak English so Livia, who is also a chef, does the translating. This afternoon we are welcome to take a stroll, go for a dip in the natural bio-organic pool up the hill, or perhaps have a nap. I opt for the latter, opening the windows in my large bedroom with its beamed ceiling to doze off to birdsong and the fresh country breeze. Later, the popping of corks and aromas wafting from the kitchen draw us down to dinner where Gabriella has prepared some of her family favourites: potato and pea soup, roast veal, sweet spring braised onions, fried eggplant, and a platter of just-picked cucumbers and tomatoes. Dessert is a marvelous quince tart followed by a tad too much Grappa.

Doctor’s Review • SEPTEMBER 2016

If our small convivial group has one thing in common, it’s a passion for food. We eagerly discuss favourite recipes and restaurants.

he next morning we enjoy a breakfast of homemade jams and preserves, estate yogurt, fruit and warm bread. Gabriella arrives with all the ingredients for today’s cooking lesson: pasta from scratch for vegetable pasticcio, a sort of lasagna made with zucchini and béchamel sauce. If you have never tried to knead and roll pasta, trust me it’s hard work. My square of dough is uneven and keeps shrinking, but Gabriella’s deft rolling skills save the day. Our main course is a savoury stew made with lean buffalo meat, root vegetables and a hefty splash of wine. We learn that that classic northern Italian dessert tiramisu means “pick me up.” It was created by a madam in a house of Venetian prostitutes to give her girls extra energy! Due to its proximity to both the sea and lagoons, fish is prevalent in the cuisine of the Veneto region.

ANITA DRAYCOTT

The Belmond Hotel Cipriani is on the island of Giudecca and is an oasis from the hustle and bustle of tourists.

Tiramisu means “pick me up” and it was created by a madam in a house of Venetian prostitutes to give her girls extra energy On the menu this week is a dish made with salt cod and another of sardines that are salted and soured and left to marinate a few days in the refrigerator. Risotto is another popular dish, one that Gabriella likes with fresh sweet peas. While there’s no lack of hands-on cooking experiences on a Flavours holiday, there is also ample opportunity to read, relax and explore the region. On Monday, our merry group is driven to Venice. We take a vaporetto along the Grand Canal to the famous Rialto Market where we sample spritzes at Al Merca, a cupboard-sized wine bar. The spritz cocktail that originated in Venice is made of Aperol bitters, Prosecco, a dash of mineral water and gar-

nished with a slice of orange or an olive. After a bit of shopping, Livia introduces us to cicchetti, Italian tapas on toothpicks, a cheap and cheerful way to mingle and munch with locals. We stroll through the maze of narrow streets, and up and over countless bridges (Venice has 400 of them) until we arrive at the grand Piazza San Marco that Napoleon described as the drawing room of Europe. Livia suggests we go for posh cocktails at the Belmond Hotel Cipriani (belmond.com/hotelcipriani-venice) on Giudecca Island so we hop aboard the hotel’s private launch for the five-minute cruise. Opened in 1958 by Giuseppe Cipriani, founder of Harry’s Bar in Venice and inventor of the Bellini SEPTEMBER 2016 • Doctor’s

Review

ANITA DRAYCOTT

The Malibran Winery is in Susegana, a little town amidst the hills that range from Conegliano towards Valdobbiadene.

cocktail (Prosecco with peach purée), the Cipriani is where George Clooney and his lovely bride, Amal Alamuddin, celebrated their wedding reception. Livia likes to take her guests to the Cipriani for Bellinis because the gardens and swimming pool provide an oasis in a normally bustling city. Besides, maybe there will be a Clooney sighting. When we arrive back at our villa, Gabriella has created a feast: pasta e fagioli (pasta and beans) and a turkey casserole.

n Tuesday we shop for sardines and dogfish at the fish market in Treviso. With its meandering canals, narrow cobbled streets and stunning architecture, Treviso is like a mini Venice — minus the crowds. At a local bar, we down some cappuccinos and tasty pork sandwiches before heading to the Malibran Winery (malibranvini.it) for a Prosecco lesson with our guide, Vanessa. The Veneto region is the birthplace of the glera grape used to make Prosecco. It’s a huge wine making region, but the finest Prosecco is grown in the 35-kilometre stretch between the towns of Conegliano and Valdobbiadene where the grapes are handpicked and gently processed, and the winemaking procedures rigidly certified. Only these wines carry the DOCG appellation. Prosecco from the rest of the Veneto have the DOC appellation. Now that Prosecco is so popular around the

Doctor’s Review • SEPTEMBER 2016

Unlike Champagne, Prosecco does not ferment in the bottle — it should be consumed young, preferably within three years of its vintage world, here are a few tidbits that might impress your friends: Prosecco can be spumante (sparkling), frizzante (semi-sparkling) or tranquillo (still). If the label says “dry,” the wine will be sweet. If you want a really dry wine, buy extra brut. Unlike more expensive Champagne, Prosecco does not ferment in the bottle and grows stale. It should be consumed young, preferably within three years of its vintage. Each day our group became more relaxed with each other and our animated dinner conversations carried on into the wee hours. We followed no

Help relieve her menopausal symptoms.

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

DEMONSTRATED REDUCTION OF

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

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

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

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

CA0115PRE003E

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

0.3 mg

0.625 mg

1.25 mg

regimented schedule. If we wanted to sleep late, go for a stroll and not begin cooking classes until just before noon, that was fine. One morning after indulging in a bowl of the previous night’s panacotta, Corné and I tramped up to the 13th-century Castello San Salvatore high on a hill on the Borgoluce estate and marvelled at the panoramic vistas. Another night, after considerable amounts of vino, we asked Gabriella to give us her recipe for the wonderful rabbit casserole we had just consumed with gusto. Gabriella would utter a sentence in Italian and Livia (who is fluent in English and Italian) and David (who is learning Italian) would argue about every detail. Despite considerable chaos and chuckles we managed to write out a reasonable facsimile of her recipe. There was also much dialogue about the risotto and whether arborio or carnaroli rice was superior in the traditional risi e bisi (rice and peas with pancetta). The next day, revved up by the Drinking Song from La Traviata, we gutted and de-headed sardines

This is no sterile cooking school experience; more like an intimate Italian house party where you’re welcome to raid the fridge 44

Doctor’s Review • SEPTEMBER 2016

that would be used in a classic sarde in saor, a dish of sardines, onions, raisins, pine nuts and vinegar. This dish was prepared by Venetian fishermen on their boats and solved the problem of preserving the fish for several days. During the Renaissance, folks started adding raisins and pine nuts to sweeten the breath. Another excursion took us to Conegliano, where the remains of a 10th-century castle dominates the pretty town where the Prosecco wine trail starts. After a bit of shopping, we stopped at a café for spritzes. It was Gabriella’s night off so we enjoyed a steak dinner at Osteria Borgoluce on our estate. On the morning of our last day, we head up the hill to the natural pool for a dip. Later, back in the kitchen, we labour over bigoli (thick noodles), and a sauce of salted sardines and onions. The main course is a local dogfish flavoured with little prickly cucumbers, capers and parsley. For dessert we make a sublime strawberry mousse and Livia produces some already-aged Nocino. We learn a new Italian toast: A tavola, non si invecchia mai… se si mangia tanto. “At the table you never grow old… if you eat a lot.” I swear I had not aged a day.

Flavours Holidays trips attracts people from all over the world, including Corné from Cape Town and David from Cambridge, England.

ANITA DRAYCOTT

The villa is located in the heart of Prosecco wine country so there was always a bottle or two at dinner.

COOKS IN THE KITCHEN A week at the Susegana villa with Flavours Holidays (flavoursholidays.co.uk) costs £1599 ($2765) per person and includes five cooking classes, all meals and wine, accommodation with an en-suite bathroom, tours of local towns and markets, minibus transportation and transfers to the airport. There is no single supplement. Flavours also offers cookery holidays in Tuscany, Sicily, Puglia and Amalfi Coast.

Help her treat painful intercourse.

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

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

TREATMENT OF DYSPAREUNIA, ATROPHIC VAGINITIS AND KRAUROSIS VULVAE.

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

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

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

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

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

CA0115PRE004E

INDICATION: ZENHALE® is indicated for the treatment of asthma, in patients 12 years of age and older with reversible obstructive airway disease. CLINICAL USE: ZENHALE® is not indicated for patients whose asthma can be managed by occasional use of a rapid-onset, short-duration, inhaled beta2-agonist, with or without inhaled corticosteroids. ZENHALE® is not indicated for the relief of acute bronchospasm. Contraindications: • Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required • Patients with untreated systemic fungal, bacterial, viral or parasitic infections, active tuberculous infection of the respiratory tract, or ocular herpes simplex • Patients with cardiac tachyarrhythmias Most serious warnings and precautions: Asthma-Related Death: Long-acting beta2-adrenergic agonists (LABA), such as formoterol, may increase the risk of asthma-related death. This is based on salmeterol data, and this finding with salmeterol is considered a class effect of the LABA, including formoterol. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. There are inadequate data to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. ZENHALE® should only be used for patients not adequately controlled on a longterm asthma control medication, such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and do not use ZENHALE® for patients whose asthma can be adequately controlled on low or medium dose inhaled corticosteroids.

Other relevant warnings and precautions: • Should not be stopped abruptly • Serious adverse event risk due to adrenal insufficiency and unmasking of pre-existing allergy in patients transferred from systemically active corticosteroids • Risk of systemic effects of inhaled corticosteroids o Hypercorticism, adrenal suppression, growth retardation in children/ adolescents, reduced bone mineral density, osteoporosis, fracture, cataracts, glaucoma • Risk of dose-dependent bone loss • Should not be used with another LABA • Do not exceed recommended dose • Small increase in QTc interval reported • Caution with cardiovascular conditions • Oropharyngeal candidiasis • Potentially serious hypokalemia • Diabetic patients • Rare systemic eosinophilic conditions • Enhanced effect of corticosteroids in patients with cirrhosis or hypothyroidism • Risk of immunosuppression • Immediate hypersensitivity reactions may occur • Not for rapid relief of bronchospasm or other acute episode of asthma • Serious asthma-related adverse events and exacerbations may occur; seek medical advice if symptoms remain uncontrolled or worsen • Possible paradoxical bronchospasm • No adequate studies in pregnant/nursing women • Risk of labour inhibition • Monitoring of: HPA axis function and haematological status periodically during long-term therapy, use of short-acting inhaled bronchodilators, bone and ocular effects, height of children and adolescents For more information: Please consult the Product Monograph at http://www.merck.ca/assets/en/pdf/products/Zenhale-PM_E.pdf for important information relating to adverse reactions, drug interactions, and dosing/administration information which have not been discussed in this advertisement. The Product Monograph is also available by calling us at 1-800-567-2594.

. Printed in Canada

Member of Innovative Medicines Canada

In France,

the pharmacist rules Omnipotent and self-important come to mind by Karen Burshtein

MARC LAGNEAU / FLICKR

ears ago, when I was a student in France, I had a breakout of acne, a rarity for lucky teen me. As it was unusual, I made an appointment with a dermatologist and came out of my consultation with a

SEPTEMBER 2016 • Doctor’s

Review

prescription as thick as any senior thesis. I took it to the closest pharmacist who didn’t blink an eye. Any time you sniffle in France your friends and neighbours (all amateur diagnosticians), will quickly recommend all number of pills and sirops, any one of which is guaranteed to knock you out for a week. They know what to take for whatever kind of headache ails you. Toddlers in France can tell you if their mal de tête is stress-related or whether your angine is a petite angine or a grande angine. Or whether you have one of the ailments that I’ve only ever heard of in France. My favourite is the ever rampant “crise de foie.” Far be it from me to suggest that France is a nation of hypochondriacs, but let’s just say their comprehensive healthcare system — which hovers at the top of the WHO’s best healthcare lists — makes it rather easy to be one. A network of mandatory health coverage policies that are largely reimbursed makes it even easier. The French visit the doctor more than in any other country. And there is a cultural consensus that the doctor isn’t treating you well unless you come away with a prescription. Or two. Or three. Ninety percent of doctor-patient appointments end with a prescription. French physicians are labelled as heavy prescribers and France has one of the highest levels of pharmaceutical consumption in the world. Next stop: la pharmacie. I can’t honestly remember ever walking into a pharmacy in any French city or town, and not seeing it full of people: elderly ladies, sniffling young students, well-suited men and chic women with equally chic kids in tow, all lining up to present their ailments and receive the benefit of the pharmacists’ wisdom. There are all kinds of theories, on a sliding conspiracy scale, about the tight and mutually beneficial relationships between pharmacies and doctors in France, but it is generally accepted that France is one of the most highly “prescribed” countries. When everything from prescriptions to seawater spa therapies is covered it’s easy to understand why. Indeed the pharmacy and the pharmacist’s importance in French society cannot be exaggerated. And it goes beyond the nature of the healthcare system.

Doctor’s Review • SEPTEMBER 2016

JACQUES CAFFIN / FLICKR

he French fixation with all that is scientifically au courant has ensured that le pharmacien is embedded in the Gallic esprit as omnipotent. Since the days of Molière, Voltaire and Flaubert, the self-important pharmacist has been celebrated and lampooned (as have their patients) as he dispenses pseudo-scientific potions to a nation of hypochondriacs. Remember Monsieur Homais in Flaubert’s Madame Bovary who represented scientific progress and modernity, but whose overzealous prescribing is fraught with error. Since my first visit to une pharmacie, my fascination has grown. They are always one of my first stops on

PIERRE-OLIVIER / SHUTTERSTOCK.COM

TOURISME MULHOUSE

trips to the country. One is never hard to find. The sheer ubiquity of them means that you will see the flashing green cross indicating “Pharmacie” on nearly every street in every town, village or city. Pharmacies throughout France look as important as they are. Many are elegant old shops with polished wood counters and glass shelves lined with antique vessels holding arcane formulas. Some have chandeliers. The Pharmacie de la Bourdonnais, near the Eiffel Tower, for example, is a 19th-century establishment that has been deemed an historic monument.

No trip to France is complete without a visit to a pharmacy and a discussion of the unique skin care and slimming products they offer.

All pharmacists are required to study mushroom taxonomy and to provide the service of examining your foraged fungi French pharmacies are different from North American drugstores. Cartesian to the core, French pharmacies are single-minded places, so you won’t find cigarettes, greeting cards, water wings, magazines, groceries or other things associated with the one-stop, convenient drugstore. Conversely, pharmacies, with their monopoly on selling prescriptions, make it impossible to buy so much as aspirin at a supermarket. The key relationship between the customer and pharmacist, who is usually also the owner, is trust, as opposed to convenience or price along the lines of our pharmacies. The pharmacist is heavily involved in advising customers and patients on the appropriate over-the-counter medicine and/or the most appropriate toothpaste.

he reverence with which the pharmacist’s advice is held carries over to skincare products. Perhaps unsurprisingly, in France proper skincare is treated seriously. Children are taught by their mothers about moisturizing procedures from very young ages. I like to observe conversations between client and pharmacist with the latter’s weighted opinions on, say, the correct dandruff shampoo. I rarely see anyone question the authority of the pharmacist or even their lieutenants: no-nonsense, lab-coated salesladies. They’ll analyze skin problems and lead you to anything from mink oil face cream to Homéoplasmine, a waxy balm traditionally used to soothe nursing mothers’ SEPTEMBER 2016 • Doctor’s

Review

NEW

VIACORAM

En route towards BP control.

A new option in the treatment of mild to moderate essential hypertension in initial therapy In an 8-week study, VIACORAM® 3.5 mg/2.5 mg • Demonstrated superiority vs. placebo, perindopril arginine 3.5 mg and amlodipine 2.5 mg on reducing SBP (secondary endpoint)/DBP: mean change from baseline to last post-baseline value* was -22.0/-13.6 mmHg for VIACORAM® 3.5 mg/ 2.5 mg vs. -14.2/-9.3 mmHg, -16.3/-9.7 mmHg and -16.0/-10.3 mmHg for placebo, perindopril arginine 3.5 mg and amlodipine 2.5 mg, respectively; p<0.001 for all.1†‡

3.5 mg / 2.5 mg

• Demonstrated non-inferiority vs. perindopril arginine 5 mg and amlodipine 5 mg on reducing SBP (secondary endpoint)/DBP: mean change from baseline to last post-baseline value* was -22.0/-13.6 mmHg for VIACORAM® 3.5 mg/ 2.5 mg vs. -18.2/-10.5 mmHg and -21.8/-12.6 mmHg for perindopril arginine 5 mg (p<0.001) and amlodipine 5 mg (p=0.003/p<0.001), respectively.1†§

mg mg perindopril arginine/ amlodipine

• Demonstrated better controlled rate (secondary endpoint) (SBP<140 mmHg and DBP<90 mmHg) vs. perindopril arginine 5 mg (43.5% versus 33.3%, p=0.018, 95% CI: [1.8; 18.5]) and a trend toward a better controlled rate than amlodipine 5 mg (43.5% versus 37.9%, p=0.202, 95% CI: [-3.0; 14.1])1‡

mg mg perindopril arginine/ amlodipine

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). Dosages of the perindopril arginine in VIACORAM® are not marketed individually. Patients cannot be titrated with the individual drugs currently on the market prior to the initiation of VIACORAM, since dosages of perindopril arginine in VIACORAM are not equivalent to those marketed individually (perindopril as erbumine or arginine salt).

Available in three dosage strengths perindopril arginine/ amlodipine

7 /5

14 /10

INDICATED IN INITIAL THERAPY

3.5mg Perindopril arginine / 2.5mg Amlodipine

The ONLY antihypertensive medication that combines an ACEi (perindopril arginine) and a dihydropiridine CCB (amlodipine besylate)1¶ Clinical use not discussed elsewhere in the piece VIACORAM® is not indicated for the initiation of treatment in elderly patients (>65 years of age). There are 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. Contraindications VIACORAM® is contraindicated in: • 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<60ml/min/1.73m2) • 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

any time during therapy. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, it may be fatal; emergency therapy should be administered promptly. Syndrome starting with cholestatic jaundice and progresses to fulminant hepatic necrosis: May lead to death. Use with Low-Density Lipoproteins (LDL) apheresis: May lead to life-threatening anaphylactoid reactions.

Other relevant warnings and precautions • Caution in driving a vehicle or performing other hazardous tasks • Co-administration of ACE inhibitors, including the perindopril component of VIACORAM®, with other agents blocking the RAS, such as ARBs or aliskirencontaining drugs, is generally not recommended in patients other than patients with diabetes mellitus (type 1 or type 2) and/or moderate to severe renal impairment (GFR<60ml/min/1.73m2) as it is contraindicated in these patients • Risk of hypotension; closely monitor patients at high risk of symptomatic hypotension. Similarly monitor patients with ischaemic heart or cerebrovascular disease; an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident • Risk of mild to moderate peripheral edema • Safety and efficacy of VIACORAM® in hypertensive crisis have not been established • Risk of angina worsening/acute myocardial infarction after starting therapy or dose increases • Risk of hyperkalemia; monitor serum potassium periodically • Risk of neutropenia/agranulocytosis, thrombocytopenia and anemia • Increases in serum transaminase and/or bilirubin levels, cholestatic jaundice, cases of hepatocellular injury with or without cholestasis • Not recommended in patients with impaired liver function Most serious warnings and precautions • Angioedema • Risk of anaphylactoid reactions during desensitization or Pregnancy: When used in pregnancy, angiotensin membrane exposure (hemodialysis patients) converting enzyme (ACE) inhibitors can cause injury or even death of the developing fetus. When pregnancy • Risk of nitritoid reactions in patients on therapy is detected, VIACORAM® should be discontinued as with injectable gold soon as possible. • Patients undergoing major surgery or during anesthesia with agents that produce hypotension Hyperkalemia (serum potassium >5.5 mEq/L): Can cause serious, sometimes fatal arrhythmias; serum • Black patients vs. non-blacks potassium must be monitored periodically in patients • Not recommended in patients with a recent kidney transplantation receiving VIACORAM®. Concomitant use with potassium supplements, potassium-sparing diuretics, or potassium- • Risk of changes to renal function in susceptible containing salt substitutes is not recommended. patients; potassium and creatinine should be monitored in these patients Collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procain- • Risk of cough amide, or a combination of these complicating • Dermatological reactions factors (especially if there is pre-existing impaired • Not indicated for the initiation of treatment in the renal function): May lead to serious infections, which may elderly (>65 years) patients; not recommended in not respond to intensive antibiotic therapy. If VIACORAM® pediatrics (children <18 years of age) is used in such patients, periodic monitoring of white blood • Patients with diabetes treated with oral antidiabetic cell counts is advised and patients should be instructed agents or insulin, glycemic control should be closely to report any sign of infection to their physician. monitored during the first month of treatment with VIACORAM® Angioedema: May be life-threatening and occur at • 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/index-eng.jsp for uncomplicated essential hypertension important information relating to adverse reactions, (i.e., not at high cardiovascular risk and without target organ damage, supine 95 ≤DBP <110 mmHg and 150 ≤SBP drug interactions, and dosing information which have <180 mmHg, mean baseline SBP/ DBP was 161/101 mmHg) received not been discussed in this piece. treatment with perindopril arginine 3.5/amlodipine 2.5 mg (n=246), The product monograph is also available by calling us perindopril arginine 3.5 mg (n=268), perindopril arginine 5 mg (n=270), amlodipine 2.5 mg (n= 270), amlodipine 5 mg (n=261), or placebo (n= 248). at 1-800-363-6093. References: 1. Servier Canada Inc. VIACORAM® Product Monograph. February 17, 2016. 2. Laurent S et al. Randomized evaluation of a novel, fixed-dose combination of perindopril 3.5 mg/amlodipine 2.5 mg as a first-step treatment in hypertension. J Hypertens. 2015; 33(3):653-661. BP=blood pressure; SBP=systolic BP; DBP=diastolic BP; ACEi=angiotensin converting enzyme inhibitors; CCB=calcium channel blockers * For patients with a last post-baseline value not under treatment but with a post baseline value under treatment, the last post-baseline value under treatment was taken into account. † 8-week multicenter, international, randomized, double-blind, placebocontrolled, parallel group factorial study in patients with mild to moderate

The primary efﬁcacy endpoint was changes in supine DBP from baseline to last post-baseline visit. Baseline supine SBP (mmHg): VIACORAM® (161.8/100.7), placebo (161.0/100.5); perindopril 3.5 mg (161.4/100.7); amlodipine 2.5 mg (161.2/100.6); perindopril 5 mg (160.7/100.1) and amlodipine 5 mg (162.3/100.6). ‡ Superiority tests of perindopril 3.5/amlodipine 2.5 as compared to reference treatment (placebo, perindopril 3.5, amlodipine 2.5); one-sided type I error rate: 0.025. § Non-inferiority tests of perindopril 3.5/amlodipine 2.5 as compared to reference treatment (perindopril 5, amlodipine 5); Non-inferiority limit: 2 mmHg for DBP -3 mmHg for SBP; one-sided type I error rate: 0.025. ¶ Comparative clinical signiﬁcance has not been established. ® VIACORAM is a registered trademark of Servier Canada Inc.

chafed nipples, now the Parisians’ preferred remedy for chapped lips, to Embryolisse Lait-Crème Concentré, the well-priced and truly wonderful face cream with the disconcerting name. While I heard that, at one time, the product contained sheep embryo extract, the company assured me that that is not the case. A number of these products have achieved cult status in the skincare industry and are now available in Canada at drugstores like Shoppers Drug Mart, Rexall, London Drugs or Jean Coutu. But most other tried-and-true staples like green clay, which is used to cure everything from acid reflux to the PH balance in hair, remain out-of-reach products in this country and continue to carry old-world mystery and allure. Elaborate window displays change according to the seasons. At exam time, the pharmacy window will be full of ads for, and boxes of, things that truly I’ve only seen in France: memory pills, anti-snoring tablets and, of course, pills and supplemental regimes for la fatigue. After exams come summer holidays so remedies for slimming are given the spotlight. Slimming creams have traditionally been standard practice in the fight to reduce — anticellulite pills, pre-bronzing capsules, gel for “heavy legs” — as opposed to the rather vulgar American alternative: a visit to the gym. By the fall, pharmacist windows are filled with fascinating fungi charts. Autumn is wild mushroom season bringing in cèpes, girolles, chanterelles and the sinister sounding trompettes de la mort (trumpets of death), which are in fact edible (the reason I know this is because the pharmacist told me). One of the most important functions of the French pharmacist is mushroom indicator. All French pharmacists are required to study mushroom taxonomy as part of their training and provide the service of examining your basket of foraged fungi. Lines of men and women bringing filled-plastic bags or straw baskets into the pharmacy to have their bounty inspected by the pharmacist is one of the enduring images of fall in France. Alas, as with many other icons of French culture such as cafés and bistros, the pharmacy as it exists is facing threats. The current government has floated the idea of deregulating pharmacies, which pharmacists worry will allow supermarkets to begin selling over-the-counter drugs and which will also potentially allow corporations to buy up the typically owner-run pharmacies. The highly personalized service would be just one casualty of that model, they say. To protest, they upheld another French tradition: they went on strike.

Servier Canada Inc., 235 Armand-Frappier Boulevard Laval, Quebec, H7V 4A7, 1-888-902-9700 SEPTEMBER 2016 • Doctor’s

Review

Meatloaf to stop a man in his tracks.

The Southern table Enjoy a supper a National Pie Champion serves when she’s not blue-ribbon baking recipes by

Francine Bryson

with

Ann Volkwein

photos by

outh Carolinian Francine Bryson has won more than 200 local and national baking competitions, and was the runner-up on CBS’s The American

Baking Competition. Most people don’t know, however, that her first foray in competitive cooking involved a savoury dish when she was just 16: apricotstuffed pork loin. Bryson’s pork recipe

Doctor’s Review • SEPTEMBER 2016

Sara Remington

won first place in its category and kick started her career with food. Her first cookbook, Blue Ribbon Baking from a Redneck Kitchen, became a bestseller; Country Cooking from a Redneck Kitchen,

published by Clarkson Potter, is the follow-up. The 125 recipes featured are “Southern through and through.” From chicken dinners to burgers and more barbecue must-haves, make-andtake casseroles to dips and other Redneck whatnots, they’re “meals that get you through a day of hard work.” An easy Sunday pie follows — good for weeknights too, we think — as does meatloaf with a twist.

MEATLOAF TO STOP A MAN IN HIS TRACKS According to Bryson, if anyone tells you “you can’t catch a man with food,” well, they are sooo wrong. Food will catch a husband faster than all the bikinis in the world. It will also make your family happy. Prepare a meatloaf and bring the family back to the table. Pull this out of the oven and watch how it can make the kids put down the game controls and wash up for supper without a fight. This recipe uses 90-percent lean ground chuck bound with rolled oats, but it’s the touch of whole-grain mustard that brings it all together. This meatloaf is not shy on flavour. 2 lbs. (1 kg) 90-percent lean ground chuck 2 large eggs 1 medium onion, finely chopped 1 tbsp. (15 ml) chopped fresh parsley ¹⁄³ c. (80 ml) old-fashioned rolled oats ¼ c. (60 ml) mayonnaise 3 tbsp. (45 ml) ketchup 1 tbsp. (15 ml) whole grain mustard 1 c. (250 ml) Italian-style bread crumbs 1 tsp. (5 ml) salt barbecue sauce, homemade or storebought for serving

Preheat the oven to 350°F (180°C). In a large bowl, mix together the beef, eggs, onion, parsley, oats, mayonnaise, ketchup, mustard, bread crumbs, salt and pepper (use your hands; they work best). Shape the meat into a 5 x 12-inch (13 x 30-cm) loaf and put it on a rimmed baking sheet. Bake until the juices run clear, about 1 hour. Serve slices topped with barbecue sauce, if you like. Serves 6.

SUNDAY SUPPER PIE This is one from Bryson’s Mama. She would prep this butternut squash, potato and beef pie, and bake it once the family got home from church. Though they lived about 30 kilometres south, they went to church in the South Carolina town that Bryson lives in now. By the time they got home, it had already started getting dark. This pie was in the oven while they had baths and got their school clothes ready for Monday morning. 1 unbaked, 9-inch (23-cm) pie crust 1 medium butternut squash, peeled and diced (about 2 c. / 500 ml) 3 medium russet (baking) potatoes, peeled and diced (about 2 c. / 500 ml)

5 tbsp. (75 ml) olive oil 1 tsp. (5 ml) Lawry’s seasoned salt (or an alternative) 1 tbsp. (15 ml) dried thyme 1 lb. (500 g) beef, cut into ½ in. (1.25-cm) cubes (or use pre-cut stew meat) 1 c. (250 ml) beef broth 2 tbsp. (30 ml) cornstarch salt and black pepper

Preheat the oven to 375°F (190°C). Fit the pie dough into a 9-inch (23-cm) pie pan. Arrange the squash and potatoes on a baking sheet. Drizzle with 2 tablespoons (30 ml) of the oil and sprinkle with the Lawry’s and thyme. Toss to coat. Roast in the oven until tender, about 25 minutes. Sunday supper pie.

Fried okra.

Meanwhile, in a skillet over medium-high heat, heat the remaining 3 tablespoons (45 ml) oil. Add the beef pieces and brown well on all sides, about 8 minutes. Drain the beef on paper towels. Reserve the skillet. Add the beef, squash and potatoes to the pie shell. Pour the beef broth into the pan juices in the skillet. Whisk in the cornstarch. Bring to a boil over high heat and whisk until thickened, about 4 minutes. Season with salt and pepper. Pour the pan gravy over the meat and veggies. Bake until the crust is golden brown, about 25 minutes. Let cool for 10 minutes before cutting and serving. Serves 8.

FRIED OKRA Francine Bryson admits that okra isn’t one of her favourite things.... In fact, it’s one of the two foods, along with salmon, that she will not eat. Her daughter, on the other hand, eats fried okra faster than she will a T-bone steak. So in honour of her youngest child, here’s the way she enjoys her favourite vegetable best.

Doctor’s Review • SEPTEMBER 2016

½ c. (125 ml) self-rising flour 1 c. (250 ml) cornmeal 1 tsp. (5 ml) salt 1 tsp. (5 ml) black pepper 4 c. (1 L) sliced fresh okra (about 2 pounds / 1 kg) ½ c. (125 ml) peanut or vegetable oil

In a large bowl, whisk together the flour, cornmeal, salt and pepper. Add the okra and toss to make sure all the pieces are covered. In a skillet over medium-high heat, heat the oil until hot. Using a slotted spoon, scoop up the okra from the bowl, shaking off any excess flour, and drop it into the hot oil. Stir occasionally and fry, in batches, until the okra is browned and crisp, about 6 minutes. Remove the okra from the oil using the same slotted spoon. Drain on paper towels. Serve hot. Serves 6. Excerpted from Country Cooking from a Redneck Kitchen. © 2016 Francine Bryson. Published by Clarkson Potter/Publishers, an imprint of Crown Publishing Group, a Penguin Random House Company. Reproduced by arrangement with the Publisher. All rights reserved.

Indications and clinical use: • As an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus inadequately controlled on metformin or in patients already being treated with the combination of sitagliptin and metformin. • In combination with a sulfonylurea 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. • In combination with pioglitazone in adult patients with type 2 diabetes mellitus to improve glycemic control when diet and exercise, and dual therapy with metformin and pioglitazone do not provide adequate glycemic control. • In combination with premixed or long-/intermediate-acting insulin as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus inadequately controlled on metformin, and premixed or long-/intermediate-acting insulin. Use with caution as age increases. Contraindications: • Unstable and/or insulin-dependent (type 1) diabetes mellitus • Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma, history of ketoacidosis with or without coma • History of lactic acidosis, irrespective of precipitating factors • Renal impairment or when renal function is not known and in patients with serum creatinine levels above the upper limit of normal range • Excessive alcohol intake, acute or chronic • Severe hepatic dysfunction • Cardiovascular collapse and in disease states associated with hypoxemia • During stress conditions • Severe dehydration • Pregnancy and breastfeeding • Temporary discontinuation in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials and in patients undergoing any surgical procedure necessitating restricted intake of food and fluids Serious warnings and precautions: • Lactic acidosis: rare, but serious, metabolic complication that can occur due to metformin accumulation • Alcohol: caution against excessive intake, either acute or chronic, since alcohol intake potentiates the effect of metformin on lactate metabolism Other relevant warnings and precautions: • Not for use in type 1 diabetes or for the treatment of diabetic ketoacidosis • Careful patient selection and follow-up • Pancreatitis • Hypoglycemia • Hypersensitivity reactions, including anaphylaxis, angioedema and exfoliative skin conditions including Stevens-Johnson syndrome • Not recommended in patients with congestive heart failure • Hypoxic states • Change in clinical status of previously controlled diabetes: should be evaluated promptly • Loss of blood glucose control • Consider therapeutic alternatives in secondary failure • Impairment of vitamin B12 absorption • Avoid in patients with hepatic disease • Efficacy and safety not established in immunocompromised patients • Temporary suspension for any surgical procedures • Renal adverse events • Caution in concomitant use with medications that may affect renal function or metformin disposition • Monitoring for skin disorders recommended • Monitoring of glycemic parameters, hematologic parameters and renal function For more information: Please consult the product monograph at http://www.merck.ca/assets/ en/pdf/products/JANUMET-PM_E.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 1-800-567-2594. References: 1. JANUMET® and JANUMET XR® Product Monograph. Merck Canada Inc. August 21, 2015. 2. IMS Brogan data, May 2015.

P H OT O FI NI S H by

Dr L ou r e n e R ood e

APL THEN AND NOW CONTINUED FROM PAGE 31

Rare form

These pictures are from a trip to France that I did a few years ago. The Musée Rodin has been a longtime favourite of mine. The larger than life statues in the beautifully manicured rose gardens are breathtaking. I loved the light on this marble hand. The hand so soft, made from rock-hard marble: it works, it feeds, it caresses, it writes, it chisels…. Once only an infant size, now a grown man. Where has it been all its life?

14. Tallman MS, Altman JK. How I treat acute promyelo cytic leukemia. Leukemia. 2009;114(25):5126-5135. 15. Paulson K, Serebrin A, Lambert P, et al. Acute promyelocytic leukaemia is characterized by stable incidence and improved survival that is restricted to patients managed in leukaemia referral centres: A pan-Canadian epidemiological study. Br J Haematol. 2014;166(5):660-666. 16. Park JH, Qiao B, Panageas KS, et al. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood. 2011;118(5): 1248-1255. 17. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Acute Myeloid Leukemia, Version 1.2016. Fort Washington, PA; 2016. 18. Kotiah SD, Besa EC. Acute Promyelocytic Leukemia Clinical Presentation. Medscape Drugs & Diseases. 2015. http://emedicine.medscape. com/article/1495306-clinical. 19. Seftel MD, Schuh AC, Barnett MJ, et al. A Canadian consensus on the management of newly diagnosed and relapsed acute promyelocytic leukemia in adults. Curr Oncol. 2014;21(5):234-250. 20. Cicconi L, Lo-Coco F. Current management of newly diagnosed acute promyelocytic leukemia. Ann Oncol. 2016;27(8):1474-1481. 21. Lundbeck Canada Inc. PrTRISENOX® (arsenic trioxide) Product Monograph. 2013. 22. CHEPLAPHARM Arzneimittel GmbH. VESANOID® (all-trans retinoic acid/tretinoin) Product Monograph. 2013. 23. Chen Y, Kantarjian H, Wang H, Cortes J, Ravandi F. Acute promyelocytic leukemia: a population-based study on incidence and survival in the United States, 1975-2008. Cancer. 2012;118(23):5811-5818.

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FAIR BALANCE INFORMATION Janumet........................................................54 Zenhale........................................................46 SEPTEMBER 2016 • Doctor’s

Review

Experience ANORO ELLIPTA ®

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

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

A once-daily LAMA/LABA dual bronchodilator for COPD.* • Endocrine and Metabolism: Use with caution in patients with convulsive disorders, thyrotoxicosis and patients who are unusually responsive to sympathomimetic amines. Use with caution in patients predisposed to low levels of serum potassium or patients with ketoacidosis or diabetes. • Respiratory: Treatment should be discontinued if paradoxical bronchospasm occurs and alternative therapy instituted if necessary. • Hypersensitivity: As with all medications, immediate hypersensitivity reactions may occur after administration of ANORO® ELLIPTA®. Patients with severe milk protein allergy should not take ANORO® ELLIPTA®. • Use during pregnancy, labour and in breastfeeding women should only occur if the potential benefit justifies the potential risk. • Drug interactions: Avoid co-administration with other anticholinergics. Caution should be exercised when considering the co-administration with inhibitors of cytochrome P450 3A4; drugs that prolong the QTc interval (e.g. monoamine oxidase inhibitors and tricyclic antidepressants); betaadrenergic receptor blocking agents; and non-potassium-sparing diuretics (i.e. loop or thiazide diuretics). Adverse Events: Adverse reactions reported at a frequency of ≥1% and greater than placebo include: pharyngitis, sinusitis, lower respiratory tract infection, diarrhea, constipation, pain in extremity, muscle spasms, neck pain and chest pain.

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

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

01445 04/16

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