In this first episode of the New Year (Episode #35) we review nine (not ten) old drugs that should, in most circumstances, still likely play an important role in your day-to-day prescribing and recommendations. Dr Robert Rangno again joins us for this episode and provides us with some great clinical experience and some mediocre humour. Mike and James, as usual laugh about a variety of things that in hindsight really aren’t all that funny.

Show Notes

Chlorpheniramine

1) Editorial on antihistamines

CMAJ 1997;157:37-8

2) Tolerance to the sedative effects of 100 mg of diphenhydramine occurs within 3 days

J Clin Psychopharmacol 2002:22:511–15

Thiazides

1) ALLHAT JAMA 2002;288:2981-97

2) ACE inhibitors no better than thiazides in diabetics

Arch Intern Med 2005;165:1401-9

Spironolactone

1) RALES/CHF study New Engl J Med 1999;341:709-17

2) Spironolactone for resistant hypertension

AJH 2003;16:925–30 Journal of Hypertension 2007;25:891-4

3) Polycystic ovarian disease

J Clin Endocrinol Metab 2004;89:2756-62

Reserpine

1) Potentially useful agent

Clin Pharmacol Therap 1996;60:368–73

2) Treatment of diastolics of 115-129 mmHg – VA Study JAMA 1967;202:1028-34 (NO LINK – Archived)

Amoxicillin

1) Once daily amoxicillin for Strep throat

Arch Disease Childhood 2008;93:474-8

Pediatrics 1999;103:47-51

Doxycycline

1) No appreciable resistance to doxycycline, including pneumococcus

Chest 2004;125:1913

Arch Int Med 1999;159:266-70

2) Community acquired MRSA

Antimicrob Agents Chemother 2007;51:2628-30

Clin Infect Dis 2005;40:1429-34

3) Low dose (20 mg twice daily) for acne

Arch Dermatol 2003;139:459-64

Sulfa drugs

Allergy to penicillin increases your risk of reacting to sulfa drugs

N Engl J Med 2003;349:1628-35

Nitrofurantoin

Still good for bladder infections

British Journal of General Practice 2002;52:729-34

In Episode 34, we review some of the myths and beliefs common in many cultures. A renowned and profound guest joins us (Dr Robert Rangno). We start with a study of Santa Claus and then move on to a variety of myths like the need for bed rest, cold exposure causing infective illness, swimming after eating, etc. It is light-hearted and lacks intellectual content (even more than usual). We end with the Christmas Poem “A Sick Night before Christmas.”

In our 33rd episode we follow-up our discussion of osteoarthritis by examining the risks and benefits of oral anti-inflammatories including Cox-2 inhibitors. We review the effects on pain relief and the theory of anti-inflammation. We discuss the possible gastrointestinal effects and possible approaches to reduce the risk. We consider the cardiovascular risks and debate the choices in prescribing. We finish by struggling to get in the last word.

Show Notes

1) Eradication of H. Pylori decreases the chance of a GI bleed in patients about to receive NSAIDs

Lancet 2002;359:9-13

2) Misoprostol decreases the chance of bleeds but increases the number of GI side effects

Ann Int Med 1995;123:241-9

3) PPI added to ASA (in patients with previous ulcer on ASA)

NEJM 2005;352:238-44

4) Naprosyn possibly protective for cardiac events

Lancet. 2004;364:2021-9

5) Possible impaired fracture healing with NSAIDs

Injury 2008;39:384-94

J Bone Joint Surg (Br) 2007;89:1553-60

Emerg Med J 2005;22:652-3

In our 32nd episode we review the therapeutic options for the treatment of osteoarthritis. We first deal with lifestyle interventions for osteoarthritis. We consider the pain pharmaceuticals like acetaminophen, topical or oral NSAIDs, and opiates as well as some of the other osteoarthritis therapies such as glucosamine or steroid injections. We also summarize a number of other interventions (cold compresses to surgical debridement).

Show Notes

1) Obesity and hip OA

Rheumatology 2002;41:1155-62

2) Exercise for OA of the knee

Cochrane Library

3) Aquatic exercise for knee and hip OA

Cochrane Library

4) Glucosamine for OA

Cochrane Library

5) Topical NSAIDs for OA

Longterm efficacy of topical nonsteroidal antiinflammatory drugs in knee OA

J Rheumatol 2006;33:1841-4

Topical diclofenac for OA of the knee

J Rheumatol 2004;31:2002-12

Meta-analysis of topical NSAIDs for OA

BMJ 2004;329:324

Meta-analysis of topical NSAIDs for OA

BMC Musculoskeletal Disorders 2004;5:28

Bandolier on topical NSAIDs

6) Oral NSAIDs including COX-2s for OA

BMJ 2004;329:1317

7) Oral NSAIDs vs Acetaminophen

A meta-analysis

Ann Rheum Dis 2004;63:901-7

A systematic review

J Rheumatol 2004;31:344-54

Versus diclofenac/misoprostol

Arthritis Rheum 2001;44:1587-98

8) Steroid injections for OA of the knee

BMJ 2004;328:869

Can Fam Physician 2004;50:241-8

Cochrane Library

9) Opioids for OA

Oxycodone

Arch Intern Med 2000;160:853-60

Codeine

J Rheumatol 2000;27:764-71

Morphine

J Pain Symptom Manage 2002;23:278-91

Tramadol

J Rheumatol 2007;34:543-55

10) Hyaluronic acid injections

Meta-analysis showing no effect

CMAJ 2005;172:1039-43

Cochrane review showing an effect

Cochrane Library

11) Surgical debridement

Cochrane review showing no benefit

Cochrane Library

12) Other

TENS

Cochrane review

Cochrane Library

Thermotherapy

Cochrane review

Cochrane Library

Ultrasound

Cochrane review

Cochrane Library

Balneotherapy for OA (Mineral Baths)

Cochrane review

Cochrane Library

Acupuncture

Meta-analysis

Rheumatology 2006;45:1331-7

In our 31st episode we offer an approach to new drugs. We look at the last five years of new product introduction and consider the frequency of new drugs being truly novel and a substantial addition. We examine how medicines termed “new” are frequently modifications that make no measurable change in the product. Finally, we consider a basic approach to new products. James gets militant on the theme (but not the message) while Mike runs for cover.

Show Notes

1) Number of drugs considered to be a “substantial” improvement – 2001 to 2007 – category 2 is considered substantial improvement (14 out of 147) PMPRB 2007 Annual report

2) Prescrire review of new drugs Can J Clin Pharmacol 2005;12:e10-e21

3) Drugs withdrawn from the Canadian market for safety reasons CMAJ 2005;172:765–7

4) Guideline recommendations are not necessarily based on “solid” evidence and are often opinion-based Example – Canadian Cardiovascular Society position statement – Recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease

Can J Cardiol 2006;22:913-927

Of the 15 specific recommendations in this document:

4 were considered Level A – Data derived from multiple randomized controlled trials or meta-analyses

0 were considered Level B – Data derived from a single randomized controlled trial or large, nonrandomized studies

11 were considered Level C – Consensus of opinion by experts and/or small studies, retrospective studies or registries

The topic for our 30th episode is stolen from the headlines. We look at the much publicized Jupiter trial of C-Reactive Protein (CRP) and the use of a statin. We review the details, strengths and weakness of the trial. From there we look at related questions of risk assessment with CRP, reducing CRP and the uncertainty in the lipid hypothesis. We end by concluding that although trust in mechanisms and theories can lead to poor decisions they are generally less confusing than our podcasts.

Show Notes

1) Jupiter – statins, lipids and CRP

NEJM 2008;359:2195-207

2) Knowing CRP doesn’t change estimation of cardiovascular risk

NEJM 2006;355:2631-9

Arch Intern Med 2006;166:1368-73

3) Web site calculator that uses CRP

Reynolds Risk Score

4) Ezetrol Study (reduces CRP but no other change)

N Engl J Med 2008;358:1431-43.

5) Mechanistic mistaken thinking Beta-blockers in CHF

Arch Intern Med 2002;162:641-8

Anti-oxidant studies

Lancet 2002;360:23-33

Lancet 2003;361:2017-23.

Atenolol for BP but not for outcomes

Lancet 2004;364:1684-9

In Episode 29, we review questions around informed decision-making, risk-benefits of statins across different populations (women, chronic kidney disease, etc), and comparisons of calculated risks and trial results. We also talk about prescribing of new antimicrobials, differentiating typical from atypical pneumonias and then attempt to clarify a few trials including HOPE. James desperately searches for pearls among Mike’s explanations of the uncertainty and gaps in the research.

Show Notes

1) The HOPE trial

NEJM 2000;342:145–53

2) HOPE was actually more like a blood pressure trial than originally thought – 24 hour blood pressure differences between the 2 groups were 10/4 mmHg

Hypertension 2001;38;e28-e32

4) Meta-analysis of statins in patients with chronic kidney disease

BMJ 2008;336:645-51

5) Meta-analysis CMAJ on high vs low dose statin in secondary prevention

CMAJ 2008;178:576-84

6) Mediterranean diet – no difference between the groups in weight, cholesterol or blood pressure at the end of the study but cardiovascular events were reduced

Lancet 1994;343:1454-9

7) ACCORD and ADVANCE trials

Podcast #9

8)UKPDS (recent results)

NEJM 2008;359:1577-89

9) BP trial for patients over age 80

NEJM 2008;358:1887-98

In Episode 28, we review questions around osteoporosis including: bone density testing and the limits of medical tests in general; the risks (including osteoporosis) and benefits of proton pump inhibitors for heartburn; and assessing calcium intake and the possible risks of calcium. We also briefly discuss topics of risk assessors of CVD, an approach to patients using complementary alternative therapies, and make a few random, but obviously brilliant suggestions.

Show Notes

1) Comparison of H2 Blocker vs PPI

CADTH report on the Evidence for PPI Use in GERD

2) Studies suggesting risk from PPI for osteoporosis/fracture and C. difficile CMAJ 2008;179:319-26 JAMA 2005;294:2989-95.

3) Calcium and vascular events BMJ 2008;336:262-6 Circulation 2007;115:846-54

4) STENO – multifactorial intervention for type 2 diabetes N Engl J Med 2008;358:580-91

5) The book The Bedford Murder: An Evidence-Based Clinical Mystery (Paperback) by Marshall Godwin & Geoffrey Hodgetts

In episode 27, we examine the management of COPD Exacerbation and adjunctive treatments. We review the relatively good evidence for antibiotics and steroids in Exacerbations including the options in choice, dosing, and mode of administration. We briefly examination some of the other treatment options in chronic COPD with combination puffers, immunizations, theophyline, and home oxygen. We close by discussing the general use of methylxanthines (like chocolate) for overall well-being.

Show Notes

1) Vaccinations

“An annual influenza vaccination reduces morbidity and mortality from the disease by as much as 50% in the elderly and reduces the incidence of hospitalization by as much as 39% in patients with chronic respiratory conditions. The benefit of pneumococcal vaccine in COPD is less well established”

Can Respir J 2007;Vol 14 Suppl 5b-32b

Influenza vaccine

“It appears, from the limited number of studies performed, that inactivated vaccine reduces exacerbations in COPD patients”

Cochrane Library 2008

Pneumococcal vaccine

“There is no evidence from randomised controlled trials that injectable pneumococcal vaccination in persons with COPD has a significant impact on morbidity or mortality

Cochrane Library 2008

2) Work-up for Exacerbation

Can Respir J 2003;10 Suppl A:11A-65A Ann Intern Med. 2001;134:600-620.

3) Acute Exacerbation “Treatment of an exacerbation of COPD with oral or parenteral corticosteroids significantly reduces treatment failure and the need for additional medical treatment”

Cochrane Library 2008

“This review shows that in COPD exacerbations with increased cough and sputum purulence antibiotics, regardless of choice, reduce the risk of short-term mortality by 77%, decrease the risk of treatment failure by 53% and the risk of sputum purulence by 44%; with a small increase in the risk of diarrhoea”

Cochrane Library2008

Can Respir J 2007;Vol 14 Suppl 5b-32b

4) Home Oxygen

Ann Intern Med. 2007;147:633-638 Ann Intern Med. 2007;147:639-653.

5) Theophylline

“This systematic review shows that orally administered theophylline improves lung function and levels of oxygen and carbon dioxide in the blood. However, there is limited data on its effect on symptoms, exercise capacity or quality of life. Despite being associated with increased side effects, particularly nausea, subjects preferred theophylline over placebo.”

Cochrane Library 2008

In episode 26, we examine the initial management of COPD. We first discuss the diagnosis of COPD and if screening is recommended. We encourage an initial focus on smoking cessation and then episodic, symptom control. We then review long acting puffers and the large body of confusing research with underwhelming and at times conflicting results. Unfortunately, the data available for long acting puffers serves as a good example of how more information can exacerbate confusion.

Show Notes

1) Diagnosis data

JAMA 2000;283:1853-7

Ann Intern Med. 2007;147:633-638.

2) Lung decline and smoking

JAMA 2003;290:2301-2312.

3) Evidence only for symptomatic and FEV<60%

Ann Intern Med 2007;147:639-653

4) Outcomes for puffers in COPD

Overall

Ann Intern Med 2007;147:639-653

Tiotropium

JGIM 2006;21:1011-9

LABA/Steroid

NEJM 2007;356:775-89 LABA/steroid

5) Latest tiotropium data

JAMA 2008;300:1439-50 NEJM 2008;359:1543-54

6) Inhaled steroid adverse events

Chest. 2005;127:89-97 NEJM 2000;343:1902-9

Cochrane 2007;4: CD 006829

NEJM 2007;356:775-89