In episode 39 we get to the 4 studies we didn’t get to in the previous podcast. We discuss evidence that BMI is as useful as cholesterol when it comes to estimating cardiovascular risk, inhaled corticosteroids increase risk of pneumonia in patients with COPD – but don’t worry just put them on daily erythromycin – and finally we discuss yet another antihypertensive trial. Mike demonstrates some sensitivity approaches to medicine in general and James ignores him.

Show Notes

1) BMI predicts risk as well as knowing a patient’s cholesterol

Lancet 2008;371:923-31

2) Meta-analysis of inhaled corticosteroids in COPD – no difference in mortality, reduction in exacerbations but pneumonia was increased by 4% (absolute) over a period of a year

JAMA 2008;300:2407-16

3) Erythromycin 250 mg BID for one year compared to placebo – exacerbations reduced to a similar degree as to that seen with inhalers

Am J Respir Crit Care Med 2008;178:1139–47

4) ACCOMPLISH – Benazepril plus Amlodipine or Hydrochlorothiazide for Hypertension in High-Risk Patients

N Engl J Med 2008;359:2417-28

In episode 38 we try to go over 8 new studies in one podcast but only get half-way there. We cover 2 inhaled anticholinergic studies, one new glucose lowering trial and the latest smoking cessation RCT. Mike and James wax poetically about a variety of issues and demonstrate clearly their well-honed technique of how not to stay foccussed, succint and to-the-point which explains why we only got to half the studies.

Show Notes

1) Inhaled anticholinergics – for better or worse?

Tiotropium given for 4 years on-top of existing therapy – no increase in mortality and fewer myocardial infarctions

N Engl J Med 2008;359:1543-54

Inhaled anticholinergics increases risk of cardiovascular death – but not total mortality

JAMA 2008;300:1439-1450

2) VADT – trial – the third study showing either no benefit or harm from aggressively lowering blood glucose – glycated hemoglobin level reduced from 8.4% to 6.9%

N Engl J Med 2009;360:129-39

3) Varenicline for smoking cessation Varenicline verus transdermal nicotine

Thorax 2008;63:717-24

Evidence showing 0.5 mg BID of varenicline is as effective as 1 mg BID

FDA document

In Episode 37, we again review listener questions and comments around such diverse topics as Bell’s Palsy, viruses that break bones, glucose monitoring, glitazones and COPD. Both James and Mike give diverse answers with diverse meanings that even they don’t really understand.

Show Notes

1) The third study showing either no benefit or harm from aggressively lowering blood glucose – glycated hemoglobin level reduced from 8.4% to 6.9%

NEJM 2009;360:129-39

2) Studies of monitoring blood sugar in type 2 diabetics showing no benefit and increased depression scores

BMJ 2007;335:132

BMJ 2008;336:1177-80

3) Beta-blockers and thiazides do appear to increase the chance of developing diabetes

Am J Cardiol 2007;100:1254–62

4) 10-year follow-up of intensive glucose control in Type 2 diabetes

NEJM 2008;359:1577-89

5) COPD guidelines recommending inhaled steroids as one of the first line inhalers

Ann Int Med 2007;147:639-53

In episode 36, we take up where we left off in episode 35 by reviewing eight more (not ten) old drugs that hopefully you are still using – if not, get with the progam – in your day-to-day practice. Dr Bob joins us yet again for this episode and provides us with some great clinical experience and finally some reasonable humour. Mike tries to deliver some useful clinical pearls and James tries to keep things flowing smoothly – neither have tremendous success.

Show Notes

Nortriptyline

1) Chronic headache JAMA. 2001;285:2208-2215

2) Smoking cessation Antidepressants for smoking cessation. Cochrane Database of Systematic Reviews 2007, Issue 1

Fluoxetine

1) Weight loss in diabetics Arch Intern Med 2004;164:1395-1404

Metformin

1) Metformin’s contraindications should be contraindicated CMAJ 2005;173:502-504

Colchicine

1) Gout – uptake of colchicine into leukocytes Clin Pharmacol Ther 1993;54:360-7

2) Does colchicine work? The results of the first controlled study in acute gout Aust NZ J Med 1987;17:301-4 Br J Clin Pharmacol 1988;26:488-9

3) Pericarditis Arch Intern Med 2005;165:1987-91

4) Osteoarthritis Arth Care Res 2002;47:280-4 Osteoarthritis Cartilage 2002; 10:247-52

5) Cirrhosis NEJM 1988;318:1709-13

Vitamin B12

1) Oral vs IM Vitamin B 12 Fam Pract 2006;23:279-85

Iron

1) Low dose (15 and/or 50 mg) is as good as high doses (150mg) Am J Med 2005; 118: 1142-7

Nitroglycerin

1) Tennis elbow Am J Sports Med 2003;31:915-20

2) Acute pulmonary edema Amer J Emerg Med 1999;1716:571-4

3) Anal/bum fissures Lancet 1997;349:11-4

4) Raynaud’s Lancet 1982;1:76-7

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