In episode 23, we begin the discussion of antibiotic prescribing in common respiratory tract infections with a focus on pneumonia. We talk about the limited evidence for the clinical exam in diagnosing pneumonia. We review the variability in antibiotics suggested in guidelines and evidence for coverage of atypical pneumonia. We also discuss the research on dosing and duration of antibiotics. We find out what antibiotic James and Mike would take (and some infections they have had)!

Show Notes

1) Contributions of symptoms, signs, and other things to the diagnosis of pneumonia.

Br J Gen Pract 2003;53:358–64

2) Do you cover for atypical organisms or not when you are treating pneumonia?

Community acquired

BMJ 2005;330:456-9

Hospitalized patients

Cochrane Review

3) Amoxicillin for community acquired pneumonia – use 500 to 1000 mg TID

Thorax 2001;56(Suppl 4):iv1-iv64

4) Shorter duration and treating until “feeling better” for 72hours “

Until further data are available, it seems reasonable to treat bacterial infections such as those caused by S. pneumoniae until a patient is afebrile for 72 h”

Lancet 2003;362:1991–2001

Three days of antibiotics for hospitalized patients with community acquired pneumonia

BMJ 2006;332:1355

In our 22nd episode we continue our low dose discussion. We talk about the concept of n-of-1 trials and allowing patients to determine their dose. We review some of the benefits of low-dose prescribing, such as low side-effect risk and reduced costs, but emphasize the medical conditions in which low doses are inappropriate. We end by offering some practical suggestions to assist patients with very low doses (in which James forces Mike to acknowledge the superior power of pharmacists).

Show Notes

1) Placebo what it is and should you use it – go with low dose instead?

BMJ 2008;336;1020

BMJ 1995; 311:551-3

2) Cost has an effect on adherence

Med Care 2001 39: 296–301

J Manag Care Pharm 2006 12: 377–382

In our 21st episode we jump into our ongoing debate about low and very low dose of medication. We present the reason why initial doses of new drugs are often too high and the logic for trialing lower doses in patients. We also review over 10 examples of medications proven in randomized control trials to be equally effective (or more) at lower doses. Although promoting low dose, the size of the podcast is moderate dose (while the quality is high dose with minimal side-effects).

Show Notes

1) Examples of evidence for effective lower doses – these examples typically show lower doses were as effective as higher doses, but in some of the examples higher doses were somewhat more effective but lower doses nonetheless produced clinically important results

6.25 mg of hydrochlorothiazide is effective at lowering blood pressure, and comes in a number of combination products – initially 50 to 200 mg was the recommended starting dose

Arch Int Med 1994;154:1461-8

6.25 mg of captopril has been shown to be effective for blood pressure yet captopril 25 mg PO TID is still a commonly recommended initial starting dose for hypertension.

Circulation 1983;67:1340-6

25 mg of sildenafil (Viagra) has been shown to be an effective dose for erectile dysfunction

Bandolier

25 mg of sumatriptan (Imitrex) works almost as well as100 mg and in fact for most drugs in this class there is a flat dose-response curve seen at the doses studied.

Cephalalgia 2002;22:633-58.

5 mg daily of fluoxetine (Prozac) has been shown to have an effect similar to 20 mg daily.

N Engl J Med 1994;331:1354-61

0.25 mg (1/40th of the recommended initial starting dose of 10 mg) of ezetimibe (Ezetrol) provides 50% of the LDL lowering effect seen with 10 mg

Clin Ther 2001;23:1209-30

15 mg of elemental iron daily has been shown to be as effective for anemia as 50 mg and 150 mg, with a lower incidence of side effects.

Am J Med 2005;118:1142-7

150 mg daily of bupropion (Zyban) produces the same rate of smoking cessation at one year as 300 mg daily.

N Engl J Med 1997;337:1195-202

200 mg of ibuprofen (Motrin) is as effective as 400 mg for migraine headache.

Headache 2001;41:665-79

25 mg of ranitidine (Zantac) has been shown to be as effective as 125 mg for heartburn relief.

Aliment Pharmacol Ther 1999;13:475-81

Compared to standard-dose treatment, low-doses of depot antipsychotics improve psychosocial function and reduce the frequency of side effects.

Schizophrenia bulletin 1993;19:155-64

Tricyclic antidepressant doses of 75-100mg are as effective for depression as doses greater than100mg.

BMJ 2002;325:991-5

500 and 1000 µg of oral B12 was more effective than 2.5, 100 or 250 µg at improving the surrogate marker of B12 deficiency (methylmalonic acid).

Arch Intern Med. 2005;165:1167-1172

Meta-analysis showing higher doses of statins produced greater reductions in cardiovascular events – as an aside, a number of these trials compared different drugs in addition to different doses and the difference in outcome was approximately 1.5% in cardiovascular outcomes

CMAJ 2008;178:576-84

2) Doubling the dose of inhaled corticosteroids for asthma exacerbations is not effective

Lancet 2004;363:271-5

Thorax 2004;59:550–6

In our 20th episode we try to answer our accumulating listener mail. We review questions around cardiovascular disease risk-benefits and try to demystify the calculators. Listeners question antidepressants: when they should start to work, when to change dose/type and their use for chronic pain. Other issues include stopping bisphosphonates, addressing the placebo effect and uncertainties with industry funded trials. In the end, Mike talks about Giraffes and James becomes spastic.

Show Notes

1) Meta-analysis data for mortality benefit with statins in primary prevention

TI meta-analysis on statins in women for primary prevention.

“For women without cardiovascular disease, lipid lowering does not affect total or CHD mortality. Lipid lowering may reduce CHD events, but current evidence is insufficient to determine this conclusively.”

JAMA 2004;291:2243-52

2) Don’t change the doses of antidepressants too quickly

Br J Psyc 2006;189:309–16

3) How quickly do antidepressants work?

Arch Gen Psyc 2006; 63: 1217-23. (for how fast anti-depressants work)

4) How long do we use bisphosphonates?

N Engl J Med 2004;350:1189–1199

JAMA 2006;296:2927-38

Options in treatment, which ones have evidence of non-vertebral fracture and the absolute benefits of those treatments. We discuss reliability of monitoring bone density of patients on therapy and the duration of therapy.

Show Notes

1) Evidence for fracture reduction

There is good evidence from randomized controlled trials (RCTs) that alendronate, etidronate, ibandronate, risedronate, calcitonin, 1-34 PTH, and raloxifene prevent vertebral fractures compared with placebo.

There is good evidence from RCTs that risedronate and alendronate prevent both nonvertebral and hip fractures compared with placebo.

There is good evidence that zoledronic acid prevents vertebral and nonvertebral fractures, and fair evidence that it prevents hip fractures.

Agency for healthcare research and quality – report

2) Calcitonin appears to be effective in the management of acute pain associated with acute osteoporotic vertebral compression fractures by shortening time to mobilization

Osteoporosis Int 2005;16:1281-90

3) Relative and absolute benefits from using alendronate for 2-3 years

Approximately

45% reduction in vertebral fractures – 2% absolute reduction for primary and 6% for secondary

20% reduction in non-vertebral – just secondary prevention – 2% absolute reduction

50% reduction in hip fractures – just secondary prevention – 1% absolute reduction

Cochrane Library

In episode 18 we consider the approach to questions of bone density and fracture risk. We use a series of cases to work through the risk of osteoporosis (using a simple tool) and help us decide on bone mineral density testing. We discuss initial options in the prevention of fractures including weight-bearing exercise, Calcium and Vitamin D (and its additional advantages).

Show Notes

1) Osteoporosis self-assessment tool – estimating risk of osteoporosis

2) Vitamin D and Calcium (for fracture)

3) Vitamin D and falling risk

JAMA 2004;291:1999-2006

4) Meta-analysis of Vit D on Mortality

Arch Intern Med 2007;167:1730-1737

In episode 17 we look at managing the treatment of depression once we’ve started a medication. We discuss the patient conversations necessary for initiating treatment including the patient perception of the illness, expectations and potential side-effects. We debate the quandaries around starting doses, when or if to increase, duration of therapy and relapse prevention. Although we use available evidence, we acknowledge some of our advice is Best-Guess based medicine.

Show Notes

1) Monitoring form for using antidepressants in children and adolescents

2) Clinical tool to monitor antidepressant treatment

3) Scales, doctors finding benefit (when there isn’t any)

Lancet 2004;363:1341-5

4) Investigators’ conclusions on the efficacy of newer antidepressants in childhood depression have exaggerated their benefits

BMJ 2004;328:879-83

5) Benefit seen in 1 week with antidepressants

Arch Gen Psychiatry 2006;63:1217-23

6) The risk of recurrence progressively increases with each successive episode and decreases as the duration of recovery increases

Am J Psychiatry 2000;157:229–233)

7) Relapse due to stopping meds – relapse at 12 months – 18% on drugs 41% on placebo

Lancet 2003;361:653–51

8) 5mg of fluoxetine works Psychopharmacology Bulletin 1988;24:183-8

Click here to download article

In episode 16 we look at initiating treatment for depression. We briefly review screening and the diagnosis of depression before discussing the non-drug treatment options (therapy, exercise, sleep hygiene). We search for the anti-depressant of choice (being any) and end up deciding to tailor the choice based on factors such as side-effect profile, targeted symptoms, and cost. Although we stress the importance of regular follow-up, James refuses to come to see Mike or Adil.

Show Notes

1) Two screening questions for depression – do you feel depressed, do you have little interest in doing things

BMJ 2003; 327:1144-46

J Gen Intern Med. 1997;12:439-45

2) Benefit seen in 1 week with antidepressants

Arch Gen Psychiatry 2006;63:1217-23

3) No difference between the second generation antidepressants in effect

Ann Intern Med. 2005;143 :415-26

4) Weight benefit with fluoxetine.

Arch Intern Med 2004;164:1395-1404

5) Amitriptyline is as effective as other tricyclics or newer agents

Cochrane Library

6) Monitoring form for using antidepressants in children and adolescents

7) Clinical tool to monitor antidepressant treatment

In episode 15 a guest assists us in addressing the evidence suggesting anti-depressants are not as effective as believed. We review some biases in the anti-depressant research including publication bias (how good studies are published more than bad studies). We discuss how the benefits of anti-depressants over placebo increase as the severity of depression worsens. James prompts us to explain the effectiveness of the medications; although we dodge, some vague commitments do manage to escape.

Show Notes

1) Selective publication of selective serotonin reuptake inhibitors data

BMJ 2003;326:1171-73

2) Another select report on the selective publication of selective serotonin reuptake inhibitors

NEJM 2008; 358: 252

3) Antidepressants have a clinically important effect above placebo only in patients with severe depression

PLOS 2008:5(2):0260-8

4) Fluoxetine – evidence for benefit in children – others maybe not?

Lancet 2004;363:1341-5

5) In children, with antidepressants, the magnitude of benefit is unlikely sufficient to justify the harms

http://www.bmj.com/cgi/content/full/328/7444/879

In episode 14 we attempt to answer some of the mail received from listeners. We talk about using the evidence to promote shared decision-making. We review calculating risk, the limitations of risk calculators and presenting the data in the positive (chance of not having an event). We address heart disease as the leading cause of mortality (despite advancement in treatment) and emerging discussions of statin use in children (age ?8). We unwrap these enigmas to create more confusion.

Show Notes

1) Some references showing high cholesterol in patients over age 75-80 is not necessarily associated with increased mortality or sometimes not even increased cardiovascular disease.

Ann Epidemiol 2004;14:705–21

JAMA 1994;272:1335-40

Ann Int Med 1997;126:753-60

J Am Geriatr Soc 2004;52:1639-47

Arch Int Med 2003;163:1549-54

J Am Geriatr Soc 2005;53:2159-64

J Am Geriatr Soc 2005;53:219-26

2) Treatment of hypertension in patients 80 years of age or older reduces the chance of a cardiovascular event by 3% over 2 years

NEJM 2008;358:1887-98