Myth-Busting: Forgotten and Forgettable Medical Management G. Michael Allan Associate Professor, Family Med, U of A

Myth-Busting: Forgotten and

Forgettable Medical Management

G. Michael AllanAssociate Professor, Family Med, U of A

Conflict of Interest

• Family Doctor for >10 yrs

• Academic 7 years

• Pay from U of A and Alberta Health

• Research and Speaking Fees– Non-Profit Sources (ACFP, CEDAC, ENPCN, TI,

TOP, etc)– No funding from Industry

What we’ll cover

1) Pediatricsa) Treating Fever: Acetaminophen or Ibuprofenb) Treating Musculoskeletal Pain in Pediatricsc) Pediatric Coughd) Plus: Sleepless Infant, Vomiting, Croup

2) Dermatologya) Laceration Repairb) Plus: Punch Biopsy & Acne

3) Vitamins & Cure-Alls1) Vitamin D, B12, A&E2) Motivating patients to move

Fever Fever

• A 5 year old has a nasty fever but otherwise is classic URTI. His mother wants some advice to treat this fever.

• You say: If you want something, ibuprofen is probably best.• True: RCT,1 kids, Paracetamol or ibuprofen or both• 1° outcome time w/o fever 1st 4hr

– Both > para = 55.3mins (p<0.001) but not > than ibuprofen. – Time w/o fever in 24hrs (ss): para+ibu> para (4.4hr), para + ibu> ibu

(2.5hr)

– Overdosing of meds reported in 33 children. • Ibu shown previously to be superior to acetaminophen for

relief of fever.2

1. BMJ 2008;337:a13021. 2 Arch Pediatr Adolesc Med 2004;158:521-6.

Are acetaminophen and ibuprofen equivalent in the treatment of pediatric fever

• Clinical Question: If we provide a recommendation regarding the treatment of pediatric fever, is acetaminophen or ibuprofen superior?


• Meta-analysis & RCT provide some guidance;• Review of Ibuprofen vs Acetaminophen1

– 10 trials, 1078 patients– Dose: ibuprofen 5-10 mg/kg & acetaminophen 10-15mg/kg – Outcome:

• Ibuprofen statistically superior at 2, 4 and 6 hours.• 4-6 hours ≈15% more will have fever reduction (NNT 7)


• PITCH: RCT, 156 children (age ½ - 6 years), ibuprofen 10mg/kg q6-8 hours, acetaminophen 15mg/kg q4-6 hours or combo2

• Time without fever in first 4 hours: Combo >acetaminophen (55.3mins) but not ibuprofen.

• Ibuprofen and combination clear fever faster • Combo had reduced fever time in first 24 hours

• acetaminophen 4.4 hours more• ibuprofen 2.5 hours more

– Overdosing of medications reported in 33 (21%) children. – Authors recommended ibuprofen;

• Ibuprofen superior to acetaminophen, • Combo only slightly > ibuprofen in a few outcomes (but not others), • Possible risk of excess dosing with a combo.


• Debate:

– No evidence that fever itself is harmful3

– Do not prevent febrile seizures.4

– No evidence treating fever mild harmful.

– Goal should be comfort5 (not adequately studied)

• Adverse events of ibuprofen as compared acetaminophen

– Asthma: Ibuprofen no risk or perhaps slightly lower6

– Reye Syndrome: No increased risk7,8

– GI Effect & Renal: No evidence of risk.9 • Warning if a child is not “drinking reasonably well.”5

– “Systemic” Reaction: No evidence of risk7


• Bottom-line: Treatment of pediatric fever is debated and should be discussed with parents/patients.

• If recommending a treatment, ibuprofen offers superior fever reduction with no increase in adverse events.

Opioids always trump NSAIDs • A 11 year old boy has a rolled ankle. It looks pretty bad but

X-ray is negative. His mom asks about pain medications.• You say: Here’s acetaminophen with codiene, it’s the best.

• False: Ibuprofen best. 3 trials of pediatric MSK injury • 336 children; ibuprofen, acetaminophen or codiene.1

– Ibuprofen better than either (for pain score and attaining “adequate” pain relief.

• 68 children; ibuprofen or aceta+codiene2

– No difference in pain scores.

• 336 children; ibuprofen vs acetaminophen+codeine3

– No difference in mean pain scores– Ibuprofen less functional limitation & adverse events

1) Pediatrics 2007;119:460-7. 2) Acad Emerg Med 2009;16(8):711-716. 3) Ann Emerg Med 2009 Oct;54(4):553-60. Epub 2009 Aug 19.

ENT: Pediatric cough

• 2 children (age 3 & 5) are in coughing with an URTI. Mom would like a suggestion about an OTC cough med or even honey.

• You say: OTC medicines & honey have no effect on cough in pediatric patients?

• True– Meta-analysis1,2: 8 studies, 616 kids, – Statistical improvements were very infrequent, not

consistent and of doubtful clinical significance. – Honey3: 1 RCT of 105 kids, honey vs DM vs nothing– Stat sign but never reached clinical significance

1. Cochrane 2008; 1: CD001831. 2. Arch Dis Child 2002;86:170–175. 3. Arch Pediatr Adolesc Med 2007;161:1140-6.

Pediatric Cough: Do Honey or OTC cough suppressants help?

• 2 children (age 3 & 5) are in coughing with an URTI. Mom asks about an OTC cough med or even honey.

• You say: OTC medicines & honey have no effect on cough in pediatric patients?

• OTC Cough Suppressants: Cochrane sys review1

– 8 RCTs (poor quality), 616 children, in pediatric/primary clinics. Mean ages 2 to 7.5 years.

– Outcomes: cough scores, number of patients who were cough free, patient rated improvement/satisfaction & parent evaluations.

– Statistical improvements were very infrequent, not consistent and of doubtful clinical significance.

Pediatric Cough: Do Honey or OTC cough suppressants help?

• Honey: One RCT of 105 kids, mean age 5: one night-time dose of honey, Dextromethorphan (DM), or nothing.2

– Authors report honey best, stat significant improvement in:

• 5 out of 5 different cough/sleep scores, Honey> DM> nothing.• In 2 out 5 paired comparison, honey statistically > “nothing”

– BUT: Neither honey or DM got to the study defined clinically important improvements vs no treatment

– AND randomization not assured & funding=Honey Board– Cochrane review felt evidence insufficient evidence3

1. Cochran 2008;1:CD001831 2. Arch Pediatr Adolesc Med 2007;161:1140-6. 3. Cochran 2010; 1:CD007094 4. J Fam Pract 2009;58:559a-c. Am Fam Physician 2007;75(4):515-20

Sleepless in Seattle

• A young mother is frazzled by her sleepless 1 y.o. infant. She is considering Benadryl?

• You say: We don’t know if it works

• False: We know it doesn’t!

• RCT 44 kids 6-15 months. – 3 (14%) placebo vs 1 (5%) in diphenhydramine

got better night-time sleeping.– No diff in parental happiness

Arch Pediatr Adoles Med. 2006;160:707-712

Holding your Cookies• A 6 year old is in with his mother. He is vomiting

and looks mild+ dehydrated. Mom is worried that he ended in ER last time & asks if there is anything.

• You Say: There is nothing we can offer him.• False: Sys Rev, Ondansetron (6 trials, 745 pts) ER

trials– Ondansetron usually one dose: IV 0.15-0.3 mg/kg OR

oral 2-8mg or 1.6 – 4 mg (wgt/age based). • Outcomes

– Admission: 7.5% vs 14.6% (NNT 14)– Need IVF: 13.9% vs 33.9% (NNT 75)– Still vomiting in ER: 16.9% vs 37.8% (NNT 5)– Caused more diarrhea in 48 hours (No # given)

Arch Pediatr Adolesc Med 2008; 162(9): 858-65.

ENT: Mild Croup

• A 3 year old child is in with his mother. He has a barking cough and mom reports a classic stridor episode early today. She is concerned and would like a medicine.

• You say: Dexamethasone only benefits patients with moderate to severe croup.

• False – RCT, 720pts, mild croup, oral 0.6mg/kg, 1 dose – Return med care: 15% vs 7% (NNT 13)

1. NEJM 2004; 351: 1306-13.

Dermatology

Lacerations: Sterile Gloves & Water?

• Clinical Question: In the management of simple lacerations, are sterile gloves and sterile saline required to reduce infection?


• Sterile Gloves: RCT, sterile vs non-sterile gloves, suturing lacerations.1 – 816 patients (age ≥ 1), blinding patients & outcome

assessors.– Infection rates (23 days): 4.3% non-sterile vs 6% sterile

(no stat diff).

• Sterile Water: Cochrane, 3 RCTs (1338 pts) meta-analysis, tap water vs saline, irrigation.2

– Infection rates: 4.4% tap water vs 7% saline, (stat diff p=0.045).

– 2 largest RCT (94% of pts) used sterile saline, one small study (77 pts) used non-sterile saline (so not perfect sterile vs non)


• Only RCT of non-sterile gloves but high quality & reasonable in size.

• 2 older studies (50 & 408 pts),3,4 no gloves vs sterile gloves– Infections did not increase. – Significant quality limitations (randomization) & suturing without

gloves is not appropriate.– However, support that sterile gloves likely offer little advantage.

• In the Cochrane review of tap water, possible saline increasing infection but – But includes a small study of non-sterile saline & one of questionable

randomization. – Focusing on best study - high quality RCT of 713 pts comparing tap

water and sterile saline with no difference in infections.5


• Bottom-line: The present evidence indicates simple lacerations can be cleaned with tap water and repaired with clean non-sterile gloves without an increased risk of infection.

Punch with or without sutures• Diagnosis of persistent rash has eluded you. You

take a 4 mm punch biopsy. • You say: Suturing biopsies <4mm is not helpful• RCT, 9 Month f/u, 82 (164 wounds) – mean age 47

(70% ♀)1

– 4 mm: Docs VAS score =, pt pref = (slight favor 2nd)– 8mm: Doc VAS score = (thigh scar size > 2nd), pt pref is 1°

(NNT=9 “very satisfied” & NNT=3 preferred 1°)– 1° healed 3 vs 4 wks, ↓ pain (NNT=9), no diff

bleed/infection– Can use absorbable.2

Arch Dermatol 2005; 141: 1093-99. Dermatol surg 2000; 26: 750-2

Acne: What’s on First?

• A 20 y.o. ♂ complains of facial acne, has moderate severity & wants oral Abx.

• You say: Topical meds are just as effective. • True: RCT, 650 pts x18 wks, 5 arms

– Oral: Tetracycline 500 BID; Minocycline 100 OD– Topical: 5% B.P. (BID); 5% B.P. with 3% Erythro (BID);

2% Erythro (am) and 5% B.P. (qhs).

• No Diff (except AE: oral was GI, Topical was skin)

– cost: Minocycline 8x Erythro + BP– Erythro + B.P. (63-66%) vs oral Abx (54-55%)

•Lancet 2004; 364: 2188-95.

Vitamins & cure-alls

Fan of Fads: Vitamin D

• A 55 year old woman wonders if she should take Vitamin D and does she need a test?

• 3 Met-analysis show it helps (stat sign)– Fracture (19 trials)1: >400IU/day Vitamin D

• Reduced Non-vertebral fractures 1.1%, NNT 93

– Falls (5 trials)2: Reduced 7%, NNT 15 – Mortality (18 trials)3: ↓ Mortality ~ 0.4%, NNT 147

• Study1-3 doses varied but the most common was 800IU.

Fan of Fads: Vitamin D• Vitamin D insufficiency is variably defined but

frequently cited at <75nmol/L4-6

• Vitamin D insufficiency is highly prevalent – Calgary5, 97% had levels <80nmol/L, once/year– UK6, 87% had levels <75nmol/L, once/year– USA7, 77% had levels <75nmol/L

• Holik review: screening not recommended but daily Vitamin D of 800 IU does recommend.4

• Bottom-line: Vitamin D 800 IU (or 1000) daily reduces fractures, falls and overall mortality in older patients (likely ≥50 years old). There is currently no high level evidence to support regular testing older patients for Vitamin D insufficiency.

What’s the approach to Vitamin D: Toxicity:

• Review of doses 2,000 – 100,000 IU

- no toxicity BUT

- big doses were 4 days only or bolus q 4 months

- 21 studies: 20 had <250 patients

most < 1 year

• RCT, 2256 pts, ≥70 years, followed 3-5 years- Given yearly 500,000 IU or placebo

- Falls (≥1): 74% Vit D vs 68% placebo, NNT 18 (Rate ↑)

- Fractures: 4.9%/year Vit D vs 3.9%/year placebo

Am J Clin Nutr 2007;85:6 –18. JAMA. 2010;303(18):1815-1822

Vitamin B12 Deficiency: Monthly shots or daily pills?

• Mrs Jones, a 73 year old woman has long-standing B12 def. Last year she lost her license and she tells you taking a cab is quite pricey for her (for these B12 shots).

• You say: Why don’t we try B12 pills?• Evidence: Cochrane Review1 of 2 RCTs2,3

– 38 outpatients & 70 patients: • 3-4 month oral B12 as effective as IM therapy1 in:

– B12 levels and associated biochemical B12 markers (total homocysteine and serum methylmalonic acid)

– Hematological and neurological responses. – Both trials limited: small, short, unblinded & lack ITT

Vitamin B12 Deficiency: Monthly shots or daily pills?

• 5-20% of elderly patients are B12 deficiency4

• Well-designed, longer (18 months) cohort study showed that 1000mcg orally a day was effective7 – Review also recommends 1000 mcg orally a day8

• Works in B12 def dietary, pernicious anemia, gastric or ileal surgery, malabsorption syndrome2,3,7 – Celiac disease and IBD are not well studied.

• Bottom-line: Oral Vitamin B12 is as effective as IM in most B12 deficient patients. A dose of 1000mcg (1mg) orally a day appears to be adequate and most commonly recommended. – Patients switched to oral should likely have their B12

levels checked to confirm they are not declining.9

Antioxidant vitamin cure-alls• Case: A 65 year old female is taking vitamin E and B-

carotene (Vit A). She has mild congitive impairment but is otherwise well.

• Question: Anti-oxidants vitamins (A, E and C)? • Meta-analysis1,2 of 68 RCT

– 232,606 (70% healthy, 30% pre-existing).1 • Focusing on high-quality RCTs:

– Antioxidants increased mortality: RR1.05 (1.02-1.08)1 & NNH=180.3 – Beta carotene, A and E individually statistically significant

• No statistical diff in mortality for vitamin C or selenium.2 • Previous meta-analyses4,5 & new RCTs find similar results6,7

• Bottom-line: Patients should be dissuaded from using beta-carotene and vitamins A & E as may increase mortality.

Motivating Patients to Activity – A Light at the End of the Couch?

• Clinical Question: How do I motivate my patients to participate in regular physical activity?

• 2007 review (26 studies, 2767 pts) pedometers physical activity levels & improve health.1 – Pedometers steps/day 2491 in RCTs & 2183 in observational.– “Step goal” predicted increased activity (work-up to 10,000 steps/day) – Mean intervention duration was 18 weeks.– Heterogeneity in study design & corresponding results (p<0.001).


• 2009 lower quality review (32 studies) of pedometers,2

– An increase of approximately 2000 steps per day. – Benefit of “step goal” (p<0.001)– Benefits in studies >15 weeks were not less than shorter studies.

• Newer RCTs show pedometers increase steps per day by approximately 2000 or more.3,4 – Including sustained results up to 1 year.4


• Activity reduces mortality, Examples,– Cohort study (252,925 pts): regular moderate activity (brisk

walking ≥30 minutes most days), 27% relative decrease in mortality vs no activity5

• Regular vigorous activity reduced mortality 50%. – Cohort study (9,777 men): mortality rates of active men

33% that of inactive men6 • Active 40/10,000 patient years • Inactive 122/10,000 patient years


• Other benefits of pedometers include– Weight reductions 1.3 kg (CI 0.7kg-1.8kg) over 16 weeks7

– Reduced systolic BP 3.8 mmHg (p<0.001) over 18 weeks1

– Improved blood sugar readings in patients with impaired glucose tolerance up to 12 months later4:

• Fasting glucose reduced 0.31 mmol/L (CI 0.03-0.59)• 2 hour glucose reduced 1.3 mmol/L (CI 0.4-2.2)

– Can cost less than $30.


• Bottom-line: Pedometers, used with specific exercise goals, provide an inexpensive, tangible measure of a patient’s physical activity, and have been demonstrated to increase physical activity levels.


• Implementation: Written, goal oriented exercise program increase physical activity levels.8

• A sample “prescription” for pedometer,– Wear your pedometer every day for one week. – Calculate your daily steps (feel free to average to the closest 1000

increment). – Add 500 steps per day to your daily average. Walk that each day

for the next week. – Repeat step 3, adding 500 steps to last week’s daily goal and walk

that each day for the next week. – Continue to your target of 10,000 steps per day.

Promise to Disappointment

• Testosterone (transdermal gel) in older men:– CVD: All (21.7% vs 4.9%, p<0.001, NNH 6),

• Events: increase BP or syncope all the way to stroke/MI & death. • More serious CVD events: NNH 12 (stat sign)

• Sibutramine in Diabetics and CVD risk:– Wgt= 1.7kg loss vs 0.7 gain, 1 yr (slow gain after)

• CVD composite: 11.4% sib vs 10% plac, NNH 72• Nonfatal MI: 4.1% vs 3.2%, NNH 112• Nonfatal stroke: 2.6% vs 1.9%, NNH 143

• Rimonabant in obese with higher CVD risk– CVD outcomes: composite not diff (3.9% rim vs 4% placebo),

• Neuropsych (anxiety, dep,…): 32.3% vs 21.4%, NNH 10/y• Serious Pysch (no clear): 2.5% vs 1.3%, NNH 84

NEJM 2010; 363:109-22. NEJM 2010;363:905-17. Lancet 2010; 376:517-23.

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Myth-Busting: Forgotten and Forgettable Medical Management G. Michael Allan Associate Professor, Family Med, U of A