Presenter: Dr. Michael Allan• Speakers Bureau/Honoraria: Alberta College of Family Physicians, CFPC

Chapters, CPD Departments of Canadian Medical Schools, Misc. Medical Schools

• Consulting Fees: N/A• Grants/Research Support: Alberta College of Family Physicians, NAFMASC,

CIHR, PRIHS • Patents: N/A• Other: Paid employee of the College of Family Physicians of Canada and

University of Alberta• The Alberta College of Family Physicians has provided support in the form

of a speaker fee and/or expenses.

Presenter: Mike Kolber• Speakers Bureau/Honoraria: N/A

• Consulting Fees: N/A

• Grants/Research Support: ACFP, BCCFP, Alberta Expert Drug Committee –Honorariums for presentations and consulting

• Patents: N/A

• Other: Co-founder of for profit company helping proceduralists collect data on the quality of medical procedures – Electronic Medical Procedure Reporting Inc. Paid employee of the University of Alberta.

• The Alberta College of Family Physicians has provided support in the form of a speaker fee and/or expenses.

Presenter: Dr. Tina Korownyk• Speakers Bureau/Honoraria: Medical Director - Alberta College of Family

Physicians

• Consulting Fees: N/A• Grants/Research Support: Alberta College of Family Physicians; College of

Family Physicians of Canada, Toward Optimized Practice, CIHR, PRIHS • Patents: N/A• Other: Director PEER, Member Canadian Taskforce Preventative Healthcare

Paid employee of the University of Alberta.• The Alberta College of Family Physicians has provided support in the form

of a speaker fee and/or expenses.

Presenter Name: Adrienne Lindblad

• Speakers Bureau/Honoraria: N/A• Consulting Fees: N/A• Grants/Research Support: N/A• Patents: N/A• Other: Employee of the Alberta College of Family Physicians.

LEARNING OBJECTIVES

• Recognize high level evidence for a number of clinical questions• Incorporate best evidence in the management of a number of clinical

questions in primary care• Differentiate between interventions with minimal benefit andt hose

with strong evidence for patient - oriented outcomes

JEOPARDY 2020: Pearls from Tools for Practice

Tina Korownyk, Mike Allan, Mike Kolber, Adrienne LindbladPEER, ACFP Evidence & CPD Team

Faculty/Presenter Disclosure• Faculty/Presenters: Tina Korownyk, Mike Allan, Michael R. Kolber, Adrienne

Lindblad

• Relationships with commercial interests:– Grants/Research Support: ACFP, Toward Optimized Practice, CIHR, PRIHS, etc. – Speakers Bureau/Honoraria: AB, ON, NFLD, PEI, BC College of Family Physicians;

Multiple University CPD departments, miscellaneous conferences, Alberta Health (Expert Drug Committee), Alberta Society of Endoscopic Practice

– Consulting Fees: Not applicable– Other:

– 2 RCTs (publicly funded)– Employed by CFPC (MA), University of Alberta, Alberta Health (or ACFP - AL), locum (MA)– Electronic Medical Procedure Reporting Systems Inc (EMPRSS)– Member Canadian Taskforce Preventative Healthcare– The Alberta College of Family Physicians has provided support in the form of a speaker fee and/or expenses.

JEOPARDY

JEOPARDY

Turn around: the Epley Maneuver

Zoster vaccine: is newer better?

Z-drugs: Catch some ZZZ’s?

Relaxing back pain?

Antidepressants for IBS

Rest Easy: Infant Sleep

E-Cigs

Nauseous? Smell this

New Irons: solid evidence?

Treating Bell’s PalsySimilar enough? Biosimilars

Healing the Heal: steroids for plantar

fasciitis

Protecting your sweet heart? DPP-4

Will coffee kill you? Did that T#3 cause OUD?

Inflamed Evidence for NSAIDs?

A real fun guy: onychomycosis

Point-of-care for Group A Strep

Lung Cancer ScreeningHTCZ and SCC

Less pancakes, more bacon? Keto diet

A B C D

What’s new is old: statins & the

elderly

Isotretinoin: is lower better?

Supervised Consumption Sites

Turn around: the Epley Maneuver

Zoster vaccine: is newer better?

Z-drugs: Catch some ZZZ’s?

Relaxing back pain?

Antidepressants for IBS

Rest Easy: Infant Sleep

E-Cigs

Nauseous? Smell this

New Irons: solid evidence?

Treating Bell’s PalsySimilar enough? Biosimilars

Healing the Heal: steroids for plantar

fasciitis

Protecting your sweet heart? DPP-4

Will coffee kill you? Did that T#3 cause OUD?

Inflamed Evidence for NSAIDs?

A real fun guy: onychomycosis

Point-of-care for Group A Strep

Lung Cancer ScreeningHTCZ and SCC

Less pancakes, more bacon? Keto diet

A B C D

What’s new is old: statins & the

elderly

Isotretinoin: is lower better?

Supervised Consumption Sites

How many people need an Epley for one not to be dizzy?

• 6 sys revs: Most recent (11 RCTs, 745 pts)• Epley vs control at 24 hrs-4 wks:

• Resolution (5 RCTs, 273 pts): 56% vs 21%, NNT=3. • Negative Dix-Hallpike (8 RCTs, 507 pts): 80% vs 37%, NNT=3• Equivalent or superior to other maneuvers.

• Post-Epley movement restriction. Most no effect except,..• Negative Dix-Hallpike (9 RCTs, 528 pts): 89% vs 78%.

• Bottom-line: Epley maneuvers will lead to the complete resolution of symptoms in every 2-3 patients treated. Post-Epley movement restriction does not improve symptom resolution but might promote a negative Dix-Hallpike for one in every 10 patients treated.

TFP #144

Can Inhaled (smelling) Isopropyl Alcohol Treat Nausea in Emerg?• 2 blinded RCTs in Emergency Dept. (non-pregnant adults, mainly gastroenteritis):

• N=122, mild-moderate nausea. Randomized to inhaled isopropyl alcohol, ondansetron or both (with matching placebos). At 30 minutes from baseline 50/100 nausea scale:

• Isopropyl alcohol decreased to 20, ondansetron decreased to 40.• Higher patient satisfaction on 100-point scale with isopropyl alcohol (20 versus 44 ondansetron)• No difference: ED length of stay or vomiting rates

• N=84, baseline nausea 6/10 randomized to isopropyl alcohol or saline soaked pads. At 10 minutes:

• Lower nausea 3 versus 6 (placebo)• Patient satisfaction: 4 versus 2 out of 5 (placebo)• No serious adverse effects

• SR in post-op patients (4 RCTs, n=215): fewer patients required rescue antiemetics (26% versus 39% placebo, NNT=8), but other outcomes inconsistent.

• Bottom-Line: Smelling isopropyl alcohol improves nausea from 50/100 to 20/100 compared to 20/200 with ondansetron after 30 minutes. Adverse effects only reported in 1 study, but none found.

TFP #213, June 4, 2018

Do E-Cigs help smokers quit smoking?• Evidence: 4 large RCTs: ≥4/52 duration + objective abstinence. Patients: ~40 yo, ~1

pack/day X ~20 yrsSmokers motivated to quit: • 657 New Zealand RCT: 6 month abstinence: NEC 7%, nicotine patch 6%, or placebo ecig

4%: NSS• 886 UK RCT (publically funded): 1 year abstinence: NEC 18%, NRT 10%: NNT = 13. Smokers not intending to quit:• 300 Italian RCT: 1 year abstinence: NEC 11%, placebo EC 4% NNT=15• 1191 American workers: multi-interventions: education <1%, NRT 3%, NEC 5% (NSS)

• Monetary rewards 10%, Redeemable deposits 13%• Safety: cases of serious lung disease (EVALI): 48 deaths in US

• 80% of EVALI hospitalizations have THC in productBottom Line: Compared to NRT or placebo ecigs, two RCTs demonstrate that nicotine e-cigs aid in smoking cessation with NNT=13, 15. Two RCTs found no difference in cessation. Serious lung disease and deaths have been associated with e-cigs. THC and vitamin E acetate e-cigs should be avoided.

TFP # 252 Feb 3, 2020

GLP-1 Medications, Diabetes and Hard Outcomes ? • Liraglutide: 9340 pts, ~4 yrs: A1c 8.7% to ~7.7% v 8.1% placebo

• CVD: 13% vs 14.9%, NNT=53, Mortality: NNT=72• Gallbladder disease, NNH=83.

• Semaglutide: 3297 pts ~2 yrs: A1c 8.7% to ~7.5% v 8.3% placebo • CVD: 6.6% versus 8.9%, NNT=44, Mortality: No difference, • Retinopathy NNH=83.

• Lixisenatide: 6068 pts ~2 yrs: A1c 7.6% to ~7.3% v ~7.6% placebo • CVD or mortality: No difference.

• Neoplasm (benign/malignant) numerically up but not statistically

• Bottom-line: Semaglutide and liraglutide, but not lixisenatide, reduce CVD for ~1 in 50 diabetics with existing CVD over 2-4 years, irrespective of specific A1c targets (attaining ~7.5%). These drugs reduce weight 0.7-4.3kg, but around one in 25 more than placebo will stop due to GI. Some uncertainty around neoplasm remains.

TFP #180, Feb 6, 2017.

Can steroids shots help plantar fasciitis without rupture?

• RCT 65 pts, u/s steroid (20 mg methylprednisolone), palpation steroid or u/s placebo: 100 point VAS improve:

• U/S steroid 29 (6 wks), 34 (12 wks), palpation steroid 35 & 37, Placebo 5 & 2. (MCID ~12)

• No adverse events (i.e. rupture) reported.• RCT 82 pts, u/s steroid (4mg Dexamethasone) vs placebo. 100 point questionnaire

at 4 weeks:• Steroid: 22.1 vs Placebo 11.7 points. (MCID 13), NNT =3.• No adverse events (i.e. rupture) reported.

• Bottom-line: Small, RCTs demonstrate that corticosteroid injections significantly reduce plantar fasciitis pain for 1 in 3 people at 4 wks. Benefit beyond 12 wks has not been well demonstrated. Risk of rupture is likely less than what has been reported in observational studies.

TFP #140

Do new irons improve anemia more with less side effects?

• RCT. General population adults (at ~12 weeks) • 80 patients: iron polysaccharide (Niferex™) vs ferrous fumarate, both ~150mg/day elemental iron.

• Ferrous fumarate Hgb (28.4g/L) vs iron polysaccharide (6g/L), & others (e.g. serum ferritin) better but nausea (31% vs 3%).

• 80 children (~2 yrs ): Iron polysaccharide (NovaFerrum™) vs ferrous sulfate, same elemental iron.• Ferrous sulphate Hgb (10g/L), resolved IDA (29% vs 6%, NNT=5), less diarrhea (35% vs 58%).

• RCTs adults (n=43) & premature infants (n=32): no difference

• Subgroups: 8-26 weeks• Dialysis patients: ferrous salts vs newer – similar except ferrous sulphate better Ferritin ~(160µg/L)• Post-gastric bypass (n=14): Ferrous sulfate improved hemoglobin but not heme iron (Proferrin ES™). • Blood Donors (n=97) / pregnant patients (n=90): same but Fumarate more constipation (35% vs 14%).

• Bottom-line: Newer iron formulations likely inferior to older ferrous salts. Ferrous salts improve hemoglobin ≤10-20g/L more and ~1in 5 more attain anemia resolution at 3 months. Unclear if newer formulations have less adverse effects.

TFP #234: April 29, 2019.

Does drinking coffee impact mortality or other health outcomes in the general population?• Evidence: 400,000 (US) x 14 yrs (+ other cohorts)

• Increased mortality with coffee (but lots of confounders)• Men: About 10% relative reduction for ≥2 cups/day • Women: About 15% relative reduction for ≥2 cups/day

• Bottom-line: Coffee consumption is associated with no change or a small reduction in mortality in cohort studies. While the evidence is not strong enough to recommend non-drinkers to start consuming coffee, coffee drinkers can be reassured that it does not appear to result in excess harm (except in pregnancy).

TFP #74: October 1, 2012; CFP Volume 59: March 2013

What is the best treatment for Bell’s Palsy?

• Evidence: 2 high-quality RCTs• Unsatisfactory recovery at ≥4 months: corticosteroid 16% vs Placebo 26% (NNT 10)• Antivirals, with or without steroid, no additional benefit

• New meta-analysis: Anti-virals do not impact outcome -unless outcomes assessment is not blinded (ie detection bias).

Bottom-line: The best evidence indicates that corticosteroids (in doses of prednisolone 25 mg BID or 60 mg x5 days then tapered by 10 mg/day) improve the odds of complete recovery from Bell’s Palsy. Antivirals (used either alone or in addition to prednisolone) do not offer any additional benefit.

#4 July 9, 2009 Updated July 8, 2013. Turgeon RD Am J Med 2015

Are Biosimilars ‘Similar’ to Biologics for Inflammatory Conditions?

Switching: publicly funded non-inferior RCT of 482 IBD, RA, psoriasis pts; stable on Infliximab --> continue or switch to biosimilar • Outcomes (1 year): “Disease worsening” (~30% each arm).

• No difference for individual condition, disease remission, QOLStarting: • 7 RCTs RA (infliximab, etanercept), 1 Crohn’s (infliximab): similar outcomes (disease

improvement) @ 6-12 months• Crohn’s: 220 patients randomized: start biosimilar or biologic infliximab. • At 30 weeks: clinically relevant symptom improvement: 77% biosim, 75% biologic.Bottom Line: Biosimilars and biologics have similar clinical outcomes and adverse events. Given cost, starting or switching to biosimilars should be encouraged.

TFP # 236, May 2019.

What is the clinical (macro vs micro-vascular) benefit of DPP-4? • 4 systematic reviews, 3 RCTs (36,543 pts) over ~2.5yrs Vs placebo, DPP4-inhibitors:

• Improved HbA1c: 0.3-0.5%• No effect on CVD outcomes, Overall or CVD mortality, MI, or stroke.

• In those with or without previous CVD: No CVD benefit.3

• 3 other systematic reviews (with smaller studies) find similar

• Microvascular: Neuropathy – no studies. • Retinopathy: Meta (7 RCTs), DPP-4 increased risk (vs placebo):11 NNH=430• Nephropathy: 2 meta & one large RCT (~7K pts)

• DPP-4 improve albuminuria: progression in 6% vs 7.5% placebo (NNT=30)• Do not improve renal composite outcome of ESRD, death, or 40% decline GFR vs placebo

• Bottom-line: DPP-4 inhibitors have no effect on patient-oriented outcomes like CVD (ie. MI or stroke) or death. They increase the risk of hypoglycemia, pancreatitis and likely heart failure hospitalization. Second line therapies should focus on drugs that reduce patient oriented outcomes.

TFP #150: Nov 9, 2015, updating 2019.

What’s New is Old Again: Elderly patients & Statins

• 2015 - Tools for Practice: “No evidence to start statins in primary prevention patients >75.”

• 2015 – Simplified Lipid Guideline: “Primary prevention patients > 75 yrs: We discourage routinely testing lipid levels, estimating CVD risk, and prescribing statins (moderate-level evidence).” (few rare exceptions )

• Meta-analysis of 186,854 pts (8% age ≥75) from 28 RCTs, followed ~5yrs• Divided up by 5 year age increments & with or without past CVD.

TFP #129, Jan 5, 2015. Can Fam Physician 2015; 61: 857-867. Lancet 2019; 393: 407–15

Lancet 2019; 393: 407–15

All the same

If past CVD, statins reasonable regardless of age.

If past CVD, statins reasonable regardless of age.

If no past CVD, statins generally reasonable. But, once elderly (>75) they may not work.

Lancet 2019; 393: 407–15

What is the Risk of OUD after prescribed Opioids?

• Systematic review (12 studies, 310,408 pain patients): opioids ≥3 mons

• Incidence of OUD = 3.1% in higher quality studies (4.7% if all) • Diagnostic criteria = incidence varies (from 1-11%)

• Systematic review (24 studies, 2507 pain patients): ~26 mons• Incidence of OUD = 3.3% • 0.2% without a history of “substance abuse/addiction” versus 5% with.

• Prevalence: 0.05%-23%. differing study quality, diagnostic criteria/terminology, inconsistent reporting, and populations studied.

• Bottom Line: Prescribed opioids in chronic pain associated with OUD ~3% (over ~2 years) but causation uncertain. Factors associated with lower risk are: No history of substance use disorders, shorter durations or lower doses.

TFP #240July 22, 2019.

Do NSAIDs reduce inflammation?• NSAIDs vs Other drugs: 10 soft tissue injury RCTs.

• Mostly no difference NSAIDs (e.g diclofenac 150mg/day) vs acetaminophen and/or opioids. Except for (at 3 days),…

• 1 RCT: naproxen 1100mg/d ~6% less swelling.• 1 RCT: diclofenac 150mg/day ~8% more swelling

• NSAID vs Placebo: 8 RCTs (e.g ibuprofen 2400mg/d)• 2 RCTS No difference in volumetric measures or % with swelling • 3 RCTs Volumetrically less (2-11%) • 2 RCTs report “no swelling”: 71% NSAID vs 35% & 20% NSAID vs 48%

• Bottom-line: RCTs of NSAIDs effect on MSK injury swelling are highly inconsistent: Some slight improvements (2-11%), some slight worsening (8%) and most no effect. It is unlikely NSAIDs have any reliable effect on acute injury swelling but they do improve pain for ~1 in 4 over 1 week.

#159. March 29, 2016

Toenail Onychomycosis• Oral: meta-analysis 43 RCTs (9700 patients), example 65% nail involvement. Tx for

12-16 weeks. Follow-up 4 months-2 years. Clinical cure:• Terbinafine (8 RCTs) : 48% versus 6% placebo, NNT=3.• “Azoles” (9 RCTs): 31% versus 1% placebo, NNT=4.• Terbinafine vs azoles (15 RCTs): 58% versus 46%, NNT=9.

• Topicals: ~40% nail involvement, tx for 36-48 weeks. Clinical and micrological cure:• Ciclopirox: 3 RCTs, 6-8% versus 1% placebo, NNT=15-23.• Efinaconazole: 3 RCTs, 16-22% versus 4-9% placebo, NNT~9.

• Bottom Line: Up to 45-60% of patients on oral treatments (terbinafine best), 6-22% on topicals (efinaconazole best), and <10% on placebo will be “cured” after ~1 year. Topicals should be reserved for cases with minimal (<40%) nail involvement.

#242. December 20, 2019

For patients with acute gout, is colchicine an effective treatment and when would its use be indicated?

• Evidence: Low dose (1.2 + 0.6 at 1 hr) vs Placebo,• 50% reduction in pain 38% vs 16% (NNT 5)• High dose no better but more side effects• Diarrhea: High dose NNH 2; Nausea NNH 8

• Bottom-line: Colchicine is a reasonable option for the treatment of acute gout, especially in patients in whom NSAIDs are contraindicated. Optimal dosing which balances treatment benefit with potential adverse events still remains to be determined, but low dose is recommended.

#57 November 29, 2011.

Do supervised injection sites (SIS) reduce mortality, hospitalizations ambulance calls or disease transmission? • Evidence: Mortality: pre and post SIS opening

• 253 165/100,000 PYs = 1 less OD death / 1137 users

• Hospitalizations: indirect comparisons• ↓ admissions for skin infections (differing cohorts)• Nurse referral ↑admissions, but ↓ LOS

• Ambulance calls for OD: ↓ 67%• HIV transmission: ↓: limited by modeling, not counting HBV, needle

exchange confounderBottom-line: Best evidence from cohort or modeling studies suggest that SIS are associated with lower overdose mortality (88 fewer overdose deaths/100,000 person years), 67% fewer ambulance calls for overdoses and decrease in HIV infections. Effects on hospitalizations are unknown.

TFP # 195 Sept 2017, Can Fam Phys 2017: 866.

Does screening high-risk individuals with low dose CT (LDCT) result in reduced lung cancer mortality?

2 Large RCTs: Current or former smokers, age ~50-74 • 53,454 smokers (30-py). LDCT or chest x-ray annually x 3, followed 5 years.

• Lung cancer mortality: 1.3% vs 1.7%, NNS = 306 x 8 years• Overall mortality: 7.0% versus 7.5%, NNS 217• Concerns: 96.4% of positive LDCTs were false positives.

• 15 792 smokers. LDCT x 4 up to 5.5 years or no screening, followed ~ 10 years.• Lung cancer mortality: 2.4% versus 3.2%, NNS = 134 x 10 years• All cancer mortality: 7.3% versus 7.5% Not Sign• Overall Mortality: 13.9% versus 13.8% Not Sign• Concerns: downstream harms including needle biopsies, surgeries or complications not

reported• Indeterminate tests requiring further testing: 2069/22 600 (9.2%)

Bottom Line: Screening for lung cancer with LDCT has demonstrated a reduction in lung cancer mortality. Impact on overall mortality is conflicting. The high number of false positives, which require further, sometimes invasive investigations, remains a concern. Smoking cessation should remain the priority to decrease lung cancer mortality.

TFP #78, updated Feb 2020.

Does hydrochlorothiazide increase the risk of squamous cell carcinoma (SCC) of the skin?

Systematic review: 2 cohort and 7 case-control studies (395,789 patients)• SCC and thiazide diuretics: Odds Ratio (OR)=1.9

• Subgroup: HCTZ / HCTZ combinations SCC risk: OR=2• Long-term HCTZ (≥4.5 years) SCC risk OR=3.3

• Largest case-control study: 80,162 SCC cases• HCTZ ≥50,000mg cumulative dose (~6 years) SCC risk: OR=4.• Dose-response relationship (~20 years) SCC risk: OR=7.4• Dose-response effect SCC lip cancer (~10 years): OR=7.7

• Baseline SCC risk varies with ethnicity, age, sex, and geography• UK cohort <0.1% per year, metastasis in 1.1-2.4%

• Thiazide and thiazide-like agents reduce morbidity and mortality • Bottom Line: Observational data suggest an association between HCTZ and SCC. Risk

appears to consistently increase with dose and duration (example: 5 years of use increases risk 3-4 times). Baseline incidence of SCC is <0.1% annually. The same risk has not been established with thiazide-like diuretics (like indapamide or chlorthalidone).

Does Cyclobenzaprine improve Back Pain? • Muscle relaxants vs placebo: 3 sys rev (9-46 RCTs, 820-5401 pts),

• Pain: ~12 points on 100 VAS at 10 d• Pain target: NNT 4-7 at 2-7 days

• Cyclobenzaprine vs Placebo: • 1 Sys review (14 RCTs, 3023 pts): Global improve, NNT 3 at ~14 days• 2 RCTs on Dosing: 1384 patients at 7 days

• Backache: 50% 5mg TID vs 38% placebo, NNT 9 (No diff: 5mg vs 10mg)• 2 RCTs of Extended or Immediate Release: 504 patients at 4 days

• Global improve: NNT 7 (No diff: ER 30mg OD vs IR 10mg TID)• Somnolence: 10% placebo, 29% for 5mg TID, 38% for 10mg TID• Bottom-line: Cyclobenzaprine provides reduced pain and global improvement over

placebo for one in every 3-9 patients in the first week. Cyclobenzaprine is as good or better than diazepam. Cyclobenzaprine 5mg TID is as effective as 10mg TID with less somnolence.

#143 July 20, 2015

How accurate are point-of-care tests in the diagnosis of Group A beta-hemolytic streptococcal pharyngitis?

Rapid antigen detection tests versus culture: 3 systematic reviews, 43-98 studies, (18 464-101 121 patients)

• Sensitivity ~85%, Specificity ~95%. • LR+ 16.8, LR- 0.16

Nucleic acid detection tests versus culture: 1 systematic review, 6 studies (1937 patients)• Sensitivity=92%, Specificity=99%.• LR+ 92, LR- 0.08

• Limitations: studies had high heterogeneity, test not currently funded publicly.Clinical decision rules (i.e. CENTOR) have limited predictive value:

• Sensitivity=49% specificity=82%.• Many international guidelines consider GABHS pharyngitis self-limiting and do not recommend

treatment. • Antibiotics reduce: Sore throat day three: 44% versus 71%, (NNT)=4

• Peritonsillar abscess 0.1% versus 2%, NNT=47• Rheumatic fever 0.6% versus 1.7%, NNT=90

Bottom Line: Point-of-care testing is useful for ruling in a diagnosis of GABHS when positive (specificity 95%-99%). Nucleic acid detection tests may be more sensitive (92% versus 85%).

Are high doses better than low doses in CHF patients?

• Evidence: largest 5 RCTs: 2 BB, 2 ACE, 1 ARB• typically ♂ 60–70 yo, class 2 HF, previously on or tolerated

study medication (or run in)• All-cause mortality: no difference: (3 studies)

• ARB RCT: death or admission for HF: 43% vs 46%, NNT =30 (driven by admits)

• ↑AEs: patients: dose reduce (NNH 5), stop meds (NNH 13-50)• Bottom-line: Higher dose ACEI, BB (compared to lower doses),

result in non-significant ↓in death, and inconsistent ↓ in HF hospitalizations. High dose patients may have 4-15% ↑in dizziness or hypotension, 20% ↑require dose reductions and 2-8% will stop medications. Start on low doses and focusing on tolerability.

TFP #174: Nov 7, 2016

How well do z-drugs work for insomnia?• 7 sys reviews with 3-48 RCTs (96-10,926 pts). Vs placebo,

• Falling asleep faster: ~13-22 minutes.• Total sleep time: Not diff except by patient diary, 32 minutes more.• Perceived sleep quality: No diff in 2 meta-analyses. Another (SMD 0.48).• Time asleep while in bed: no difference or improved ~5%.

• Adverse effects:• Meta-analysis 367 patients: No effects on speed of processing, working/verbal memory or attention nine

hours after drug administration, except• Zolpiderm: Verbal memory (+ zopiclone) & attention down (SMD 0.42-0.56)

• Meta-analysis (13,211 pts): increased mild infections (6.9% vs. 4.6%, x36 d)

• Bottom-line: Z-drugs help people fall asleep faster (~13-22 minutes) & perhaps get ~5% more time sleeping. Z-drugs may increase the risk of mild infections (one in 43 pts) & have some inconsistent cognitive effects like reduced verbal memory or attention.

TFP #126 Nov 24 2014

Recombinant Zoster Vaccine (ShingrixTM)

• Live zoster vaccine: Zostavax TM: @ 60: 60 / 360• Recombinant VZ (Shingrix TM Two industry supported placebo-controlled RCTs in patients without

shingles or previous vaccine. Outcomes converted to 3 years.• Shingles (Adults >50 yo):

• RZV: 0.08 vs 2.7% placebo, NNT~40 (40/440)• Shingles (Adults > 70 yo):

• Recombinant:2 0.4% vs 3.5% placebo, NNT ~30 (@ 70: 30 /330)• Comparable live vax (pts ≥ 60 years): NNT~60.

• Indirect comparison: NNV 112 with RZV for 1 less HZ compared to LZV• Post Herpetic Neuralgia: All ages: Recombinant: NNT= 422, Live ~360• RZV: 2 doses, costs: 320$ vs 200$Bottom Line: RZV prevents 1 additional case of shingles for ~40 patients treated compared to 1 for ~60-70 with live vaccine. Both vaccines ↓ risk of post-herpetic neuralgia. RVZ is more expensive and requires 2 injections.

TFP #224 Nov 2018, # 77 Nov 2012 NEJM 2015; 372:2087, NEJM 2016; 375: 1019, NEJM 2005; 352:2271.

Ketogenic diet for weight loss• Most relevant systematic reviews compared to low-fat diet:

• 13 RCTs, n=1577. At 12-24 months, keto:• Lost 0.9 kg more• Meaningless changes in surrogate markers (LDL 0.12 mmol/l higher).• Drop-outs 13-84%

• 11 RCTs, n=1369. At 6-24 months, keto:• Lost 2.2 kg more, but results inconsistent• No difference if focus on higher quality studies• No RCTs examined mortality or CVD

• 2018 RCT, n=609. At 1 year: • Low-CHO 6kg loss versus 5.3 kg low fat (no statistically different)• Patient genotypes had no impact on weight loss.• Individual weight change varied -30 to +10kg.

• Bottom Line: At best, keto helps patients lose ~2kg more than low-fat diet at 1 year (highest quality=no difference). Weight loss peaks ~5 months, but not sustained. An individual’s weight change can vary -30 to +10kg with any diet. No RCTs on mortality or CVD. 23andme won’t help.

TFP #220, Sept 24, 2018

Do antidepressants improve IBS symptoms?• Evidence: SR: 18 RCTs; 1127 adult patients; 42-100% ♀. Patient reported

outcomes (where available).

• Limitations: sample sizes, short duration, likely publication bias. • TCAs for IBS-diarrhea subtype, SSRIs for IBS-constipation subtype.Bottom Line: TCAs and SSRIs may improve overall IBS symptoms. ~ 55% of patients treated with TCAs or SSRIs will benefit compared to ~35% with placebo. TCA studies reported more drowsiness and dry mouth.

TFP # 251: Jan 2020, Am J Gastro 2019; 114(1): 21

MedicationClass

# RCTs; pts Global Symptom Improvement

Abd Pain improvement

Adverse Events

TCAs 12; 787 57% vs 36% NNT = 5

T59% vs 28%NNT=4

36% vs 20%NNH=7

SSRIs 7; 356 55% vs 33%NNT=5

45% vs 26%NSS

37% vs 27%NSS

Is low dose Accutane as effective and safer?• 3 RCTs: conventional to low dosing:

• 60 moderate acne pts, ~0.25mg/kg/d vs ~0.5mg/kg/d x24 wks• Equal efficacy but better satisfaction (76% very satisfied vs 31%)

• 150 severe acne pts, 0.1mg/kg/d vs 1.0mg/kg/d x20 wks: equal • 16-35% fewer common AE (chapped lips, dry skin & epistaxis)• More relapse: low to high dose: 42% vs 10%

• 120 pts, 20mg alternating days vs 1mg/kg/day x16 wks: ↓ acne 95% vs 81%• 638 patients cohort, 20mg/day x24 wks:“good results” in ~94%, ↓ AE and 5% relapse at 4

years. • Bottom-line: Small RCTs and observational studies demonstrate low-dose (~20mg/day)

isotretinoin improves acne similar to conventional dosing. Low-dose may ↓side effects (chapped lips, dry skin, epistaxis) by 16-35% but may be associated with increased relapse rates, particularly with severe acne (perhaps lowered if max accumulated dose reached).

TFP #158: March 14, 2016; Can Fam Physician. 2016;62:409.

Infant Sleep Training• 2 large RCTs, n=235-328, age 7 months, with “infant sleep problems”1) 6-week RCT: sleep training (compared to safety education) reduced:

• Severe sleep problems 4% vs 14%, NNT=10• # with >2 awakenings/night: 31% vs 60%, NNT=4

2) Cluster RCT. Sleep intervention (training) compared to usual care @ 10 months:• ↓ Infant sleep problems: 56% vs 68%, NNT=9• ↓ Mom’s with depression: 28% vs 35% (NSS)

At 2 years: reduced depressive symptoms 15% vs 26%, NNT=9At 5 years: no diff in any outcome: child behaviour, mom mental health…• Bottom Line: Sleep training improves infant sleep problems with about 1 in 4 to 1 in 10

benefitting over no sleep training, with no adverse effects reported after 5 years. May also improve maternal mood.

TFP #160, April 11, 2016 .

END

What are the Risks and Benefits of PSA screening?

• Bottom-Line: Men going for screening should likely have a conversation about risks & benefit?

Time NNS (Screen) NNT9 yrs 1410 4814 yrs 293 12

Does drinking coffee impact mortality or other health outcomes in the general population?

• Evidence: 400,000 (US) x 14 yrs (+ other cohorts)• Increased mortality with coffee (but lots of confounders)• Men: About 10% relative reduction for ≥2 cups/day • Women: About 15% relative reduction for ≥2 cups/day

• Bottom-line: Coffee consumption is associated with no change or a small reduction in mortality in cohort studies. While the evidence is not strong enough to recommend non-drinkers to start consuming coffee, coffee drinkers can be reassured that it does not appear to result in excess harm (except in pregnancy).

TFP #74: October 1, 2012; CFP Volume 59: March 2013.

What is the Risk of OUD after prescribed Opioids?

• Systematic review (12 studies, 310,408 pain patients): opioids ≥3 mons • Incidence of OUD = 3.1% in higher quality studies (4.7% if all) • Diagnostic criteria = incidence varies (from 1-11%)

• Systematic review (24 studies, 2507 pain patients): ~26 mons• Incidence of OUD = 3.3% • 0.2% without a history of “substance abuse/addiction” versus 5% with.

• Prevalence: 0.05%-23%. differing study quality, diagnostic criteria/terminology, inconsistent reporting, and populations studied.

• Bottom Line: Prescribed opioids in chronic pain associated with OUD ~3% (over ~2 years) but causation uncertain. Factors associated with lower risk are: No history of substance use disorders, shorter durations or lower doses.

TFP #240July 22, 2019

Will Spending less time in bed make you more well rested?

• 7 RCTs: 20-179 patients, 4-24 weeks, vs sleep hygiene. Findings:• Sleep efficiency: 4/6 RCTs: 79-87% with SRT vs 68-79%.• Sleep Latency: 3/6 studies, SRT: Asleep 6-19 mins faster vs control.• Other Outcomes: Total Time Asleep no better.

• NNT=2 any improve to NNT=6 remission.• Stopping hypnotic medications: 53% with SRT vs 15%, NNT=3.

• Best RCT (highest quality and used primary care patients): All 97 patients got sleep hygiene advice and half randomized to SRT.

• SRT: sleep script from GP + 1 follow-up (then self-administered). • Results similar to above, plus: sleep quality better & less fatigue

• Bottom-line: Sleep restriction therapy (SRT) improves time to fall asleep by 12 minutes and time asleep while in bed by 5-10%. Sleep restriction will improve sleep for one in every two to six patients compared to sleep hygiene alone.

TFP #188: Can Fam Physician. 2017 Aug;63(8):613.