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UPDATE IN OUTPATIENT MEDICINE
2017 Neil Argyle, MD, MPH
Associate Chief of Staff for Education
VISN 20 Academic Affiliations Officer
Boise VAMC
DISCLOSURES
• I have no relationships with any entity producing,
marketing, re-selling, or distributing health care
goods or services consumed by or used on
patients.
• I’m a Chicago Cubs fan, and I truly believe this
will be “our” year… again… Go Cubs!
• I’ll be using Poll Everywhere today, use your
phone, go to: PollEv.com/NEILARGYLE251 to
access polls for today, or text neilargyle 251 to
37607 to join the session, then text your answer.
OBJECTIVES
• Update on Literature published in the last year
• Change the way you practice medicine
• Introduce you to emerging EBM
• Keep you awake
• Not embarrass myself
CASE 1: MS. LOE IRONS
• Ms. Irons is a 40 yo woman who presents to your office for
routine follow-up. She states she maybe has a little bit of low
energy, but overall is doing quite well.
• PE: unremarkable
• VS: normal
• Labs: low normal Hgb/Hct, TSH: WNL, FT4: WNL, Iron: low, Iron
saturation: low, TIBC: high.
CASE 1: MS. LOE IRONS
• What do you do next?
• A: Start her on Ferrous Sulfate three times daily
• B: Start her on Ferrous Sulfate twice daily
• C: Start her on Ferrous Sulfate once daily
• D: Start her on Ferrous Sulfate once, every other day
• E: Give her an infusion of Iron Dextran in the infusion clinic
• F: Tell her to suck it up, check her labs in a few months, and
if her Hgb/Hct fall out of the normal range, then consider
doing something… but in the mean time, she should eat a
steak… yum… steak.
CASE 1: MS. LOE IRONS
• What do you do next?
• A: Start her on Ferrous Sulfate three times daily
• B: Start her on Ferrous Sulfate twice daily
• C: Start her on Ferrous Sulfate once daily
• D: Start her on Ferrous Sulfate once, every other day
• E: Give her an infusion of Iron Dextran in the infusion clinic
• F: Tell her to suck it up, check her labs in a few months, and
if her Hgb/Hct fall out of the normal range, then consider
doing something… but in the mean time, she should eat a
steak … yum… steak.
PATHOPHYSIOLOGY
• Daily iron supplements, in single doses or divided doses increases
serum hepcidin and thus reduces iron absorption and iron levels.
• Hepcidin, a protein, synthesized in the liver, normally reduces
extracellular iron in the body
• Lowers dietary iron absorption by reducing gut absorption
• Reduces iron exit from macrophages (where iron is stored)
• Reduces iron exit from liver
• (Works on the transmembrane iron transporter: ferroportin)
• Alternate day dosing optimizes iron absorption
PATHOPHYSIOLOGY
STATISTICS
• Study 1: (P = 0.0013) Statistically significant difference, 60 mg FeSO4
• Group 1: consecutive day dosing:
• Fractional iron absorption: 16.3%, total 131.0 mg absorbed
• Hepcidin higher in this group (P = 0.0031)
• Group 2: alternate day dosing:
• Fractional iron absorption: 21.8% (P = 0.0013)
• total 175.3 mg absorbed (P = 0.0010)
• Study 2: (P = 0.33) No difference between groups, 120 mg total iron administered
• Group 1: once daily dosing, Iron absorption: 11.8%, total 44.3 mg absorbed
• Group 2: twice daily dosing, Iron absorption: 13.1%, total 49.4 mg absorbed
• Serum hepcidin higher in twice daily than once daily dosing (P = 0.013)
TAKE HOME POINT
• Every other day dosing of iron appears to be more effective to replete
iron stores than standard daily or multiple-doses per day.
CASE 2: MR. FIT NESS • Mr. Ness, a 60 yo M, telemetry nurse, presents to your office for routine
follow-up. You had seen him last year and had a long discussion about
how using a Fit-Bit doesn’t actually help people lose weight. He
presents again to discuss his overall health.
• PMH: IFG, HTN, HLD, obesity
• VS: BMI of 30, afebrile, RR 20, HR 80, BP 130/80, sat 97% on RA
• Meds: metformin, Lisinopril, atorvastatin
CASE 2: MR. FIT NESS
• What do you tell him to do?
• A: If you don’t have time during the week, exercise on the
weekend.
• B: Get out and get active, it will reduce your risk of heart
disease, regardless of your BMI
• C: Take 15 min walks after eating to help improve your
blood sugars
• D: Exercise is good for your heart, more is better,
vigorous is best
• E: All of the above
CASE 2: MR. FIT NESS
• What do you tell him to do?
• A: If you don’t have time during the week, exercise on the
weekend.
• B: Get out and get active, it will reduce your risk of heart
disease, regardless of your BMI
• C: Take 15 min walks after eating to help improve your
blood sugars
• D: Exercise is good for your heart, more is better,
vigorous is best
• E: All of the above
LITERATURE
WEEKEND WARRIORS
• 63,591 adults, mean age of 58.6 years
• Compared
• Inactive: no moderate intensity activity
• Insufficiently active: (< 150 min per week of moderate intensity with
< 75 min/wk of intense activity)
• Weekend warrior: > 150 min/wk in mod intensity or > 75 min/wk
intense activity in 1-2 sessions)
• Regularly active: > 150 min/wk in mod intensity or > 75 min/wk
intense in >3 sessions
• Outcomes: all cause, CVD, and cancer mortality
WEEKEND WARRIORS
• 1-2 sessions per week of moderate to vigorous intensity physical
activity may be sufficient to reduce risks for all-cause, CVD, and cancer
mortality.
LITERATURE REVIEW
BMI AND ACTIVITY
• 5344 patients, 55 years and older, 15 years of follow-up
• 866 experienced a CV event
• Overweight & obese + low physical activity
• Higher CVD risk than normal weight participants with
high physical activity.
• Overweight and obese with HIGH physical activity
• CVD risk NOT increased
• (HR 1.03 CI: 0.82-1.29, and HR 1.12 CI 0.83-1.52)
• Beneficial impact of physical activity on CVD might
outweigh the negative impact of body mass index.
DIABETIC WALKS
DIABETIC WALKS • Inactive older adults, non-smoking
• IFG between 105-125
• 3 random exercise protocols, 4 weeks apart
• 48 hour stay in observed room
• Day 1 was control
• Day 2 was intervention
• Post meal walking for 15 min or 45 min of sustained walking at 1030 am or 430 pm
• Walking done on treadmill, with absolute intensity of 3 METs
• Continuous glucose monitoring
• Sustained morning walking and post-meal walking significantly improved 24 hour glycemic
control when compared to control day
• Post-meal walking was significantly (P<0.01) more effective than 45 min of sustained morning or
afternoon walking in lowering 3 hour post-dinner glucose
ACTIVITY / INTENSITY / DEATH
ACTIVITY / INTENSITY / DEATH
• Lower all-cause mortality HR: 0.90 [ 0.87 – 0.93 ], steeper at lower vs higher exercise
• Lower CV mortality HR: 0.92 [ 0.88- 0.96 ]
TAKE HOME POINTS
• 1-2 sessions per week of mod/high intensity exercise reduces risks for
all-cause, CVD, and cancer mortality.
• Positive impact of exercise on CVD might outweigh the negative
impact of elevated BMI on middle-aged / elderly patients.
• 15 min walks three times a day after eating is an effective way to
control post-prandial hyperglycemia in older patients.
• Exercise is good for your heart, more is better, vigorous is best
CASE 3: MS. CHLOE STRIDIA
• Ms. Stridia is a 58 yo W, who presents after recent dental
abscess, for which she received amoxicillin/clavulanate.
• Dental issues are resolving; however, following the
antibiotics she developed a severe, foul-smelling
diarrhea & presented to the ER.
• She was admitted for recurrent c. difficile, treated with
vancomycin, and her diarrhea resolved.
• This was her third recurrence of c. diff.
• VS: HR 80, BP 160/88, RR 18, Temp 38 C, sat 98% on RA
• Labs: All WNL
CASE 3: MS. CHLOE STRIDIA
• What do you tell her now?
• A: Never take antibiotics again
• B: You should only take an antibiotic when taking a probiotic as well
• C: At her next recurrence, start her on fidaxomicin (instead of
vancomycin) to reduce risk of recurrence
• D: Start her on Bezlotoxumab to reduce risk of RCDI while on
vancomycin at her next recurrence.
• E: Consult GI for a colonoscopy delivered fecal microbiota transplant
• F: Consult GI for endoscopically delivered fecal microbiota
transplant
• G: Prescribe fecal microbiota transplant in a capsule regimen
C-DIFF POLLEV SLIDE HERE
CASE 3: MS. CHLOE STRIDIA
• What do you tell her now?
• A: Never take antibiotics again
• B: You should only take an antibiotic when taking a probiotic as well
• C: At her next recurrence, start her on fidaxomicin (instead of
vancomycin) to reduce risk of recurrence
• D: Start her on Bezlotoxumab to reduce risk of RCDI while on
vancomycin at her next recurrence.
• E: Consult GI for a colonoscopy delivered fecal microbiota transplant
• F: Consult GI for endoscopically delivered fecal microbiota
transplant
• G: Prescribe fecal microbiota transplant in a capsule regimen
LITERATURE
LITERATURE
• Non-inferiority: 116 patients, 57 capsule 59 colonoscopy
• Given the same amount of “donor stool” in each method
• Colonoscopy: 360 ml of fecal slurry in the cecum
• Capsule: 40 capsules under DOT
• 10+ days of vancomycin for symptom resolution, then treated with BID dosing of
vancomycin twice daily until 24 hours prior to FMT
• 4L GoLYTELY the night before FMT
• Prevention of RCDI after a single treatment was 96.2% in both arms
• A significantly greater proportion of participants receiving capsules rated their
experience as “not at all unpleasant” (66% vs 44%, P =0.01)
TAKE HOME POINT
• Oral capsule administration of FMT is as efficacious as colonoscopy delivery
• More efficacious than endoscopy
• Higher dose used in this study
• Bowel prep used prior to administration
• Could also consider the use of the following alternative regimens:
• Fidaxomicin (instead of vancomycin)
• Shown to reduce risk of recurrence compared to vancomycin
• Bezlotoxumab and Vancomycin reduces the risk of RCDI
CASE 4: MR. KID KNEIGH
• Mr. Kneigh is a 65 yo M, who presents for evaluation of non-specific
chest pain of several weeks duration. His ECG does not show any
evidence of ischemia at rest. He had a negative stress-echo a month
ago. After discussion with cardiology it is determined he should
undergo angiography.
• PMH: Diabetes, HLD, HTN, possible TIA, Stage III CKD, Tobacco use.
• VS: HR 95, RR 20, BP 155/85, Sat: 94% on RA
• Labs: Creatinine of 1.5, eGFR of 30, A1c: 7.2, Lipids WNL, CBC WNL
CASE 4: MR. KID KNEIGH
• What do you do now?
• A: Non-contrasted CT scan of heart
• B: Pre-hydrate with normal saline, then proceed with contrasted CTA
• C: Use sodium bicarbonate / NAC and fluids, then proceed with contrasted CTA
• D. Obtain an MRI of the heart with gadolinium
• E: Obtain an MRI of the heart without contrast
• F: You don’t need the study, modern clinicians rely too much on imaging anyway… be like
the ol’ country doc and perform a better physical exam
CASE 4: MR. KID KNEIGH
• What do you do now?
• A: Non-contrasted CT scan of heart
• B: Pre-hydrate with normal saline, then proceed with contrasted CTA
• C: Use sodium bicarbonate / NAC and fluids, then proceed with contrasted CTA
• D. Obtain an MRI of the heart with gadolinium
• E: Obtain an MRI of the heart without contrast
• F: You don’t need the study, modern clinicians rely too much on imaging anyway… be like
the ol’ country doc and perform a better physical exam
LITERATURE
LITERATURE
• 2 by 2 factorial design, 4993 participants in the intention to treat analysis
• Randomly assigned 5177 patients with stage III and IV CKD
• IV 1.26% sodium bicarbonate or IV 0.9% NS AND 5 days of NAC or placebo
• Primary end point: composite of death, dialysis, increase in creatinine
• Secondary end points:
• Contrast associated AKI, Death at 90 days, Dialysis at 90 days
• Persistent kidney impairment at 90 days
• Hospitalization for ACS, Heart failure, or stroke at 90 days
• All cause hospitalization at 90 days
• Trial stopped after prespecified interim analysis
LITERATURE
LITERATURE
LITERATURE
• Primary end point of death: NO SIGNIFICANT BETWEEN-GROUP DIFFERENCES
• 110/2511 in sodium bicarb group
• 116/2482 in sodium chloride group
• 114/2495 in N-acetylcysteine group
• 112/2498 in the placebo group
• Secondary end point AKI: NO SIGNIFICANT BETWEEN-GROUP DIFFERENCES
• 239/2511 in sodium bicarb group
• 206/2482 in sodium chloride group
• 228/2495 in N-acetylcysteine group
• 217/2498 in the placebo group
TAKE HOME POINT
• Among patients with Stage 3 and 4 CKD, who will undergo angiography,
• There was no benefit for using sodium bicarbonate over IV normal saline.
• There was no benefit for using oral NAC over placebo.
• No benefit for:
• Death
• Dialysis
• Persistent kidney dysfunction
• Prevention of contrast associated AKI
CASE 5: MR. LUM BAUGHGO
• 68 yo M with HTN, HLD, depression, presents for low back pain. This has been a
chronic issue for him, with acute exacerbations intermittently. No bowel or bladder
incontinence.
• PMH: DM, HTN, HLD, obesity.
• Exam: 5/5 strength BLE, limited by pain, confined to his lower back bilaterally.
• X-rays: unremarkable
• MRI: (had already been undertaken by his outside provider). Mild central lumbar
spinal stenosis (LSS) L2-3, L3-4, no spondylolisthesis, mild right sided foraminal
stenosis at same levels.
CASE 5: MR. LUM BAUGHGO
• What do you do for Mr. Baughgo?
• A: Give him scheduled acetaminophen for the pain
• B: Give him scheduled NSAIDs for the pain
• C: Give him scheduled gabapentinoid (gabapentin/pregabalin) for the pain
• D: Start him on low dose narcotics, with a gradual titration up to effective dose
• E: Send him for some PT with some mindfulness based stress reduction
CASE 5: MR. LUM BAUGHGO
• What do you do for Mr. Baughgo?
• A: Give him scheduled acetaminophen for the pain
• B: Give him scheduled NSAIDs for the pain
• C: Give him scheduled gabapentinoid (gabapentin/pregabalin) for the pain
• D: Start him on low dose narcotics, with a gradual titration up to effective dose
• E: Send him for some PT with some mindfulness based stress reduction
Just Kidding
CASE 5: MR. MR. LUM BAUGHGO
• What do you do for Mr. Baughgo?
• A: Give him scheduled acetaminophen for the pain
• B: Give him scheduled NSAIDs for the pain
• C: Give him scheduled gabapentinoid (gabapentin/pregabalin) for the pain
• D: Start him on low dose narcotics, with a gradual titration up to effective dose
• E: Send him for some PT with some mindfulness based stress reduction
LITERATURE
LITERATURE
• Acetaminophen: 13 trials
• Ineffective for reducing pain intensity, disability, or improving quality of life
• Nearly 4 times as likely to have abnormal results on LFT
• Minimal short term benefit for pain
• Results support reconsideration of recommendations to sue acetaminophen for patients
with lower back pain
LITERATURE
• Gabapentin vs. Placebo:
• Minimal improvement in pain
• Pregabalin vs. other analgesic group
• Greater improvement in the “other” analgesic group
• Side effects more common with gabapentin than placebo
• Dizziness, fatigue, difficulties with mentation, visual disturbances
LITERATURE: GUIDELINE
• Most with acute or subacute low back pain improve over time regardless of
treatment:
• Heat, massage, acupuncture, spinal manipulation (low)
• NSAIDS or muscle relaxants (moderate evidence)
• Chronic low back pain: initial treatment should include: (strong recommendation)
• Exercise, multi-disciplinary rehabilitation, acupuncture, mindfulness-based stress
reduction
• Chronic low back pain: inadequate response to non-pharmacologic therapy
• NSAIDs first line
• Tramadol or duloxetine as second line
• Opioids if all other modalities have failed (weak recommendation)
REFERENCES:
• Iron Absorption from oral iron supplements given on consecutive versus alternate days
and as single morning doses versus twice-daily split dosing in iron depleted women: two
open label, randomized trials. Stoffel NU, et al. Lancet haematol. 2017 Nov:4(11):e524-
e533. Epub 2017 Oct. 9
• Effect of Oral Capsule – vs Colonoscopy-Delivered Fecal Microbiota Transplantation on
Recurrent Clostridium difficile infection. Kao, D, et al. JAMA. 2017;318(20):1985-1993.
• Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal
pain and osteoarthritis: systematic review and meta-analysis of randomised placebo
controlled trials. The BMJ. 2015;350:h1225. doi:10.1136/bmj.h1225.
QUESTIONS?