VUR, UTI and antibiotic prophylaxis. How to use an article about therapy or prevention

Август 23, 2022

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VUR, UTI and antibiotic prophylaxis. How to use an article about therapy or prevention

Содержание

2. The Case Kali is a 14mo female who presents to WRAMC ED with fever to 102.
3. The Case Kali is a 14mo female who presents to WRAMC ED with fever to 102.
4. The Case Kali is a 14mo female who presents to WRAMC ED with fever to 102.
5. The Question Should we treat her prophylactically? Short-term: Will this decrease recurrent infections? Long-term: Will this
6. Background Vesicoureteral Reflux (VUR) Primary – congenital incompetence of VU valve (shortened submucosal tunnel) Secondary –
7. Background Incidence 1-10% Siblings 30-45% (3/4 asymptomatic) Diagnosed via VCUG UTI workup – 40% (girls); 70%
8. Background Natural hx of VUR: spontaneous resolution UTI ? VUR? ■ VUR ? UTI? VUR ?
9. Current Treatment Recs Workup: Febrile UTI (any age) UTI UTI x2 in school-age girls UTI in
10. AUA Treatment Guidelines
11. Current Treatment Recs AUA Pediatric VUR Guidelines Panel (1997) “The panel recommendations to offer continuous abx
12. The State of the Art Williams et.al. (2001) Systematic review of RCTs on UTI/abx prophy Five
13. We Need A Study That… Will help us decide whether or not to prophylax this patient
14. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized,
15. Study Questions Does VUR correlate with ?UTI/renal scarring? Does antibiotic prophylaxis correlate with ?UTI/renal scarring?
16. Study Design Randomized, controlled, multicenter trial Inclusion: 3mo-18yo Acute pyelonephritis Exclusion: Grade IV-V VUR Anatomic abnormalities
17. Study Design Met inclusion criteria ? VCUG Pyelo treated: IV abx ? po for 14-day course
18. Follow Up At entry: UA/UCx, DMSA, VCUG, Renal US At Q3mo clinic visit: UA/UCx At 6mo:
19. Study Results
20. Analysis of Results Fisher’s Exact Test 2x2 comparison tables Control vs. variable Smaller sample size Gives
21. Study Results Recurrence of UTIs Timing Type Recurrent Pyelonephritis & Antibiotics Recurrent Pyelonephritis & VUR Degree
22. Study Results Recurrence of UTI Overall – 20.1% VUR not significant No abx (p=.9999) VUR –
23. Study Results Recurrent Pyelo and Antibiotics No benefit of abx (p=.0291) 7:1 abx:none Recurrent Pyelo and
24. Study Results Renal Scarring No evidence VUR? increased scarring (p=.9999) VUR (6.2%) = No VUR (5.7%)
25. Study Conclusions Mild/moderate VUR not associated with ?UTI, pyelonephritis, or scarring Antibiotic prophylaxis not associated with
26. Critically Evaluating… (JAMA Users’ Guide) Are the results valid? What were the results? Will the results
27. Are the results valid? Primary Guides Was the assignment of patients to treatment randomized? YES. Were
28. Are the results valid? Secondary Guides Were pts, clinicians, & study personnel blinded? NO (no blinding
29. What were the results? How large was the treatment effect? ARR – risk difference of variable
30. What were the results? How large was the treatment effect? ARR/RRR not reported! How precise was
31. What were the results? POWER! Ability of a study to detect a true difference Directly related
32. Will the results help me take care of my patient? Can the results be applied? YES.
33. Criticisms: Study Population What about Present earlier = Higher-grade reflux? Already abx? Included in study? Exclusion
34. Criticisms: Study Design DMSA as inclusion criteria (multicenter)? Account for 18 lost before study end? Unknown
35. Criticisms: Data Analysis Reporting of CIs, ARR/RRR? Magnitude/precision of treatment effect Rule in/out effect different from
36. Further Questions… UTI prophylaxis vs. intermittent therapy? And risk of renal scarring Over time, given resolution
37. Back to our patient… What would you do? Call Dr.Cartwright and Dr.Lechner and get those patients
38. References Atala A, Keating MA. Vesicoureteral reflux and megaureter. In Campbell’s Urology Vol 2, 7th ed.
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Слайд 2

The Case
Kali is a 14mo female who presents to WRAMC ED

with fever to 102. Your stellar Peds Intern suggests obtaining a UA/UCx, which results in the diagnosis of acute pyelonephritis.

Слайд 3

The Case
Kali is a 14mo female who presents to WRAMC ED

with fever to 102. Your stellar Peds Intern suggests obtaining a UA/UCx, which results in the diagnosis of acute pyelonephritis.
Kali is admitted to Wd51 for 48hrs of IV abx, then, afebrile, discharged to complete po course.

Слайд 4

The Case
Kali is a 14mo female who presents to WRAMC ED

Слайд 5

The Question
Should we treat her prophylactically?
Short-term:
Will this decrease recurrent infections?
Long-term:
Will this

decrease renal scarring?
Why else would it matter?

Слайд 6

Background
Vesicoureteral Reflux (VUR)
Primary – congenital incompetence of VU valve (shortened submucosal

tunnel)
Secondary – multiple anatomic abnormalities

Слайд 7

Background
Incidence 1-10%
Siblings 30-45% (3/4 asymptomatic)
Diagnosed via VCUG
UTI workup – 40%

(girls); 70% (infants <1yo)
Antenatal hydronephrosis – 9% (boys)
Why worry?
VUR ? pyelonephritis ? renal scarring ?
HTN, renal insufficiency, ESRD, pre-eclampsia

Слайд 8

Background
Natural hx of VUR: spontaneous resolution
UTI ? VUR? ■ VUR ?

UTI?
VUR ? Pyelo? ■ VUR ? Scarring?

Слайд 9

Current Treatment Recs
Workup:
Febrile UTI (any age)
UTI <5yo
UTI x2 in school-age girls
UTI

in any boy
To treat or not to treat?

Imaging:
Renal US
40% sensitive (VUR)
VCUG
Diagnostic!
DMSA

Слайд 10

AUA Treatment Guidelines

Слайд 11

Current Treatment Recs
AUA Pediatric VUR Guidelines Panel (1997)
“The panel recommendations to

offer continuous abx prophylaxis…are based on limited scientific evidence. To our knowledge controlled studies comparing the efficacy of continuous prophylaxis and intermittent therapy on health outcomes…have not been performed.”
No controlled studies?
Then what are we basing treatment on?

Слайд 12

The State of the Art
Williams et.al. (2001)
Systematic review of RCTs on

UTI/abx prophy
Five trials, 1968-1978
Best 2: 71 patients total, normal anatomy, 92% girls
Garin et.al. (1998)
UTI ? VUR? no ■ VUR ? Pyelo?
VUR ? UTI? no ■ Degree VUR ? Scars?
VUR ? Scarring? no

Слайд 13

We Need A Study That…
Will help us decide whether or not

to prophylax this patient
Includes patients with symptomatic VUR
Compares antibiotic prophylaxis to a control
Looks at clinically important outcomes

Слайд 14

Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after

acute pyelonephritis: a multicenter, randomized, controlled study.

Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos A, Young L.
Pediatrics 2006;117:626-632.

Слайд 15

Study Questions
Does VUR correlate with ?UTI/renal scarring?
Does antibiotic prophylaxis correlate with

?UTI/renal scarring?

Слайд 16

Study Design
Randomized, controlled, multicenter trial
Inclusion:
3mo-18yo
Acute pyelonephritis
Exclusion:
Grade IV-V VUR
Anatomic abnormalities
Pregnancy

Слайд 17

Study Design
Met inclusion criteria ? VCUG
Pyelo treated: IV abx ? po

for 14-day course
Abx: TMP/SMX or nitrofurantoin for 1 year

VUR

No VUR

Abx

No Abx

Слайд 18

Follow Up
At entry: UA/UCx, DMSA, VCUG, Renal US
At Q3mo clinic visit:

UA/UCx
At 6mo: DMSA
At 12mo: VCUG, Renal US
Endpoints:
Recurrent UTI
Renal scarring

Слайд 19

Study Results

Слайд 20

Analysis of Results
Fisher’s Exact Test
2x2 comparison tables
Control vs. variable
Smaller sample size
Gives

p value
Does not give CI
Goal: p<.05!

http://www.childrensmercy.org/stats/ask/fishers.asp

Слайд 21

Study Results
Recurrence of UTIs
Timing
Type
Recurrent Pyelonephritis & Antibiotics
Recurrent Pyelonephritis & VUR Degree
Renal

Scarring
VUR
Antibiotics

Слайд 22

Study Results
Recurrence of UTI
Overall – 20.1%
VUR not significant
No abx (p=.9999)
VUR –

22.4%
No VUR – 23.3%
Abx (p=0.633)
VUR – 23.6%
No VUR – 8.8%

Type of Recurrence
Cystitis (no p value)
VUR – 8.6%
No VUR – 13.3%
Pyelonephritis (p=.3781)
VUR – 7.1%
No VUR – 3.8%

Слайд 23

Study Results
Recurrent Pyelo and Antibiotics
No benefit of abx (p=.0291)
7:1 abx:none
Recurrent Pyelo

and VUR Degree
6/8 Grade III (cystitis: 46%)
2/8 Grade II (cystitis: 40%)
4/4 pts without VUR

Слайд 24

Study Results
Renal Scarring
No evidence VUR? increased scarring (p=.9999)
VUR (6.2%) = No

VUR (5.7%)
Abx (7.0%) = No Abx (5.1%)
Grade I VUR – 5.3% with scars
Grade II VUR – 5.2%
Grade III VUR – 13.5%

Слайд 25

Study Conclusions
Mild/moderate VUR not associated with ?UTI, pyelonephritis, or scarring
Antibiotic prophylaxis

not associated with ?UTI, pyeloneprhitis, or scarring

Слайд 26

Critically Evaluating… (JAMA Users’ Guide)
Are the results valid?
What were the results?
Will the

results help me to take care of my patient?

Слайд 27

Are the results valid? Primary Guides
Was the assignment of patients to treatment

randomized? YES.
Were all who entered the study accounted for?
Was follow-up complete?
NO. Enrolled 236, lost 18
Lost from what groups?
Would this change results?
Were patients analyzed in the groups assigned to?
NO. Exclusion of noncompliants

Слайд 28

Are the results valid? Secondary Guides
Were pts, clinicians, & study personnel blinded?
NO

(no blinding to +/- VUR, abx; no placebos)
Were groups similar at start, & treated equally?
YES (age, gender, degree of reflux)

Слайд 29

What were the results?
How large was the treatment effect?
ARR – risk

difference of variable vs. control
RRR – variable reduced risk by Z% relative to that occurring in control patients; bigger = better!
For example, in presence of VUR:
23.6% of those on abx developed UTI (X%)
22.4% without abx developed UTI (Y%)
ARR = X-Y = .236-.224 = .012
RRR = (1-Y/X)x100% = (1-.224/.236)x100% = 5.1%

Слайд 30

What were the results?
How large was the treatment effect?
ARR/RRR not reported!
How

precise was the estimated treatment effect?
Confidence Intervals (CIs) not reported!
95% CI:
Range that includes the true RRR 95% of time
Positive? Negative? Zero?
Statistically vs. clinically significant results

Слайд 31

What were the results?
POWER!
Ability of a study to detect a true

difference
Directly related to sample size
1-β (β = type II error)
Study powered to detect a clinically significant difference of 20% (power 80%), 95% CI
Need 60/group = 240 subjects
Enrolled 236, Completed 218
“POWER : research design :: SENSITIVITY : diagnostic test”

Слайд 32

Will the results help me take care of my patient?
Can the

results be applied? YES.
Could Kali have been enrolled?
All clinically important outcomes considered? YES.
Substitute endpoints vs. “POEMS”
Adverse effects on other outcomes
Are likely benefits worth potential harms/risks?
NNT = 1/ARR
Consider baseline risk without intervention

Слайд 33

Criticisms: Study Population
What about <3mo?
Present earlier = Higher-grade reflux? Already abx?
Included

in study?
Exclusion of noncompliants?
Exclusion of pyelonephritis x2?
Initial presentation with cystitis?
Febrile UTI without DMSA changes?
How many therefore excluded?

Слайд 34

Criticisms: Study Design
DMSA as inclusion criteria (multicenter)?
Account for 18 lost before study

end?
Unknown prognostic factors
Recalculate results assuming they did well/poorly
Blinding of patients/personnel?
Placebo
Diagnosis
Larger sample size?

Слайд 35

Criticisms: Data Analysis
Reporting of CIs, ARR/RRR?
Magnitude/precision of treatment effect
Rule in/out effect different

from Ho
Data crunching using Chi-Square?
Different data combinations?
Did not achieve POWER

Слайд 36

Further Questions…
UTI prophylaxis vs. intermittent therapy?
And risk of renal scarring
Over time,

given resolution VUR
Larger sample size
VUR in context of abnormal anatomy?
Mechanism of scarring in pyelonephritis?
What else?

Слайд 37

Back to our patient…
What would you do?
Call Dr.Cartwright and Dr.Lechner and

get those patients enrolled!

Слайд 38

References
Atala A, Keating MA. Vesicoureteral reflux and megaureter. In Campbell’s Urology

Vol 2, 7th ed. Philadelphia: WB Saunders 1988.
Behrman Re, Kliegman RB, Jenson HB. Nelson Textbook of Pediatrics, 17th ed. Philadelphia: Saunders, 2004.
Biggi A et.al. Prognostic value of the acute DMSA scan in children with first urinary tract infection. Pediatr Nephrol 2001;16:800-804.
Bjorgvinsson E, Majd M, Eggli KD. Diagnosis of acute pyelonephritis in children: comparison of sonography and 99mTc-DMSA scintigraphy. Am J Roentgenol 1991;157(3):539-543.
Dawson B, Trapp RG. Basic and clinical biostatistics, 3rd ed. New York: Lange Medical Books 2001.
DeSadeeler C et.al. A multicenter trial on interobserver reproducibility in reporting on 99mTc-DMSA planer scintigraphy: a Belgian survey. J Nucl Med 2000;41(1):23-26.
Elder JS et.al. Pediatric vesicoureteral reflux guidelines panel summary report on the management of primary vesicoureteral reflux in children. J Urol 1997;157(5):1846-1851.
Garin EH et.al. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics 2006;117:626-632.
Garin EH, Campos A, Homsy Y. Primary vesicoureteral reflux: review of current concepts. Pediatr Nephrol 1998;12:249-256.

VUR, UTI and antibiotic prophylaxis. How to use an article about therapy or prevention

Содержание

The CaseKali is a 14mo female who presents to WRAMC ED

The CaseKali is a 14mo female who presents to WRAMC ED

The CaseKali is a 14mo female who presents to WRAMC ED

The QuestionShould we treat her prophylactically?Short-term:Will this decrease recurrent infections?Long-term:Will this

BackgroundVesicoureteral Reflux (VUR)Primary – congenital incompetence of VU valve (shortened submucosal

BackgroundIncidence 1-10% Siblings 30-45% (3/4 asymptomatic)Diagnosed via VCUGUTI workup – 40%

BackgroundNatural hx of VUR: spontaneous resolutionUTI ? VUR? ■ VUR ?

Current Treatment RecsWorkup:Febrile UTI (any age)UTI <5yoUTI x2 in school-age girlsUTI

AUA Treatment Guidelines

Current Treatment RecsAUA Pediatric VUR Guidelines Panel (1997)“The panel recommendations to

The State of the ArtWilliams et.al. (2001)Systematic review of RCTs on

We Need A Study That…Will help us decide whether or not

Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after

Study QuestionsDoes VUR correlate with ?UTI/renal scarring?Does antibiotic prophylaxis correlate with

Study DesignRandomized, controlled, multicenter trialInclusion:3mo-18yoAcute pyelonephritisExclusion:Grade IV-V VURAnatomic abnormalitiesPregnancy

Study DesignMet inclusion criteria ? VCUGPyelo treated: IV abx ? po

Follow UpAt entry: UA/UCx, DMSA, VCUG, Renal USAt Q3mo clinic visit:

Study Results

Analysis of ResultsFisher’s Exact Test2x2 comparison tablesControl vs. variableSmaller sample sizeGives

Study ResultsRecurrence of UTIsTimingTypeRecurrent Pyelonephritis & AntibioticsRecurrent Pyelonephritis & VUR DegreeRenal

Study ResultsRecurrence of UTIOverall – 20.1%VUR not significantNo abx (p=.9999)VUR –

Study ResultsRecurrent Pyelo and AntibioticsNo benefit of abx (p=.0291)7:1 abx:noneRecurrent Pyelo

Study ResultsRenal ScarringNo evidence VUR? increased scarring (p=.9999)VUR (6.2%) = No

Study ConclusionsMild/moderate VUR not associated with ?UTI, pyelonephritis, or scarringAntibiotic prophylaxis

Critically Evaluating… (JAMA Users’ Guide)Are the results valid?What were the results?Will the

Are the results valid? Primary GuidesWas the assignment of patients to treatment

Are the results valid? Secondary GuidesWere pts, clinicians, & study personnel blinded?NO

What were the results?How large was the treatment effect?ARR – risk

What were the results?How large was the treatment effect?ARR/RRR not reported!How

What were the results?POWER!Ability of a study to detect a true

Will the results help me take care of my patient?Can the

Criticisms: Study PopulationWhat about <3mo? Present earlier = Higher-grade reflux? Already abx?Included

Criticisms: Study DesignDMSA as inclusion criteria (multicenter)?Account for 18 lost before study

Criticisms: Data AnalysisReporting of CIs, ARR/RRR?Magnitude/precision of treatment effectRule in/out effect different

Further Questions…UTI prophylaxis vs. intermittent therapy?And risk of renal scarringOver time,

Back to our patient…What would you do?Call Dr.Cartwright and Dr.Lechner and

ReferencesAtala A, Keating MA. Vesicoureteral reflux and megaureter. In Campbell’s Urology

Похожие презентации

The Case
Kali is a 14mo female who presents to WRAMC ED

The Case
Kali is a 14mo female who presents to WRAMC ED

The Case
Kali is a 14mo female who presents to WRAMC ED

The Question
Should we treat her prophylactically?
Short-term:
Will this decrease recurrent infections?
Long-term:
Will this

Background
Vesicoureteral Reflux (VUR)
Primary – congenital incompetence of VU valve (shortened submucosal

Background
Incidence 1-10%
Siblings 30-45% (3/4 asymptomatic)
Diagnosed via VCUG
UTI workup – 40%

Background
Natural hx of VUR: spontaneous resolution
UTI ? VUR? ■ VUR ?

Current Treatment Recs
Workup:
Febrile UTI (any age)
UTI <5yo
UTI x2 in school-age girls
UTI

Current Treatment Recs
AUA Pediatric VUR Guidelines Panel (1997)
“The panel recommendations to

The State of the Art
Williams et.al. (2001)
Systematic review of RCTs on

We Need A Study That…
Will help us decide whether or not

Study Questions
Does VUR correlate with ?UTI/renal scarring?
Does antibiotic prophylaxis correlate with

Study Design
Randomized, controlled, multicenter trial
Inclusion:
3mo-18yo
Acute pyelonephritis
Exclusion:
Grade IV-V VUR
Anatomic abnormalities
Pregnancy

Study Design
Met inclusion criteria ? VCUG
Pyelo treated: IV abx ? po

Follow Up
At entry: UA/UCx, DMSA, VCUG, Renal US
At Q3mo clinic visit:

Analysis of Results
Fisher’s Exact Test
2x2 comparison tables
Control vs. variable
Smaller sample size
Gives

Study Results
Recurrence of UTIs
Timing
Type
Recurrent Pyelonephritis & Antibiotics
Recurrent Pyelonephritis & VUR Degree
Renal

Study Results
Recurrence of UTI
Overall – 20.1%
VUR not significant
No abx (p=.9999)
VUR –

Study Results
Recurrent Pyelo and Antibiotics
No benefit of abx (p=.0291)
7:1 abx:none
Recurrent Pyelo

Study Results
Renal Scarring
No evidence VUR? increased scarring (p=.9999)
VUR (6.2%) = No

Study Conclusions
Mild/moderate VUR not associated with ?UTI, pyelonephritis, or scarring
Antibiotic prophylaxis

Critically Evaluating… (JAMA Users’ Guide)
Are the results valid?
What were the results?
Will the

Are the results valid? Primary Guides
Was the assignment of patients to treatment

Are the results valid? Secondary Guides
Were pts, clinicians, & study personnel blinded?
NO

What were the results?
How large was the treatment effect?
ARR – risk

What were the results?
How large was the treatment effect?
ARR/RRR not reported!
How

What were the results?
POWER!
Ability of a study to detect a true

Will the results help me take care of my patient?
Can the

Criticisms: Study Population
What about <3mo?
Present earlier = Higher-grade reflux? Already abx?
Included

Criticisms: Study Design
DMSA as inclusion criteria (multicenter)?
Account for 18 lost before study

Criticisms: Data Analysis
Reporting of CIs, ARR/RRR?
Magnitude/precision of treatment effect
Rule in/out effect different

Further Questions…
UTI prophylaxis vs. intermittent therapy?
And risk of renal scarring
Over time,

Back to our patient…
What would you do?
Call Dr.Cartwright and Dr.Lechner and

References
Atala A, Keating MA. Vesicoureteral reflux and megaureter. In Campbell’s Urology