1. Deflux® The Family Friendly Option
November 15, 2018
Deflux® The Family Friendly Option

2. Presentation Overview
November 15, 2018
Presentation Overview
What is Vesicoureteral Reflux (VUR)?
The Clinical Consequences of VUR
Overview of Treatment Options
Antibiotics
Endoscopic injection
Surgery
Treatment Preferences
November 15, 2018

3. What is Vesicoureteral Reflux (VUR)?
November 15, 2018
What is Vesicoureteral Reflux (VUR)?
VUR is a bladder valve defect that allows urine to reflux from the bladder through one or both ureters and up to the kidneys1
Affects about 1% of children, usually diagnosed in the first few years of life, after a UTI
November 15, 2018
1Hensle 2007a

4. What is Vesicoureteral Reflux (VUR)?
November 15, 2018
What is Vesicoureteral Reflux (VUR)?
The severity of VUR is based upon a grading system, reflecting the extent of reflux and ureter abnormality1
It should be pointed out that Deflux is only approved for grades II-IV.
Always carry a package insert when you give this presentation.
More severe VUR is associated with more severe renal scarring and increased complications2,3
1Jacobson 1999; 2Gonzalez 2005; 3Caione 2004
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5. The Clinical Consequences of VUR
November 15, 2018
The Clinical Consequences of VUR
Urine traveling back up to the kidneys increases the likelihood of having a urinary tract infection1
There is a 70% overall incidence of upper UTI (acute pyelonephritis) in children with first febrile UTI2
more than half (57%) of these children developed renal scars
Urinary tract infections resulting in renal scarring and damage can potentially lead to early hypertension and end-stage renal disease (ESRD)3
It should be pointed that VUR in the absence of a urinary tract infection is not of any clinical significance.
More severe VUR is associated with more severe renal scarring and increased complications.
1Panaretto 1999; 2Lin 2003; 3American Academy of Pediatrics 1999
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6. The Clinical Consequences of VUR
November 15, 2018
The Clinical Consequences of VUR
The risk of renal scarring increases with each febrile UTI episode1
Renal damage usually occurs within the first 3-5 years of life2
The 1999 AAP Practice Parameter focuses on the diagnosis, treatment, and evaluation of febrile infants and young children with a UTI .
Febrile UTIs are more concerning from a clinical perspective.
Also of note, renal damage may occur prenatally.
1American Academy of Pediatrics 1999; 2Sherbotie 1991
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7. The Clinical Consequences of VUR
November 15, 2018
The Clinical Consequences of VUR
Consequences of Renal Scarring and Damage
In Smellie’s study of 226 children with VUR, it was found that 8.8% of them had hypertension. In McNiece’s study of adolescents in a normal population the incidence of hypertension was 3.2%.
Again from Smellie’s study of 226 children with VUR, it was found that 5.8% had ESRD compared to the overall population with <1% (2007 USRDS and US Census Bureau).
It is important when using this slide to stress the point that these are 5 independent sources and that the data presented is not linked in any way other than for illustrating the point that VUR can and does have long term clinical implications for payers and patients.
Please be aware that the 5.8% rate of ESRD is taken from the Smellie data which is data from the early nineties and this figure may be less currently. This could support the premise that early screening and treatment is effective.
5.8% of VUR patients had end stage renal disease – p 729, C2, ¶6: “Only 13 (5.8%) of the whole group of adults had been attending hospital regularly for renal causes.”
0.9% of the population will have ESRD by age 30—Based on work by Kiberd, the rate of ESRD by age 30 was calculated to be 0.9%, however, upon further examination of the equation used to calculate the age dependent prevalence, there is an error. As such, we attempted to use the graphic to determine approximate estimates (Kiberd P 1, 638, Figure 3). Based on the graph, we conservatively put 0.9% as the prevalence, when actually the prevalence was much lower. As such, we have modified the graphic to state <1% prevalence by age 30. Additionally, we have calculated the prevalence of ESRD by age 30 from the 2007 USRDS Annual Data Report, table B1, sum of columns 0-29 from year 2005, which provides a prevalence point of 24,758 persons. Based on the 2005 census, there were 122,547,840 people between 0-29 years of age, giving a prevalence of 24,758/122,547,840 = 0.02%. For ease of presentation, <1% was specified on the graph.
These data are a graphical representation of the data within these studies.
1Smellie 1998; 2McNiece 2007; 3Kiberd 2002; USRDS Annual Data Report; 5 US Census Bureau.
November 15, 2018

8. Definition of Success Aim of Treatment Definition of Success
In the United States success is defined as reduction of VUR to Grade 0
Prevent Renal Scarring
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9. Treatment of Vesicoureteral Reflux
November 15, 2018
Treatment of Vesicoureteral Reflux
Prophylactic Antibiotics
Open Surgery
Not Curative
5 – 13% Annual
Resolution1
Curative
95% Success Rate2
69% Success Rate3
Endoscopic Injection
Success rates higher
than 69% have been
reported4,5
This slide is bridge to the options available to manage VUR. The success rates for all of the options are again derived from independent studies and there has to date been no randomized prospective study reported looking at the effectiveness of all three interventions.
The 69% success rates used for Deflux are derived from our package insert.
Higher success rates are seen among pediatric urologists who have treated a higher number of patients which gives them more experience with the procedure.
It is important to point out Deflux is indicated for grades II-IV only in the USA.
1Schwab 2002; 2Capozza 2004; 3Deflux Package Insert (link); 4Kirsch 2004;5Yu 2006
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10. Treatment of Vesicoureteral Reflux
November 15, 2018
Treatment of Vesicoureteral Reflux
Spontaneous Resolution
13% annual resolution rate during first 5 years (Grades I-III)1
5% annual resolution rate during first 5 years (Grades IV-V)1
Click on calculator image for hyperlink to the Spontaneous Resolution Calculator (this can only be achieved if you have access to the internet).
Please stress that the rates of resolution vary by grade, laterality and age at presentation.
Also note Deflux is approved for grades II-IV only in the USA.
Deflux is approved for treatment of Grades II-IV
Spontaneous Resolution Calculator2,3
1Schwab 2002; 2www.deflux.com; 3AUA 1997 Guidelines
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11. Prophylactic Antibiotics
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Treatment Options
Prophylactic Antibiotics
Open Surgery
Curative
69% Success Rate**
Duration of Treatment
1 – 5 years*
Cost of Treatment
$2,2001(3-year)
Endoscopic Injection
95% Success Rate
up to 3 days (inpatient)1
$15,4101
$6,5301
Not Curative
5 – 13% Annual
Resolution
* Optimal duration of antibiotic prophylaxis is undetermined but clinical studies have used 1-5 years
** Majority of patients are cured after a single treatment
1 day (outpatient)1
It is important to note that costs may vary by institution as well as by state.
Per Kobelt (Table 1, page 1482):
The total 3-year cost of antibiotics is $2200
Antibiotic treatment, 1 month ($23) + Annual follow up ($431) + Management of minor urinary tract infection ($140)
Total annual cost $738.75
The total cost of endoscopic injection is $6530 (one time in 3 years)
Endoscopic injection ($ ) + Injection material ($1,295) + Post injection follow-up ($468)
The total cost of surgery is approximately $15,410 (one time in 3 years)
Surgical intervention ($10, ) days of inpatient stay ($4,050) + post op follow-up ($413.60)
Diagnostic evaluation for the first diagnosis (including VCUG) is a sunk cost since it applies to all scenarios
Per physician survey:
Antibiotics: During the annual follow up, ultrasound and VCUG are performed in 50% to 60% of patients
Surgery: Between 1-3 months after surgery, the model assumes 20% of patients will undergo a repeat VCUG
Deflux: The persistence of reflux was assessed with VCUG 3-12 months after the procedure
1Kobelt 2003
November 15, 2018

12. Prophylactic Antibiotics
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Treatment Options
Prophylactic Antibiotics
Duration of Treatment
1 – 5 years
Cost of Treatment
$2,200 (3-year)
Not Curative
5 – 13% Annual
Resolution
Antibiotic Effectiveness
The Garin study is the only study which is a randomized prospective study looking at the effectiveness of low dose prophylactic antibiotics.
Among patients with VUR, there was no clinical advantage to the use of urinary antibiotic prophylaxis to recurrent UTIs.
The 5-year rate of UTI recurrence in VUR patients treated with ABX is 29%-42%, with febrile UTI rates averaging 22%2
1Garin 2006; 2Wheeler 2003
November 15, 2018

13. Prophylactic Antibiotics
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Treatment Options
Prophylactic Antibiotics
Duration of Treatment
1 – 5 years
Cost of Treatment
$2,200 (3-year)
Not Curative
5 – 13% Annual
Resolution
Probability of Antibiotic Resistance
Pathogens: Escherichia coli (78%), other gram-negative rods, Enterococcus, and other organisms
Prophylactic antimicrobials prescribed: cotrimoxazole (61%), amoxicillin, nitrofurantoin, and other antimicrobials including first- through third-generation cephalosporins
Conway et al calculated the predicted probability of a recurrent UTI being antimicrobial resistant and found that prophylactic antibiotics actually increase resistance in children younger than 2 years with VUR.
Based on the study, 85.3% of normal patients who have an UTI would have been resistant to prophylactic antibiotics. When antibiotics are given, the resistance rate increases to 95.1%, highlighting that the presence of prophylactic antibiotics increases the likelihood of bacteria resistance.
Antibiotic resistance rate calculated as 95.1% and 83.5% for prophylactic and no prophylactic cohorts, respectively.
*Prophylactic calculated by average row one and five ( )/2 = 95.1
*No prophylactic calculated by average row four and eleven ( )/2 = 83.5
The above calculation is derived from Table 4*, page 184 in the Conway et al study published in JAMA July 11, 2007 – Vol 298, No. 2. For more details, please see the Conway study 2007 JAMA in the reference list.
1Conway 2007
These data are a graphical representation of the data within this study.
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14. Prophylactic Antibiotics
November 15, 2018
Treatment Options
Prophylactic Antibiotics
Duration of Treatment
1 – 5 years
Cost of Treatment
$2,200 (3-year)
Not Curative
5 – 13% Annual
Resolution
ABX includes: TMP-SMX, amoxicillin-clavulanate, ampicillin, cefazolin, ciprofloxacin, and nitrofurantoin
Antibiotic Resistance
Gaspari et al found that antibiotic resistance can lead to multidrug resistance and that >20% children aged 1 month to 12 years having resistance to two or more antibiotics.
1Gaspari 2006
These data are a graphical representation of the data within this study.
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15. Prophylactic Antibiotics
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Treatment Options
Antibiotic Resistance
Prophylactic Antibiotics
Duration of Treatment
1 – 5 years
Cost of Treatment
$2,200 (3-year)
Not Curative
5 – 13% Annual
Resolution
Antibiotic Non-Compliance1
N=10,975
These data are derived from a claims data base and was designed to assess the compliance rate among patients diagnosed and seeking treatment for VUR.
The data are from PharMetrics, a nationally representative claims data base in the USA.
Only 17% of patients were greater than 80% compliant and only 10% were 100% compliant based on Medication Possession Ratio (MPR) values.
This is also supported by the Panaretto study which looked at the expression of antibiotic metabolites in the urine of children receiving low dose prophylactic ABXs for VUR.
This may explain why a number of recent studies have reported a significant number of UTIs in patients treated with low dose antibiotics. Compliance may well be playing a significant factor? According to the World Health Organization (WHO), patient non-compliance with recommended treatment of antibiotics is a factor that encourages the spread of resistance.
As a follow up to this study Q-Med Scandinavia is supporting a prospective chart review to look further at this issue in patients with VUR.
Antibiotic Resistance2
1Hensle 2007b; 2Who Antibiotic Fact Sheet
November 15, 2018

16. Re-implant Ureter inside the Bladder1
November 15, 2018
Treatment Options
Re-implant Ureter inside the Bladder1
Open Surgery
Ureter
Curative
95% Success Rate
Duration of Treatment
3 days (inpatient)
Please note this diagram depicts the intravesical procedure (more common than extravesical technique).
Open surgery (reimplantation surgery) for VUR involves placing the child under general anesthesia and surgically reattaching the ureter(s) to correct the VUR.
The procedure involves mobilization of the ureter and reimplantation using stronger muscular backing to create a functional valve at the vesicoureteral junction (where the ureter joins the bladder).
In effect, the surgeon creates a new valve structure by reattaching the ureter and creating a new tunnel through the bladder wall. This modifies the anatomical abnormality that is allowing the reflux.
The majority of these procedures require an inpatient stay, however some surgeons do undertake this procedure as an outpatient treatment.
Cost of Treatment
$15,410
Bladder Wall
Trigone
1Handbook of Pediatric Urology
November 15, 2018

17. Treatment Options Impact on UTIs Endoscopic Injection Curative
November 15, 2018
Treatment Options
Endoscopic Injection
Curative
69% Success Rate
Duration of Treatment
1 day (outpatient)
Cost of Treatment
$6,530
Impact on UTIs
Another study using claims data was undertaken to compare the rate of UTIs in patients treated initially with endoscopic correction or ABX.
The study matched patients 3:1 (ABX vs Deflux) for age, gender and UTI rate prior to diagnosis. This was done to ensure the robustness of the diagnosing physician specialty data and the results and it is a standard methodology used in this type of analysis to compensate for non-randomization.
One challenge faced with this analysis due to the time frame when the claims were made , was that only a small number of patients had been treated with Deflux, as the product was approved in Sept 2001 and few cases were done in the first year after launch.
1Elder 2007
November 15, 2018

18. Treatment Options Impact on UTIs Endoscopic Injection Curative
November 15, 2018
Treatment Options
Endoscopic Injection
Curative
69% Success Rate
Duration of Treatment
1 day (outpatient)
Cost of Treatment
$6,530
Impact on UTIs
A recent study in 100 patients from a single institution reported that following correction with Deflux there was a significant reduction in the rate of UTIs post treatment. Note that the patients were followed pre and post treatment meaning that they are their own controls.
Five-fold reduction in incidence of UTIs after treatment.
1Wadie 2007
These data are a graphical representation of the data within this study.
November 15, 2018

19. Treatment Options Impact on Febrile UTIs1 Objective:
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Treatment Options
Impact on Febrile UTIs1
Endoscopic Injection
Curative
69% Success Rate
Duration of Treatment
1 day (outpatient)
Cost of Treatment
$6,530
Objective:
To investigate outcomes and experiences with Deflux
Methods:
-Long term observational study
-Eligible patients were sent a 21-item
questionnaire
Results:
Of 179 patients initially treated successfully* with Deflux, 3.4% experienced a febrile UTI years after treatment
A total of 308 patients in a study in Sweden with VUR grade III-V were treated endoscopically with Deflux between May 1, 2003 and April 30, All patients with VUR grade III or above after treatment were sent for open surgery (n=49) and not eligible for this study. Swedish guidelines suggest that the risk associated with VUR grade I-II are low and recommend re-evaluation of these patients only if recurrent febrile UTI occur.
Therefore, children with VUR resolved to grades 0-II (Grades I-II are considered positive outcomes in Europe) after treatment were included (n=259) in the study and sent a questionnaire. Of these 259 patients, 28 were later excluded as they had VUR grade III or above (16), died (2), unknown or secret address (4), moved abroad (1), not allowed to answer (1), duplicate patient (1) and did not remember treatment (3).
179 patients of the remaining 231 returned the questionnaire that was sent 7-12 years following treatment.
All patients (n=179, 100%) had been diagnosed with VUR after experiencing at least 1 febrile UTI (this is clinical practice in Sweden).
45 (25.1%) patients experienced a UTI post treatment with DEFLUX
6 (3.4%) patients experienced a confirmed febrile UTI post treatment with DEFLUX (confirmed with at least two of the following: personal telephone contact, patient records analysis, and analysis of the hospital database)
Most of the post treatment UTIs (82.2%) occurred more than 12 months after treatment.
Of note is that due to the stability of the Swedish population and the structure of how healthcare is practiced allows for this type of research to be carried out.
Please note, the 3.4% rate for febrile UTI reflects the potential recurrence of VUR and should not be compared to the incidence of UTI in clinical studies following treatment. See package insert, Slide 27.
1Stenberg 2006
*In Europe Grades I-II are considered positive outcomes.
November 15, 2018

20. Subureteric transurethral injection1
November 15, 2018
Treatment Options
Some physicians report that using the HIT technique has improved success rates over the STING technique2
Endoscopic Injection
STING
Subureteric transurethral injection1
Ureter
Bladder Wall
Deflux injection
Curative
69% Success Rate
Duration of Treatment
1 day (outpatient)
The standard STING procedure was used in clinical studies with Deflux treatment for VUR that were pivotal to approval of Deflux by the FDA. The success rates seen with this approach are approx 70%.
This type of injection procedure involves positioning of the implant just below the opening to the ureter (the ureteral orifice). The opening of the ureter is observed and the correct positioning of the implant located using a cystoscope.
Injection just below the ureter creates a bolus that increases the sub mucosal length of the ureter and may also act as a fixation point.
As you would expect there is a learning curve with any technique.
However as with many surgical techniques there have been refinements over time which have resulted in an improvement compared to the initial success rates.
A number of surgeons have reported success rates >80%.
If you have recorded your success rates then please feel free to quote them.
Cost of Treatment
$6,530
1Handbook of Pediatric Urology; 2Kirsch 2004
November 15, 2018

21. Deflux for Grades II – IV VUR
November 15, 2018
Deflux for Grades II – IV VUR
The Deflux advantage
Capozza et al directly compared the outcome of long-term antibiotic prophylaxis with Deflux injection. Patients (n=21) were treated with antibiotics for 12 months and compared with 39 patients receiving Deflux injection. Both treatment groups included patients with reflux grades II–IV, diagnosed by VCUG prior to treatment. After 12 months, a significantly greater response was observed following Deflux injection.
Deflux Response Rate
Grade II = 95%
Grade III = 71%
Grade IV = 43%
Antibiotic Response Rate
Grade II = 37%
Grade III = 33%
Grade IV = 0%
Deflux is FDA approved for treatment of grades II – IV VUR
Deflux has shown a greater response rate in the treatment of grades II – IV VUR1
* A response was defined as reflux grade 0 or 1
1Capozza 2002
November 15, 2018

22. Risks and Limitations of Treatments
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Risks and Limitations of Treatments
Prophylactic Antibiotics1,2,3
Open Surgery4
Endoscopic Injection3
1. Allergic Reaction
2. Diarrhea
3. Resistance
4. Not Curative
5. Requires ongoing
invasive diagnostics
6. Non-compliance
1. Rare cases of obstruction have been reported
2. Postoperative infection
Anesthesia risks
Postoperative discomfort (bladder spasm)
1. Infection and bleeding
risk associated with
cytoscopic procedures
2. Anesthesia risks
Rare cases of obstruction have been reported
4. Rare cases of dilatation
Antibiotics Once on antibiotic prophylaxis, the child will usually be tested with a VCUG each months to monitor if VUR has resolved .
Surgery usually requires a hospital stay, and it can be stressful and uncomfortable for the child. In addition impact on the family due to the need for time off school etc should not be underestimated.
DEFLUX should only be administered by qualified surgeons experienced in the use of a cystoscope and trained in subureteral injection procedures.
Adverse events are usually of the type seen with cystoscopic procedures and subureteral injection. Rare cases of postoperative dilatation of the upper urinary tract have been reported.
For more information on Deflux please review the package insert (these should always be available at every presentation).
1Hensle 2007a; 2Gupta 1999; 3Deflux Package Insert 2007 (link); 4Fanos 2004
November 15, 2018

23. Treatment Preference Parent preferences1 November 15, 2018
When explained the risks and benefits of antibiotics, surgery, and endoscopic injection, 80% of parents prefer endoscopic injection for their child with VUR1
Note: This is an European preference study and the results could vary if undertaken in a North American setting.
This is an optional slide.
1Capozza 2003
November 15, 2018

24. Deflux is the Family Friendly Option
November 15, 2018
Deflux is the Family Friendly Option
Minimally Invasive
Curative in Majority of Patients after Single Injection
Reduction of UTIs
Reduces Risk of Antibiotic Resistance
November 15, 2018

25. November 15, 2018
Additional Questions?
November 15, 2018

26. Product Information November 15, 2018 Intended Use/Indications
Deflux® is indicated for treatment of children with vesicoureteral reflux (VUR) grades II-IV.
Contraindications
Deflux is contraindicated in patients with any of the following conditions:
• Non-functional kidney(s)
• Hutch diverticuli
• Ureterocele
• Active voiding dysfunction
• Ongoing urinary tract infection
Warnings
• Do not inject Deflux intravascularly. Injection of Deflux into blood vessels may cause vascular
occlusion.
Precautions
• Deflux should only be administered by qualified physicians experienced in the use of a cystoscope and
trained in subureteral injection procedures.
• Treatment of duplex systems has not been prospectively studied.
• Ureters with grossly dilated orifices may render the patient unsuitable for treatment.
• The risks of infection and bleeding are associated with the cystoscopic procedure used to inject Deflux.
The usual precautions associated with cystoscopy (e.g. sterile technique, proper dilation, etc.) should be
followed.
• The safety and effectiveness of the use of more than 6 ml of Deflux (3 ml at each ureteral orifice) at the
same treatment session have not been established.
• The safety and effectiveness of Deflux in the treatment of children under 1 year of age have not been
established.
November 15, 2018

27. Product Information November 15, 2018 Adverse Events
List of treatment-related adverse events for 39 patients from a randomized study and 170 patients from
nonrandomized studies. (Follow-up for studies was 12 months).
Adverse Event Randomized (n=39 Deflux) Nonrandomized (n=170)
Urinary tract infection (UTI) (i) 6 (15.4%) (ii, iii) 13 (7.6%) (ii, iii)
Ureteral dilatation (iv) 1 (2.6%) (3.5%)
Nausea/Vomiting/Abdominal pain (v) 0 (0%) (1.2%)
(i) Cases of UTI typically occurred in patients with persistent reflux.
(ii) Patients in the nonrandomized studies received antibiotic prophylaxis until the 3-month VCUG.
After that only those patients whose treatment had failed received further antibiotic prophylaxis.
The patients in the randomized study received antibiotic prophylaxis 1 month post-treatment.
(iii) All UTI cases were successfully treated with antibiotics.
(iv) No case of ureteral dilation required intervention and most cases resolved spontaneously.
(v) Both cases of nausea/vomiting/abdominal pain were resolved.
November 15, 2018

28. Product Information Adverse Events Continued
November 15, 2018
Product Information
Adverse Events Continued
Although vascular occlusion, ureteral obstruction, dysuria, hematuria/bleeding, urgency and urinary frequency have not been observed in any of the clinical studies, they are potential adverse events associated with subureteral injection procedures. Following approval, rare cases of postoperative dilation of the upper urinary tract with or without hydronephrosis leading to temporary placement of a ureteric stent have been reported.
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29. November 15, 2018
References
American Academy of Pediatrics. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. American Academy of Pediatrics Committee on Quality Improvement, Subcommittee on Urinary Tract Infection. Pediatrics Apr;103(4 Pt 1): May;103(5 Pt 1):1052, 1999 Jul;104(1 Pt 1):118. Erratum in: Pediatrics Jan;105(1 Pt 1):141.
American Urological Association 1997 Guidelines.
Caione P, Villa M, Capozza N, De Gennaro M, Rizzoni G. Predictive risk factors for chronic renal failure in primary high-grade vesico-ureteric reflux. BJU Int Jun;93(9):
Capozza N, Caione P. Dextranomer/hyaluronic acid copolymer implantation for vesico-ureteral reflux: a randomized comparison with antibiotic prophylaxis. J Pediatr Feb;140(2):
Capozza N, Lais A, Matarazzo E, Nappo S, Patricolo M, Caione P. Treatment of vesico-ureteric reflux: a new algorithm based on parental preference. BJU Int Aug;92(3):
Capozza N, Lais A, Nappo S, Caione P. The role of endoscopic treatment of vesicoureteral reflux: a 17-year experience. J Urol Oct;172(4 Pt 2): ; discussion 1629.
Conway PH, Cnaan A, Zaoutis T, Henry BV, Grundmeier RW, Keren R. Recurrent urinary tract infections in children: risk factors and association with prophylactic antimicrobials. JAMA Jul; 11;298(2):
Deflux [Product Information] Uppsala, Sweden: Q-Med AG; 2007 May. Available at:
Elder JS, Shah MB, Batiste LR, Eaddy M. Endoscopic injection versus antibiotic prophylaxis in the reduction of urinary tract infection in patients with vesicoureteral reflux. Curr Res Med Opin Sep;23(Suppl 4):S15-S20.
Fanos V, Cataldi L. Antibiotics or surgery for vesicoureteric reflux in children. Lancet Nov 6-2;364(9446):
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30. November 15, 2018
References
Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos A, Young L. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics Mar;117(3):
Gaspari RJ, Dickson E, Karlowsky J, Doern G. Multidrug resistance in pediatric urinary tract infections. Microb Drug Resist Summer;12(2):
Gonzalez E, Papazyan JP, Girardin E. Impact of vesicoureteral reflux on the size of renal lesions after an episode of acute pyelonephritis. J Urol Feb; 173:571–575.
Gupta K, Scholes D, Stamm WE. Increasing prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in women. JAMA Feb 24;281(8):
Handbook of Pediatric Urology, Second Edition, Laurence S. Basken, Barry A. Kogan.
Hensle TW, Grogg AL. Vesicoureteral reflux treatment: the past, present and future. Curr Res Med Opin Sep;23(Suppl 4):S1-S6. (Hensle 2007a)
Hensle TW, Hyun G, Grogg AL, Eaddy M. Examining pediatric vesicoureteral reflux: a real-world evaluation of treatment patterns and outcomes. Curr Res Med Opin Sep;23(Suppl 4):S1-S6. (Hensle 2007b)
Jacobson SH, Hansson S, Jakobsson B. Vesico-ureteric reflux: occurrence and long-term risks. Acta Paediatrica. 1999;431:22-30.
Kiberd BA, Clase CM. Cumulative risk for developing end-stage renal disease in the US population. J Am Soc Nephrol Jun;13(6): Erratum in: J Am Soc Nephrol Oct;13(10):2617.
Kirsch AJ, Perez-Brayfield M, Smith EA, Scherz HC. The modified sting procedure to correct vesicoureteral reflux: improved results with submucosal implantation within the intramural ureter. J Urol Jun;171(6 Pt 1):
Kobelt G, Canning DA, Hensle TW, Lackgren G. The cost-effectiveness of endoscopic injection of dextranomer/hyaluronic acid copolymer for vesicoureteral reflux. J Urol Apr;169(4): ; discussion
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31. November 15, 2018
References
Lin KY, Chiu NT, Chen MJ, et al. Acute pyelonephritis and sequelae of renal scar in pediatric first febrile urinary tract infection. Pediatr Nephrol Apr;18(4):
McNiece KL, Poffenbarger TS, Turner JL, Franco KD, Sorof JM, Portman RJ. Prevalence of hypertension and pre-hypertension among adolescents. J Pediatr Jun;150(6):
Panaretto K, Craig J, Knight J, Howman-Giles R, Sureshkumar P, Roy L. Risk factors for recurrent urinary tract infection in preschool children. J Paediatr Child Health Oct;35(5):
Q-Med Scandinavia Inc. [homepage on the Internet]. Princeton, NJ. Spontaneous Resolution Calculator; [1 screen]. Accessed: 2007 Sep 20. Available at:
Q-Med Scandinavia Inc. [homepage on the Internet]. Princeton, NJ. Injection Techniques; [4 screens]. Accessed: 2007 Sep 20. Available at:
Schwab CW, Wu HY, Selman H, Smith GH, Snyder HM, Canning DA. Spontaneous resolution of vesicoureteral reflux: a 15-year perspective. J Urol Dec;168(6):
Sherbotie JR, Cornfeld D. Management of urinary tract infections in children. Med Clin North Am Mar;75(2):
Smellie JM, Prescod NP, Shaw PJ, Risdon RA, Bryant TN. Childhood reflux and urinary infection: a follow-up of years in 226 adults. Pediatr Nephrol Nov;12(9):
Stenberg A, Läckgren G. Treatment of vesicoureteral reflux in children using stabilized non-animal hyaluronic acid/dextranomer gel: A long-term observational study. J Ped Urol Nov;3:80-85.
United States Renal Data System Annual Data Report
U.S.Census Bureau, Population Division, Interim State Population Projections, 2005.
Wadie GM, Tirabassi MV, Courtney RA, Moriarty KP. The deflux procedure reduces the incidence of urinary tract infections in patients with vesicoureteral reflux. J Laparoendosc Adv Surg Tech A Jun;17(3):
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32. November 15, 2018
References
Wheeler D, Vimalachandra D, Hodson EM, Roy LP, Smith G, Craig JC. Antibiotics and surgery for vesicoureteral reflux: a meta-analysis of randomised controlled trials. Arch Dis. Child. 2003;88:
World Health Organization Antibiotic Fact Sheet.
Yu R, Roth D. Treatment of VUR using endoscopic injection of nonanimal stabilized hyaluronic acid/dextranomer gel: Initial experience in pediatric patients by a single surgeon. Pediatrics 2006; 118;
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