Treatment of Urinary lncontincnce — Urinary incontinence in Adults: Acute and Chroni... Page 21 of 31
`
`- Placement ofan artificial sphincter.
`
`The sling procedure has been used only occasionally in men, and the information available is insufficient for
`providing effective recommendations at this time.
`
`The preoperative evaluation may require a cystoscopy, and a simple cystometry or complex videourodynamic studies,
`depending on the suspected etiology. Special care and followup are required in neurologically impaired individuals
`
`due to a significant incidence ofbladcler compliance changes following therapy to increase outlet resistance. Before
`
`injection or sphincter implantation, it is advisable to wait at least 6 months to a year and to have the patient undergo
`
`behavioral and pharmaeologic intervention during the intervening months. If an artificial sphincter is being
`considered, it is important to assess whether the patient has enough manual dexterity and ability to operate the device.
`
`Periurethral Butklng injections
`
`Pcriurethral bulking injections are recommended as a first-line surgical treatment for men with ISD. (Strength of
`[Evidence '= B.)
`
`Periurethral bulking injections can improve urinary loss in men with stress incontinence. The mechanism for
`
`improvement after injection therapy is still unclear but may reflect an improvement in urethral coaptation and possibly
`compression. Pcriurethral injections are less likely to succeed in male than in female patients and in all patients who
`
`have undergone pelvic radiation therapy or who have extensive periurcthral scarring. Success is more common in
`patients who have stress incontinence alter transurcthral or open prostatectomy than in those alter radical
`
`prostatectomy. The literature does not support the use of bulking agents in men with severe postprostatectomy
`
`incontinence (Appell, 1994). Experience and followup are limited for treatment by injections with collagen and fat,
`
`which are absorbed by patients over time. There -are no randomized studies comparing the efficacy of different
`
`materials or of injection therapy with other forms of treatment. The analysis included 9 studies of 1,005 men treated
`with periurethral injection (Kaufman, Lockhart, Silverstein, et al., 1934; Corrie, Rodriguez, and Thompson, I989;
`
`Deane, linglish, llehir, et al., 1985; McGuire and Appell, i994; Osther and Rohl, I988; Smart, 1991; Stanisic,
`
`Jciniings, et 211., I99]; Politano, I992; Santarosa and Blavias, I994), Sample sizes ranged from a minimum of3 to a
`
`‘maximum of 720. The mean age was 69 years, and mean followup time was 2,0 years. The "cure" rate was reported in
`
`eight studies and ranged from 0 to 66 percent, with a mean of 20 percent‘. The "cure"-improvement rate was reported
`in nine studies and ranged from 0 to 81 ‘percent, with a mean ol‘42 percent.
`
`Complications reported with PTFFZ included infection, urinary retention, fever, temporary erectile dysfunction,
`
`pcriurclhral inflammatory reaction, extrusion ofthe material into the urine or perineal area, and burning sensation or
`
`perineal discomfort. Particles of PTFE have been found in patients‘ lungs after periurethral injection of PTFE, but the
`
`exact incidence and the clinical significance of this migration are not known.
`
`Placement of an Artificlai Sphincter
`
`Artifcial sphincter may be elected for ISD during the 6 months after prostatectomy, Behavioral intervention
`should also be tried during this period. (Strength of Evidence = B.)
`
`Before pcriurethral injection therapy became available, placement of an artificial urinary sphincter was the most
`
`commonly used surgical procedure for the treatment of underactive outlet in men. Data on the current rate of
`comparative utilization ofthese two techniques are not available. Before implantation, urodynamic evaluation to
`
`confirm a stable, compliant, low pressure bladder is critical.
`
`The analysis included it) studies that presented data on 346 men, with sample sizes ranging from I
`
`l to 96 (Brito,
`
`Mulcahy, Mitchell, et al.. I993: Gundian, Barrett, and Parulkar, 1989; Marks and Light, 1989', Nordling, Holm-
`
`Bentzen, and llald, 1986; Lowe, Schertz, and Parsons, 1988; Malloy, Wein, and Carpiniello VL, I989; Motley and
`
`Barrett. 1990; Schreiter, I985; Wang and Hadley, I99]; Warwick and Abrams, i990). The average age of the patients
`
`http://www.ncbi.nlm.11il1.g.ov/books/NBK52166/‘?rcport#printable
`
`2/20.’20l 5
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2033 - 0051
`
`

`
`Treatment of Urinary incontinence — Urinary Incontinence in Adults: Acute and Chroni... Page 22 0131
`
`was ti l .4 years. The "cure" rate was presented in nine studies and ranged from 33 to 88 percent, with a mean of 66
`percent. The "cure" or improvement rate in the 10 studies ranged from 75 to 94.5 percent, with a mean of 85.3 percent.
`
`Initial preoperative complications are mainly associated with urethral or bladder injury during implantation. Delayed
`complications included mechanical problems such as pump malfunction, fluid leak, or tubing kink; infection; or cuff-
`rclated site atrophy, incomplete compression, or erosion. In addition, urethral injury, pump erosion, and herniated
`reservoir were reported in fewer patients.
`
`The utilization ofthc artificial urinary sphincter in patients after radiation therapy, cryotherapy, or pelvic fracture with
`urethroplasty is controversial because ofconcern about compromising the urethral blood supply. Also controversial is
`the use of intermittent catheteriaation alter sphincter implantation. The experience ofthe implanting surgeon may be
`related to the incidence of complications.
`
`Urge incontinence: Detrusor Instability
`
`Use of‘ surgical procedures in the management of urge incontinence is uncommon. Surgical treatment is usually
`considered only in highly symptomatic patients in whom nonoperative management has failed repeatedly.
`
`The surgical procedures reviewed for the treatment ofovcractive bladder include
`
`- Augmentation intestinocystoplasty or urinary diversion.
`
`- Bladder denervation procedures.
`
`Augmentation intestinocystoplasty is recommended for those patients with intractable, severe bladder instability
`or poor bladder compliance that is unresponsive to nonsurgical therapies. (Strength of Evidence = B.)
`
`Urinary diversion is recommended in "severe intractable cases ofdetrusor instability or poor bladder compliance
`
`that is unresponsive to other therapies. (Strength of Evidence ~‘ C.)
`
`Augmentation lntestlnocystoplasty or Urinary Diversion
`
`Various surgical procedures have been proposed for treating, intractable, severe bladder instability and poor
`
`compliance. Augmentation cystoplasty with a patch of detubularized intestine is usually considered the procedure of
`
`choice. Urinary diversion with a urostomy or continent urinary diversion may be utilized as a last resort.
`
`The risks oi" augmentation cystoplasty, in addition to those of any bowel surgery, include voiding difficulties that may
`require catheterization, mucus or stone formation, metabolic dccompensation, and the rare long~range possibility of
`tumor formation. Contraindications for augmentation cystoplasty include renal insufiiciency, bowel disease,
`
`intractable urethral disease. and inability to perform selflcatlteterization.
`
`Twelve articles were reviewed (Bramble, 1982; l-‘con, Conn, German, et al., 1992; George and Russel, 1991;
`
`Kockelbergh, I99]; Linder, Leach, and Rex, 1983; Lockhatt, Ellis. l-lelal, et al., 1990; Mandy and Stephenson, i985:
`Raz, lihrlieh. Zeidman. et 21]., I988; Robertson, Davies. et al.. i991; Sctltia, Webb, ‘and Neal, I991; Sidi, Becher,
`
`Redd)‘. ct al.. 1990; Strztwbridgc. Kramer, Castillo. Et al,. 1989). The studies included 403 subjects, with sample sizes
`
`ranging From I
`
`l to I I2. The mean age was 35.8 years and the known mean followup was 2.2 years (four studies). All
`
`studies included both men and women but did n.ot separate out results. 'li‘hirty—eight percent ofpatients were rendered
`
`continent with spontaneous voiding (range 0«8,7 percent). If patients continent with C ICS are included, then the mean
`"cure" rate is 82 percent (range 56—lU0 percent) and the improvement rate is 90 percent (7l—l0D percent).
`
`Complications included. recurrent UT] (29 patients), persistent mucus formation (1 1 patients), hourglass stricture at the
`
`vcsicocccal anastomosis (1 patient), and complications from the artificial sphincter (3 mechanical problems, 1 pump
`erosion,
`l cuff erosion). The total complication rates were 47 01°87 (54 percent) For the augmentation and S of22 (44
`
`percent) for the artificial sphincter.
`
`http://www.ncbi.nlm.nih. gov/books/N BK52166/?rcport=printab1e
`
`2/20/2015
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2033 - 0052
`
`

`
`Treatment of Urinary Incontinence — Urinary .Inc0ntinence in Adults: Acute and Chroni... Page 23 ol‘31
`
`Bladder Denervation Procedures
`
`Subtrigonal phenol injections (Blackford. Murray, Stephenson, et al.. 1984; Ewing, Bultitudc, and Shuttleworth. 1982;
`
`Norclling, Steven, Meyhoff, et al., 1986; Rosenbaum, Shaw, and Worth, 1990; Wall and Stanton, 1989) and bladder
`dcnervation. (/\|loussi, Loew, Mast, ct al., 1984: Diokno, Hollander, and Aldcrson, 1987; Hodgkinson and Drukker,
`1977; Lucas, Thomas, Clarke, et al., 1988; McGuire and Savastano, 1984; Opsomer, Klarskov, Holm—Bentzen, et al.,
`
`1984; Rockswald, Chou, and Bradley, 1978; Torring, Petersen, Kelmar, et al., 1938) are not presently recommended
`because the "cure" rates are low. and therefore the risk—to—benefit ratio is too great.
`
`Subtrigonal or transvesical phenol injection
`
`1-‘ ive series of patients treated with subtrigonal phenol injections were reviewed and combined to include a total ol'244
`
`patients (Blackford, Murray, Stephenson, et al._, 1984; Ewing, llultitude, and Shuttlcworth, 1982; Nordling, Steven,
`Meyhoff, et al., 1986; Roscnbaum, Shaw, and Worth, 1990; Wall and Stanton, 1989). "Cure" was not defined in all
`
`studies, but a short-term (< 6 months) response was reported in I42 patients. Almost all patients had relapsed by 2
`
`years, however. For the combined series, complications included trigonal ulcer, vesicovaginal fistula, hematuria,
`
`vcsicouretcral reflux, partial sciatic nerve palsy, obstructive voiding symptoms, and permanent urinary retention. The
`total complication rate was 12.3 percent.
`
`Of these five studies subjected to meta—analysis, two reported treating both men and women (Nordling, Steven,
`
`Meyhoff, et al., 1986; Rosenbaum, Shaw, and Worth, 1990), and the other three included female patients only.
`
`Combined analysis ofall male subjects revealed that the phenol injection produced no "cure" or improvement. Of the
`
`234 female subjects, 8.6 percent were "cured" and an average of 52.5 percent were "cured" or improved.
`
`'l'hus, transvesical phenol injection appears to be totally ineffective in "curing" or improving male continence,
`
`incl'i'ectivc in "curing" female incontinence, and only possibly effective in improving female incontinence.
`
`Bladder denervation
`
`[fight studies ofbladder denervation were reviewed. In three, bladder denervation was used to treat idiopathic D1 in
`
`patients with no demonstrable neurologic lesions (/\|loussi, Loew, Mast, ct al.. 1984; Diokno, Vinson, and
`
`Mtiiillicuddy, I977; llodgkinson and Drukker, I977), Three other studies examined patients with Dl-l from known
`
`ncurolog-ic problems (McGuire and Savastano, 1984', Rockswald, Chou, and Bradley, 1978; Torring, Peterson,
`Kelmar, et al., 1988). Two studies included patients in both categories (Lucas, Thomas, Clarke, et al., I988; Opsomer,
`Klarskov, 1-lolm-13entzen,etal., I984).
`
`The three studies concerning only idiopathic D1 included a total of 52 patients (Alloussi, Lowe, Mast, et a1., 1984;
`Diokno, Vinson, and McGillicu.ddy, 1977: Hodgkinson and Drukker, 1977). Denervation was accomplished. by
`
`selective sacral rhizotomy, S3 foramen injection, or transvaginal denervation. Only 20 patients had ‘a stated followup
`
`period longer than 1 year. Combined analysis of all treated patients revealed an average of 40.4 percent "cured" and an
`
`average of 59.4 percent "cured" or improved. The only complication listed was pcrineal hypoesthcsia.
`
`The three studies concerning only true neurologic disease included 34 patients (McGuire and Savastano, 1984;
`
`Rockswald, Chou, and Bradley. 1978; 'l'orrir1g, Peterson, Keltnar, et al., 1988). 'Fwenty—three had multiple sclerosis,
`
`nine had paraplegia or quadriplegic, and two had cerebral lesions. Dcnervation was accomplished by selective sacral
`rhixotomy in 19, sacral rhizotomy in 12. and 2-4 dorsal root ganglionectomy in three. Followup ranged from 2 to 10
`years. Combined analysis of all treated patients revealed an average of 47.1 percent "cured" or improved.
`
`Complications included one wound infection and two episodes of intra~operative bleeding. The two studies concerning
`
`both types of instability were the only studies in which long—term followup (at least 4 y-ears) was reported for all
`
`patients after selective sacral rhizotomy (opsomer, Klarskov, l*lolm~Bcntzen, et al., 1984; Lucas, Thomas, Clarke, ct
`al.. I988). Thirteen patients (50 percent) had either persistent or recurrent incontinence, and six others were dry only
`with additional trea_tmcnl with anticholincrgics. Thus. the long-term results were not favorable.
`
`http://www.nc bi.nlm.r1ih.gov/books/NBK52 1 66/‘?rcport=jprintable
`
`2/20/2t)15
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2033 - 0053
`
`

`
`Treatment of Urinary Incontinence — Urinary Incontinence in Adults: Acute and Chroni... Page 24 of 31
`
`Overflow Incominence: Biadcier Neck or Urethral Obstruction
`
`Symptoms ofoverllow or incontinence secondary to urethral obstruction can be addressed with a surgical
`procedure to relieve the obstruction. (Strength of Evidence 1 B.)
`
`Intermittent catheterization or an indwelling catheter may be considered in patients who are not candidates for
`surgery and suffer overflow incontinence due to urethral obstruction. (Strength of Evidences‘ C.)
`
`There is no evidence to support the use of urethral dilation for the treatment of incontinence in women. although
`it may be useful in the extremely rare cases of primary obstruction. (Strength of Evidence = C.)
`
`Internal urcthrotomy is not recommended for treating urethral obstruction in women. (Strength of Evidence 1 C ..)
`
`Overflow incontinence should be ruled out during the basic evaluation. PVR volume can be evaluated by
`cathetcrization or by pelvic ultrasound. If overflow incontinence is discovered. its cause —— anatomic obstruction.
`detrusor weakness. or both —— should be determined.
`
`A patient with a persistently underactivc detrusor with or without obstruction is best treated by intermittent
`
`catheterization (IC). A patient with an underactive dctrusor and outlet obstruction has a significantly lower chance ol‘
`
`favorable surgical outcome than a patient with normal detrusor activity. if the patient or caregivers are unable to
`
`perform urethral cathetcrization. other options include indwelling urethral or suprapubic drainage, or supravesical
`diversion.
`
`lf the etiology is anatomic obstruction with an adequately contracting detrusor and the patient has an acceptable level
`
`of surgical risk. the best treatment is surgery.
`
`The Female Patient
`
`ln women. anatomic obstruction can result from prior anti—incontincnce surgery or severe pelvic prolapse. For women
`
`who have anatomic obstruction alter anti-incontinence surgery, two procedures can relieve the obstruction,
`
`Obstruction from an endoscopic nccdle bladder neck suspension can be relieved by cutting one of the suspending
`
`sutures. To evaluate the outcome of this procedure. five studies were reviewed (Araki, Takamoto, l-lara, et 21].. I990;
`
`Fowler. I986; Huland and Bucher, I984; Mundy, 1983; Vordermark, Brannen, Wettlauffer, et al., I979). The
`
`combined series ot'4 studies included 182 patients who had had a needle bl-adder neck suspension. Ten patients (5
`
`percent) developed obstructive voiding symptoms, which were resolved alter one suture was out; only one patient had
`a recurrence ol" incontinence.
`
`The other procedure —— urethrolysis (rcmobilization ofthc periurcthrai adi1CSi0US)'With 01' Without resuspcnsion —— can
`be used alter almost any type ofanti-incontinence surgery. Three studies included 41 patients who were classified by
`
`symptoms and urodynamic studies and underwent urcthrolysis through a transvaginal approach in combination with a
`
`repeat endoscopic suspension regardless of the presence or absence of preoperative incontinence McGuire, Letson,
`
`and Wang, 1989; Nitti and Raz, 1994; Zimmern, Hadley. Leach, ct al., 1987). Seventy—one percent of the patients had
`
`improved voiding patterns by urodynamic evaluation, and 80 percent had some improvement in symptoms, with 79
`percent ofthose who were incontinent preoperatively exhibiting resolution of their stress incontinence.
`
`The Male Patient
`
`in elderly men‘ the most common cause of anatomic obstruction is benign prostatic hyperplasia (BPH). The treatment
`
`of BPH is multifaceted and is addressed inBem'gn ]’rostat.r'c Hyperplasr'a..' Diagnosis and '1':-e'atment. C'£in:'cai’ Practice
`Clzrideline.
`
`Other ttfteascrcs and Supportive Devices
`
`http:1’/www.ncbi.nlm.nih.go-v/.books/NBK52166/‘?report=printable
`
`2/20/2015
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2033 - 0054
`
`

`
`Treatment of Urinary Incontinence - Urinary Incontinence in Adults: Acute and Chroni... Page 25 of 31
`
`Other measures and supportive devices used in the management of U1 include the following:
`
`-
`
`-
`
`Intermittent catheterization.
`
`lndwelling urethral catheterization.
`
`- Suprapubic catheters.
`
`- External collection systems.
`
`- Penile compression devices.
`
`- Pelvic organ support devices.
`
`- Absorbent pads or garments.
`
`irttermittent Catheterizatien
`
`IC is recommended as a supportive measure for patients with spinal cord injury, persistent U], or chronic urinary
`retention secondary to underactivc or partially obstructed bladder. (Strength of Evidence '~ B.)
`
`IC has become standard treatment for persons with spinal cord injuries and for patients with other forms of chronic
`
`urinary retention due to an underactive or partially obstructed bladder. This procedure can be performed by patients or
`
`their caregivers using sterile or clean catheters to provide intermittent routine bladder emptying every 3-6 hours.
`Long—term use of lC appears preferable to indwelling catheterization in regard to complications such as infections and
`
`bladder and renal stones; however, well-designed comparison studies have not been performed( Webb, Lawson, and
`
`Neal, 1990; Warren, I990). In spinal cord patients, the incidence of bacteriuria is I-3 percent per IC, and between one
`
`and four episodes per I00 days of eatltctcrizzttion using IC four times a day Warren, 1994). Other complications
`
`include urethral inflammation, stricture, false passage, hydronephrosis. and epididymitis (Webb, Lawson, and Neal,
`W90).
`
`Clean technique for IC is recommended for young, male, neurologically impaired individuals. (Strength of
`Evidence ‘ B.)
`
`Sterile technique for IC is recommended for elderly patients and patients with compromised immune system.
`
`tfittengthoflividencc C.)
`
`l(.T may be performed as a clean or sterile procedure. among young, neurologically impaired individuals. The nonsterile
`
`clean approach appears to result in rates of infection lower than those noted with indwelling catheters. Furthennore,
`the infections that do occur are usually managed without complication provided vesicourethral rcllux does not exist,
`and bladder overdistension and trauma are avoided (Diokno, Sonda, Hollander, et al., l983; Perkash and Giroux,
`1993; Wyndaele and Macs, l990).
`
`King, Carlson, Mervine, ct al. (1992) compared the incidence of urinary tract infection (U'l‘l)' using sterile and clean
`procedures in 46 randomly assigned, hospitalized. young patients with spinal cord injuries. Sterile catheter kits and
`
`procedures were utilized during lC of23 subjects, and the remainder used the clean technique but did use a new sterile
`catheter every 24 hours. Results showed no statistical differences in symptomatic or asymptomatic infections between
`
`the two groups. The investigators recommended the use of a new sterile catheter every 24 hours if the clean procedure
`is used.
`
`A followup study ofclean [C in 50 nonhospitalizcd male patients with spinal cord injuries (mean age Le 46; range A
`
`l9~70 years). with a followup period of 3 months to 6.5 years (mean of22 months), reported that 43 ofthe 50 subjects
`
`(86 percent) developed significant bacteriuria, and 3] genitourinary complications occurred in 2| patients (Perkash
`and Giroux, 1993). The investigators concluded that clean intermittent cathetcrization can be a long~term management
`
`http://www.ncbi .nlm.nih. gov/books/'NB K52 1 66/‘?rcport=printable
`
`2/20/20] 5
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2033 - 0055
`
`

`
`lreatmcnt of Urinary incontinence — Urinary Incontinence in Adults: Acute and Chroni... Page 26 of '31
`
`approach for spinal cord patients; however, this intervention is not without risk of secondary complications. Thus,
`close monitoring is required so that early and etiective treatnient can be provided to prevent serious problems.
`Furthermore, the investigators also noted that maintenance of acceptable intravesical pressures with the use of
`anticholinergic therapy was important in avoiding serious complications in this group ofpatients.
`
`The susceptibility of older persons to develop nosocomial infections puts them at higher risk than younger persons For
`developing bacteriuria and other complications caused by IC. Elderly and other persons with impaired immune
`systems and atrophic mucosa are. also at risk (Tcrpenning, Allada, and Kau-ffman, I989; Warren, I990). Although the
`incidence of infection and other complications for elderly patients using sterile versus clean [C is not well established,
`it appears that sterile IC is the safest method for this high—risk population (Terpenning, Allada, and Kauffman, I989).
`Older persons who have the physical and cognitive abilities and who are motivated can be taught to perform IC. A
`caregiver can also be instructed to perform IC for impaired individuals.
`
`Routine use of long—temi suppressive therapy with antibiotics in patients with chronic, clean IC is not
`recommended. (Strength of Evidence 2 B.)
`
`In high—risk populations, for example, those with an internal prosthesis or those who are immunosupptessed
`because ol‘agc or disease. the use ofantibiotie therapy for asymptomatic bacteriuria must be individually
`reviewed. (Strength ciflividetice ‘ C.)
`
`As a general rule. the use of long—tcrm suppressive therapy with antibiotics in people regularly using clean IC. is
`undesirable because it is associated with the emergence of resistant bacterial strains. It is generally agreed that.
`
`symptomatic U’l‘l should be treated. In high—risl< populations, for example, those with an internal prosthesis or those
`
`who are immunosuppressed because of age or disease, the use of antibiotic therapy for asyrnptomatie bacteriuria must
`
`be individually reviewed (Joseph, Jacobson, Strausbaugh, ct a_l,, I991; Wahlquist, McGuire, Greene, ct al., 1983).
`Controlled trials are needed to further evaluate the bencIit—risk ratio of these methods of continence management.
`
`indwelling Urethral Catheters
`
`indwelling, catheters may be recommended as a supportive measure for patients whose incontinence is caused by
`
`obstruction and for whom other interventions are not feasible. indwelling catheters are recommended for selected
`
`incontinent patients who are terminally ill or for patients with pressure ulcers as short—term treatment. (Strength
`of Evidence = B.)
`
`indwelling catheters are recommended in severely impaired individuals in whom alternative interventions are not
`
`an option and when a patient lives alone and a caregiver is unavailable to provide other supportive measures.
`(Strength ol'l-lvidence =- C.)
`
`An indwelling urethral (Foley) catheter is a closed sterile system inserted through the urethra to allow bladder
`
`drainage. The use of indwelling catheters should be restricted to persons whose incontinence is caused by urinary tract
`
`obstruction that cannot otherwise be treated and for which alternative therapy is not feasible. Examples include acutely
`
`ill persons for whom incontinence interferes with necessary monitoring oftluid balance and terminally ill or severely
`
`impaired persons for whom bed and clothing changes are painful or disruptive. in situations where the severity of the
`
`incontinence and the complexity of the person's care have contributed to skin irritation or pressure ulcers (Stage III or
`IV), an indwelling catheter may be indicated for short-term therapy until the skin condition resolves.
`
`Studies suggest that approximately 50 percent ofnursing home patients are incontinent and that approximately 2-4
`
`percent may require urinary catheterization; however, the actual prevalence of use oi" indwelling catheters measured in
`
`several nursing homes ranges from 6 to 28 percent (Ouslander, Kane, and Abrass, 1982; Warren, Steinbcrg, Hebel, ct
`al., I989). indwelling catheter use in the homebound patient is common and requires supervision by a registered nurse
`
`http://www.ncbi.nlm.nih.gov/booksfNBK52166/?rep0rt=printable
`
`2/20/20] 5
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2033 - 0056
`
`

`
`Treatment of Urinary Incontinence — Urinary Incontinence in Adults: Acute and Chroni... Page 27 of 31
`
`and additional personal hygiene care by paraprofessionals. The use of these devices in homcbound individuals
`
`increases the cost of caring for these persons.
`
`l.ong-te-rm use of indwelling catheters is a significant cause of bactcriuria and U’I‘l. Bacteriuria, which may be caused
`by encrustation formation of mineral and bacteria complexes, develops in most persons within 2-4 weeks after catheter
`insertion (Bjork. Pelletier, and Tight, 1984-, Cox, liukins, and Sutton, I989; Tenncy and Warren, 1988; Warren,
`Muncie. and Hall-Craggs, 1988). Cases of sepsis and death from severe UTI have been reported. In a nursing home
`population. mortality was three times higher in those with indwelling catheters than in noncatheterized patients. with
`significantly increased mortality in cathetcrized females (Kunin, Chin, and Chambers, 19873; Kunin, Chin, and
`
`Chambers. l987b). Other complications associated with indwelling catheters include obstruction secondary to
`encrustation. leakage. unprescribed removal, pain, bladder spasms. urethral erosion, stones, epididymitis, urethritis.
`pcriurcthial abscess, chronic renal inflammatory changes, fistula fonnation, hcmaturia, and urinary leakage (Kunin,
`i989: Warren, Muncic, and Hall-Craggs, 1988). Patients who are being managed with indwelling catheters over a long
`period oftime should have their bladders evaluated by urologists on a routine basis.
`
`Management ofindwelling catheters varies. The usual practice is to change indwelling catheters every 30 days, but no
`
`data are available on the optimal frequency of catheter changes. Patients found to have encrustations and blockage
`
`might do better if their catheters were changed more frequently than every 30 days Kunin, Chin, and Chambers,
`l987a). If the patient has symptomatic UTI, the entire catheter and system must be changed and a new urine culture
`
`obtained when the new catheter is inserted (Grahn, Norman, White, et al., 1985; Rubin, Berger, Zodda. ct al.. 1980).
`
`No studies have idcnti tied an ideal catheter size, balloon size, or type of indwelling catheter, although most experts
`agree that the standard catheter size is l4FR, l6FR. or I81“-‘R with a 5-cc balloon filled with I0 cc of sterile water.
`
`There is evidence to refute the practice of catheter irrigation and clamping before removal; in addition. disinfection of
`urinary drainage bags is ineffective in preventing infection (Thompson, Haley, Scarcy, ct al., 1984). Routine bladder
`
`irrigation ofcathcters not only is ineffective in eradicating bacteriuria but also may further disrupt the already
`
`damaged bladder epithelium, predisposing the patient to further infection (Elliott, Gopal Rao, Reid, et al., 1987;
`Ruwaldt, I983). Routine irrigation is not recommended if obstruction occurs. In patients with frequent obstruction, the
`
`system should be changed and other types of catheters or alternative management should be considered. A person with
`
`an indwelling catheter must be reassessed periodically to detcmiinc whether a voiding trial or bladder retraining
`
`program might be effective in eliminatingthe need for the catheter or whether surgical risk might now be improved
`
`such that a surgical procedure could be performed to relieve obstruction.
`
`It is not known which type ofcatheter (c.g., silicone, latex, Teflon) is best. Specific risks are difficult to assess because
`
`studies generally do not report the type or brand of catheter used. The development of silver-coated, antimicrobial,
`lubricous-coated, and. female catheters may decrease the formation of cncrustation and other complications; however,
`
`further research on these products is needed to determine their effectiveness (Blacklock, 1986; Brocklehurst, Hickey,
`
`Davies. et al., I988; Johnson. Roberts, Olsen, et al.. I990; Kunin and Finkelberg, 1971; Liedberg and Lundeberg,
`
`i990‘. Licdberg, Lundeberg, and Ekman, I990).
`
`Suprapubic Catheter-5
`
`Suprapubic catheters are for short-term use following gynecologic, urologic, and other surgery, or as an
`alternative to long—term catheter use. Suprapubic cathetcrization is contraindicated as a long-term management
`option in persons with chronic unstable bladder (DI, DH) and ISD. (Strength ol'E-lvideticc ~= B.)
`
`Suprapubic calhetcri7ation involves pcrcutancous or surgical introduction of a catheter into the bladder through the
`anterior abdominal wall. Indications include short-term use following gynecologic, urologic, and other types of
`
`surgery or as an alternative to long-tcmi catheter use in men and in women with urethral closure. Suprapubic Catheters
`are contraindicated in persons with chronic unstable bladder (DI, DH) or ISD. Stowcr, Massey, and Fencley (1989)
`
`treated 50 patients with diagnoses of neurogenic bladder with suprapubic catheterization and urethral closure. Patients
`
`in this series had either severe ncurologic disease or pressure ulcers, or had refused an ileal conduit. Complications
`
`http://www.ncbi.nlm.nil1.guv/books/NBK52166/?report"==printablc
`
`2/20/2015
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2033 - 0057
`
`

`
`treatment of‘ Urinary Incontinence — Urinary Incontinence in Adults: Acute and Chroni... Page 28 of‘ 31
`
`included leakage around the catheter (17 percent), bladder stone formation at percent), symptomatic UTI (90
`percent), and recurrent blocked catheter (10 percent).
`
`Barnes, Shaw, Timoney, et al. (1993) studied 40 outpatients (23 women, 17 men) with a mean age of 45 years in
`
`whom suprapubic catheters were used to manage Lll over a 2-year period. Thirty-five of the subjects had suffered
`traumatic spinal cord injury, and five had spinal cord lesions of nontraumatic origin. All had failed or declined to use
`
`[C to empty their bladders. Cathetemelated problems were common, and only five patients had -experienced no
`
`problems since insertion. The researchers reported good results utilizing size I4-16 French catheters, antieholincrgic
`
`drug therapy, and daily clamping ofthe catheter. Only patients not using the medication and daily clamping, regimen
`
`experienced reflux and decrease in bladder capacity. Leakage from the urethra and blocking of the catheter was
`
`reported for Five patients. No discussion of problems with bactcriuria was presented. immediate complications
`
`included ccllulitis, hematoma, and bowel injury of 32 patients who expressed an opinion; 27 were satisfied with this
`form of‘ bladder management, Long—term complications were similar to those associated with the use of indwelling
`Catheters (Feneley, 1983; Stower, Massey, and Feneley, 1989).
`
`l-‘urthcr studies are needed on the use ofsuprapubic catheterizatitfn for long—term management of‘ U I. In the absence of‘
`data. panel consensus is that a suprapubic catheter is preferable to an indwelling catheter in the patient" who requires
`
`chronic bladder drainage and for whom no other alternative therapy is possible, because it eliminates urethral
`
`complications. However, management of suprapubic catheters presents potential problems such as uncontrolled urine
`
`leakage, skin erosion, and hematoma, and problems with catheter reinsertion. Long-term medical management of
`
`suprapubie catheterization may also be problematic ifhealth care providers lack knowledge and expertise and ifthe
`
`hon-rebound patient lacks quick