minimised by performing a limited resection [1015] or
`by performing TURP within 2 years of brachytherapy
`[1012].
`In the latter study, two of 24 patients (8%)
`that underwent TURP within 2 years of treatment
`were incontinent and 5 of 14 patients (36%) that un-
`derwent TURP 2 years or more after brachytherapy
`were incontinent (p=0.04)_ However, others suggest
`that delaying TURP until 5 years after radiation can
`actually reduce the risk of incontinence [1016-1018].
`
`V. CONCLUSIONS
`
`Incontinence in the male as in the female can be
`
`broadly divided into causes related to bladder and!
`or sphincter dysfunction. The pathophysiology of
`incontinence as it relates specifically to the male
`is fairly well described; however advances in sci-
`ence and anatomy will undoubtedly provide a more
`intricate understanding in the future. For example,
`the causes of sphincter insufticiency are known (i.e.
`damage to muscle, nerve andfor supporting struc-
`tures) but clinicians are not able to accurately as-
`sess the exact cause of sphincter insufficiency in
`any given patient. Therefore much of our under-
`standing of post
`treatment
`incontinence "patho-
`physioiogy” is derived from reports of incontinence
`(incidencelprevalence) after surgery or radiation. In
`addition investigators have not adequately defined
`the incidence of incontinence related to interven-
`
`tions for prostatic disease. whether benign or ma-
`Iignant. Some work has been undertaken to under-
`stand and discriminate the issue of pre- and post
`operative related incontinence, but because of the
`shortened hospitaliztion those prospective investi-
`gations, which are mandatory for the understanding
`of the physiological functioning and the pathophysi—
`ology, which might become clinically significant after
`the intervention. Problems have been two-fold: first
`
`in defining incontinence and what is bothersome!
`significant and second in accurately reporting data.
`New technologies for the treatment of BPH have
`provided us with Level
`1 evidence regarding the
`incidence of incontinence in trials comparing new
`technology to TURP and Level 2 evidence through
`meta-analysis and prospective series. Data regard-
`ing the incidence of post-radical prostatectomy and
`postradiation incontinence has been less robust
`and of a lower quality - level 2-4.
`
`H. CAUSE OF TRANSIENT
`
`INCONTINENCE IN OLDER ADULTS
`
`I. URINARY INCONTINENCE
`
`Transient causes probably account for one-third
`of incontinent cases among community-dwelling
`older people (>65 years old). up to one—half of
`
`cases among acutely-hospitalised older people,
`and a significant proportion of cases among nurs-
`ing home residents [1019-1023]. Transient uri-
`nary incontinence rises suddenly. lasts less than
`six months, and results from reversible causes
`[1024]. Most causes of transient incontinence in
`the older population lie outside the lower urinary
`tract but two points are worth emphasising. First,
`the risk of transient incontinence is increased if,
`in addition to physiologic changes of the lower
`urinary tract, the older person also suffers from
`pathological changes [1025, 1026]. Overflow in-
`continence is more likely to result from an anti-
`cholinergic agent in a person with a weak or ob-
`structed bladder, just as urgency incontinence is
`more likely to result from a loop diuretic in some-
`one with detrusor overactivity and/or impaired
`mobility [1027, 1028].
`
`This fact may explain why some controversy per-
`sists regarding some causes of transient incon-
`tinence.
`It also emphasises that continence de-
`pends on the integrity of multiple domains-mental
`state, mobility, manual dexterity, medical factors,
`and motivation, as well as lower urinary tract func-
`tion. Although in younger individuals incontinence
`usually results from lower urinary tract dysfunction
`alone, incontinence in older patients often results
`from deficits in multiple domains that together re-
`sult in incontinence [1023, 1029]. Attention to any
`one or more of these risk factors can restore con-
`
`tinence or at least improve it. Second, although
`termed "transient," these causes of incontinence
`may persist if left untreated, and so they cannot be
`dismissed merely because the incontinence is of
`long duration.
`
`1. QUALITY OF DATA
`
`In older people, continence status may not be ab-
`solute, especially in those who are frail. Infrequent
`leakage of small amounts may appear and disap-
`pear, and reporting accuracy varies as well [1030]
`Sometimes the changing status of incontinence is
`the initial symptom of LUTS, neurological disorder
`(Parkinson's disease, MS etc_), cardiac changes
`or diabetes. Furthermore, ethical constraints and
`methodological issues preclude robust investiga-
`tions of the conditions commonly impugned as
`causes of transient incontinence. Thus,
`it is not
`surprising that evidence supporting the associa-
`tion between these conditions and transient in-
`
`continence consists predominantly of case reports
`and case series.
`
`2. RESULTS OF LITERATURE REVIEW
`
`Transient causes of incontinence in older people
`are shown in Table 6 and can be recalled using
`the mnemonic DIAPPERS
`(Delirium.
`Infection,
`Atrophic vaginitis, Pharmaceuticals, Psychological
`condition, Excess urine output, Reduced mobility,
`Stool impaction) [1024, 1031-1033].
`
`330
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2062 - 0166
`
`

`
`Table 6: Transient‘ incontinence in Older Adult
`DIAPPERS
`
`Delirium
`
`Infection
`
`Atrophic vaginitis
`Pharmaceuticals
`
`Stool impaction
`
`Psychological condition
`
`Excess urine output
`
`Reduced mobility
`
`a) Delirium
`
`“D" is for delirium, a confusional state characterised
`by fluctuating inattentiveness and disorientation. Its
`onset occurs over hours to days, as contrasted with
`dementia, which develops over years. Delirium can
`result from almost any medication and from virtu-
`ally any acute illness,
`including congestive heart
`failure, deep vein thrombosis, or infection. Many of
`these conditions may present atypically in older pa-
`tients, and if the patient becomes confused because
`of them, incontinence may be the first abnormality
`detected [1D34]. Delirium leads the list because, if
`unrecognised, it is associated with significant mor-
`tality [1035]. Thus, in this case, meticulous medical
`evaluation - not cystometry - is crucial [W36].
`
`1:) Urinary infection
`
`Symptomatic urinary infection is another cause of in-
`continence, although it is supposing uncommon one
`[1022]. However, asymptomatic urinary infection, is
`much more common in older people [1037, 1038].
`Women with recurrent urinary tract infection had the
`highest increase in Ul by 230% for weekly Ul [1039]
`and for monthly UI [1040], 220% for Ul
`in the past
`year [936], and by 470% for ever having Ul [1041].
`In addition Arya at al. reported that women with re-
`current UTIs have greater urinary frequency and in-
`creased perceived bladder sensation in the absence
`of an active infection than control women [10-12].
`
`c) Atrophic vaginiiis
`
`Atrophic vaginitis in older women is frequently asso-
`ciated with lower urinary tract symptoms, which oc-
`casionally include incontinence [1 043]. As many as
`80% of such women attending an incontinence clinic
`are reported to have physical evidence of atrophic
`vaginitis, characterised by vaginal mucosal atrophy,
`friability, erosions, and punctuate haemorrhages.
`While the evidence supporting the use of oestrogens
`in lower urinary tract dysfunction remains contro-
`versial there are considerable data to support their
`use in urogenital atrophy and the vaginal route of
`administration correlates with better symptom relief
`by improving vaginal dryness. pruritus and dyspe-
`reunia, greater improvement in cytological findings,
`and higher serum oestradiol levels [1044]. Atrophic
`
`331
`
`vaginitis has been associated with urgency and oc-
`casionally a sense of “sca|ding" dysuria, but both
`symptoms may be relatively unimpressive_ More re-
`cent epidemiological and clinical studies have called
`these beliefs into question since they have dem-
`onstrated an association with systemic oestrogen
`treatment and the onset of incontinence [Sievert et
`al ICI-RS paper 2012]. Unfortunately, limitations in
`their design allow for the possibility of both bias and
`confounding factors. Further research is warranted.
`
`d) Medications
`
`Pharmaceuticals are one of
`
`the most common
`
`causes of incontinence in older people, with sever-
`al categories of drugs commonly implicated [1045,
`1046]. Of note, many of these agents are also used
`in the treatment of incontinence, underscoring the
`fact that most medications used by older people are
`“doub|e-edged swords." The first category of relevant
`drugs is the long-acting sedativeihypnotics, such as
`diazepam and flurazepam, which can cloud an older
`patient's memory. “Loop" diuretics. such as furose-
`mide or bumetanide, by inducing a brisk diuresis,
`can also provoke leakage. Drugs with anticholinergic
`side effects are a particular problem and include ma-
`jor tranquilizers, antidepressants, anti-Parkinsonian
`agents (e.g., benztropine mesylate or trihexypheni-
`dyl), first generation (sedating) antihistamines, anti-
`arrhythmics
`(disopyramide), antispasmodics. and
`opiates. By decreasing detrusor
`contractility, they
`can cause urinary retention and overflow inconti-
`nence. They also can cause confusion. Antichollner-
`gic agents are particularly important to ask the pa-
`tient about for two reasons. First, older patients may
`often take more than one of them at a time. Second,
`they are contained in many non-prescription prepa-
`rations that older people frequently take without con-
`sulting a physician.
`
`Adrenergically-active agents have also been as-
`sociated with incontinence. Many alpha—adrenore—
`ceptor antagonists (used mainly for treatment of hy-
`pertension) block receptors at the bladder neck and
`may induce stress incontinence in women [1047].
`Older women are particularly at risk because their
`urethral length and closure pressure normally de-
`cline with age. Thus, prior to considering other in-
`terventions for stress incontinence in a woman tak-
`
`ing such a drug, substitution of an alternative agent
`should be tried and the incontinence re—eva|uated.
`Calcium channel blockers can cause incontinence.
`
`they can increase
`As smooth muscle relaxants,
`residual volume, especially in older adults with im-
`paired detrusor contractility. The increased residual
`urine may occasionally lead to stress incontinence
`in women with a weak urethral sphincter, or to over-
`flow incontinence in men with concurrent urethral
`
`obstruction. Finally, angiotensin converting enzyme
`inhibitors, by inducing cough (the risk of which is
`age—related), may precipitate stress incontinence
`in older women whose urethra has shortened and
`
`sphincter weakened with age [1048]_
`
`
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2062 - 0167
`
`

`
`e) Diuresis
`
`Excess urinary output can also cause incontinence.
`especially in individuals with impaired mobility, men-
`tal state, or motivation, particularly if they also have
`detrusor overactivity. Causes of excess output in-
`clude excess intake. diuretics (including theophy|-
`line—containing fluids and alcohol), and metabolic
`abnormalities
`(e.g., hyperglycemia and hypoca|—
`caemia). Nocturnal incontinence can be caused or
`exacerbated by disorders associated with excess
`nocturnal excretion, such as congestive heart failure,
`peripheral venous insufficiency. hypoalbuminemia
`(especially in malnourished older people), and drug
`induced peripheral oedema associated with NSA|Ds,
`thiazolidinediones. and some calcium channel block-
`ers (e.g., dihydropyridines such as nifedipine,
`isra-
`dipine, and nicardipine).
`In addition certain foods
`are natural diuretics like asparagus, parsley, beet-
`root, grapes, green beans, leafy greens, pineapple.
`pumpkin. onion. leeks, and garlic. as well as juices
`such as orange juice. The role of caffeine and tim-
`ing of drinking fluids (e.g.
`in the evening or before
`bedtime) is still not clear, but should nonetheless be
`considered a possible contributing cause for nocturia
`and nocturnal incontinence, whereas it is known to
`increase the bowel motility [1049~1051].
`
`1‘) Restricted mobility
`
`Restricted mobility is an easily understood but fre-
`quently overlooked cause of incontinence [1052].
`In
`addition to obvious causes, restricted mobility may be
`associated with orthostatic or postprandial hypoten-
`sion, poorly-fitting shoes. poor physical state. or fear
`of falling, all of which are common geriatric conditions.
`All of these reasons together with restricted mobility
`might be the cause of incontinence due to nocturia.
`
`g) Nocturia
`
`For frailiolder people with bothersome nocturia. as-
`sessment should focus on identifying the potential
`underlying cause(s), including (GR: C):
`
`- Nocturnal polyuria;
`
`- Primary sleep problem (including sleep apnoea);
`
`- Conditions resulting in a low voided volumes
`(e.g. elevated post-voiding residual) co-morbidity.
`
`Post-void residual (PVR) volume
`
`A post—void residual volume (PVR) is impractical
`to obtain in many care settings. However, there is
`compelling clinical experience for measuring PVR
`in selected frail! older persons with:
`
`- Diabetes mellitus (especially if longstanding);
`
`~ Previous episodes of urinary retention or history
`of high PVR;
`
`- Recurrent UTls;
`
`- Medications that impair bladder emptying (e.g.
`anticholinergics);
`
`- Chronic constipation;
`
`- Persistent or worsening UI despite treatment with
`antimuscarinics;
`
`- Previous urodynamic study demonstrating detru—
`sor underactivity andior bladder outlet obstruction
`(GR: C).
`
`h) Faecal impaction
`
`II. FAECAL INCONTINENCE
`
`1 . BACKGROUND
`
`The prevalence of faecal incontinence in older adults
`ranges from 33-27% in community dwelling elderly
`persons to over 50% in nursing home residents [(302,
`603, 605, 606, 636, 637, 6?2, 709, 1053, 1054].
`In
`addition faecal incontinence is a common reason for
`
`referral of elderly persons to a nursing home. [565,
`1055] Underreporting is an issue with both urinary
`and faecal
`incontinence [656, 1054, 1056, 1057];
`memory—loss and dementia exacerbate that the prob-
`lem in the elderly. While the prevalence is fairly well
`documented,
`the percentage of those people who
`have transient as opposed to long-term incontinence
`is not well known. There is significant financial and
`social cost associated with management of faecal
`incontinence in the community and nursing homes
`[607, 656, 1058-1062]. Identifying transient and reme-
`diable causes would benefit patients, caregivers and
`the health care system. One confounding aspect in
`the discussion of transient incontinence is the largely
`unknown natural history of faecal incontinence.
`It is
`clear that the symptom is intermittent in some patients
`and spontaneously resolves in others. As noted ear-
`lier in this chapter, continence for stool is a complex
`mechanism involving the consistency and transit time
`of steel, rectal capacity and pelvic floor function. Rec-
`tal capacity and pelvic floor function are less likely to
`undergo transient changes but stool consistency, tran-
`sit time of the intestinal tract and other medical condi-
`
`tions may change. It is well established that the preva-
`lence of faecal incontinence increases with age, even
`if the mechanism is not completely understood: the
`increase in prevalence suggests progressive deterio-
`ration of some aspect of anorectal function [602—604,
`606, 607, 636. 640, 656]. Theoretically, alternations in
`stool consistency, transit time and medical conditions
`would be more likely to result in incontinence in the el-
`derly although that there is minimal confirmatory data.
`The literature on transient faecal incontinence is limit-
`
`ed with a dominance of case series and retrospective
`reports. Some information is inferred from data from
`large studies of prevalence and risk factors. Treat-
`ment recommendations are frequently based upon an
`empirical rather than evidence—based approach.
`2. CAUSES
`
`Faecal incontinence occurs when the propulsive forc-
`es in the colon and rectum overwhelm the resistant
`
`forces of the pelvic floor. Continence for stool requires
`the receipt and recognition of the urge to defaecate,
`mobility to reach the toilet in time, and the ability to
`postpone defaecation until reaching the bathroom.
`
`332
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2062 - 0168
`
`

`
`[606, 608. 636. 640. 674. 1054. 1066-1070]; one study
`identified loose stool as the most important indepen-
`dent risk factor [607]. Any condition or medication re-
`sulting in loose stools may also lead to incontinence
`including acute infection,
`intestinal
`inflammatory
`processes, medication and supplements (Table 7).
`Medications with the side effects of diarrhoea andlor
`
`steatorrhea may result in faecal incontinence. Table 8
`lists the medications, which cause diarrhoea or steat-
`orrhoea with reasonable frequency. [605. 1071, 1072]
`Laxatives and the medications used for bowel prepa-
`ration for colonoscopy and surgery frequently result in
`temporary incontinence in older patients.
`
`Although rarely described in the literature, intuitively
`cessation of the causative medication should de-
`
`crease the incontinence. In a case report, withdrawal
`of the offending medication, metformin, resolved the
`incontinence.[648]
`
`e) Constipation
`
`Paradoxically faecal incontinence may occur in pa-
`tients with faecal impaction. [641. 662, 1073-1075]
`immobility,
`inadequate dietary and fluid intake, de-
`pression, metabolic disorders neurological conditions,
`connective tissue disorders and medications contrib-
`
`ute to constipation.[641, 662] impaction may result in
`overflow incontinence with loose stool leaking around
`the faecal bolus. [663] Evaluation of impacted patients
`compared to elderly controls revealed similar resting
`and squeeze pressures although both groups had
`lower pressures than younger healthy controls. How-
`ever perianal and rectal sensation was impaired in
`74% of the impacted patients.[613, 1076] The theory
`is the patients with impaired sensation do not expe-
`rience the urge to defaecate with the typical volume
`of stool. The stool bolus causes the usual reflex re-
`
`laxation of the internal anal sphincter but the lack of
`perception prevents the normal contraction of the ex-
`ternal sphincter muscle. lncontinence is often aggra-
`vated by the use of laxatives to relieve constipation.
`
`Table 7:05-uses of Loose Stool
`
`Infection
`
`Acute viral or bacterial gastroenteritis
`Clostridium difficile colitis
`Inflammation
`lschaemic colitis
`
`I C
`
`-
`
`Medications
`
`inflammatory bowel disease flare
`(ulcerative colitis. Crohn's colitis)
`Microscopic colitis
`
`Supplementsldietary elements
`Caffeine
`Fructose
`
`High dose probiotics
`Magnesium
`Omega-3 fatty acids
`Orlistat
`
`Delaying defaecation requires sufficient rectal capac-
`ity and compliance and adequate neurologic and anal
`sphincter function.
`
`a) Altered mental status
`
`illness, hospitalisation, surgery and
`Acute medical
`medications such as opiates and sedatives may re-
`sult in delirium or disorientation in the elderly. The
`reported rates of mental status changes to as high as
`74% after surgery and from 11 to 42% during medical
`hospitalisation [1063. 1064].
`In a systematic review of
`delirium associated with medication, opiods, benzodi-
`azepines, and dihydropyridines were found to clearly
`increase the risk of delirium. There was uncertainty
`regarding antihistamines,
`tricyclic antidepressants.
`anti—Parkinson mediations, steroids and non—steroidal
`anti-inflammatory medication [1065]. Delirium, confu-
`sion and other transient changes in cognitive function
`may impair a patient's ability to recognise the urge to
`defaecate andlor their motivation to remain continent.
`
`The limited investigations of the relationship between
`delirium and incontinence studied patients with chron-
`ically altered mental status; any relationship of acute
`delirium andfor confusion with faecal incontinence is
`
`inferred from those data. Studies of the impact of de-
`lirium on continence show that delirium plays an im-
`portant role in the development of incontinence [670,
`708]. The impact of altered mental status on conti-
`nence has also been inferred from studies showing
`improvement in continence with scheduled toileting
`programs [1066, 1067]. Ignoring the urge to defae-
`cate combined with the effect of medications may
`result in faecal impaction followed by incontinence.
`Delirium may require the use of restraints. Need for a
`restraint has been reported as an independent factor
`in incontinence [709].
`
`b) Impaired mobility
`
`Lack of adequate mobility may prevent a patient from
`reaching the bathroom in time to avoid incontinence. In
`addition to the causes described in the urinary incon-
`tinence section, musculoskeletal ailments, such as ar-
`thritis and bone fractures, occur more commonly in the
`elderly and limit mobility. During the recovery phase
`from joint replacements ambulation may be slow
`and unsteady. Acute neurological conditions such as
`stroke may affect a patient's gait as well as debilitated
`states from other illness. Faecal incontinence is fairly
`common (up to 30% in first week) immediately after
`a stroke; with rehabilitation, the rate decreases [605.
`681, 1066]. The use of anti-cholingeric medication and
`requiring assistance to reach the toilet were significant
`independent factors [681]. For patients temporarily re-
`quiring assistance to reach the bathroom. the timeli-
`ness of the assistant may affect their continence.
`
`c) Stool‘ consistency
`
`Change in stool consistency affects continence;
`both constipation and diarrhoea may result in
`faecal incontinence.
`
`d) Diarrhoea
`
`Loose stool is clearly a risk factor for incontinence
`
`Tube feedings
`
`333
`
`
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2062 - 0169
`
`

`
`Table 8: Medications causing diarrhoea
`
`_
`_
`_
`_
`A||3h3'Q|UC05'd35e lnhlbltors
`Aiiiiiioiics
`Al'|tll'et|'0VlT3l therapy
`Biguanides (e_g. Metformin)
`
`B“e acids
`Chemotherapy agents
`
`Cholinergic drugs
`co|Chicine
`_
`_
`Dlacerem
`Digoxin
`
`_
`Immunosuppressive agents
`Mesalamine
`
`_
`Metocopramide
`
`Ill. SUMMARY
`
`Apart from data for aIpha—ad renergic agents (Level of
`Evidence = 2), the level of evidence for most of these
`:::::::d%:::;3:.l::2:::::::iio”:.°:,:?;l:i:2i,:;:
`the lower urinary tract and perianal area, they are
`worth identifying even if the evidence is not strong.
`
`iv. RECOMMENDATIONS
`
`Despite the lack of robust data about the incidence
`and causes.
`transient urinary and faecal
`inconti-
`nence are t::|intilc;1aI|ytcomi|11:in lprol£'i|e‘m:t.f Sinci: ii‘;
`mos cases ea
`en is rea iveysraig orwar ,
`I
`is important to consider the causes discussed in this
`section when elderly patients present with new onset
`incontinence. Moreover, addressing them may im-
`prove the incontinence even if it does not eliminate it,
`and it may make the incontinence more amenable to
`subsequent therapy. (Grade of recommendation 0)
`
`Non-steroidal anti-inflammatory agents
`
`V. RESEARCH PRIORITIES
`
`Orlistat
`Qsmotic Laxatives
`.
`Prostaglandms
`Seiective serotonin reuptake inhibitors
`_
`,
`,
`Tlclopldme
`Tyrosine kinase inhibitors
`
`Further research should be performed on the mecha-
`nisms, prevalence, incidence, and remission rates of
`each of the known causes of transient incontinence,
`and possible additional causes should be identified
`as well. Since the clinical circumstances of older
`people are heterogeneous. studies should be con-
`ducted among several subgroups,
`including inde-
`pendent and homebound and community—dwelling
`older people, bedbound and mobile institutionalised
`older people and acutely hospitalised older people.
`
`LIST OF ABBREVIATIONS
`
`AC3 American College of
`Surgeons
`Autonomic Nervous System IPSS
`ANS
`Acetylcholine
`ACh
`AChE Acetylcholinesterase
`ASR
`Anal Sphincter Rupture
`ATP
`Adenosine Triphosphate
`BPH
`Benign Prostatic
`Hyperplasia
`Benign Prostatic Obstruction MRI
`BPO
`Central Nervous System
`CNS
`Confidence Interval
`Cl
`cAMP Cyclic Adenosine
`Monophosphate
`Detrusor Overactivity
`Diabetes Mellitus
`
`International Consultation on
`Incontinence
`International Prostate
`Symptom Score
`Intrinsic Sphincter
`Deficiency
`Levator Ani Muscle
`Lower Urinary Tract
`Symptoms
`Magnetic Resonance
`Imaging
`Multiple Sclerosis
`Nitric Oxide
`Nitric Oxide Synthase
`Nerve Growth Factor
`Overactive Bladder
`
`RRP
`
`PNTML Pudendal Nenre Motor
`Terminal Motor Latency
`Radical Retropubic
`Prostatectomy
`RCOG Royal College of
`Obstetricians and
`Gynaecologists
`Relative Risk
`Selective Serotonin
`Re—uptal<e Inhibitor
`Stress Urinary Incontinence
`SUI
`TURP Transurethral
`Prostatectomy
`Transurethral Incision of the
`Prostate
`Tetrodotoxin
`
`RR
`SSRI
`
`TUIP
`
`TTX
`
`ICI
`
`ISD
`
`LAM
`LUTS
`
`MS
`NO
`NOS
`NGF
`OAB
`
`DO
`DM
`
`Odds Ratio
`OR
`DSD Detrusor Sphincter
`Pontine Micturition Centre
`PMC
`Dyssynergia
`Pelvic Floor Dysfunction
`PFD
`Electromyography
`Pelvic Floor Muscle
`PFM
`External Anal Sphincter
`Pelvic Organ Prolapse
`Inflammatory Bowel Disease POP
`Irritable Bowel Syndrome
`POP—Q Pelvic Organ Prolapse
`Internal Anal Sphincter
`Quantification
`
`EMG
`EAS
`IBD
`IBS
`IAS
`
`VLPP Valsalva Leak Point
`Pressure
`Urinary Incontinence
`Urodynamic Stress
`Incontinence
`
`Ul
`USI
`
`334
`
`
`
`Patent Owner, UCB Pharma GmbH — Exhibit 2062 - 0170
`
`

`
`REFERENCES
`
`Abrams. F., et al., The standardisation of terminology of
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`Patent Owner, UCB Pharma GmbH — Exhibit 2062 - 0171
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