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Advances in understanding and treatment of feline inappropriate elimination

TOPICAL REVIEW
Advances in Understanding and Treatment of FelineInappropriate Elimination Feline inappropriate elimination is the number one behavioral reason for relinquishment of cats to shelters andhas historically been the most commonly reported feline problem addressed by behavior professionals. Veter-inarians are hence challenged to uncover the underlying motivation for this behavior so that an accuratediagnosis can be made and an effective treatment plan implemented. Before a behavioral diagnosis can bemade, underlying medical disease must be addressed, making a comprehensive physical evaluation imperative.
After all medical issues have been addressed, a behavior diagnoses list is made based on detailed historicalinformation obtained from the cat owner. A distinction is first established between marking and inappropriatetoileting, according to elimination postures described by the owner and the social relevance of the sites ofinappropriate eliminations. Next, inadequacies of the litter box management are identified and subsequentaversions and preferences, including litter box aversion, substrate aversion, location aversion, substrate pref-erence, and location preference, can be diagnosed. The practitioner should be cognizant of the fact that anxietyfrom the environment and social conflict may play a major role in both marking and inappropriate toiletingbehaviors. Once both the medical and behavioral diagnoses are established, a treatment plan catered to theindividual cat, owner, and household environment can be formulated. This should include acceptable forms ofmarking when indicated, appropriate litter box management and hygiene, reduction of environmental stres-sors, including resolution of social conflict in multicat households, proper treatment and restricted access tosoiled areas, pheromone application, and, when indicated, anxiolytic drug therapy.
2010 Elsevier Inc. All rights reserved.
Keywords: cat, feline, elimination, litter box, behavior
Feline inappropriate elimination is defined as urination Making a Diagnosis and/or defecation outside of an owner-designated elimi- Before a definitive behavioral etiology for elimination prob- nation location. Although the cat may not recognize its own lems can be made, underlying medical disease must be ruled elimination patterns as problematic, owners of such cats find out and addressed. Although the medical evaluation should it quite undesirable, making it the number one behavioral encompass all physical aspects, special attention should be reason for relinquishment of cats to and a common paid to factors causing discomfort to the lower urinary tract reason for the return of a previously adopted cat to a (i.e., urinary tract infection, urolithiasis, neoplasia, cystitis) Furthermore, elimination problems have historically been or gastrointestinal system (any cause of diarrhea, constipa- the most commonly reported feline problem addressed by tion, or pelvic pain), and to organ system or endocrine dis- ease that might increase elimination volume and, therefore, that this frequency may be on the This decline in urgency (i.e., hyperthyroidism, diabetes mellitus, chronic presentation to behavioral specialists suggests that the gen- kidney disease). A thorough physical examination and a min- eral companion animal practitioner is better equipped to di- imum diagnostic database, including a complete blood agnose and treat such problems. This article aims to boost count, serum chemistry profile, total T4, fecal analysis, and general practitioners’ knowledge regarding the current diag- urinalysis should rule out most of these factors. Further di- nosis and treatment strategies available for cats with elimi- agnostic testing, such as urine culture, abdominal/pelvic ra- diographs, and abdominal ultrasound, should be performedbased on the results of the minimum database. If a medicaletiology is not determined, then a behavioral diagnosis can be From the Behavioral Medicine Clinic, The Ohio State University Collegeof Veterinary Medicine, Columbus, OH USA.
pursued. Practitioners should be cognizant that medical and Address reprint requests to: Meghan E. Herron, DVM, DACVB, The Be- behavioral pathologies often coexist and both aspects should havioral Medicine Clinic, The Ohio State University College of Veterinary be addressed to have a successful treatment outcome. Cats Medicine, 601 Vernon L. Tharp St, Columbus, OH 43210. E-mail: suffering from medical disease also benefit from behavioral 2010 Elsevier Inc. All rights reserved.
1527-3369/06/0604-0171\.00/0 The behavioral diagnosis is made based on a complete behavioral history. Characterization of the elimination hab- Topics in Companion Animal Medicine
its, such as frequency and duration of the problem, elimina- tion posture, volume eliminated, location of soiling, and sub- flowchart for diagnosing feline inappropriate elimination strates or objects on which the cat eliminates, is pertinent for a behavioral diagnosis. Information regarding the litter boxcharacteristics and management, as well as litter type, should also be obtained. Furthermore, environmental and house-hold details, including adults, children, and other animals When urine marking, the cat assumes a standing posture with living in or frequenting the home, any recent home renova- the tail raised and sprays urine back against an object. Often tions or changes in the daily routine, and presence of outdoor the tail quivers as a small amount of urine is sprayed and no cats, is equally important information because it provides a digging or covering behaviors are Objects means of identifying underlying stressors that may be con- marked are typically items of social significance, such as win- tributing to the elimination behavior. An efficient means of dows or doors where outdoor cats are detectable, areas of the collecting elimination, litter box, and environmental infor- home where interactions of conflict have occurred, or items mation is having owners complete a behavioral history ques- containing the scent of a particular person or animal in the tionnaire, as presented in before the appointment.
Marking from a squatting posture is less com- Gathering this information allows one to discern the mo- mon, but should be diagnosed if urine or feces are found tivation behind the elimination pattern and, therefore assign deposited primarily in socially relevant locations. Marking a behavioral diagnosis. Understanding the motivational di- with feces, middening, is less common and its diagnosis is agnosis then dictates the path of treatment. The first step in based on the social importance of the and a lack of making a behavioral diagnosis is to discriminate between digging and covering behavior. Urine marking in intact cats is marking, a form of communication, and inappropriate toi- a normal signal of reproductive yet 10% of neutered leting, a means of voiding bladder and/or bowel contents.
males and 5% of spayed females persist in showing urine- Keep in mind some cats will present with concurrent marking marking Motivations for neutered cats to urine Table 1. Feline Behavioral History Questionnaire
1) Does your cat’s urine or stools ever appear abnormal, either inside or outside of the box?2) Does your cat have any history of urinary or gastrointestinal tract problems, including a urinary tract infection or 3) Does your cat urinate outside the box? If so, please list all locations.
4) If your cat urinates outside the box, have you ever witnessed it? If so, please describe your cat’s posture (i.e., squatting vs. standing, tail down and to the side vs. erect).
5) Does your cat have bowel movements outside of the litter box? If so, please list all locations.
6) Are there certain objects or materials outside of the box on which your cat will eliminate? If so, what?7) Does your cat cover up his eliminations in the litter box?8) Does your cat ever show scratching or digging behaviors before eliminating outside the box?9) What products do you use to clean areas where your cat has soiled? 1) How many litter boxes do you have?2) Where are the litter boxes located?3) What type of litter do you use? Is this a clumping litter?4) Do some or all of your litter boxes have covers?5) Do some or all of your litter boxes have liners?6) How deep is the litter in the box?7) How often do you scoop the urine or stools from the box?8) How often do you empty the entire contents of the box and clean it? 10) Please list all the people living in your household.
11) Please list all the animals in the household in the order in which they were obtained.
12) If you have a multiple cat household, do you ever notice staring, growling, hissing, chasing, or fighting between 13) How does your pet react to strangers?14) How does your cat react to loud noises?15) Has your household changed since acquiring this pet? If so, when and how?16) Was anything unusual going on in your cat’s environment before the onset of the elimination problem?17) Does your cat have access to the outdoors?18) If you cat is strictly indoors, does he have visual access to outdoor cats? If so, what is his reaction? Volume 25, Number 4, November 2010
Figure 1. Flowchart for diagnosing feline behavioral inappropriate elimination disorders.
mark include territorial signaling and anxiety associated with aromatic pine or cedar shavings, or because of an unpleasant social conflict or environmental Multicat texture, such as large gravel or A common cause of households are often the source of anxiety-induced urine litter box or substrate aversion is the experience of a painful marking and, in fact, the incidence of marking increases as bowel movement or urination from medical disease. Once the number of cats in a home Anxiety as a result the medical problem has resolved, the cat may still recall the of household or family changes, poor litter box management, unpleasant experience and, therefore, avoid the previously the inability to escape the presence of outdoor cats, or the used litter box or substrate Signs of “dissatisfaction” absence of the owner is also a major cause of urine-marking with the litter box or substrate include a cat that investigates and then avoids entering a box, avoids digging and circling orcovering waste while in the box, scratches the surrounding wall or sides of the litter box rather than the litter, andperches on the sides of the Moreover, cats with elim- Unlike marking, toileting behaviors serve the purpose of ination problems spend less time in the litter and voiding bladder and bowel and are associated with a squat- ting Toileting cats will typically display diggingbehaviors before and covering behaviors after and will typically deposit a large volume, as would be asso-ciated with a fully voided bladder or bowel, onto a horizontal A location aversion can develop as the cat has a quarrel with Toileting behaviors that occur outside of the litter another household cat, is startled by loud noise or commo- box are often related to litter box as cats de- tion, or has difficulty accessing the elimination area. This can velop aversions to the available litter box options and pref- be a problem with multiple-cat households where social con- erences for those outside of the owner-designated elimination flict may prevent some of the household cats from entering Determining the specific aversions and preferences the designated elimination area. Geriatric cats may have dif- will aid in the diagnosis and treatment of inappropriate toi- ficulty accessing litter that require the cat’s ascending or descending a flight of stairs or hurtling gates or otherobstacles that may have been set up to keep other animals or children from accessing the box. Litter box, substrate, andlocation aversions are not mutually exclusive and often there Aversion to the litter box can develop as a result of poor are multiple motivational diagnoses.
cleaning hygiene or from other unpleasant characteristics ofthe box. For example, covered litter boxes may trap odors and prevent the cat from having a safe vantage point for theapproach of other animals during elimination, causing them As the various aversions prevent cats from using their desig- to eliminate in a more open and safe area. Litter boxes that nated elimination areas, preferences for alternative substrates are too small, do not contain enough litter, or contain liners subsequently develop. For example, if the litter box is not that are potentially aversive for cats with intact can scooped regularly and the cat chooses to eliminate on another also create an aversion to the elimination area. Substrate clean substrate, it may develop a preference for the new, nona- aversions may develop as a result of scented such as versive material. Substrate preferences can develop with or Topics in Companion Animal Medicine
without the presence of an aversion and are most commonly associated with a preference for soft, absorbable material, such Cleanliness is crucial in successful litter box management.
as bedding, piles of clothing, and Less common are cats Proper litter box hygiene can improve both urine marking that prefer open, hard surfaces, such as wood or linoleum floors.
and inappropriate toileting The box should be Finally, cats with medical illness that may not have been able to scooped daily and the contents fully emptied allow- reach the litter box may develop preferences for substrates on ing for washing with mild soap and water. Although plastic liners allow for easy and efficient cleaning, they should beavoided because they are potentially aversive for cats withintact Self-cleaning litter boxes offer increased clean- liness, but they are avoided by some cats because they are Location preferences may develop as a result of a cat’s desire associated with aversive noise and movement. As far as litter for privacy, preference for a safe, quiet area, or ease of access type, cats have a natural preference for unscented and finely to a specific location. Furthermore, cats are attracted to pre- particulate litter making clumping litter a desir- viously soiled and may be more likely to eliminate in a able option. Because strong perfumes and scents can createsubstrate aversions, unscented litter is In fact, location where other cats have eliminated, or where the cat one study found that the use of scented litter was associated eliminated at a time when the litter box was not accessible.
with a higher incidence of elimination A recent Owners may attempt to relocate the litter box and find the cat study suggested that the addition of an odor eliminator (Zero Odor; Zero Odor, LLC, Pound Ridge, New York, USA) tostandard clumping litter increased the attractiveness of thelitter box and decreased the frequency of inappropriate elim- Each individual cat has a unique threshold for tolerating Appropriate litter box size, shape, and location may also poor litter box management. Anxiety-provoking events and reduce the incidence of inappropriate elimination. Cov- the presence of underlying stressors can change this threshold ered litter boxes may trap odors and prevent the cat from quickly. A cat who previously tolerated a dirty litter box or a having a safe vantage point for the approach of other difficult-to-access location may suddenly develop aversions animals during elimination, making them a less desirable or preferences with the addition of environmental stressors, option for most cats. If, however, a covered box is being such as new pets or people in the home, household renova- used by at least one cat, the owners should avoid immedi-ately removing the covers from all boxes. Instead, a non- tions, or agonistic interactions with the owner or other cats.
covered box can be placed next to a frequently used cov- Furthermore, cats with anxiety about new household mem- ered box to determine a preference for box type. If the bers or other household changes may be too nervous to ven- covered box is then no longer used, it can be removed.
ture to the location of their litter Cats may also toilet Large, open boxes, such as plastic storage outside of the litter box as a result of separation provide room for elimination posturing and pre-elimina- either during the work day or after an extended absence.
tion/postelimination digging and covering behaviors. This Although anxiety is more commonly associated with urine principle of first offering the option of a new box and marking, it is equally important to recognize when anxiety is establishing a preference before removing old boxes that playing a role in inappropriate toileting behaviors and to are being used by some of the cats in the home applies to all major litter box conformation changes. In multicat house-holds, the number of litter boxes should equal the numberof cats plus one additional box so that there is always a box available at any given Each cat should haveaccess to a litter box in a separate, safe, quiet area to For urine-marking cats, neutering is recommended and prevent one cat’s blocking another’s access to the litter box should resolve the problem for 90% of males and 95% of location. This means owners should offer multiple loca- For cats that urine mark while standing in the litter tion options for elimination, including at least one box on box, the addition of a vertical litter box placed so that the end each floor of the house. Boxes should be kept at a distance of the horizontal box fits into it can create an acceptable place from food and water bowls, as well as loud appliances, to urine In addition, other forms of marking behav- such as washer/dryers and furnaces that may have created ior such as scratch marking should be Sub- a location aversion. See for details regarding litter strates such as sisal-covered posts or real bark-covered logs in frequently visited areas of the home are appealing becausethey allow the cat to hook its claws in the The remaining basic treatment principles are universal for bothmarking and inappropriate toileting behaviors and can work Because cats are attracted to previously soiled areas and may as an adjunct in treating medical elimination problems.
be inclined to overmark or use them for proper Volume 25, Number 4, November 2010
ate scratching substrates, rotating toy options, and comfort- Table 2. Basic Recommendations for Litter Box Manage-
also take special care to provide daily social contact with the cat in this room, such as petting, brushing, or permitting timeto sleep on the owner’s Confinement is also helpful in establishing substrate and box type preferences in that a “buffet” of options can be presented in one location. Various substrates, such as different brands of clay, potting soil, sand, shredded newspapers, and absorbable pads can be offered in multiple boxes, as well as varying box For cats with a preference for hard surfaces, flat pans or trays of differing material can be offered as When a cat has a strong aversion to a particular litter box or substrate based on a frightening or painful experience, the “buffet” of box options offered may need to be substantially different than the original box. Once a substrate and box preference has been established and the cat is eliminating appropriately, the preferred box/litter type can be used through the home and the cat’s access to the home can be slowly clean with soap and waterAutomatic/self-cleaning Because social distress and anxiety are common underlying components in urine marking for neutered cats, reducingstress and intercat conflict is key. A starting point for reduc- *Some cats prefer covers. Offer an uncovered box next to a covered box
to determine preference.
ing stressors is providing 1) a living space that keeps the catfree from fear and distress and 2) a predictable daily routine †Fastidious daily scooping may allow for longer time between cleaning.
and owner interactions over which the cat perceives it hassome Cats should have full access to areas ofthe house where stressors, such as loud noises, dogs, other cleaning is necessary. Although a variety of pet waste clean- cats in the household, outdoor cats approaching the windows, ing products exist, studies have shown that enzymatic clean- and pursuit by small children, are minimized. Throughout ers are the most effective at reducing and preventing the the household, cats need perching options that offer safety return of urine If the problem is chronic, the un- and a decent vantage point above people and other animals.
derlying carpet pads and baseboards may need to be replaced If the cat is agitated by cats outside the home, windows out to completely eliminate excrement Once the areas which the cat has visual access should be In mul- have been treated, the cat’s ability to resoil them should be ticat households there should be enough space for each cat to managed. This can be accomplished by placing plastic or foil keep a social distance of at least 1 to 3 when they are in coverings on top of them to create an unappealing tactile a room together. Some cats will rest together and groom/rub sensation when the cat walks in that area and to preventresoaking of the carpet, should another elimination incidentBlocking access to bedding and picking upthrow rugs and laundry are also important for cats with soft Table 3. Checklist for Creating a Cat “Safe Haven.” The
substrate preferences. Should the cat repeatedly soil a partic- Following Table Lists Recommendations for Creating a ular area despite these changes, it may be an indication of a Safe Refuge for a Cat Inside the Home.
location preference and a litter box should be placed directly Scratching optionsHiding placesHigh resting areas/perches In some cases the cat’s access to previously soiled areas must completely restricted. If the soiling is limited to one room in the home, that room can be closed off from access. If there are Other pets in the home causing social conflict are denied multiple areas or if the main area cannot be blocked off, then accessVisual access to outdoor cats blocked the cat should be confined to a room or “safe haven” when Soft music to muffle sounds outside of area not directly supervised. Within this “safe haven” there should be fresh food and water, clean litter boxes, appropri- Topics in Companion Animal Medicine
each other in an affiliative manner, while most cats use the same resting/perching sites at different times per Early studies indicated moderate efficacy with the use of pro- Hence, it is important to offer multiple safe and comfortable gestins for urine marking in Because of the high potential for adverse effects, such as diabetes mellitus and One means of providing the individual cat with a low- bone marrow and the development of safer, stress environment is to set up a refuge from household stres- more effective drugs, progestin treatment has fallen out of sors. Each cat should have access to its own quiet area of the favor. The benzodiazepine, diazepam, was found to reduce home or “safe haven” Electronic cat doors can be urine marking in 55% of treated however, accounts of installed to allow access only to the individual cat wearing acute fulminant hepatic failure after oral administration have the door-activating In single-cat households, a baby been making its use potentially hazardous.
gate raised several inches in the door jamb will permit the cat Later, treatment with the azapirone, buspirone (0.5-1 mg/kg to enter the room, keeping out dogs and small children.
every 12 showed some promise in controlling urinemarking in multiple-cat but reports of in- creased intercat aggression problems have been More recently, several studies have demonstrated efficacy of Punishment should be avoided in both marking and toileting clomipramine (0.25-1.3 mg/kg every 24 in treating problems. Because many elimination problems are based in urine marking in Clomipramine is a tricyclic antide- anxiety or social conflict, punishment is likely to exacerbate pressant whose serotonin-enhancing properties are effective the problem. Should an owner catch a cat in the act of elim- at reducing Side effects may include sedation, con- inating outside of the box, the behavior can be calmly inter- stipation, urine retention, pupil dilation, and appetite rupted with as little movement as possible on the owner’s changes. Daily doses less than 0.5 mg/kg are associated with In the author’s experience, teaching the cat an “inter- fewer side Even greater efficacy for the treatment of ruptor” cue and then redirecting the cat to an appropriate urine marking can be gained with the use of the selective elimination site can be beneficial. The interruptor cue is serotonin reuptake inhibitor fluoxetine (0.5-1.5 mg/kg every taught pairing a sound (nonstartling), such as the shaking or 24 In fact, one study found that 100% of cats crinkling of a treat pouch or the jingling of a bell, with the treated with 1 mg/kg of oral fluoxetine once daily had a 90% cat’s favorite food treat, a process known as classical condi- or greater reduction in marking Because the se- Once conditioned, the owner can use this cue to lective serotonin reuptake inhibitors as a class are more se- interrupt early elimination postures, call the cat away from lective for serotonin enhancement and do not have major its intended elimination area, and then give the food reward anticholinergic/anti-adrenergic properties, fluoxetine is asso- for compliance. For cats with inappropriate toileting prob- ciated with fewer side effects than the tricyclic antidepres- lems, they can then be calmly taken to the litter box and sants, with decreased appetite and lethargy being the most praised and given another food treat for appropriate elimi- common. Suppression of appetite is of concern, especially This method gives the owner a means of stopping with finicky eaters or obese cats; therefore, caution should be undesirable elimination without causing fear or anxiety, exercised with fluoxetine use in such cases. Finally, a pilot study using the dietary supplement (Anxitane; Virbac AnimalHealth, Fort Worth, Texas, USA) containing L-theanine hasshown promise in treating anxiety problems in cats, includ- ing inappropriate L-theanine is an amino acidfound in green tea and has been shown to promote mental The pheromone product Feliway (Ceva Animal Health, Inc., and physical relaxation in Further studies are St. Louis, Missouri, USA) has been shown to reduce the oc- needed to determine its safety and efficacy in feline elimina- currence of urine marking as well as to increase relaxed be- havior in stressful Hence, its use may be Regardless of drug class, efficacy, or side effects, it is im- beneficial in cases in which stress or anxiety is an underlying portant to recognize that no psychotropic drugs are labeled factor in the elimination problem. Feliway is an analog of the for use in cats. Cat owners should be made aware of the facial pheromone deposited when cats facially rub or bunt on off-label use and cautioned regarding potential side effects objects—a behavior performed when cats feel comfortable and toxicities. In addition, the use of psychotropic drugs with their Because cats do not typically urine should be an adjunct to environmental changes and proper mark in locations where they have deposited facial phero- litter box management. The precise starting dose and dura- mones, it serves as an antagonist of urine marking. For cases tion of drug therapy vary with each cat. Starting at or below of urine marking, Feliway can be sprayed directly to marked the published dose range and titrating up to effect over sev- areas 1 to 3 times Alternatively, a plug-in diffuser can eral weeks is recommended. Typically, several months at the be used to obtain a broader and more consistent distribution maintenance dose are necessary to obtain acceptable resolu- of the pheromone product in a particular room of the tion. Once the new elimination habits have developed and been maintained for 2 to 3 months, the medication can be Volume 25, Number 4, November 2010
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UNITED STATES DISTRICT COURT WESTERN DISTRICT OF NEW YORK ABBOTT LABORATORIES and LABORATOIRES FOURNIER S.A., Plaintiffs, ________ BIOVAIL LABORATORIES INTERNATIONAL SRL and BIOVAIL CORPORATION, COMPLAINT FOR PATENT INFRINGEMENT Defendants. Abbott Laboratories ("Abbott") and Laboratoires Fournier S.A. ("Fournier") for their Complaint

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Cyclosporine Concentration Prediction usingG. Camps-Valls∗, E. Soria-Olivas∗, J. J. P´erez-Cruz‡, A. R. Figueiras-Vidal‡, A. Art´∗ Dept. Enginyeria Electr`onica. Universitat de Val`encia, Spain. C/ Dr. Moliner, 50, 46100 - Burjassot (Val`† Pharmacy Service. Dr. Peset University Hospital. Val`encia, Spain∗. ‡ Dpto. Teor´ıa de la Se˜nal y las Comunicaciones. Universidad Ca

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