Animal Health Research Reviews 9(2); 135–148Antimicrobial resistance in swine productionFrank M. Aarestrup1*, C. Oliver Duran2 and David G. S. Burch31National Food Institute, Technical University of Denmark, Bulowsvej 27, DK-1790 Copenhagen V,Denmark2Moss Veterinary Partners IDA Estate, Monread Road, Naas, Co. Kildare, Ireland3Octagon Services Ltd, Old Windsor, Berkshire, UKReceived 15 Septem
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Udaonline.net2Int Urogynecol J (2011) 22:395–400DOI 10.1007/s00192-010-1252-8 Treatment choice, duration, and cost in patientswith interstitial cystitis and painful bladder syndrome Jennifer T. Anger & Nasim Zabihi &J. Quentin Clemens & Christopher K. Payne &Christopher S. Saigal & Larissa V. Rodriguez Received: 12 June 2010 / Accepted: 4 August 2010 / Published online: 2 September 2010 # The Author(s) 2010. This article is published with open access at Springerlink.com Keywords Interstitial cystitis . Treatment . Bladder pain .
Introduction and hypothesis In order to better understand provider treatment patterns for interstitial cystitis (IC)/painfulbladder syndrome, we sought to document the therapiesutilized and their associated expenditures using a national dataset.
Methods A cohort was created by applying the ICD-9 Interstitial cystitis/painful bladder syndrome (IC/PBS) is a diagnosis of IC (595.1) to INGENIX claims for the year debilitating disease that presents with a constellation of 1999. Subjects were followed for 5 years, and patterns of symptoms including pelvic pain, urinary urgency, frequency, care and related expenditures were evaluated.
nocturia, and small voided volumes in the absence of other Results Of 553,910 adults insured in 1999, 89 subjects had a identifiable etiologies. Reports of its prevalence vary; it is diagnosis of IC with 5-year follow-up data. All subjects were reported to affect 10/100,000 of the population in Finland[ treated with oral medication(s), 26% received intravesical In 1989 it was estimated to affect 501/100,000 individuals treatments, and 22% underwent hydrodistension. Total (0.5%) in the US Studies have shown that this disease expenditures per subject were $2,808.
significantly impacts quality of life; patients with IC/PBS Conclusions The majority of IC expenditures were attribut- score lower than women without IC/PBS in four out of able to oral medical therapy. Hydrodistension and intravesical seven dimensions measured by the short-form health instillations were utilized in less than 25% of patients.
survey (SF-36) questionnaire including physical function, Hydrodistension was used more frequently among subjects vitality, social function, and bodily pain domains ]. A with a new diagnosis; this may reflect its utilization as part of a study in a population of managed care patients in the US demonstrated that this disease is underreported; theprevalence may be 30–50-fold higher in women and 60–100-fold higher in men.
Presented at the Society for Urodynamics and Female Urology Annual The economic burden of IC/PBS is significant. Incremental medical costs are estimated to exceed $100 million per year and total income lost to IC in 1987 was estimated to be from J. T. Anger : N. Zabihi : C. S. Saigal : L. V. Rodriguez (*)Department of Urology, UCLA, $177 to $311 million ]. In a study by the Urologic Diseases Box 951738, Los Angeles, CA 90095-1738, USA in America Project, the average total annual medical cost per person with an IC/PBS diagnosis was $7,597; more thandouble the figure for those without the diagnosis, after J. Q. ClemensDepartment of Urology, University of Michigan, controlling for several factors ]. A study of a managed care population found costs associated with IC/PBS to be $4,000greater than for age-matched controls . A multimodal treatment approach is usually employed in treating these Department of Urology, Stanford University,Palo Alto, CA, USA patients. The goal of this study is to better understand provider treatment patterns and likely treatment efficacy insured population in the dataset was 58.5 and 59 years, through the use of a national dataset.
respectively. The mean and median age among the cohortwith IC/PBS was 63.3 and 65 years, respectively, and that ofthe incident cases was 63 and 64.5 years. The age distribution All patients had at least one claim for an oral medication This study was part of the Urologic Diseases in America indicated for symptoms of IC/PBS. Medications used by Project. Ingenix is a claims-based dataset, which captures more than 10% of the subjects in prevalent and incident cases, utilization of medical services for approximately 1.8 million respectively, were PPS (35%, 15%), tolterodine (31%, 31%), employees, retirees, and dependants of 25-large Fortune 500 amitriptyline (25%, 13%), gabapentin (19%, 15%), and employers The sample used consisted of primary oxybutinin (18%, 17%); the average duration of therapy for beneficiaries, age 18–64 years, who were continuously all of these medications in all patients was 72 weeks. Among enrolled for the year 1999. A cohort was created by applying medications used to treat IC/PBS, anticholinergics were the the ICD-9 diagnosis code for IC/PBS (595.1) to claims for most common class utilized (49% for tolterodine and the year 1999. We did not exclude the diagnosis of oxybutinin combined, Table Narcotic pain medications overactive bladder (OAB), partly because there is no ICD- were utilized by 84% of the subjects (Table 9 code specific for OAB other than 596.51 (hypertonicity of Twenty-two percent of all subjects and 30% of the incident bladder). Since many of the symptoms of OAB overlap with cases underwent hydrodistension; intravesical therapies were IC codes, such as frequency/urgency/nocturia, and OAB is used in treatment of 26% and 17% of all and incident cases, not easily diagnosed with codes, we chose not to exclude respectively (Table These therapies were not repeated these patients. Although it is possible that there are cases that when used, with the exception of one patient who had a were misdiagnosed, we suspect that this number is small.
repeat intravesical instillation. Additionally, when treated This cohort was followed for 5 years in order to obtain long- with intravesical therapies, not all subjects received a full 6- term data on these subjects. Claims for both prevalent and week course of treatment; treatments ranged from 2 to incident cases were analyzed. Incident cases were identified 6 weeks, with an average of 4.4 weeks.
by excluding subjects with a claim for IC/PBS in 1998.
Expenditures for all IC/PBS-specific treatments combined The medical claims in the Ingenix dataset include financial for the cohort were $2,808 per patient over 5 years. This does information, diagnosis, and procedure codes, drug claims, and not include related expenditures for physician evaluation, national drug codes which were used to examine utilization of laboratory and/or radiology testing. Oral medical therapy specific drugs. We identified oral medications and procedures represented 82%, hydrodistension 15%, and intravesical utilized as well as their duration of use and associated instillations 3% of the overall expenditures. Among the expenditures; Appendix identifies the medications queried medications used by more than 10% of the subjects, PPS and Appendix summarizes procedures and their associated was the most costly at $36/week, followed by gabapentin at $20/week, oxybutinin at $18/week, and tolterodine at $17/week. The duration of utilization was the highest for PPS(99.5 weeks), followed by gabapentin (87.4 weeks), oxy- butinin (55.3 weeks) and tolterodine (48.5 weeks).
In the year 1999, a total of 553,910 individuals were covered.
A total of 321 women had IC/PBS in 1999, including both incident and prevalent cases. Eighty-nine women had follow-up data for 5 years; out of these, 54 subjects were incident This study has several important findings that shed light on cases, i.e., they had no claims for IC/PBS in 1998 and had IC/ the patterns of care for adults with IC/PBS. First, we found PBS claims in 1999. The mean and median age in the total that all of the subjects were treated with at least one oral patients with IC in cohort(prevalent and incident cases) medication used to treat patients with IC/PBS during the with little side effects and are willing to continue these study period. Of these, narcotics were the most commonly medications since they were not offered other therapies.
utilized class of medications. This might indicate that many A substantial minority of patients were treated with commonly prescribed IC/PBS-specific medications are less centrally acting medications including gabapentin and tricy- effective than narcotics. Alternatively, the narcotics may clic antidepressants. These medications have been used in have been used to treat other pain complaints arising from treatment of chronic pain conditions such as Complex sites other than the bladder. Anticholinergics were the Regional Pain Syndrome Type-I (CPRS-I) with success. It second most commonly utilized class of medications used has been suggested that the pathophysiology of IC/PBS may by 49% of subjects (tolterodine and oxybutinin combined) partly be due to deregulation of the central nervous system, with an average utilization period of approximately 1 year.
similar to CPRS-I . Gabapentin, an antiepileptic, has been This utilization period is actually longer than that docu- effective in treatment of chronic sympathetically mediated mented for women with overactive bladder symptoms pain syndromes and there are reports of its efficacy in In the Interstitial Cystitis Data Base (ICDB) study, treatment of IC/PBS  . Tricylic antidepressants such a multicenter, observational study designed to document the as amitriptyline also have demonstrated efficacy in treating treatment history of IC/PBS and patient characteristics, only patients with IC/PBS In our cohort, gabapentin and 2–4% of patients received anticholinergics as monotherapy amitriptyline were among the five most commonly used or in combination with other medications ]. However, medications and were used to treat 19% and 25% of patients, this was a select cohort of patients who were recruited from respectively. This is slightly higher than the 17% of subjects a limited number of tertiary care centers. Our data suggest treated with amitriptyline in the ICDB study Given that anticholinergic agents are used much more widely in the theory that the etiology of IC/PBS/chronic pelvic pain the community setting. This observation reinforces the may reside partly in the central nervous system, a shift inherent difficulty in distinguishing between the clinical toward treatments aimed at regulating the nervous system is syndromes of overactive bladder and IC/PBS, since many of logical. While claims data cannot be used to infer the reasons symptoms overlap. It is possible that there is therapeutic for the low rate of utilization of centrally acting medications benefit gained from this group of medications by patients with in the Ingenix cohort, possible explanations include a lack of IC/PBS, or alternatively, they may have seen a slight benefit provider awareness of the potential role of central nervous Table 3 Narcotic usage among patients with IC Number of people who took any narcotic in 1999 Percentage of people who took any narcotic in 1999 (%) Number of people who took any narcotic 1999–2003 Percentage people took any narcotic 1999–2003 (%) Total number of scripts filled 1999–2003 Total day supply of narcotics 1999–2003 system dysregulation in this syndrome or low perceived tool more frequently and less so as a therapeutic maneuver. It efficacy of available agents to mitigate this dysregulation.
is also possible that when used for therapy, it was not Further prospective work in this area would be helpful to In our cohort, 26% of the patients had intravesical In our cohort, PPS was utilized by 35% of all subjects and instillations; the average number of instillations ranged from 15% of the incident cases with a mean utilization period of two to six. A variety of Intravesical instillations have been 99.5 and 82 weeks, respectively. PPS is the only oral used to treat IC/PBS, including silver nitrate, marcaine/ medication approved by the Food and Drug Administration lidocaine, dimethyl sulfoxide (DMSO), hyaluronic acid, (FDA) for the treatment of IC/PBS. One theory of the heparin, PPS, Bacillus Calmette-Guerin (BCG), and rosin- pathophysiology of IC/PBS implicates a defect in the bladder iferatoxin. DMSO is the only FDA approved intravesical glycosaminoglycan layer as partially responsible for symp- agent for the treatment of this condition. The available Ingenix toms of IC/PBS. PPS, which is available in oral formulation data do not allow us to identify the exact agent used for the and is excreted in urine, is prescribed with the intent to correct instillations. These instillations are sometimes given as a 4– this defect . The studies evaluating its efficacy have 6 week course of therapy, while at other times they are given shown a wide array of clinical responses. A multicenter as ‘rescue’ therapy for symptom flares. These different uses randomized controlled trial showed that 32% of those on may explain the variable numbers of instillations observed in PPS compared to 16% of patients on placebo reported more than 50% improvement in a global self-evaluation of their A summation of all individual incremental care in patients symptoms . However, the Interstitial Cystitis Clinical with IC/PBS, exclusive of indirect costs, is estimated at $100 Trials Group conducted a placebo-controlled trial to evaluate million in the US alonand medical expenditures among the efficacy of PPS and hydroxyzine, and found no IC/PBS patients are double the figure associated with those statistically significant benefit to treatment with PPS.[In without the diseasIn our cohort, the overall expendi- a systematic review of the pharmacologic management of IC/ tures related to the treatment of IC/PBS were $2,808 per PBS by Dimitrakov et al., the pooled estimate of the effect of subject over 5 years, the majority of which were related to pentosan polysulfate therapy suggested a modest benefit, with oral medical therapy. PPS, the only FDA approved medica- a relative risk of 1.78 for patient-reported improvement in tion, was the most expensive at $36 per week. The weekly symptoms (95% confidence interval, 1.34–2.35The cost of $18 for oxybutynin and tolterodine is likely related to long utilization period identified in our database also points the use of the brand name or extended release formulations, to at least some therapeutic benefit enjoyed by the subjects.
which are more costly than short-acting formulas.
Alternatively, it may be a result of the manufacturer's Although detailed clinical information cannot be obtained recommendations that long-term therapy (greater than 1 year) from claims-based data, claims data provides information may be needed before a clinical effect occurs.
about real-world practice patterns, including pharmacy care, We also found that more patients who were newly in a large population of individuals. However, this study, like diagnosed with IC/PBS (31%) underwent hydrodistension, may claims-based analyses, has limitations. It is also compared to those with a previous diagnosis (11%), and that important to note that this project is not designed to study the procedure was not repeated at a high rate. Hydrodistension the epidemiology of the disease, or to understand the rationale has historically been used both for diagnosis and treatment of behind treatment, but rather studies a cohort of patients from IC/PBS; however, after the NIH Interstitial Cystitis Database 1 year treated by multiple providers. Claims-based data are study documented that over 60% of patients regarded as designed for billing purposes, and therefore lack important having IC would have been excluded if the NIDDK criteria information about severity of illness and reasons for treatment were appliethe diagnostic value of hydrodistension in discontinuation. Coding is often incomplete or inaccurate, and clinical practice has been questionedThe ICDB study our cohort may have included some patients with overactive similarly revealed that hydrodistension was utilized more bladder symptoms or other types of pelvic pain unrelated frequently among those newly diagnosed (48.4%) compared to IC/PBS. It is also possible that we excluded some to those with a previous diagnosis (25.7%)Our findings subjects if their condition was coded using a combination could partly reflect the use of this procedure as a diagnostic of ICD-9 codes such as bladder pain and urgency/ frequency, since we identified the cohort by the ICD-9 diagnosis for IC/PBS (595.1). Also, our cohort was older (mean age 63.3 years) than the reported mean age forpatients with IC/PBS (age range 43–59 years) [ This could be partly due to the population under study; the population studied consists of the retirees, employees, and their dependants with a mean and median age of 58.5 and 59 years, respectively during the study year of 1999. Thus, our findings may not be entirely generalizable to a younger IC/PBS population.
The majority of treatment costs for IC/PBS were attribut- able to oral medical therapy. Anticholinergics, PPS, tricyclic antidepressants, and gabapentin are the most commonly used group of such treatments. Subjects likely tolerated these medications well, as the average length of treatment exceeded 1 year. Hydrodistension and intravesicalinstillations were utilized in less than a quarter of thepatients and not repeated when used. This may be due to itsutilization as part of diagnostic algorithm more frequentlythan as a treatment modality.
This work was funded by the NIDDK as part of the Urologic Diseases in America Project.
Table 6 IC treatments and corresponding CPT codes JQ Clemens: Merck, Investment interest; Pfizer, consultant; Lilly, consultant; Medtronics, proctor. Payne C: Allergan, consultant; Astellas, consultant; Celgene, Investigator; Coloplast, Investigator; Curant, Investment Interest; Medtronic, Investigator. All other authors have no conflict of interest.
This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which per- mits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
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