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      Opioid-induced constipation in patients with chronic noncancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review

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          Abstract

          Background

          The characteristics of patients who suffer from noncancer pain and opioid-induced constipation are not well understood.

          Methods

          Cross-sectional patient survey and chart review data from the baseline assessment of an ongoing longitudinal study in the USA, Canada, Germany, and the UK were evaluated via descriptive statistics. Participants had confirmation of daily opioid therapy ≥30 mg for ≥4 weeks and self-reported opioid-induced constipation. Response to laxatives was defined by classifying participants into categories of laxative use and evaluating the prevalence of inadequate response to one laxative agent and two or more agents from at least two different laxative classes. Outcomes included the Patient Assessment of Constipation-Symptoms, Work Productivity and Activity Impairment Questionnaire-Specific Health Problem, EuroQOL 5 Dimensions, and Global Assessment of Treatment Benefit, Satisfaction, and Willingness to Continue.

          Results

          Patients reported a mean of 1.4 bowel movements not preceded by laxatives and 3.7 bowel movements with laxative use per week; 83% wanted at least one bowel movement per day. Most commonly reported on Patient Assessment of Constipation-Symptoms were straining/squeezing to pass bowel movements (83%), bowel movements too hard (75%), flatulence (69%), and bloating (69%). Eighty-four percent were taking natural or behavioral therapies; 60% were taking at least one over-the-counter laxative; and 19% were taking at least one prescription laxative. Prevalence of inadequate response to one laxative agent was 94%; inadequate response to two or more agents from at least two different laxative classes was 27%. Mean Work Productivity and Activity Impairment Questionnaire-Specific Health Problem values for percent work time missed, percent impairment while working, and percent activity impairment were 9%, 32% (equivalent of 14 hours of lost productivity per week), and 38%. Mean EuroQOL 5 Dimensions index and visual analog scale scores were 0.49 and 50.6, respectively. Forty-four percent reported being satisfied with their treatment for constipation.

          Conclusion

          Patients treated with opioids for noncancer pain commonly endure constipation symptoms that limit their work productivity and overall health-related quality of life while adhering to treatments that provide little relief. Further research is needed to identify more efficacious constipation therapies for this patient population.

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          Most cited references34

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          Incidence, prevalence, and management of opioid bowel dysfunction.

          Opioid bowel dysfunction (OBD) is a common adverse effect associated with opioid therapy. OBD is commonly described as constipation; however, it is a constellation of adverse gastrointestinal (GI) effects, which also includes abdominal cramping, bloating, and gastroesophageal reflux. The mechanism for these effects is mediated primarily by stimulation of opioid receptors in the GI tract. In patients with pain, uncontrolled symptoms of OBD can add to their discomfort and may serve as a barrier to effective pain management, limiting therapy, or prompting discontinuation. Patients with cancer may have disease-related constipation, which is usually worsened by opioid therapy. However, OBD is not limited to cancer patients. A recent survey of patients taking opioid therapy for pain of noncancer origin found that approximately 40% of patients experienced constipation related to opioid therapy ( 50% of the time. Laxatives prescribed prophylactically and throughout opioid therapy may improve bowel movements in many patients. Nevertheless, a substantial number of patients will not obtain adequate relief of OBD because of its refractory nature. Naloxone and other tertiary opioid receptor antagonists effectively reduce the symptoms of constipation in opioid-treated patients. However, because they also act centrally, they may provoke opioid withdrawal symptoms or reverse analgesia in some patients. There are 2 peripherally selective opioid receptor antagonists, methylnaltrexone and ADL 8-2698 (Adolor Corporation, Exton, PA, USA), that are currently under investigation for their use in treating OBD. Early studies confirm that they are effective at normalizing bowel function in opioid-treated patients without entering the central nervous system and affecting analgesia. With a better understanding of the prevalence of OBD and its pathophysiology, a more aggressive approach to preventing and treating OBD is possible and will likely improve the quality of life of patients with pain.
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            Opioid-induced bowel dysfunction: prevalence, pathophysiology and burden

            As a result of the undesired action of opioids on the gastrointestinal (GI) tract, patients receiving opioid medication for chronic pain often experience opioid-induced bowel dysfunction (OBD), the most common and debilitating symptom of which is constipation. Based on clinical experience and a comprehensive MEDLINE literature review, this paper provides the primary care physician with an overview of the prevalence, pathophysiology and burden of OBD. Patients with OBD suffer from a wide range of symptoms including constipation, decreased gastric emptying, abdominal cramping, spasm, bloating, delayed GI transit and the formation of hard dry stools. OBD can have a serious negative impact on quality of life (QoL) and the daily activities that patients feel able to perform. To relieve constipation associated with OBD, patients often use laxatives chronically (associated with risks) or alter/abandon their opioid medication, potentially sacrificing analgesia. Physicians should have greater appreciation of the prevalence, symptoms and burden of OBD. In light of the serious negative impact OBD can have on QoL, physicians should encourage dialogue with patients to facilitate optimal symptomatic management of the condition. There is a pressing need for new therapies that act upon the underlying mechanisms of OBD.
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              Canadian Valuation of EQ-5D Health States: Preliminary Value Set and Considerations for Future Valuation Studies

              Background The EQ-5D is a preference based instrument which provides a description of a respondent's health status, and an empirically derived value for that health state often from a representative sample of the general population. It is commonly used to derive Quality Adjusted Life Year calculations (QALY) in economic evaluations. However, values for health states have been found to differ between countries. The objective of this study was to develop a set of values for the EQ-5D health states for use in Canada. Methods Values for 48 different EQ-5D health states were elicited using the Time Trade Off (TTO) via a web survey in English. A random effect model was fitted to the data to estimate values for all 243 health states of the EQ-5D. Various model specifications were explored. Comparisons with EQ-5D values from the UK and US were made. Sensitivity analysis explored different transformations of values worse than dead, and exclusion criteria of subjects. Results The final model was estimated from the values of 1145 subjects with socio-demographics broadly representative of Canadian general population with the exception of Quebec. This yielded a good fit with observed TTO values, with an overall R2 of 0.403 and a mean absolute error of 0.044. Conclusion A preference-weight algorithm for Canadian studies that include the EQ-5D is developed. The primary limitations regarded the representativeness of the final sample, given the language used (English only), the method of recruitment, and the difficulty in the task. Insights into potential issues for conducting valuation studies in countries as large and diverse as Canada are gained.
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                Author and article information

                Journal
                Clinicoecon Outcomes Res
                Clinicoecon Outcomes Res
                ClinicoEconomics and Outcomes Research
                ClinicoEconomics and Outcomes Research: CEOR
                Dove Medical Press
                1178-6981
                2014
                23 May 2014
                : 6
                : 269-281
                Affiliations
                [1 ]Evidera, Bethesda, MD, USA
                [2 ]AstraZeneca, Wilmington, DE, USA
                [3 ]UBC: an Express Scripts Company, Montreal, QC, Canada
                [4 ]University Hospital Gasthuisberg, Leuven, Belgium
                Author notes
                Correspondence: Karin S Coyne, Evidera, 7101 Wisconsin Ave, Suite 600, Bethesda, MD 20814, USA, Tel +1 301 654 9729, Fax +1 301 654 9864, Email karin.coyne@ 123456evidera.com
                Article
                ceor-6-269
                10.2147/CEOR.S61602
                4041290
                69c626fa-dc36-4c7b-8262-60341c7adac8
                © 2014 Coyne et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Economics of health & social care
                opioid,constipation,pain,laxatives,quality of life
                Economics of health & social care
                opioid, constipation, pain, laxatives, quality of life

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