CLINICAL RESEARCH STUDY

Systematic Review of the Symptom Burden, Quality of Life Impairment and Costs Associated with Peptic Ulcer Disease Alan Barkun, MD, PhD,a Grigorios Leontiadis, MD, PhDb a Division of Gastroenterology, McGill University, Montreal, Quebec, Canada; bDivision of Gastroenterology, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT BACKGROUND: Management of peptic ulcer disease has improved over the past few decades. However, the widespread use of nonsteroidal anti-inflammatory drugs and low-dose acetylsalicylic acid means that the burden of peptic ulcer disease remains a relevant issue. METHODS: We systematically searched PubMed and EMBASE for articles published 1966-2007 that reported symptoms, impairment of well-being or health-related quality of life, and costs associated with peptic ulcer disease. RESULTS: Thirty studies reported the prevalence of patient-reported gastrointestinal symptoms in individuals with endoscopically diagnosed symptomatic peptic ulcer disease. Average prevalence estimates, weighted by sample size, were 81% (95% confidence interval [CI], 77%-85%) for abdominal pain (11 studies), 81% (95% CI, 76%-85%) for pain specifically of epigastric origin (14 studies), and 46% (95% CI, 42%-50%) for heartburn or acid regurgitation (11 studies). On average, 29% (95% CI, 25%-34%) of patients with peptic ulcer disease presented with bleeding, often as the initial symptom (11 studies). Patients with peptic ulcer disease had significantly lower health-related quality of life than the general population, as measured by the Psychological General Well-Being index (P ⬍.05; 7 studies) and the Short-Form-36 questionnaire (P ⬍.05; 2 studies). Direct medical costs of peptic ulcer disease based on national estimates from several countries were USD163-866 per patient. The most costly aspects of peptic ulcer disease management were hospitalization and medication. Complicated peptic ulcer disease is particularly costly, estimated to be USD1883-25,444 per patient. CONCLUSION: Peptic ulcer disease significantly impairs well-being and aspects of health-related quality of life, and is associated with high costs for employers and health care systems. © 2010 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2010) 123, 358-366 KEYWORDS: Costs; Peptic ulcer disease; Quality of life; Symptom burden

About 10% of the population in the Western world will experience peptic ulcer disease at some point during their lives.1,2 Individuals with peptic ulcer disease may present with a variety of gastrointestinal (GI) symptoms including abdominal pain, vomiting, and reflux symptoms. Furthermore, peptic ulcer disease is the most common cause of conditions such as upper GI hemorrhage and perforation,3 which are associated with high mortality

and morbidity.4 Over the past few decades there has been an increase in the use of pharmaceuticals known to be associated with the development of peptic ulcer disease, such as nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelet agents such as low-dose acetylsalicylic acid, and selective serotonin re-uptake inhibitors.5,6 This means that the burden imposed by peptic ulcer disease is currently a very relevant health issue.

Funding: Writing support was provided by Dr. Catherine Henderson (Research Evaluation Unit, Oxford PharmaGenesis Ltd, Oxford, UK), funded by AstraZeneca R&D Mölndal, Sweden. Conflict of Interest: Dr. Alan Barkun is a consultant for AstraZeneca Inc. Dr. Grigorios Leontiadis has received speaker honoraria from AstraZeneca, Sanofi-Aventis, GlaxoSmithKline, and JanssenCilag.

Authorship: This work is original, and the authors meet the criteria for authorship and accept responsibility for the scientific content of the manuscript. Requests for reprints should be addressed to Alan Barkun, MD, PhD, Division of Gastroenterology, McGill University, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada. E-mail address: [email protected]

0002-9343/$ -see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2009.09.031

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GI symptoms and complications can impair health-related symptomatic peptic ulcer disease (Table 1). Pooled average quality of life, cause absenteeism, and reduce productivity prevalence estimates weighted by sample size are shown in while at work (presenteeism). As well as having an impact on Figure 2. The majority of patients suffered from general individuals, there are wider implications for health care sysabdominal pain (81%; 95% confidence interval [CI], 77%tems and employers in terms of the costs associated with peptic 85%, 11 studies), or from pain specifically of epigastric ulcer disease. The aim of this reorigin (81%; 95% CI, 76%-85%, view is to quantify the burden of 14 studies). Night-time pain, repeptic ulcer disease by assessing flux symptoms, belching, vomitCLINICAL SIGNIFICANCE symptom prevalence, health-related ing, and nausea also were comquality of life, absenteeism, presenmon. On average, 29% (95% CI, ● Most patients with peptic ulcer disease teeism, and costs associated with 25%-34%) of patients with peptic have abdominal pain. the disease. ulcer disease presented with bleed● Symptoms are less common in older paing (11 studies). One study retients with peptic ulcer disease than in ported that 37% (10/27) of paMETHODS younger patients. tients presenting with bleeding Systematic searches of PubMed and peptic ulcer had no history of pep● Peptic ulcer disease impairs well-being EMBASE were performed to coltic ulcer disease-related pain.9 In a and aspects of health-related quality of late articles published 1966-2007 larger study of 623 patients with that reported symptoms, health-relife. gastric ulcer, 206 of whom had lated quality of life impairment, bleeding ulcers, bleeding was ● Peptic ulcer disease is associated with work loss, and costs associated with significantly associated with abhigh costs for employers and health peptic ulcer disease (Figure 1). We sence of pain (odds ratio 8.0; care systems. aimed to answer the following spe95% CI, 5.0-12.8; P ⬍.001).16 cific research questions: ● There are no time trends for the burden Abdominal pain was the most and costs associated with peptic ulcer prominent symptom in 91% of ● What is the prevalence of disease. cases in the only study to specifsymptoms in patients presentically investigate which symping with peptic ulcer disease tom was predominant.34 We also who have endoscopically coninvestigated time trends in the firmed disease? ● Do patients with peptic ulcer disease have impaired prevalence of symptoms associated with peptic ulcer dishealth-related quality of life? ease. Table 1 details the prevalence of abdominal or ● What is the cost of peptic ulcer disease to health care epigastric pain, arranged by the date of study publication. systems and employers? We found no clear trend; similar proportions of patients with peptic ulcer disease presented with abdominal or The prevalence of symptoms associated with peptic ulcer epigastric pain in older studies (published 1984-1993; was obtained from endoscopic case series; that is, endorange 39%-99%) and more recent studies (published scopic verification of peptic ulcer was needed and symp1994-2006; range 46%-100%). toms had to be assessed at the time of endoscopy. EndoAmong 4 studies comparing the presenting signs and scopic case series that included only patients with symptoms associated with peptic ulcer disease in older bleeding peptic ulcer or suspected bleeding were exadults with those found in younger patients (Table 2), cluded from this section of the analysis. Pooled average abdominal pain was more prevalent among younger patients prevalence estimates weighted by sample size were calthan older patients, while the opposite was found for bleedculated. Articles reporting health-related quality of life in ing.7,12,30,33 A fifth study assessed symptoms of peptic ulcer patients with peptic ulcer disease were included only if they used validated questionnaires, and these health-redisease in patients aged ⬎80 years (n ⫽ 65).32 The most lated quality-of-life studies could include patients with common symptoms were epigastric pain (74%), nausea suspected peptic ulcer disease. Full reasons for exclusion (23%), and vomiting (20%). are detailed in Figure 1. Estimated country populations One study reported symptom burden using the Gastrointestaken from national population databases were used to tinal Symptom Rating Scale.37 The highest score of 7 indicates calculate per-patient costs in order to compare across the highest symptom burden, and a 0.5-point difference in studies from different countries. mean score is considered clinically meaningful.38 Mean Gastrointestinal Symptom Rating Scale scores for patients with gastric and duodenal ulcers, compared with Swedish general RESULTS population norm values,39 are shown in Figure 3. Patients with Symptom Burden in Peptic Ulcer Disease an ulcer scored significantly and clinically meaningfully higher than general population norms for abdominal pain, indigestion, In total, 30 studies reported the prevalence of GI symptoms among adults of all ages with endoscopically diagnosed reflux, and constipation.

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Impact of Peptic Ulcer Disease on Health-related Quality of Life

reported that patients with peptic ulcer disease had significantly worse SF-36 scores than healthy controls in almost every domain.40,41 Only one of these studies reported actual SF-36 scores (rather than significance levels only).40 From a total possible score of 100 (higher scores indicate less impairment), the 35 patients with peptic ulcer disease scored 32.8 on average, while the 40 healthy controls scored 94.0. The worst-affected domain was role-physical (32.8 for peptic ulcer disease vs 94.5 for controls). The only domain that was not significantly lower in patients with peptic ulcer disease than in controls was role-emotional (52.4 for peptic ulcer disease vs 70.0 for controls). Six studies used the Psychological General Well-Being index to assess health-related quality of life in Swedish patients with peptic ulcer disease or suspected peptic ulcer disease before treatment.37,42-46 Scores in patients with peptic ulcer disease ranged from 82-91, lower than the general Swedish population norm of 100-105,39 indicating impaired health-related quality of life in these patients. Two studies used the Psychosocial Adjustment to Illness Scale to assess health-related quality of life in patients with duodenal ulcer, and reported scores of 16.5 and 23.5 (maximum score 42, lower scores show better adjustment to illness).47,48 The impact of peptic ulcer disease in terms of health-related quality of life also is indicated by 4 studies that used validated measures to show significant improvements in health-related quality of life after ulcer treatment (Table 3, online).49-52 In a study that was part of a UK Health Technology Agency project (n ⫽ 57),53 patients admitted to the hospital with peptic ulcer bleeding were surveyed using the EuroQol visual analogue scale 7 days after the bleeding episode, or when discharged from the hospital, and then at 4 weeks after the bleed. Higher scores indicate better quality of life, with possible scores ranging from 0 to 10. Patients in the study had a mean quality-of-life score of 5.98 at 7 days after the bleeding episode, or at hospital discharge, compared with 7.96 at 4 weeks. Groenveld and colleagues54 interviewed 73 patients with peptic ulcer disease or gastritis about their preferences with regard to peptic ulcer disease and associated complications using the time trade-off method. Patients were asked what proportion of their life expectancy they would be willing to trade for improvements in peptic ulcer disease symptoms and to avoid complications. The cost of peptic ulcer disease was calculated in terms of quality-adjusted life years (QALYs), where a year of perfect health is assigned a value of 1.0 QALY. Assuming an annual frequency of ulcer complication of 5%, it was estimated that peptic ulcer disease cost 0.11 QALY. Of this, approximately 0.09 was attributable to dyspeptic symptoms, and 0.02 to complications.

Assessment of the Effect of Peptic Ulcer Disease on Health-related Quality of Life Using Validated Tools. Fifteen studies used validated tools to measure health-related quality of life in individuals with peptic ulcer disease. The only 2 studies that used the Short-Form-36 (SF-36) to compare peptic ulcer disease patients with healthy controls

Impact of Peptic Ulcer Disease on Absenteeism and Work Productivity. Studies from the 1970s and 1980s show high rates of absenteeism due to peptic ulcer disease, and also show a trend for a reduction in absenteeism over time. Higashi et al,55 publishing in 1988, found that 10% of

Figure 1 QUOROM diagram showing the search strategy and progress of articles through the selection process.

Barkun and Leontiadis Table 1

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361

Studies Reporting Gastrointestinal Symptoms in Patients with Endoscopically Confirmed Peptic Ulcer Disease

Reference 7

Clinch et al, 1984 Thompson, 19848 Glynn and Kane, 19859 Talley and Piper, 198610 Sharma and Choudhari, 198811 Scapa et al, 198912 Johannessen et al, 199013 Ahmed et al, 199014 Ahmed et al, 199015 Brazer et al, 199016 Goenka et al, 199117 Johnsen et al, 199118 Grebenev and Sheptulin, 199219 Ahmed et al, 199220 Chunlertrith et al, 199221 Schubert et al, 199322 Mansi et al, 199323 Numans et al, 199424 Ayuo et al, 199425 Sharma et al, 199426 Kang et al, 199627 Werdmuller et al, 199728 Ahmed et al, 199729 Kemppainen et al, 199730 Abahussain et al, 199831 Seinela and Ahvenainen, 200032 Hilton et al, 200133 Kolk, 200434 Bancu et al, 200435 Karima et al, 200636

Country

Study Design

Type of Ulcer

Number of Patients with Number of Peptic Ulcer Disease Patients

UK Canada UK Australia India Israel Norway Pakistan Pakistan USA India Norway Russia Pakistan Thailand USA Italy The Netherlands Kenya India Singapore The Netherlands Saudi Arabia Finland Kuwait Finland Ireland Estonia Romania Saudi Arabia

Retrospective Prospective Retrospective Prospective Prospective Prospective Prospective Retrospective Retrospective Prospective Retrospective Prospective Retrospective Retrospective Prospective Prospective Prospective Prospective Retrospective Prospective Prospective Prospective Retrospective Prospective Prospective Retrospective Prospective Prospective Retrospective Prospective

Peptic ulcer Peptic ulcer Gastric ulcer Peptic ulcer Duodenal ulcer Duodenal ulcer Peptic ulcer Duodenal ulcer Duodenal ulcer Gastric ulcer Peptic ulcer Peptic ulcer Gastric ulcer Gastric ulcer Peptic ulcer Peptic ulcer Peptic ulcer Peptic ulcer Peptic ulcer Peptic ulcer Duodenal ulcer Peptic ulcer Duodenal ulcer Peptic ulcer Duodenal ulcer Peptic ulcer Peptic ulcer Peptic ulcer Duodenal ulcer Peptic ulcer

199 148 71 221 25 333 930 720 245 623 5948 619 425 138 208 1088 2253 861 45 500 1615 1527 126 125 200 73 277 172 2258 132

all absences were due to peptic ulcer disease, with a total of 6690 days lost per year among 33,718 male employees at 30 Japanese textile plants (1984 days/10,000 employees). A German health insurance database study covering 16.5 million employees reported sick days due to peptic ulcer disease of 2470 days/10,000 employees in 1975, falling to 1373 days/10,000 employees in 1984.56 A UK study that used national census data found a similar reduction in the impact of peptic ulcer disease on absenteeism.57 There were 613 spells of absenteeism over 3 days in length due to peptic ulcer disease in men in 1972, and 223 spells in 1983 (although for women there was little change). This reduction is likely to be due to the increasing use of histamine-2 receptor antagonists during this time period. More recent studies indicate that peptic ulcer disease still contributes substantially to absenteeism. A large database study of US employees (n ⫽ 25,985) found that those with peptic ulcer disease (n ⫽ 1414) had significantly more sick days per year than those without (mean [SD], 3.2 days [2.6] vs 2.8 days [2.3]; P ⬍.05).58 In one large general population

199 49 71 55 25 333 154 599 245 541 1188 24 425 138 55 209 145 131 13 140 118 81 126 125 23 65 106 75 2258 132

Number (%) of Patients with Peptic Ulcer Disease with Abdominal or Epigastric Pain 132 37 — 37 — 258 134 571 219 400 965 11 420 112 30 — 57 107 6 94 — 46 119 80 — 48 91 — 1772 132

(66.3%) (75.5%) (67.3%) (77.5) (87.0%) (95.3%) (89.4%) (73.9%) (81.2%) (45.8) (98.8%) (81.2%) (54.5%) (39.3%) (81.7%) (46.2%) (67.1%) (56.8%) (94.4%) (64.0%) (73.8%) (85.8%) (78.5%) (100%)

survey (n ⫽ 41,457), 17% of individuals who had received a diagnosis of peptic ulcer disease in the past 12 months reported that they were unable to work, compared with 6% of controls with no history of peptic ulcer disease.59 Among those with a recent diagnosis of peptic ulcer disease, 13.5% reported that they were unable to perform major activity for some time during the 12 months preceding the survey, compared with 4% of the controls. Individuals with recent peptic ulcer disease reported a loss of 7.8 work days in the past 12 months, compared with 3.6 days for those who had never had a diagnosis of peptic ulcer disease (age- and sex-adjusted rates). The symptoms of peptic ulcer disease also can cause reduced productivity while at work (presenteeism), as shown in a study of 117 primary care patients with peptic ulcer disease, 42% of whom reported some loss of productivity.60

Cost of Peptic Ulcer Disease Direct Cost of Peptic Ulcer Disease. Several studies have attempted to estimate the annual direct medical cost of

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Figure 2 Pooled average prevalence estimates of gastrointestinal symptoms among patients presenting with peptic ulcer disease. Means and 95% confidence intervals are shown.

Figure 3 Mean Gastrointestinal Symptom Rating Scale (GSRS) scores in patients with peptic ulcer disease, compared with general population norm values. Higher GSRS score indicates more severe symptoms. A 0.5-point difference is clinically meaningful.

peptic ulcer disease on a national level (Table 4, online). Overall, the cost of peptic ulcer disease per patient was USD163-866. The most costly aspects of peptic ulcer disease management were hospitalization (62% of the estimated total cost in 1 US study59) and medications (35% of the estimated total cost in the study from France61). In a study using the Medicare database, hospitalization for peptic ulcer disease made up 1.3% of annual Medicare claims and the average reimbursement in 1997 was USD5909 per patient with peptic ulcer disease.67 This much higher cost than that described above may again reflect the high cost of hospitalization. A US health economic analysis showed that

Table 2

management of duodenal ulcer costs USD1300-27,300 per QALY gained.54 There was no clear difference between the costs associated with peptic ulcer disease reported in the older studies performed in 1987 and 1989 (USD470 and USD866 per patient per year) and those reported in the studies carried out in 1998 (USD574 and USD163-528 per patient per year). Other studies have calculated the cost per patient with peptic ulcer disease in specific organizations. A large US study (n ⫽ 9300) of hospital outpatients or pharmacy users

Comparison of the Prevalence of Symptoms of Peptic Ulcer Disease in Older Patients and Younger Patients Age (Years)

Reference Abdominal pain Clinch et al, 19847 Scapa et al, 198912 Hilton et al, 200133 Epigastric pain Kemppainen et al, 199730 Bleeding Clinch et al, 19847 Kemppainen et al, 199730 Bleeding without pain Scapa et al, 198912 ns ⫽ nonsignificant.

Prevalence of Symptom

n

Younger Patients

Older Patients

Younger Patients

Older Patients

Significance

199 333 106

20-50 20-64 ⬍50

⬎60 65-93 ⬎60

92% (62/67) 64% (165/258) 93% (67/72)

65% (70/108) 81% (61/75) 71% (24/34)

P ⬍.001 ns P ⫽ .004

125

ⱕ65 years

⬎65 years

91% (59/65)

35% (21/60)

P ⬍.001

199 125

20-50 ⱕ65 years

⬎60 ⬎65 years

15% (10/67) 14% (9/65)

49% (35/132) 50% (30/60)

P ⬍.001 P ⬍.002

333

20-64

65-93

2.7%

9.3%

P ⫽ .02

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Peptic Ulcer Burden Systematic Review

included 611 patients with a diagnosis of peptic ulcer disease, and 3045 age- and sex-matched controls.68 The annual direct cost of peptic ulcer disease in this health care organization (population of 2.4 million insured individuals) was USD24.1 million, which included inpatient, outpatient, and pharmacy costs. Each patient with peptic ulcer disease cost USD4870 per year on average. The investigators of a large US study (n ⫽ 25,985) used a research database containing data on workplace absence, short-term medical disability and workers’ compensation, and medical and pharmacy claims data for 6 large US employers to calculate costs associated with peptic ulcer disease.58 They found that the mean direct medical cost (covering pharmacy, inpatient and outpatient costs) per employee with peptic ulcer disease was USD23,819 (SD 9240.5) per year, compared with USD22,388 (SD 9574.0) for controls without peptic ulcer disease. For a hypothetical organization with 25,000 employees, the direct cost impact of peptic ulcer disease on the employer would be USD296,500 per year. The highest per-patient costs were found in studies specifically looking at complicated peptic ulcer disease (Table 5, online). The mean cost of peptic ulcer hemorrhage was USD1883–17,933 per patient. The mean cost of peptic ulcer perforation per patient was estimated to be even higher, at USD21,660-25,444.71,73 A further US study showed that peptic ulcer hemorrhage more than tripled the cost of care for patients in intensive care (USD69,288 with hemorrhage vs USD19,850 without).74 Indirect Costs Associated with Peptic Ulcer Disease. As well as direct medical costs, peptic ulcer disease confers a cost in terms of work loss and reduced work productivity. In one US study, the estimated average loss of earnings per working person with peptic ulcer disease was USD606 over 3 months.75 In the study from Sonnenberg and Everhart, the cost of work loss due to peptic ulcer disease was equivalent to USD1.37 billion in the USA in 1993.59 A study from France estimated that work days lost due to peptic ulcer disease cost employers FRF170 million in 1987 (USD27 million).61 The total combined indirect cost of peptic ulcer disease and dyspepsia was reported as SEK1900-2530 million per year (equivalent to USD251-334 million in 1997) in a study from Sweden.76 Joish and colleagues58 estimated that the indirect cost of peptic ulcer disease in a 25,000employee organization in the US would be USD471,875 per year (USD81,250 due to absenteeism and USD390,625 due to presenteeism), which would translate to USD943 per employee with peptic ulcer disease.

DISCUSSION Peptic ulcer disease imposes a substantial burden in terms of symptoms, health-related quality-of-life impairment, and costs. The vast majority of patients with symptomatic peptic ulcer disease have abdominal pain, but reflux symptoms (likely to constitute concomitant gastroesophageal reflux disease [GERD]), belching, and vomiting are all common.

363 Patients with peptic ulcer disease have significantly worse health-related quality of life compared with the general population, as demonstrated using a number of validated tools. The burden of peptic ulcer disease has an impact on employers in terms of sick days taken from work and reduced productivity while at work. On a national level, estimates of the cost of peptic ulcer disease ranged from USD163 to USD866 per patient with peptic ulcer disease per year. Hospitalization and drugs make up the largest proportion of these costs, and complicated peptic ulcer disease is particularly costly. We found no clear trends in the burden and costs associated with peptic ulcer disease over time. A number of studies have directly compared peptic ulcer disease with other diseases in terms of cost and impact on health-related quality of life. In the US study by Sandler et al,64 peptic ulcer disease was the fourth most costly GI disease, at USD3.1 billion per year, after GERD (USD9.3 billion), gall bladder disease (USD5.8 billion), and colorectal cancer (USD4.9 billion). On a per-patient basis, the cost of peptic ulcer disease in a large US health care organization was reported as being very similar to that of GERD (USD4870 vs USD4574 per year, respectively).64 Patients with peptic ulcer disease, GERD, and ulcerative colitis have been found to score similarly in most SF-36 domains, and significantly lower than healthy controls in almost all domains.40 Swift and effective detection and treatment of peptic ulcer disease will relieve the burden of this disease and could help reduce the likelihood of serious complications. This would have benefits for patients in terms of reduced symptoms and improved health-related quality of life, and for health care systems and employers in terms of reduced costs. Effective treatment for peptic ulcer disease also would, importantly, allow patients to continue to receive NSAIDs or low-dose acetylsalicylic acid for the treatment or prevention of conditions such as myocardial infarction. Thirty-day mortality has been shown to increase if acetylsalicylic acid treatment is stopped after peptic ulcer bleeding.77 Older patients with peptic ulcer disease are less likely to have symptoms, and this may place them at higher risk of having a serious complication of peptic ulcer disease before appropriate treatment can be given. The burden of peptic ulcer disease could be reduced by prevention strategies such as Helicobacter pylori eradication in high-risk groups, or by the use of proton pump inhibitor (PPI) therapy in NSAID or acetylsalicylic acid users at higher risk of peptic ulcer disease.78 A recent study of 1436 patients with cardiovascular disease indicated that gastroprotection for patients taking acetylsalicylic acid is currently underutilized, with 44% of acetylsalicylic acid users with a prior history of upper GI complications not receiving a concomitant PPI.79 In another study of 769 patients, only 12% of patients with a history of peptic ulcer bleeding and NSAID or acetylsalicylic acid use were taking a PPI.3 The recently published US guideline document on reducing GI risk of antiplatelet therapy and

364 NSAID use recommends that a gastroprotective therapy be prescribed for patients at high risk of GI hemorrhage taking acetylsalicylic acid or NSAIDs, such as those over 65 years old, and those taking a combination of an NSAID and acetylsalicylic acid.78 Our review is the first to evaluate critically the literature on the symptomatic burden of peptic ulcer disease using a systematic process and imposing defined inclusion and exclusion criteria. The aim was to provide a broad view on the multiple factors contributing to the burden of peptic ulcer disease. However, there was often wide variation in the type of data recorded. The summary data that pertain to healthrelated quality of life are limited by study heterogeneity, with only 8 of 15 included studies adopting a well-validated tool such as the SF-36 or Psychological General Well-Being index. To further clarify the burden of peptic ulcer disease, future studies on the cost of peptic ulcer disease in countries other than the US would be beneficial. Studies assessing health-related quality of life should use validated questionnaires, which would enable direct comparisons between studies. In particular, there is a paucity of data on the indirect cost of peptic ulcer disease, and no study gave an estimate of overall total costs, including all direct costs, absenteeism, and the cost of reduced work productivity. It also would be interesting to analyze the change in the burden of peptic ulcer disease over time, particularly with respect to the emergence of better treatments. This would include H. pylori eradication as standard therapy in H. pylori-positive ulcers, as this strategy could decrease the risk of ulcer relapse and thereby have an effect on the cost of treatment and impact on work productivity. The change in H. pylori prevalence over time also might have an effect, as might the increasing use of medications, such as acetylsalicylic acid, that increase the risk of peptic ulcer disease and its complications.

ACKNOWLEDGMENT We thank Dr Catherine Henderson (Oxford PharmaGenesis Ltd) for providing writing assistance funded by AstraZeneca R&D Mölndal, Sweden.

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The American Journal of Medicine, Vol 123, No 4, April 2010 76. Jonsson B, Haglund U. Economic burden of NSAID-induced gastropathy in Sweden. Scand J Gastroenterol. 2001;36:775-779. 77. Sung J, Lau JYW, Ching JYL, et al. Early reintroduction of aspirin with proton pump inhibitor after endoscopic hemostasis for peptic ulcer bleeding: final results of a double blinded randomized study. Gut. 2007;56 (Suppl 3):A27. 78. Bhatt DL, Scheiman J, Abraham NS, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. Am J Gastroenterol. 2008;103: 2890-2907. 79. Targownik LE, Metge CJ, Leung S. Underutilization of gastroprotective strategies in aspirin users at increased risk of upper gastrointestinal complications. Aliment Pharmacol Ther. 2008;28:88-96.

Barkun and Leontiadis Table 3

Peptic Ulcer Burden Systematic Review

366.e1

Effect of Peptic Ulcer Treatment on Health-related Quality of Life Number of Patients

Reference

Type of Ulcer

Treatment

Quality of Life Measure

Domain

QLDUP (0-100, higher score ⫽ better health-related quality of life) NHP (0-100, higher score ⫽ worse health-related quality of life)

—

Rampal et al, 199449

581

Duodenal ulcer

Nizatidine continuous or on demand

Rampal et al, 199550

92

Duodenal ulcer

Ranitidine 300 mg daily

Crawley et al, 200151

155

Peptic ulcer

H. pylori eradication

QOLRAD (0-7, higher score ⫽ better health-related quality of life)

Fujiwara et al, 200252

98

Peptic ulcer

H. pylori eradication

NDI (0-100, higher score ⫽ better health-related quality of life)

Score before Treatment

Pain Mobility Energy Emotions Sleep Social isolation Emotional distress Sleep disturbance Food/drink problems Physical/social functioning Vitality Total score Successful eradication Unsuccessful eradication

Score after Treatment

P-Value

Improvement in all domains after 1 year of treatment 26 6 10 5 39 17 29 13 34 21 9 4 5.04 6.11 5.38 6.29 4.87 6.01 5.44 6.35 4.66 6.09

P P P P P P P P P P P

71.6 78.6

P ⬍.0001 ns

88.9 86.0

Not reported

⫽ .001 ⫽ .001 ⫽ .001 ⫽ .001 ⫽ .001 ⫽ .01 ⬍.0001 ⬍.0001 ⬍.0001 ⬍.0001 ⬍.0001

Abbreviations: H. pylori ⫽ Helicobacter pylori; NDI ⫽ Nepean Dyspepsia Index; NHP ⫽ Nottingham Health Profile; QLDUP ⫽ Quality of Life in Duodenal Ulcer Patients questionnaire; QOLRAD ⫽ Quality of Life in Reflux and Dyspepsia questionnaire.

Table 4

Overall Direct Medical Costs Attributed to Peptic Ulcer Disease

Reference

Country

Year of Publication

Year of Study

Costs Covered by Estimate

Estimated National Cost per Year

Ruszniewski et al61 Sonnenberg and Everhart59

France

1993

1987

Drugs, hospitalization, physician visits Hospitalization, physician visits [cost of drugs not included] Drugs, hospitalization, physician visits Drugs, hospitalization, physician visits

FRF3.37 billion (USD522 million†) USD4.28 billion

USA

1997

1989

Sandler et al64

USA

2002

1998

USD3.1 billion

Jonsson and Haglund65

Sweden

2001

1998

*From Joish et al.58 †Calculated using historical exchange rates.

SEK218–450 million (USD29–94 million†)

Estimated Prevalence of Peptic Ulcer Disease*

Estimated Cost per Patient with Peptic Ulcer Disease per Year

2%

USD470

247 million63

2%

USD866

270 million63

2%

USD574

2%

USD163–528

Estimated Population 55.6 million62

8.9 million66

366.e2 Table 5

The American Journal of Medicine, Vol 123, No 4, April 2010 Direct Costs Attributed to Complicated Peptic Ulcer Disease

Reference 69

Marshall et al Marshall et al70 Kong et al71

Country

Year of Publication

Source Population

Complication/Event

Cost per Patient

Canada Canada USA

1995 1999 1998

Secondary care Secondary care Secondary care

Peptic ulcer hemorrhage Peptic ulcer hemorrhage Peptic ulcer hemorrhage

Sweden

2002

General population

Surgery for peptic ulcer

CAD2690 (USD1883)* CAD2953 (USD2067)* USD10 667 (MarketScan) USD17 933 (HCUP-3) USD11 959 (MarketScan) USD25 444 (HCUP-3) USD2000

The Netherlands

2004

Secondary care

Peptic ulcer hemorrhage Peptic ulcer perforation

EUR12 000 (USD13 680)* EUR19 000 (USD21 660)*

Peptic ulcer perforation Agreus and Borgquist72 de Leest et al73

HCUP-3 ⫽ Hospital Cost Utilization Project. *Calculated using historical exchange rates.