Patterns of Comorbidities and Prescribing and Dispensing of Non-steroidal Anti-inflammatory Drugs (NSAIDs) Among Patients with Osteoarthritis in the USA: Real-World Study.

BACKGROUND: Osteoarthritis (OA) is a major cause of chronic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are analgesics commonly used for musculoskeletal pain; however, NSAIDs can increase the risk of certain adverse events, such as gastrointestinal bleeding, edema, heart failure, and hypertension. OBJECTIVE: The objective of this study was to characterize existing comorbidities among patients with OA. For patients with OA with and without a coexisting medical condition of interest (CMCOI), we estimated the prevalence of prescribing and dispensing NSAIDs pre-OA and post-OA diagnosis. METHODS: Data from three large administrative claims databases were used to construct an OA retrospective cohort. Databases leveraged were IBM MarketScan Medicare Supplemental Database (MDCR), IBM MarketScan Commercial Database (CCAE), and Optum's de-identified Clinformatics® Data Mart Database (Optum CDM). The OA study population was defined to be those patients who had an OA diagnosis from an inpatient or outpatient visit with at least 365 days of prior observation time in the database during January 2000 through May 2021. Asthma, cardiovascular disorders, renal impairment, and gastrointestinal bleeding risks were the CMCOI of interest. Patients with OA were then classified as having or not having evidence of a CMCOI. For both groups, NSAID dispensing patterns pre-OA and post-OA diagnosis were identified. Descriptive analysis was performed within the Observational Health Data Sciences and Informatics framework. RESULTS: In each database, the proportion of the OA population with at least one CMCOI was nearly 50% or more (48.0% CCAE; 74.4% MDCR; 68.6% Optum CDM). Cardiovascular disease was the most commonly observed CMCOI in each database, and in two databases, nearly one in four patients with OA had two or more CMCOI (23.2% MDCR; 22.6% Optum CDM). Among the OA population with CMCOI, NSAID utilization post-OA diagnosis ranged from 33.0 to 46.2%. Following diagnosis of OA, an increase in the prescribing and dispensing of NSAIDs was observed in all databases, regardless of patient CMCOI presence. CONCLUSIONS: This study provides real-world evidence of the pattern of prescribing and dispensing of NSAIDs among patients with OA with and without CMCOI, which indicates that at least half of patients with OA in the USA have a coexisting condition. These conditions may increase the risk of side effects commonly associated with NSAIDs. Yet, at least 32% of these patients were prescribed and dispensed NSAIDs. These data support the importance of shared decision making between healthcare professionals and patients when considering NSAIDs for the treatment of OA in patients with NSAID-relevant coexisting medical conditions.

Real-world healthcare costs and resource utilization in patients with von Willebrand disease and angiodysplasia.

OBJECTIVE: To describe the economic burden among VWD patients with angiodysplasia compared to VWD patients without angiodysplasia and the general population. METHODS: This was a retrospective analysis using the Merative MarketScan Commercial and Medicare Databases® (January 2011-September 2020). Selected patients had ≥1 medical claim for VWD or low VWF, ≥1 medical claim for AGD, and ≥3 GI-related bleeding episodes within a year. HCRU and all-cause costs were compared with the VWD (only) and the general cohorts. RESULTS: The mean total all-cause costs were $150,101 among patients with VWD and angiodysplasia (n = 34), higher compared to $48,249 among matched VWD patients without angiodysplasia (n = 136) and $31,029 among matched individuals of the general population [n = 136; p-value < 0.0001]. The differences in costs between groups were primarily due to inpatient care. During the 12-month follow-up, VWD patients with symptomatic (n = 35), asymptomatic (n = 81), and suspected (n = 378) angiodysplasia had an average of 4.1, 0.6, and 3.8 gastrointestinal (GI) bleeds, respectively. Desmopressin, VWF concentrates, and aminocaproic acid were the most frequent treatments used. The most frequent procedures to treat GI-related bleeding and underlying lesions were blood transfusion and laser therapy. CONCLUSIONS: Despite recent therapeutic advances, there is room for considerable reduction of the disease burden in patients with VWD and angiodysplasia.

The effects of pantoprazole vs. placebo on 1-year outcomes, resource use and employment status in ICU patients at risk for gastrointestinal bleeding: a secondary analysis of the SUP-ICU trial.

PURPOSE: Patients in intensive care units (ICUs) are at risk of stress-related gastrointestinal (GI) bleeding and stress ulcer prophylaxis (SUP), including proton pump inhibitors, is widely used in the attempt to prevent this. In this secondary analysis of Stress Ulcer Prophylaxis in Intensive Care Unit (SUP-ICU) trial, we assessed 1-year outcomes in the pantoprazole vs. placebo groups. METHODS: In the SUP-ICU trial, 3298 acutely admitted ICU patients at risk of GI bleeding were randomly allocated, stratified for site, to pantoprazole or placebo. In this secondary analysis, we assessed clinically important GI bleedings in ICU and 1-year mortality, health care resource use (e.g. readmission with GI bleeding, use of home care and general practitioner), health care costs, and employment status for the Danish participants using registry data. RESULTS: Among the 2099 Danish participants, 2092 had data in the registries; 1045 allocated to pantoprazole and 1047 to placebo. The number of clinically important GI bleedings in ICU was 1.9 percentage points [95% CI 0.3-3.5] lower in the pantoprazole group vs. the placebo group, but none of the 1-year outcomes differed statistically significantly between groups, including total health care costs (€1954 [- 2992 to 6899]), readmission with GI bleeding (- 0.005 admissions [- 0.016 to 0.005]), 1-year mortality (- 0.013 percentage points [- 0.051 to 0.026]), and employment (- 0.178 weeks [- 0.390 to 0.034]). CONCLUSION: Among ICU patients at risk of GI bleeding, pantoprazole reduced clinically important GI bleeding in ICU, but this did not translate into a reduction in 1-year mortality, health care resource use or improvements in employment status.

A high-dose 24-hour tranexamic acid infusion for the treatment of significant gastrointestinal bleeding: HALT-IT RCT.

BACKGROUND: Tranexamic acid reduces blood loss in surgery and the risk of death in trauma patients. Meta-analyses of small trials suggest that tranexamic acid decreases the number of deaths from gastrointestinal bleeding, but these meta-analyses are prone to selection bias. OBJECTIVE: The trial provides reliable evidence of the effect of tranexamic acid on mortality, rebleeding and complications in significant acute gastrointestinal bleeding. DESIGN: A multicentre, randomised, placebo-controlled trial and economic analysis. Patients were assigned by selecting one treatment pack from a box of eight, which were identical apart from the pack number. Patients, caregivers and outcome assessors were masked to allocation. The main analyses were by intention to treat. SETTING: The setting was 164 hospitals in 15 countries, co-ordinated from the London School of Hygiene & Tropical Medicine. PARTICIPANTS: Adults with significant upper or lower gastrointestinal bleeding (n = 12,009) were eligible if the responsible clinician was substantially uncertain about whether or not to use tranexamic acid. The clinical diagnosis of significant bleeding implied a risk of bleeding to death, including hypotension, tachycardia or signs of shock, or urgent transfusion, endoscopy or surgery. INTERVENTION: Tranexamic acid (a 1-g loading dose over 10 minutes, then a 3-g maintenance dose over 24 hours) or matching placebo. MAIN OUTCOME MEASURES: The primary outcome was death due to bleeding within 5 days of randomisation. Secondary outcomes were all-cause and cause-specific mortality; rebleeding; need for endoscopy, surgery or radiological intervention; blood product transfusion; complications; disability; and days spent in intensive care or a high-dependency unit. RESULTS: A total of 12,009 patients were allocated to receive tranexamic acid (n = 5994, 49.9%) or the matching placebo (n = 6015, 50.1%), of whom 11,952 (99.5%) received the first dose. Death due to bleeding within 5 days of randomisation occurred in 222 (3.7%) patients in the tranexamic acid group and in 226 (3.8%) patients in the placebo group (risk ratio 0.99, 95% confidence interval 0.82 to 1.18). Thromboembolic events occurred in 86 (1.4%) patients in the tranexamic acid group and 72 (1.2%) patients in the placebo group (risk ratio 1.20, 95% confidence interval 0.88 to 1.64). The risk of arterial thromboembolic events (myocardial infarction or stroke) was similar in both groups (0.7% in the tranexamic acid group vs. 0.8% in the placebo group; risk ratio 0.92, 95% confidence interval 0.60 to 1.39), but the risk of venous thromboembolic events (deep-vein thrombosis or pulmonary embolism) was higher in tranexamic acid-treated patients than in placebo-treated patients (0.8% vs. 0.4%; risk ratio 1.85, 95% confidence interval 1.15 to 2.98). Seizures occurred in 38 patients who received tranexamic acid and in 22 patients who received placebo (0.6% vs. 0.4%, respectively; risk ratio 1.73, 95% confidence interval 1.03 to 2.93). In the base-case economic analysis, tranexamic acid was not cost-effective and resulted in slightly poorer health outcomes than no tranexamic acid. CONCLUSIONS: Tranexamic acid did not reduce death from gastrointestinal bleeding and, although inexpensive, it is not cost-effective in adults with acute gastrointestinal bleeding. FUTURE WORK: These results caution against a uniform approach to the management of patients with major haemorrhage and highlight the need for randomised trials targeted at specific pathophysiological processes. LIMITATIONS: Although this is one of the largest randomised trials in gastrointestinal bleeding, we cannot rule out a modest increase or decrease in death due to bleeding with tranexamic acid. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11225767, ClinicalTrials.gov NCT01658124 and EudraCT 2012-003192-19. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 58. See the NIHR Journals Library website for further project information.

Acute gastrointestinal bleeding (bleeding from the gut) is a common emergency and an important cause of death and illness worldwide. In the UK, more than 65,000 people each year are admitted to hospital because of acute gastrointestinal bleeding; approximately 10% of them die within 30 days. Gastrointestinal bleeding is also common in low- and middle-income countries. The care of patients with gastrointestinal bleeding has improved in recent decades, but death rates remain high. Gastrointestinal bleeding is often caused by stomach ulcers, but also by liver damage owing to alcohol or hepatitis C infection. An effective and affordable treatment for gastrointestinal bleeding could save many lives and may reduce the need for blood transfusions, which is important because blood is a scarce resource in some health-care settings. Tranexamic acid, also known as TXA, is a cheap drug that reduces bleeding in other conditions. It helps blood to clot, thereby decreasing bleeding. A trial in bleeding accident victims found that tranexamic acid reduced the chances of bleeding to death, without any increase in side effects. We wanted to find out if tranexamic acid safely improves outcomes in patients with gastrointestinal bleeding, particularly to prevent deaths. To investigate this, the HALT-IT (Haemorrhage ALleviation with Tranexamic acid ­ Intestinal system) trial studied 12,009 patients with significant gastrointestinal bleeding in 164 hospitals across 15 countries. Half of the patients received tranexamic acid and the other half received a dummy drug, called a placebo. The treatments were assigned randomly and given in addition to all other treatments needed. Neither the patient nor the doctor knew which treatment a patient received. The trial showed that tranexamic acid did not reduce deaths from gastrointestinal bleeding. Instead, tranexamic acid was linked to an increased risk of complications, including unwanted blood clots (such as deep-vein thrombosis) and seizures. The economic analysis indicated that giving tranexamic acid to patients with gastrointestinal bleeding does not represent value for money for the NHS.

Effect of tranexamic acid in patients with colonic diverticular bleeding: A nationwide inpatient database study.

BACKGROUND AND AIM: The effect of tranexamic acid (TXA) remains unknown in patients with colonic diverticular bleeding, which is one of the most common causes of lower gastrointestinal bleeding. We investigated the efficacy of TXA for patients with colonic diverticular bleeding. METHODS: We performed a nationwide observational study using the Japanese Diagnosis Procedure Combination database and identified patients who were admitted for diverticular bleeding from 2010 to 2018. Patients who received TXA on the day of admission comprised the TXA group, and the remaining patients comprised the control group. The primary outcome was in-hospital mortality. Secondary outcomes included severe bleeding, blood transfusion within 7 days of admission, length of stay, and hospitalization costs. Propensity score matching was performed to compare outcomes between the two groups. RESULTS: Overall, 78 291 patients met our eligibility criteria, and 30 526 matched pairs were created by one-to-one propensity score matching. After matching, there was no significant difference in in-hospital mortality between the two groups (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.88-1.30); however, TXA administration was associated with significantly lower proportions of severe bleeding events (OR, 0.93; 95% CI, 0.89-0.99), blood transfusions (OR, 0.88; 95% CI, 0.84-0.92), shorter length of stay (difference, -0.23 days; 95% CI, -0.01 to -0.44 days), and lower total hospitalization costs (difference, -$233; 95% CI, -$153 to -$314). CONCLUSIONS: Although TXA was not significantly associated with lower in-hospital mortality, it may reduce severe bleeding, blood transfusions, length of stay, and hospitalization costs.

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial.

BACKGROUND: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. METHODS: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. FINDINGS: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82-1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). INTERPRETATION: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

[Use of a Delphi survey to assess the hospital economic impact of innovative products: The example of idarucizumab a dabigatran-specific reversal agent]. / Utilisation du questionnaire Delphi pour anticiper l'impact économique des innovations thérapeutiques à l'hôpital : application à l'idarucizumab, le nouvel agent de réversion spécifique au dabigatran.

OBJECTIVES: The economic impact of therapeutic innovations on the hospital patient management cannot be easily estimated. The objective of this study is to illustrate the use of a Delphi survey as a support tool to identify the changes following the use of idarucizumab in dabigatran-treated patients with uncontrolled/life-threatening bleeding or who required emergency surgery/urgent procedures. METHODS: The Delphi questionnaires have been administrated to 8 emergency physicians or anesthetists from 6 different hospital centers. Following the answers, an economic valorization has been carried out on every parameter on which a consensus was reached (at least 4 answers showing an identical trend). A mean management cost for each etiology with and without the use of idarucizumab has thus been identified. RESULTS: For gastro-intestinal and other life-threatening bleedings (excepted intracranial bleedings), the total management cost of the hospital stay was respectively 6058 € (-35%) and 6219 € (-34%) following the use of the reversal agent. The hospital management cost for intracranial bleeding is slightly increasing to 9790 € (+3%). The cost of a stay for emergency surgery decreases to 6962€ (-2%). CONCLUSIONS: This study shows a positive economic impact following the use of the dabigatran-specific reversal agent for patients with uncontrolled/life-threatening bleeding excepted in the case of intracranial bleeding. Moreover, it points out that a Delphi survey is an easy way to predict the hospital economic impact of a therapeutic innovation when no other evaluation is possible.

Gastrointestinal bleeding from vascular malformations: Is octreotide effective to rescue difficult-to-treat patients?

Gastrointestinal vascular malformations are responsible for 2-8% of all cases of bleeding and 30-40% of all obscure hemorrhages, being the most frequent cause of occult bleeding in older people. The aim of this review was to provide an up-to-date report about the use of octreotide in bleeding from both hereditary and acquired vascular malformations of the gastrointestinal tract. A systematic literature search was performed, using the keywords "gastrointestinal vascular malformation", "octreotide", "angiodysplasia", "portal hypertensive gastropathy", "gastric antral vascular ectasia", and "hereditary vascular malformations". The first line therapy of acute/chronic bleeding from digestive vascular malformations is endoscopy, followed by angiographic embolization and surgical resection when this is unsuccessful. In the setting of difficult-to-treat patients, octreotide has been proposed as an alternative therapeutic strategy. Studies reported in the literature show a high efficacy and safety of octreotide, but described only a small number of enrolled patients, heterogeneous therapeutic schedules and short-term follow-up, with the exception of acute bleeding from esophageal varices. As a consequence, the use of octreotide is not approved in this setting and it is currently still prescribed as an off-label drug. Studies in larger populations are needed to confirm the promising results observed in the small case series reports, so as to provide physicians with a treatment option for patients without available alternatives. Octreotide could also determine a strong decrease in the management costs of these clinical conditions, and especially, could dramatically reduce hospital admission costs.

Diverticular disease: changing epidemiology and management.

Diverticulosis is the most common pathological finding in routine colonoscopy. Diverticular disease comprises both diverticulitis and diverticular hemorrhage. This review examines the pathophysiological basis for disease including the importance of the elastin/collagen profile in diverticula formation. It summarizes the latest epidemiological findings with an emphasis on age- and sex-related differences. Risk factors including obesity, medications, hereditary factors, and diet are critically reviewed with the most up-to-date evidence. A detailed appraisal of therapeutic options is provided with special emphasis on 5-aminosalicylate, probiotics, mesalamine, percutaneous abscess drainage, and image-guided embolization. The role of antibiotics and surgery is discussed and compared with guideline recommendations. A more conservative approach, averting admission and even antibiotics, is explored. Finally, a careful review of the data surrounding the utility of colonoscopy in diagnosis and management is provided given the increasing number of reports citing the low incidence of colorectal neoplasia after an episode of diverticulitis. Throughout the review we focus on the older patient with diverticular disease.

Octreotide long-active release in the treatment of gastrointestinal bleeding due to vascular malformations: Cost-effectiveness study.

INTRODUCTION: Gastrointestinal hemorrhage due to vascular malformations has a negative impact on patients´ quality of life and consumes an important quantity of resources. OBJECTIVE: Analyze the cost-effectiveness of long-active releasing octreotide (OCT-LAR) in the treatment of gastrointestinal haemorrhage secondary to vascular malformations. MATERIAL AND METHODS: Retrospective study, including 19 pacients that were treated with mensual injections of OCTLAR between 2008-2013. The number of blood transfusions, hemoglobin levels, hospital admissions and possible side effects during the year before treatment and the year after the start of the treatment were assessed, and cost-effectiveness was analyzed. RESULTS: After the beginning of the treatment with OCTLAR, complete response was observed in 7 patients (36.8 %), partial response in 7 patients (36.8 %) and 5 patients (26.3 %) continued to require admissions, blood transfusions and/or endoscopic treatment. We observed significant reduction in the length of admission per year (in days) before and after the start of the treatment (22.79 versus 2.01 days, p < 0.0001) as well as in the number of blood transfusions administered (11.19 versus 2.55 blood transfusions per year, p = 0.002). The mean haemoglobin levels increased from 6.9 g/dl to 10.62 g/dl (p < 0.0001). We observed reduction of costs of 61.5 % between the two periods (from 36,072.35 € to 13,867.57 € per patient and year, p = 0.01). No side effects related to treatment were described. CONCLUSION: In conclusion, OCT-LAR seems to be a costefficient and safe pharmacological treatment of gastrointestinal haemorrhage secondary to vascular malformations, mainly in patients in whom endoscopic or surgical treatment is contraindicated.

Prevention of gastrointestinal bleeding due to stress ulceration: a review of current literature.

Our objective was to audit our current stress ulcer prophylaxis protocol (routine prescription of ranitidine and early enteral feeding) by identifying whether routine prescription of histamine-2 receptor antagonists or proton pump inhibitors as prophylaxis against stress-related mucosal disease and subsequent upper gastrointestinal bleeding is supported in the literature. We also aimed to ascertain what literature evidence supports the role of early enteral feeding as an adjunctive prophylactic therapy, as well as to search for burn-patient specific evidence, since burn patients are at high risk for developing this condition, with the aim of changing our practice. PubMed and Cochrane databases were searched for relevant articles, yielding seven randomised controlled trials comparing histamine-2 receptor antagonists and proton pump inhibitors in the prevention of upper gastrointestinal bleeding associated with stress-related mucosal disease and three separate meta-analyses. Despite level 1 clinical evidence, no significant difference in efficacy between histamine-2 receptor antagonists and proton pump inhibitor treatment groups was demonstrated. No significant difference was demonstrated in the incidence of nosocomial pneumonia between the two drugs given in this indication. However, enteral feeding was found to be safe and effective in preventing clinically significant upper gastrointestinal bleeding. Patients able to tolerate feeds demonstrated no additional benefit with concomitant pharmacological prophylactic therapy. Since all burn patients at the Royal Adelaide Hospital are fed from very early in their admission, the literature suggests that we, like our intensive care unit colleagues, should abolish our reliance on pharmacological prophylaxis, the routine prescription of which is not supported by the evidence.

[Diagnostic performance of colonoscopy in lower gastrointestinal bleeding]. / Rendimiento de la colonoscopia en la hemorragia digestiva baja.

Lower gastrointestinal bleeding is a common medical emergency that usually has a favorable prognosis. However, these events generate high resource use. The procedure of choice is colonoscopy with prior colonic preparation due to its high diagnostic performance and safety and the possibility of endoscopic therapy. Emergency colonoscopy has advantages over elective colonoscopy, showing higher diagnostic yield and superior detection of stigmata of recent bleeding, increasing the probability of endoscopic treatment. Predictive models of bleeding severity and recurrence have been published, allowing resource use to be rationalized, mainly by reducing hospital stay in low-risk patients. Nevertheless, the optimal timing of emergency colonoscopy has not been established and the impact of endoscopic treatment on prognosis is controversial.

An economic evaluation of vasoactive agents used to treat acute bleeding oesophageal varices in Belgium.

BACKGROUND AND STUDY AIMS: Increasingly, cost influences all areas of healthcare, including the management of life threatening events, such as bleeding oesophageal varices (BOV). In light of the need to control costs, an economic evaluation of vasoactive agents used to treat cirrhotic patients with BOV within the emergency setting in Belgium has been assessed. PATIENTS AND METHODS: A previously reported economic evaluation of vasoactive agents used to treat BOV was identified and adapted to the Belgium hospital setting. The economic evaluation was based on double-blind randomised controlled trials of vasoactive agents previously reported as Cochrane meta-analyses. Belgian cost data was obtained from local published sources and hospital databases. We assessed average disaggregated and aggregated treatment costs, average and incremental cost per quality adjusted life years (QALYs) and life-years gained (LYG). RESULTS: Total treatment costs at 1 year were: terlipressin Euro 2,734; somatostatine Euro 2,972; octreotide Euro 2,801; and placebo Euro 2,874. The average costs per QALY were: terlipressin Euro 4,672; somatostatine Euro 5,878; octreotide Euro 5,540; and placebo Euro 5,687. In the cost per LYG analysis terlipressin achieved the lowest cost per life-year. Results from the incremental cost per QALY and LYG analysis indicated that terlipressin was the most cost-effective agent. CONCLUSIONS: One year simulations indicate somatostatine is the most expensive treatment option and terlipressin the least costly. Amongst the vasoactive products, the incremental analysis indicated terlipressin was dominant when compared with octreotide and somatostatine because of improved survival and cost-saving potential that is likely attributed to avoiding additional and more costly interventions.

Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding.

OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of proton pump inhibitors (PPIs) in the prevention and treatment of acute upper gastrointestinal (UGI) haemorrhage, as well as to compare this with H2-receptor antagonist (H2RA), Helicobacter pylori eradication (in infected patients) or no therapy, for the prevention of first and/or subsequent bleeds among patients who continue to use non-steroidal anti-inflammatory drugs (NSAIDs). Also to evaluate the clinical effectiveness of PPI therapy, compared with other treatments, for the prevention of subsequent bleeds in patients who had previously experienced peptic ulcer (PU) bleeding. DATA SOURCES: Electronic databases and major conference proceedings were searched up to February 2006. REVIEW METHODS: Data were collected from the systematic reviews addressing each research objective. These were then entered into an economic model to compare the costs and quality-adjusted life-days of alternative management strategies over a 28-day period for patients who have had UGI bleeding. A Markov model with a Monte Carlo simulation used data from the systematic reviews to identify the most cost-effective treatment strategy for the prevention of UGI bleeding (first and subsequent) among NSAID users using an outcome of costs per quality-adjusted life-years (QALYs) over a lifetime from age 50 years. RESULTS: PPI treatment initiated after endoscopic diagnosis of PU bleeding significantly reduced re-bleeding and surgery compared with placebo or H2RA. Although there was no evidence of an overall effect of PPI treatment on all-cause mortality, PPIs significantly reduced mortality in subgroups when studies conducted in Asia were examined in isolation or when the analysis was confined to patients with high-risk endoscopic findings. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduced the proportion of patients with stigmata of recent haemorrhage (SRH) at index endoscopy compared with placebo or H2RA, but there was no evidence that PPI treatment affected clinically important outcomes. Giving oral PPI both before and after endoscopy, with endoscopic haemostatic therapy (EHT) for those with major SRH, is preferred to all others on cost-effectiveness grounds at any threshold over 25,000 pounds per QALY, even if only short-term effects are taken into account, and at any threshold over 200 pounds per life-year gained if long-term effects are included. The risk of NSAID-induced endoscopic gastric and duodenal ulcers was reduced by standard doses of PPI and misoprostol, and double doses of H2RAs. Standard doses of H2RAs reduced the risk of endoscopic duodenal ulcers. PPIs reduced NSAID-induced dyspepsia. PPIs were superior to misoprostol in preventing recurrence of NSAID-induced endoscopic duodenal ulcers, but PPIs were comparable to misoprostol in preventing the recurrence of NSAID-induced endoscopic gastric ulcers. Full-dose misoprostol reduced bleeding, perforation or gastric outlet obstruction due to NSAID-induced ulcers, but misoprostol was poorly tolerated and associated with frequent adverse effects. H. pylori eradication treatment was equally effective with PPI treatment for the primary or secondary prevention of endoscopic ulcers in NSAID users. H. pylori eradication treatment was more effective than placebo for the primary prevention of endoscopic PU and for the prevention of re-bleeding from PU in NSAID users. With regard to primary and secondary prevention of bleeding PU in NSAID users, the two most cost-effective strategies are H. pylori eradication alone, and H. pylori eradication followed by misoprostol (substituted by a PPI, if misoprostol is not tolerated) at an additional 4810 pounds per QALY. In patients who had previously experienced a bleed from a PU, re-bleeding was less frequent after H. pylori eradication therapy than after non-eradication antisecretory therapy, whether or not the latter was combined with long-term maintenance antisecretory therapy. CONCLUSIONS: PPI treatment compared with placebo or H2RA reduces mortality following PU bleeding among patients with high-risk endoscopic findings, and reduces re-bleeding rates and surgical intervention. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduces the proportion of patients with SRH at index endoscopy but does not reduce mortality, re-bleeding or the need for surgery. The strategy of giving oral PPI before and after endoscopy, with EHT for those with major SRH, is likely to be the most cost-effective. Treatment of H. pylori infection was found to be more effective than antisecretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone or eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies for preventing bleeding ulcers among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective. Further large randomised controlled trials are needed to address areas such as PPI administration prior to endoscopic diagnosis, different doses and administration of PPIs, as well as the primary and secondary prevention of UGI bleeding.

Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage: a cost-effectiveness analysis.

BACKGROUND: Erythromycin is a potent stimulator of gastrointestinal motility. Recent studies have examined the use of intravenous erythromycin to clear the stomach of blood before oesophago-gastroduodenoscopy (EGD) for acute upper gastrointestinal haemorrhage (UGIH). These studies have shown clinical effectiveness. AIM: To evaluate the cost-effectiveness of this intervention. METHODS: We sought to determine the cost-effectiveness of erythromycin before EGD from the payer's perspective. We found three relevant studies of erythromycin and used these data for the analysis. We obtained costs for intravenous erythromycin and charges for peptic ulcer hospitalization, EGD, surgery, and angiographic embolization. Complication rates were also incorporated from the literature. We implemented a model of health-related quality of life to measure the impact of the intervention. We created a decision-analysis tree and performed a probabilistic sensitivity analysis. RESULTS: A strategy of erythromycin prior to EGD resulted in a cost-effective outcome in a majority of trials using willingness-to-pay figures of USD 0, USD 50,000 and USD 100,000 per quality-adjusted life-year (QALY). CONCLUSION: Because of the implications for cost saving and increase in QALY, we would recommend giving erythromycin prior to EGD for UGIH.

Treating bleeding oesophageal varices with vasoactive agents: good value for money?

This article provides an editorial commentary to accompany the publication of an article on the economic evaluation of vasoactive agents used in the United Kingdom for acute bleeding oesophageal varices in patients with cirrhosis by Wechowski et al. From a clinical standpoint, the successful management of bleeding oesophageal varices should be based on definitive treatments such as therapeutic endoscopy or transjugular intrahepatic portosystemic stent shunt (TIPSS). Vasoactive agents such as terlipressin can be useful and potentially cost-effective additional therapy, however, particularly in patients where endoscopic treatment is likely to be delayed or is contraindicated.

An economic evaluation of vasoactive agents used in the United Kingdom for acute bleeding oesophageal varices in patients with liver cirrhosis.

OBJECTIVE: To conduct an economic evaluation of terlipressin, octreotide and placebo in the treatment of bleeding oesophageal varices (BOV) where endotherapy could be used concomitantly. METHODS: A discrete event simulation model was created with transition states: bleeding, no bleeding, no bleeding post transjugular intrahepatic portosystemic shunt, post-salvage surgery, and death. Efficacy data on survival, re-bleeding and control of bleeding were obtained from high quality studies reported in Cochrane meta-analyses. Baseline outcomes related to the course of disease and health-state utilities were derived from published sources. Vasoactive treatment costs and all related BOV costs were obtained from published UK sources. RESULTS: The average aggregated treatment cost per person for all medical interventions at 1 year was lower for terlipressin-treated patients (2623 pounds sterling) compared with those treated using octreotide (2758 pounds sterling) or placebo (2890 pounds sterling). The incremental analysis comparing terlipressin with octreotide and placebo using a cost per quality adjusted life year (QALY) and cost per life year gained (LYG) approach indicated that terlipressin was the dominant BOV treatment option (i.e. it cost less and it was more effective). Based on a maximum willingness to pay of 20,000 pounds sterling/QALY terlipressin was more effective and cost-saving compared to octreotide and placebo for simulations ranging from 42 days to 2 years. In point estimation analyses octreotide was dominant compared to placebo; however, probabilistic sensitivity analysis indicated that octreotide was unlikely to be cost-effective compared to placebo. CONCLUSIONS: The findings indicated that vasoactive treatment in BOV was cost-saving compared to no vasoactive treatment. Furthermore, terlipressin was the more cost-effective vasoactive treatment for BOV in cirrhotic patients.

[Antiplatelet therapy after aspirin-induced upper gastrointestinal bleeding]. / Platehemmerbehandling ved tidligere gastrointestinal blødning forårsaket av acetylsalisylsyre.

It is common practice to replace aspirin with clopidogrel in patients with gastrointestinal intolerance to aspirin. Recent studies suggest that a combination of aspirin and a proton pump inhibitor is a better alternative for these patients. The CAPRIE and CURE studies have not shown any clinically relevant difference in effect between aspirin and clopidogrel. The incidence of bleeding is also similar when aspirin is used in doses < 160 mg. A recent study by Chan et al. concluded that a combination of aspirin and esomeprazole is superior to clopidogrel in the prevention of recurrent gastrointestinal bleeding. Using aspirin and a proton pump inhibitor is also the least expensive alternative.