Peptic ulcer disease.

Annual prevalence estimates of peptic ulcer disease range between 0·12% and 1·5%. Peptic ulcer disease is usually attributable to Helicobacter pylori infection, intake of some medications (such as aspirin and non-steroidal anti-inflammatory medications), or being critically ill (stress-related), or it can be idiopathic. The clinical presentation is usually uncomplicated, with peptic ulcer disease management based on eradicating H pylori if present, the use of acid-suppressing medications-most often proton pump inhibitors (PPIs)-or addressing complications, such as with early endoscopy and high-dose PPIs for peptic ulcer bleeding. Special considerations apply to patients on antiplatelet and antithrombotic agents. H pylori treatment has evolved, with the choice of regimen dictated by local antibiotic resistance patterns. Indications for primary and secondary prophylaxis vary across societies; most suggest PPIs for patients at highest risk of developing a peptic ulcer, its complications, or its recurrence. Additional research areas include the use of potassium-competitive acid blockers and H pylori vaccination; the optimal approach for patients at risk of stress ulcer bleeding requires more robust determinations of optimal patient selection and treatment selection, if any. Appropriate continuation of PPI use outweighs most possible side-effects if given for approved indications, while de-prescribing should be trialled when a definitive indication is no longer present.

The Saudi Gastroenterology Association consensus on the clinical care pathway for the diagnosis and treatment of GERD.

ABSTRACT: Gastroesophageal reflux disease (GERD) is one of the most common problems encountered in outpatient general medicine and gastroenterology clinics. GERD may present with classic esophageal symptoms, extraesophageal symptoms, or mixed symptoms. The diagnosis and treatment of GERD are challenging due to the variety of symptoms and multifactorial pathophysiology. Since there is no consensus on the diagnosis and treatment of GERD in Saudi Arabia, the Saudi Gastroenterology Association established an expert group to formulate a consensus on the clinical care pathway for the diagnosis and treatment of GERD to update health-care providers in Saudi Arabia. The expert group reviewed the literature including recently published international guidelines, clinical trials, and expert opinion and conducted virtual and in-person meetings. A total of 22 statements on the definition, diagnosis, and treatment of GERD were formulated, and three algorithms for the clinical care of GERD were developed with a detailed description for each step. The expert group endorsed the new definition of GERD, the practical principles of interpretation of the diagnostic GERD evaluation, and the practical guidance for GERD treatment including medical, surgical, and endoscopic therapy. The expert group recommends further studies to investigate local data on the diagnosis and treatment of GERD.

Eosinophilic esophagitis: Current concepts in diagnosis and management.

ABSTRACT: Eosinophilic esophagitis is an antigen-mediated chronic inflammatory disorder that has risen in incidence and prevalence over the past 2 decades. The clinical presentation is variable and consists of mainly esophageal symptoms such as dysphagia, heartburn, food impaction, and vomiting. Current management relies on dietary elimination, proton-pump inhibitors, and topical corticosteroids with different response rates and relapses after treatment discontinuation. With a better understanding of the underlying pathophysiology, many molecules emerged recently as targeted treatment including dupilumab (IL4/IL13 blocker), as the first FDA-approved biological treatment, which has changed the management paradigm.

Primary and Specialty Care Trainees' Perceptions About Proton Pump Inhibitor Use.

OBJECTIVE: Proton pump inhibitors (PPIs) are widely prescribed with proven efficacy in many indications, yet longstanding controversy about potential adverse events persists. We aimed to acquire knowledge about perceptions of outpatient PPI long-term prescribing (≥8 wk) among primary and specialty care trainees at 2 Canadian Universities. METHODS: Family medicine, internal medicine, and gastroenterology trainees completed a web-based survey that included 20 clinical scenarios assessing trainee knowledge about PPI efficacy. Contextual PPI prescribing decisions were also elicited, balancing possible PPI indications versus side effects. Management strategies were compared between junior and senior trainees, as well as across training programs. RESULTS: Over a 4-month period,163 trainees (age <26 y: 12%; age 26 to 45: 88%; 59% females) participated in the survey (family medicine: 51%, internal medicine: 44%, and gastroenterology: 5%); 83% were considered junior residents. Only 42% had received formal education on prescribing PPI long-term. Overall, 93% believed they would benefit from such teaching, with 98% stating they would follow related guidelines. No between-group differences were noted in knowledge of appropriate PPI indications nor possible side effects when comparing juniors to seniors, or among different specialties. Across different management scenarios, inappropriate PPI discontinuation was chosen by 14.3% to 67.2%, whereas inappropriate PPI continuation was reported in up to 57%. Trainee seniority and specialty did not differ in appropriate deprescribing rates. CONCLUSIONS: Training level and primary versus specialty care settings are associated with frequent inappropriate PPI prescribing and deprescribing. These findings highlight the need for and may inform future educational programs on PPI usage.

Review article: Advances in the management of lower gastrointestinal bleeding.

BACKGROUND: Lower gastrointestinal bleeding (LGIB) is a common emergency with substantial associated morbidity and mortality. Elective colonoscopy plays an essential role in management, with an even more important role for radiology in the acute setting. Recent advances in the management of patients with LGIB warrant review as the management has recently evolved. AIMS: To provide a comprehensive and updated overview of advances in the approach to patients with LGIB METHODS: We performed a comprehensive literature search to examine the current data for this narrative review supplemented by expert opinion. RESULTS: The incidence of LGIB is increasing worldwide, partly related to an ageing population and the increasing use of antithrombotics. Diverticulosis continues to be the most common aetiology of LGIB. Pre-endoscopic risk stratification tools, especially the Oakland score, can aid appropriate patient triage. Adequate resuscitation continues to form the basis of management, while appropriate management of antithrombotics is crucial to balance the risk of worsening bleeding against increased cardiovascular risk. Radiological imaging plays an essential role in the diagnosis and treatment of acute LGIB, especially among unstable patients. Colonoscopy remains the gold-standard test for the elective management of stable patients. CONCLUSIONS: The management of LGIB has evolved significantly in recent years, with a shift towards radiological interventions for unstable patients while reserving elective colonoscopy for stable patients. A multidisciplinary approach is essential to optimise the outcomes of patients with LGIB.

Saudi consensus guidance for the management of inflammatory bowel disease during pregnancy.

ABSTRACT: The management of inflammatory bowel disease (IBD) in pregnant women is challenging and must be addressed on a patient-by-patient basis. Optimal patient management requires a multidisciplinary team and clear evidence-based recommendations that cater to this subset of patients. In this article, we provide concise guidelines and clinical care pathway for the management of IBD in pregnant women. Our recommendations were developed by a multidisciplinary working group that includes experts from the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacology. All recommendations are based on up-to-date information following an extensive literature review. A total of 23 evidence-based expert opinion recommendations for the management of IBD in pregnant women are herein provided.

Saudi Arabia consensus guidance for the diagnosis and management of adults with inflammatory bowel disease.

Optimal management of inflammatory bowel disease (IBD) relies on a clear understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This article provides concise guidelines for the management of IBD in adults, based on the most up-to-date information at the time of writing and will be regularly updated. These guidelines were developed by the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacy. After an extensive literature review, 78 evidence-and expert opinion-based recommendations for diagnosing and treating ulcerative colitis and Crohn's disease in adults were proposed and further refined by a voting process. The consensus guidelines include the finally agreed on statements with their level of evidence covering different aspects of IBD diagnosis and treatment.

Predictors of Anti-TNF Therapy Failure among Inflammatory Bowel Disease (IBD) Patients in Saudi Arabia: A Single-Center Study.

BACKGROUND: The advent of monoclonal antibodies (mAbs) has revolutionized the management of many immune-mediated diseases such as inflammatory bowel disease (IBD). Infliximab and adalimumab were the first mAbs approved for the management of IBD, and are still commonly prescribed for the treatment of both Crohn's disease (CD) and ulcerative colitis (UC). Although mAbs have demonstrated high effectiveness rates in the management of IBD, some patients fail to respond adequately to mAbs, resulting in disease progression and the flare-up of symptoms. OBJECTIVE: The objective was to explore the predictors of treatment failure among IBD patients on infliximab (INF) and adalimumab (ADA)-as demonstrated via colonoscopy with a simple endoscopic score (SES-CD) of ≥1 for CD and a Mayo score of ≥2 for UC-and compare the rates of treatment failure among patients on those two mAbs. METHODS: This was a prospective cohort study among IBD patients aged 18 years and above who had not had any exposure to mAbs before. Those patients were followed after the initiation of biologic treatment with either INF or ADA until they were switched to another treatment due to failure of these mAbs in preventing the disease progression. Univariate and multiple logistic regressions were conducted to examine the predictors and rates of treatment failure. RESULTS: A total of 146 IBD patients (118 patients on INF and 28 on ADA) met the inclusion criteria and were included in the analysis. The mean age of the patients was 31 years, and most of them were males (59%) with CD (75%). About 27% and 26% of the patients had penetrating and non-stricturing-non-penetrating CD behavior, respectively. Patients with UC had significantly higher odds of treatment failure compared to their counterparts with CD (OR = 2.58, 95% CI [1.06-6.26], p = 0.035). Those with left-sided disease had significantly higher odds of treatment failure (OR = 4.28, 95% CI [1.42-12.81], p = 0.0094). Patients on ADA had higher odds of treatment failure in comparison to those on INF (OR = 26.91, 95% CI [7.75-93.39], p = 0.0001). CONCLUSION: Infliximab was shown to be more effective in the management of IBD, with lower incidence rates of treatment failure in comparison to adalimumab.

Association of HER1 and HER2 Gene Variants in the Predisposition of Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is a major health concern worldwide. A series of sequential accumulation of genetic and epigenetic changes are responsible for the initiation and progression of diseases via the normal > adenoma > carcinoma sequence. Genetic variants in crucial cancer-causing genes are known to mediate the risk of cancer. OBJECTIVE: In this case-control study, we examined single nucleotide polymorphism (SNP) in HER1 (rs763317 and rs3752651) and HER2 (rs1136201 and rs1058808) genes to assess their role in the susceptibility of CRC in a Saudi population. METHODS: TaqMan allelic discrimination assay was utilized to identify the genotypes in 163 normal and 143 CRC patients. RESULTS: In the overall analysis, the rs3752651 and rs1136201 were significantly associated with the risk of CRC. Although none of the examined SNPs had any impact on the age at which CRC was diagnosed, interestingly, three SNPs showed a significant association based on gender. The rs3752651 conferred significant protection only in men, whereas rs1136201 diminished the risk and rs1058808 considerably increased the susceptibility of CRC only in women. CONCLUSIONS: Our result suggests that these SNPs in HER1 and HER2 after validation in larger cohorts of different ethnicities may be utilized as genetic screening markers for predicting colorectal cancer predisposition.

Early cholangioscopy-assisted electrohydraulic lithotripsy in difficult biliary stones is cost-effective.

BACKGROUND AND AIMS: Single-operator cholangioscopy-assisted electrohydraulic lithotripsy (SOC-EHL) is effective and safe in difficult choledocholithiasis. The optimal timing of SOC-EHL use, however, in refractory stones has not been elucidated. The following aims to determine the most cost-effective timing of SOC-EHL introduction in the management of choledocholithiasis. METHODS: A cost-effectiveness model was developed assessing three strategies with a progressively delayed introduction of SOC-EHL. Probability estimates of patient pathways were obtained from a systematic review. The unit of effectiveness is complete ductal clearance without need for surgery. Cost is expressed in 2018 US dollars and stem from outpatient US databases. RESULTS: The three strategies achieved comparable ductal clearance rates ranging from 97.3% to 99.7%. The least expensive strategy is to perform SOC-EHL during the first endoscopic retrograde cholangiography pancreatography (ERCP) (SOC-1: 18,506$). The strategy of postponing the use of SOC-EHL to the third ERCP (SOC-3) is more expensive (US$18,895) but is 2% more effective. (0.9967). SOC-EHL during the second ERCP in the model (SOC-2) is the least cost-effective. Sensitivity analyses show altered conclusions according to the cost of SOC-EHL, effectiveness of conventional ERCP, and altered willingness-to-pay (WTP) thresholds with early SOC-1 being the most optimal approach below a WTP cut-off of US$20,295. CONCLUSIONS: Early utilization of SOC-EHL (SOC-1) in difficult choledocholithiasis may be the least costly strategy with an effectiveness approximating those achieved with a delayed approach where one or more conventional ERCP(s) are reattempted prior to SOC-EHL introduction.

Prevalence, severity and associated factors of restless leg syndrome in inflammatory bowel disease patients.

BACKGROUND: The association between restless leg syndrome (RLS) and inflammatory bowel disease (IBD) has often been an under-investigated and clinically misdiagnosed entity. An emphasis should be made on the severity and associated factors, as the prevalence of both entities is on the rise globally. In this study we aimed to investigate the prevalence, severity and associated risk factors of RLS in patients with IBD. METHODS: A multi-center, prospective cross-sectional study was conducted with age and gender matched controls in the ratio of 1:3. Cases of IBD were confirmed according to European Crohns and Colitis Organization guidelines. The study recruited 377 cases and 1131 age and gender-matched controls. RLS severity and prevalence was determined using a validated International Restless Legs Syndrome Study Group questionnaire. The anthropometric and blood biochemical measurements were retrieved from the patient's medical records. Associated factors were analyzed by regression analysis. RESULTS: The prevalence of RLS in patients with IBD and non-IBD control groups was 21.5% and 9.7%, respectively (P = 0.001). The severity index of RLS symptoms in all the three categories of mild, moderate and severe RLS was higher in the IBD group (P = 0.001). Obesity (BMI >30 Kg/m2) was more prevalent in patients with IBD with RLS than without RLS (21.9%: 10.3%, P = 0.009). Ages between 46 and 59 years (OR = 18.7 [2.6-29.4], P = 0.008), obesity (OR = 22 [2.6-29.4], P = 0.005), higher TSH levels (OR = 1.7 [1.0-3.0], P = 0.033), and lower hemoglobin levels (P = 0.028) showed a greater risk associated with RLS. CONCLUSION: Prevalence and severity of RLS was higher in patients with IBD. The risk factors for RLS in IBD include increasing age, obesity, higher TSH, and lower hemoglobin.

Expression and Polymorphism of TSLP/TSLP Receptors as Potential Diagnostic Markers of Colorectal Cancer Progression.

Colorectal cancer (CRC) is the third most common malignancy and the fourth leading cause of cancer-related mortality worldwide. Inflammation is considered as a critical driver for CRC development and growth. We investigated the association between polymorphisms/expression levels of thymic stromal lymphopoietin (TSLP) /TSLP receptors and CRC risk in Saudi population. DNA samples were isolated from blood samples from 220 participants. Case subjects were 112 patients diagnosed with CRC, while control subjects were 108 healthy individuals, who were not diagnosed with any type of malignancy. We selected two single nucleotide polymorphisms (SNPs) located in the thymic stromal lymphopoietin gene (rs10043985 and rs2289276), three SNPs in TSLP receptor gene (TSLPR; rs36139698, rs36177645, and rs36133495), and two other SNPs in interleukin-7 receptor gene (IL-7R; rs12516866 and rs1053496), and designated these SNPs for a case-control genotyping study. The gene expression was analyzed using quantitative RT-PCR and immunohistochemistry assays array on 20 matching colorectal cancer/normal tissues. mRNA expressions and protein levels of TSLP, TSLPR-α subunit, and IL-7R-α subunit showed a 4-fold increase in colon cancer tissues when compared to normal colon tissues. Furthermore, two SNPs (rs10043985 of TSLP and rs1053496 of IL-7R) showed statistically significant correlations with CRC susceptibility. Interestingly, only rs10043985 showed a statistically significant association (p < 0.0001) in the genotypic and phenotypic levels with CRC for all clinical parameters (age, gender, and tumor location) tested. However, IL-7R rs1053496 genotyping results presented a significant correlation (p < 0.05) in male CRC patients and in individuals under 57 years of age. TSLP rs2289276, IL-7R rs12516866, and all TSLPR variants did not display any significant genotypic or phenotypic correlations in all tested clinical parameters. This study identified that TSLP rs10043985 and IL-7R rs1053496 SNPs, and the expression levels of TSLP and TSLPR-α subunit, can be used as markers for CRC development and treatment. However, additional investigations are required on larger group of patients from diverse ethnicities to confirm the genetic association of these variants to CRC.

Use of stents in patients undergoing chemotherapy for borderline resectable pancreatic cancer-causing biliary obstruction while awaiting surgery: A cost-effectiveness analysis.

Background and study aims Biliary stenting is indicated to relieve obstruction from borderline resectable pancreatic cancer while patients receive preoperative neoadjuvant therapy. We compared the cost-effectiveness of plastic versus metal biliary stenting in this setting. Methods A decision tree analysis compares two competing types of biliary stents (initially metal vs. initially plastic) to treat malignant distal biliary obstruction while receiving neoadjuvant therapy with different scenarios including possible complications as bridge till the patient undergoes curative surgical attempt. Using published information, effectiveness was chosen as the probability of successfully reaching a state of being ready for surgery once chemotherapy was completed. Costs (2018 US$) were based on national data. A third-party payer perspective was adopted, and sensitivity analyses were performed over a time-horizon of one year. Results Initially inserting a metal versus a plastic biliary stent was more efficacious with a higher probability of reaching the readiness for surgery endpoint (96 % vs. 85 %), on average 18 days earlier while also being less expensive (US$ 9,304 vs. US$ 11,538). Sensitivity analyses confirmed robustness of these results across varying probability assumptions of plausible ranges and remained a dominant strategy even when lowering the willingness-to-pay threshold to US$ 1,000. Conclusions Initial metal stenting to relieve malignant biliary obstruction from borderline resectable pancreatic cancer in patients undergoing neoadjuvant therapy prior to surgery is a dominant intervention in economic terms, when compared to initially inserting a plastic biliary stent as it results in a greater proportion of patients being fit for surgery earlier and at a lower cost.

Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study.

OBJECTIVE: To evaluate the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD). DESIGN: Prospective cohort study. SETTING: 21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China). PARTICIPANTS: 116 087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years. MAIN OUTCOME MEASURES: The main outcome was development of IBD, including Crohn's disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals. RESULTS: Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn's disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with <1 serving/day, P=0.006 for trend). Different subgroups of ultra-processed food, including soft drinks, refined sweetened foods, salty snacks, and processed meat, each were associated with higher hazard ratios for IBD. Results were consistent for Crohn's disease and ulcerative colitis with low heterogeneity. Intakes of white meat, red meat, dairy, starch, and fruit, vegetables, and legumes were not associated with incident IBD. CONCLUSIONS: Higher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra-processed foods. STUDY REGISTRATION: ClinicalTrials.gov NCT03225586.

NOTCH Single Nucleotide Polymorphisms in the Predisposition of Breast and Colorectal Cancers in Saudi Patients.

Breast cancer (BC) is a heterogeneous disease and is one of the most common malignancy affecting women worldwide while colorectal cancer (CRC) is estimated to be the third common cancer and second leading cause of cancer related death globally. Both BC and CRC involve multiple genetic and epigenetic alterations in genes belonging to various signaling pathways including NOTCH that has been implicated in the development of these cancers. We investigated four single nucleotide polymorphisms, each in genes encoding NOTCH1-4 receptors for their role in susceptibility to breast and colorectal cancers in Saudi population. In this case-control study, TaqMan genotypic analysis of rs3124591 in NOTCH1 and rs3820041 in NOTCH4 did not exhibit association with breast as well as colorectal cancers. However, a strong association of rs11249433 which is in close proximity to NOTCH2 was observed with breast cancer susceptibility especially with those having an early onset of the disease. Interestingly, the rs1043994 located in NOTCH3 showed gender preference and was found to be significantly associated with colorectal cancers in males. Validation of these findings in bigger populations of different ethnicities may prove beneficial in identifying rs11249433 and rs1043994 as genetic screening markers for early detection of breast and colorectal carcinomas, respectively.

The cost-effectiveness of sequential versus standard triple therapy for Helicobacter pylori eradication in Saudi Arabia.

Background: The utilization rate of different treatment regimens for Helicobacter pylori infection is believed to be high; however, the cost-effectiveness of these regimens has not been examined before. Therefore, the aim of this study was to examine the cost-effectiveness of the two commonly prescribed treatments for H. pylori infection. Methods: The data of.an open-label, single-center, randomized trial that compared the efficacy of sequential therapy (SQT) (i.e., esomeprazole 20 mg twice daily for 10 days, amoxicillin 1000 mg twice daily for 5 days, then clarithromycin 500 mg and tinidazole 500 mg twice daily for 5 days) to standard triple therapy (STT) (i.e., esomeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 twice daily for 14 days) in the eradication of H. pylori, as confirmed by the negative urea breath test (UBT), were used. Propensity score matching bin bootstrapping, with 10,000 replications and bias correction was conducted to generate the 95% confidence limits. Moreover, probabilistic sensitivity analysis was conducted by varying both the eradication rates and the costs of treatment regimens. Results: There were 82 and 88 patients who were on SQT and STT, respectively. Patients' mean age was 47 years, and approximately 55% of them were females. The mean treatment costs were SAR 2,075.51 (USD 553.47) and SAR 2,629.26 (USD 701.14) for SQT and STT, respectively. The mean eradication rates for SQT and STT were 63.41% and 67.05%, respectively. The mean difference in costs and eradication rates for SQT versus STT were SAR - 550.75 (95% CI: -563.84- -537.69) and - 3.64% (95% CI: -6.98- 5.88). The use of SQT was more likely to be cost saving and more effective with 56.25% confidence level, in comparison to STT. Conclusion: The use of SQT in the treatment of H. pylori seems to be more cost-effective than STT.

Cost-effectiveness analysis of colorectal cancer screening in a low incidence country: The case of Saudi Arabia.

Background: Colorectal cancer (CRC) screening is cost-effective in many Western countries, and many have successfully implemented CRC screening programs. For countries with a lower CRC incidence, like Saudi Arabia, the value of CRC screening is less evident and requires careful weighing of harms, benefits, and costs. Methods: We used the MISCAN-Colon microsimulation model to simulate a male and female cohort with life expectancy and CRC risk as observed in Saudi Arabia. For both cohorts, we evaluated strategies without screening, with annual or biennial faecal immunochemical testing (FIT), and with 10-yearly or once-only colonoscopy. We also considered different start and end ages of screening. For both cohorts, we estimated lifetime costs and effects of each strategy. We then identified a set of potentially cost-effective strategies using incremental cost-effectiveness ratios (ICERs) defined as the additional cost per additional quality-adjusted life year (QALY). Results: Without CRC screening, an estimated 14 per 1,000 males would develop CRC during their lifetime and 9 would die from CRC. Several strategies proved potentially cost-effective including biennial FIT at ages 55-65 (ICER of $7,400), once-only colonoscopy at age 55 (ICER of $7,700), and 10-yearly colonoscopy at ages 50-65, 45-65, and 45-75 (ICERs of $34,000, 71,000, and 375,000, respectively). For females, risk of CRC was lower and CRC screening was therefore less cost-effective, but efficient strategies were largely similar. Conclusions: Despite low CRC incidence in Saudi Arabia, some FIT or colonoscopy screening strategies may meet reasonable thresholds of cost-effectiveness. The optimal strategy will depend on multiple factors including the willingness to pay per QALY, the colonoscopy capacity, and the accepted budget impact.