Aminosalicylates

Symptomatic diverticular disease has a high prevalence in countries with a western lifestyle. Besides antibiotics for acute diverticulitis there are no established medical interventions to prevent or to treat symptomatic diverticular disease. Due to its broad spectrum of anti-inflammatory activities, mesalazine is a candidate for the treatment of symptomatic diverticular disease. A review of the literature shows that randomized open studies using various treatment designs suggest a protective role of mesalazine in preventing recurrences of diverticulitis. Currently, 5 randomized placebo-controlled trials are active which will clarify the role of mesalazine to prevent recurrence of diverticulitis in the near future. Several randomized uncontrolled studies suggest that mesalazine improves symptoms in patients with symptomatic uncomplicated diverticular disease. The analysis of secondary end points from two randomized placebo-controlled trials suggests that mesalazine improves symptoms in diverticular disease although both studies failed to show a statistically significant advantage for mesalazine for the primary study end point. In segmental colitis associated with diverticulosis no prospective systematic studies are available. However, several case reports show a high efficacy of mesalazine in segmental colitis associated with diverticulosis.     

Effect of mesalazine on epithelial cell proliferation in colonic diverticular disease

Background and aimsIncreased epithelial cell proliferation may be detected in diverticular disease, but antibiotics have failed in reducing it. We assess therefore the effect of mesalazine on epithelial cell proliferation in diverticular disease.MethodsA prospective study was conducted on 20 consecutive patients with a new endoscopic diagnosis of symptomatic uncomplicated diverticular disease. The patients were treated with mesalazine 1.6 mg/day for 1 year. The Ki-67 antigen index of the whole crypt and in the upper third was separately evaluated before and after starting the treatment.ResultsCell proliferation index was higher in diverticular disease patients than healthy controls both in the whole crypt (median 6.7%, range 2–9% vs. median 1.6%, range 1–3%, p = 0.001) and in the upper third of the crypt (median 6.8%, range 2–8% vs. median 1.8%, range 1–3%, p = 0.001).Cell proliferation decreased throughout the follow-up. In the whole crypt it was 6.7% at entry and 3.8% at the end of treatment (p < 0.005), whereas it was 6.8% at entry and 2.9% at the end of treatment in the upper third of the crypt (p < 0.005).ConclusionsWe found mesalazine effective in reducing the colonic cell proliferation in long-term treatment for colonic diverticular disease.     

Right-sided diverticulosis is an independent risk factor for bleeding in patients admitted for diverticular disease

BackgroundDiverticular bleeding is the main cause of lower gastrointestinal bleeding in both Eastern and Western countries. Several risk factors have been identified, such as comorbidities and concomitant medications. In Eastern population, the prevalence of right-side diverticulosis is higher than in Western one, and some Authors identified bilateral diverticulosis as a risk factor for bleeding.AimsTo identify risk factors for diverticular bleeding in patients admitted for diverticular disease (DD).MethodsAll patients admitted for DD from January 2017 to December 2018 were retrieved from the hospital Information System. For each patient, age, gender, clinical presentation and concomitant medication were recorded. All patient underwent imaging assessment (computed tomography, ultrasound or MRI) and colonoscopy during hospitalization or within one month.ResultsAmong 1248 patients discharged with a diagnosis of DD during the study period, 293 (52.2% male, median age 75 years) were finally analyzed; of them, 105 (35.8%) for diverticular bleeding. On multivariate analysis, male gender (OR 4.27), age (OR 1.12), anti-thrombotic medications (OR 2.60) and right-sided DD (OR 5.70) were independently correlated to diverticular bleeding.ConclusionOur study provides evidence that, together with age, male gender and concomitant anti-thrombotic treatment, right-sided DD represents an independent risk factor for bleeding.     

Continuous Versus Cyclic Mesalazine Therapy for Patients Affected by Recurrent Symptomatic Uncomplicated Diverticular Disease of the Colon

Forty consecutive patients affected by recurrent attacks of symptomatic uncomplicated diverticular disease of the colon were evaluated to investigate the effectiveness of 2 different mesalazine therapeutic schedules in preventing recurrence of the disease. The patients were randomly enrolled and treated with mesalazine 1.6 g/d (group A) or mesalazine 1.6 g/d 10 days per month (group B). Thirty-four patients completed the study (85%): 3 (7.5%, 1 in group A and 2 in group B) were lost to follow-up, 2 (5%, both group B) were withdrawn from the study for protocol violation, and 1 (2.5%) for hospital admission for stroke (group A). Twenty-three patients (67.65%) were symptom free after 24 months of treatment (overall symptomatic score, 0): 14 of 18 in group A (per-protocol, 77.78%; intention to treat, 70% [95% confidence interval [CI], 61.5–91.8]), 9 of 16 in group B (per protocol, 56.25%; intention to treat, 45% [95% CI, 61.5–91.8]; P < 0.05). Four patients (10%) improved, but were not completely symptom free. Six patients (15%) showed recurrence of symptoms: 1 in group A (5.56%) and 5 in group B (31.25%; P < 0.005; overall symptomatic score, 68). Daily mesalazine supplying seems to be more effective than cyclic supplying in maintaining remission in recurrent symptomatic uncomplicated diverticular disease.     

Mesalazine and/or Lactobacillus casei in maintaining long-term remission of symptomatic uncomplicated diverticular disease of the colon

BACKGROUND/AIMS: Four different therapeutic schedules with mesalazine and/or probiotics were assessed in preventing recurrence of symptomatic diverticular disease (DD) of the colon. METHODOLOGY: A prospective, dose-finding study was conducted on 75 patients, enrolled in an open fashion: mesalazine 800mg/daily (group M1) or mesalazine 1.6gr 10 days/month (group M2); mesalazine 800mg/daily + Lactobacillus casei DG 16 billion/day for 10 day/month (group LM1) or mesalazine 1.6gr + Lactobacillus casei DG 16 billion/day for 10 day/month (group LM2); Lactobacillus casei DG 16 billion/day for 10 day/month (group L). RESULTS: Seventy one patients completed the study (94.66%). Sixty six patients (88%) were symptom-free after the 24th month of treatment: 11 of group M1 (on i-t-t: 84% [CI 95%: 55.5-98.8]), 8 of group M2 (on i-t-t: 80% [CI 95%: 44.39-97.48]), 15 of group LM1 (on i-t-t: 93.75% [CI 95%: 69.77-99.84]), 12 of group LM2 (on i-t-t: 92.30% [CI 95%: 63.97-99.81]), 20 in group L (on i-t-t: 86.95% [CI 95%: 66.41-97.22]) (p-ns). Four patients (5.33%) suspended the treatment during the follow-up: all experienced recurrence of symptoms (100%), and 2 of them developed diverticulitis (50%). CONCLUSIONS: Mesalazine and/or Lactobacillus casei seem to be effective in maintaining remission of DD for long-time. Moreover, we found recurrence of the disease and complications in all patients suspending treatments.     

Prevention of Complications and Symptomatic Recurrences in Diverticular Disease with Mesalazine: A 12-Month Follow-up

In uncomplicated diverticular disease, treatment is aimed at relieving symptoms. The aim of the present study was to evaluate the efficacy of mesalazine for symptomatic relief of uncomplicated diverticular disease of the colon. Two hundred sixty-eight consecutive eligible outpatients (122 male, 146 female; age, 66.1 years; range, 31–81 years) were enrolled in four treatment schedules in a randomized fashion: Group R1 (66 patients), rifaximin, 200 mg bid; Group R2 (69 patients), rifaximin, 400 mg bid; Group M1 (67 patients), mesalazine, 400 mg bid; and Group M2 (66 patients), mesalazine, 800 mg bid. Treatments were administered for 10 days every month for 12 months. Clinical evaluations were performed at admission and at 3-month intervals for 12 months considering 12 clinical variables (upper and lower abdominal pain/discomfort, tenesmus, diarrhea, abdominal tenderness, fever, bloating, general illness, nausea, emesis, dysuria, bleeding) graded as 0 = no symptoms, 1 = mild, 2 = moderate, and 3 = severe. The Global Symptomatic Score (GSS) was calculated using the sum of each symptom score. Two hundred forty-four patients completed the 12- month study; 24 were discontinued (14 treated with rifaximin and 10 treated with mesalazine) either as voluntary dropouts or because they developed side effects and/or complications. Group M2 demonstrated a lower frequency of many symptoms after 6 and 12 months of treatment; the mean GSS was significantly lower in Group M2 after 6 and 12 months of therapy by both intention-to-treat and per-protocol analyses. Patients treated with mesalazine (Groups M1+M2) had a lower GSS than subjects treated with rifaximin (Groups R1+R2) during the 12-month follow-up period. We conclude that cyclic administration of mesalazine is effective for symptomatic relief of uncomplicated diverticular disease of the colon. Some symptoms showed greater improvement with mesalazine, 800 mg bid, than with the other treatment schedules.     

Oxidative imbalance and muscular alterations in diverticular disease

BackgroundIt is still a matter of debate if neuromuscular alterations reflect a primary event in diverticular disease (DD).AimsThis study aimed to assess colonic wall layers from both stenotic and non-stenotic complicated DD, bio-phenotypic alterations, inflammatory and oxidative status.MethodsA systematic analysis of colonic specimens obtained from stenotic and non-stenotic DD specimens was conducted and compared with controls. Biological activity and qPCR analysis were performed on longitudinal and circular muscles. Western blot analysis was performed throughout colonic wall layers to quantify oxidative and inflammatory markers.ResultsA homogenous increase in oxidative stress was observed through all the layers, which were more sharpened in the longitudinal muscle for a loss in antioxidant defenses. In both stenotic and non-stenotic colon, the longitudinal muscle presented an impaired relaxation and a cellular phenotypic switch driven by transforming growth factor-β with an increase in mRNA expression of collagen Iα and a decrease in myosin heavy chain. The circular muscle, as the mucosa, was less affected by molecular alterations. No peculiar increase in inflammatory markers was observed.ConclusionA longitudinal colonic myopathy is present in DD, independently from the disease stage associated with an oxidative imbalance that could suggest new therapeutic strategies.     

Distinguishing features between patients with acute diverticulitis and diverticular bleeding: Results from the REMAD registry

BackgroundPathogenesis of acute diverticulitis and diverticular bleeding remains poorly defined, and few data compare directly risk factors for these complications.Aimsto assess differences in clinical features, lifestyles factors and concurrent drug use in patients with acute diverticulitis and those with diverticular bleeding.MethodsData were obtained from the REMAD Registry, an ongoing 5-year prospective, observational, multicenter, cohort study conducted on 1,217 patients. Patient- and clinical- related factors were compared among patients with uncomplicated diverticular disease, patients with previous acute diverticulitis, and patients with previous diverticular bleeding.ResultsAge was significantly lower (OR 0.48, 95% CI: 0.34–0.67) and family history of diverticular disease was significantly higher (OR 1.60, 95% CI: 1.11–2.31) in patients with previous diverticulitis than in patients with uncomplicated diverticular disease, respectively. Chronic obstructive pulmonary disease was significantly higher in patients with previous diverticular bleeding as compared with both uncomplicated diverticular disease (OR 8.37, 95% CI: 2.60–27.0) and diverticulitis (OR 4.23, 95% CI: 1.11–16.1).ConclusionThis ancillary study from a nationwide Registry showed that some distinctive features identify patients with acute diverticulitis and diverticular bleeding. These information might improve the assessment of risk factors for diverticular complications.     

Efficacy of Mesalazine in the Treatment of Symptomatic Diverticular Disease

We aimed to improve symptoms by means of mesalazine in symptomatic colonic diverticular disease patients. One hundred seventy outpatients (98 M, 72 F; age, 67.1 years; range, 39–84 years) were assigned to four different schedules: rifaximin, 200 mg bid (Group R1: 39 pts), rifaximin, 400 mg bid (Group R2: 43 pts), mesalazine, 400 mg bid (Group M1: 40 pts), and mesalazine, 800 mg bid (Group M2: 48 pts), for 10 days per month. At baseline and after 3 months we recorded 11 clinical variables (upper/lower abdominal pain/discomfort, bloating, tenesmus, diarrhea, abdominal tenderness, fever, general illness, nausea, emesis, dysuria), scored from 0 = no symptoms to 3 = severe. The global symptomatic score was the sum of all symptom scores. After 3 months in all schedules but Group R1, 3 of the 11 symptoms improved (P < 0.03); the global score decreased in all groups but Group R1 (P < 0.0001). Mesalazine-treated patients had the lowest global score at 3 months (P < 0.001). Mesalazine is as effective as rifaximin (higher dosage schedule) for diminishing some symptoms, but it appears to be better than rifaximin for improving the global score in those patients.This work was carried out under the auspices of the Roberto Farini Foundation for Gastroenterological Research.     

Adherence,risk factors of non-adherence and patient’s preferred treatment strategy of mesalazine in ulcerative colitis: multicentric observational study

Objectives: Compliance to therapy is a key factor in the efficacy of treatment in clinical practice. The aim of our study was to evaluate the rate of compliance with mesalazine in patients with ulcerative colitis (UC), to examine risk factors of noncompliance and especially find ways on how adherence can be improved.

Materials and methods: A total of 198 outpatients with UC completed two anonymous questionnaires including information on basic demographics, details of patient´s disease and the use of mesalazine medication and quality of life.

Results: We found noncompliance (percentage of used medication per day less than 80%) with 5-ASA in 21.2% patients. Our study proved that the education level of patients significantly influenced the compliance of patients using mesalazine. A significant difference (p?=?.014) was found between the compliance of patients with secondary school education (84.1?±?16.73) and those with university education (94.1?±?9.9). The majority of patients preferred mesalazine once daily and are less likely to forget to take medication in the morning. Better quality of life was observed based on our data from WHOQOL-BREF questionnaire in statistically significant way in patients using concomitant therapy of immuosuppressive or biological therapy, lower daily doses and using sachets not tablets.

Conclusions: Our study proved that compliance with mesalazine in patients with UC was related only to education level. If we target mesalazine therapy based on patient’s preferences, we can improve the adherence with mesalazine. Our data could be beneficial for the treatment strategy in clinical practice.     

A critical appraisal of advances in the diagnosis of diverticular disease

Introduction: Diverticulosis of the colon is a common condition, and about one-fourth of those people develop symptoms, which is called ‘diverticular disease’ (DD). Since there are still some concerns about the diagnosis of DD, the aim of this review was to analyze current and evolving advances in its diagnosis.

Area covered: Analysis of clinical, radiology, laboratory, and endoscopic tools to pose a correct diagnosis of DD was performed according to current PubMed literature.

Expert commentary: A combination of clinical characteristic of the abdominal pain and fecal calprotectin expression may help to differentiate between symptomatic uncomplicated diverticular disease and irritable bowel syndrome. Abdominal computerized tomography (CT) scan is still the gold standard in diagnosing acute diverticulitis and its complications. CT-colonography may be useful as a predicting tool on the outcome of the disease. Diverticular Inflammation and Complications Assessment (DICA) endoscopic classification shows a significant relationship between severity of DICA score inflammatory indexes, as well as with severity of abdominal pain. Moreover, it seems to be predictive of the outcome of the disease in terms of acute diverticulitis occurrence/recurrence and surgery occurrence.

Finally, preliminary data found intestinal microbiota analysis is a promising tool in diagnosing and monitoring this disease.     

Usefulness of colonic motility study in identifying patients at risk for complicated diverticular disease

Colonic motility study was performed on a total of 145 patients. Of these, 55 were patients with symptomatic complicated diverticular disease, 30 had symptomatic uncomplicated diverticular disease, 30 had asymptomatic diverticular disease, and 30 were controls. The pressure sensors were positioned in the descending and the true sigmoid colon. Colonic motility index was significantly higher in symptomatic rather than in asymptomatic diverticular disease in the resting (P<0.001) and postprandial (P<0.001) states. This confirmed the association between symptomatic diverticular disease and high intraluminal pressure. The patients of the subgroup—complicated diverticular disease—were relatively young (mean age: 51.1±2.02 years) and had a short history of abdominal pain (18–36 months) and a short segment of colon with diverticula (cm 7.25±1.31). Our observations suggest that patients showing these indicators are at risk for major complication.This study was supported by M.P.I. grants.     

Metformin use in diabetics with diverticular disease is associated with reduced incidence of diverticulitis

Background and aims: There is no current, evidence-based therapy to prevent acute diverticulitis in patients with diverticular disease. Metformin has been shown to have anti-inflammatory effects in a number of disease states, in both animal models and in human observational studies. The potential therapeutic efficacy of metformin in diverticular disease has not been investigated.

This study aims to describe the relationship between metformin use and diverticular disease in patients with diabetes mellitus.

Methods: This was a retrospective case–control study. It compared metformin and other hypoglycaemic medication use in diabetic patients with uncomplicated diverticulosis to those with acute diverticulitis. Patients were identified using hospital International Classification of Diseases 10 (ICD-10) data, and radiology, pathology and scanned medical record databases were used to confirm diagnoses and collect all information. Chi square tests were used to determine significance of difference in categorical variables, and Mann–Whitney tests were used for continuous data.

Results: There were 174 patients with uncomplicated diverticulosis and 175 patients with acute diverticulitis. A diagnosis of acute diverticulitis was associated with a significantly lower incidence of metformin use, than a diagnosis of uncomplicated diverticular disease (44% compared to 60%, respectively, p?=?.002). Other oral hypoglycaemic drugs and insulin were not associated with a lower incidence of diverticulitis (p?=?.12 and p?=?.24, respectively).

Conclusion: Metformin use is associated with reduced incidence of diverticulitis in diabetic patients with diverticular disease. The utility of metformin as a therapeutic agent to reduce the risk of diverticulitis in patients with diverticular disease warrants further randomised, prospective, interventional investigation.     

Use of mesalazine in diverticular disease

Diverticular disease includes a spectrum of conditions sharing the underlying pathology of acquired diverticula of the colon: symptomatic uncomplicated diverticular disease, recurrent symptomatic uncomplicated diverticular disease, and complicated diverticular disease. Goals of therapy in diverticular disease should be to improve symptoms and to prevent recurrent attacks in symptomatic uncomplicated diverticular disease, and to prevent the complications of disease such as diverticulitis. Inflammation seems to play a key role in all forms of the disease. This is the rationale for the use of anti-inflammatory drugs such as mesalazine. Inflammation in such diseases seems to be generated by a heightened production of proinflammatory cytokines, reduced anti-inflammatory cytokines, and enhanced intramucosal synthesis of nitric oxide. The mechanisms of action of mesalazine are not yet well understood. It is an anti-inflammatory drug that inhibits factors of the inflammatory cascade (such as cyclooxygenase) and free radicals, and has an intrinsic antioxidant effect. Some recent studies confirm the efficacy of mesalazine in diverticular disease both in relief of symptoms in symptomatic uncomplicated forms and in prevention of recurrence of symptoms and main complications.     

The outcomes of Clostridioides difficile infection in patients with diverticular disease: a nationwide analysis

Abstract

Background: Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections. It contributes to significant morbidity and mortality among hospitalized patients in the United States. Prior studies suggest worse outcomes of CDI in patients with diverticulitis and increased risk for recurrent CDI. We conducted this study to evaluate the outcomes of CDI in patients with diverticular disease from a nationwide data sample (2012–2015).

Methods: The National Inpatient Sample (NIS) database between January 2012 and September 2015 was queried for CDI admissions using the International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] codes 008.45, 562.11, 562.10, 562.12, and 562.13 for diagnoses of CDI and diverticular disease.

Results: The study included 1,327,595 patients who were admitted between 2012 and 2105 for CDI. Out of all of the patients, 84,170 (6.34%) had a concurrent diagnosis of diverticular disease. After adjusting for confounding variables, the in-hospital mortality was lower [odd ratio (OR): 0.48, 95% CI: 0.44–0.52, p?<?.001] for patients with diverticular disease. The length of stay (LOS) was longer [10.5 versus 9.3?days, p?<?.001] and mean cost of hospitalization was significantly higher in patients without a history of diverticular disease.

Discussion: In a nationwide population study, admissions with CDI, patients with a concurrent diagnosis of diverticular disease had lower in-hospital mortality. The observed results are different from prior studies and might be attributed to a higher burden of normal flora in those patients and increased use of antibiotic stewardship program across many hospitals nationwide.     

Regional variation in hospitalizations and outpatient appointments for diverticular disease in Norway: a nationwide cross-sectional study

Abstract

Objective: To investigate the use of specialized health care services for diverticular disease in different hospital referral regions in Norway.

Materials and methods: Nationwide cross-sectional study with data from the Norwegian Patient Registry and Statistics Norway. All Norwegian inhabitants aged 40 years and older in the years 2012–16 (2,517,938) were included. We obtained the rates (n/100,000 population) for hospitalizations, outpatient appointments, and surgery for diverticular disease for the population in each hospital referral region. We also quantified the use of lower gastrointestinal (LGI) endoscopy in hospitalizations and outpatient appointments for diverticular disease and the use of LGI endoscopy performed on any indication.

Results: There were 131 hospitalizations and 381 outpatient appointments for diverticular disease per 100,000 population annually. Hospitalization rates varied 1.9-fold across regions from 94 to 175. Outpatient appointment rates varied 2.5-fold across regions from 258 to 655. Outpatient appointments were strongly correlated to hospitalizations (r_s=0.75, p?r_s=0.67, p?Conclusion: There was considerable regional variation in both hospitalizations and outpatient appointments for diverticular disease. The extent of variation and the correlation with diagnostic intensity of LGI endoscopy indicate that the regional variation in health care utilization for diverticular disease to a large extent can be explained by regional differences in clinical practice rather than disease burden.     

Experiencia de la vida real con el uso de mesalazina MMX en pacientes mexicanos con CUCI en dos centros de tercer nivel

Introduction and aimsThe 5-aminosalicylates, especially mesalazine, are the first option in the treatment of mild-to-moderate ulcerative colitis (UC). High rates of remission induction and maintenance have been observed with the new multimatrix (MMX) mesalazine formulation, mainly in patients with distal disease. Our aim was to describe the real-world experience with MMX mesalazine in patients with UC at two tertiary care centers.Materials and methodsA retrospective cohort study was conducted that included 142 patients with confirmed UC diagnosis, analyzed in three study groups: 1) oral MMX mesalazine as monotherapy for remission induction, 2) oral MMX mesalazine as monotherapy for remission maintenance, and 3) oral MMX mesalazine plus topical therapy for remission induction.ResultsThe frequency of clinical remission induction in group 1 was 80.3%, with biochemical remission of 74.2%. Group 2 had 100% clinical and biochemical remission maintenance. The frequency of clinical remission induction in group 3 was 88.6%, biochemical remission was 85.7%, and topical therapy was suspended in 87.3% at the end of follow-up. No adverse events were documented.ConclusionsThere were high percentages of clinical and biochemical remission in the two corresponding study groups and topical therapy was suspended in the majority of patients in a short follow-up period.     

Intermittent therapy with high-dose 5-aminosalicylic acid enemas maintains remission in ulcerative proctitis and proctosigmoiditis

PURPOSE: The aim of this study was to compare the efficacy of intermittent therapy with mesalazine enemas and continuous oral mesalazine to maintain remission of distal ulcerative colitis or proctitis. METHODS: Thirt-yeight patients with distal ulcerative colitis (n=17) or ulcerative proctitis (n=21) in clinical, endoscopic, and histologic remission were randomly assigned to receive either oral mesalazine (0.5 g three times/day, Eudragit L coating, n=19) or intermittent therapy with mesalazine enemas (4 g of 5-aminosalicylic acid enema every third night, n=19). Both groups were comparable in regard to sex, age, age at disease onset, extent and duration of disease, number and mode of treatment of previous attacks, and time in remission. Patients were reviewed at the beginning of the study and, subsequently, at two-month intervals for 24 months or until a relapse occurred. At each visit, diaries were reviewed and clinical and laboratory assessments were performed. Sigmoidoscopy was carried out and biopsies were obtained by a blinded observer. Histology was assessed without knowledge of the patient's clinical state or treatment category. RESULTS: At the end of the study, 6 of 19 patients on oral mesalazine (32 percent) and 14 of 19 patients on mesalazine enemas (74 percent) were still in full remission (log rank test: 15.280,P <0.001). Differences in relapse rates between groups were significant even when data were stratified by extent of disease (P <0.01). In the oral group, six and seven patients relapsed at 12 and 24 months, respectively. In the enema group, three and two relapses occurred in the first and second year of the study, respectively. All patients complied with the treatment satisfactorily and there were no dropouts. CONCLUSION: These results suggest that intermittent therapy with mesalazine enemas is more effective than continuous oral mesalazine in maintaining remission in patients with distal ulcerative colitis and proctitis.Read at the meeting of the First United European Gastroenterology Week, Athens, Greece, September 25 to 30, 1992.     

Genetically Predicted Adiposity,Diabetes, and Lifestyle Factors in Relation to Diverticular Disease

Background & AimsAdiposity, type 2 diabetes, alcohol and coffee consumption, and smoking have been examined in relation to diverticular disease in observational studies. We conducted a Mendelian randomization study to assess the causality of these associations.MethodsIndependent genetic instruments associated with the studied exposures at genome-wide significance were obtained from published genome-wide association studies. Summary-level data for the exposure-associated single nucleotide polymorphisms with diverticular disease were available in the FinnGen consortium (10,978 cases and 149,001 noncases) and the UK Biobank study (12,662 cases and 348,532 noncases).ResultsHigher genetically predicted body mass index and genetic liability to type 2 diabetes and smoking initiation were associated with an increased risk of diverticular disease in meta-analyses of results from the two studies. The combined odds ratio of diverticular disease was 1.23 (95% confidence interval [CI], 1.14–1.33; P < .001) for a 1-standard deviation (~4.8 kg/m²) increase in body mass index, 1.04 (95% CI, 1.01–1.07; P = .007) for a 1-unit increase in log-transformed odds ratio of type 2 diabetes, and 1.21 (95% CI, 1.12–1.30; P < .001) for a 1-standard deviation increase in prevalence of smoking initiation. Coffee consumption was not associated with diverticular disease, whereas the association for alcohol consumption largely differed between the 2 studies.ConclusionsThis study strengthens the causal associations of higher body mass index, type 2 diabetes, and smoking with an increased risk of diverticular disease. Coffee consumption is not associated with diverticular disease. Whether alcohol consumption affects the risk of diverticular disease needs further investigation.     

An economic evaluation comparing concomitant oral and topical mesalazine versus oral mesalazine alone in mild-to-moderately active ulcerative colitis based on results from randomised controlled trial

IntroductionA previous randomised controlled trial has demonstrated that oral plus topical mesalazine enema is more effective than oral mesalazine alone for achieving clinical remission in mild-to-moderately active extensive ulcerative colitis (UC). To evaluate whether this strategy is cost-effective we conducted an economic evaluation comparing 1 g topical mesalazine in combination with 4 g oral mesalazine compared to 4 g mesalazine monotherapy in mild-to-moderately active UC.MethodsThe economic evaluation was based on the ability to achieve remission using changes from baseline in the ulcerative colitis disease activity instrument (UCDAI). A cost-utility analysis was used where the main outcome was quality-adjusted life years to reflect improved quality of life associated with achieving remission compared with active disease. A simulated Markov model with five health states was constructed to model cost and outcome changes over time: (1) active UC; (2) mesalazine-refractory active UC; (3) steroid-refractory active UC; (4) infliximab-responsive active UC; and (5) remission. To reflect parameter uncertainty in the cost-effectiveness analysis probabilistic sensitivity analysis (PSA) was conducted by varying relevant clinical parameters.ResultsAverage treatment costs required to transition a patient from active UC to remission using oral and topical mesalazine compared with oral alone were £1812 and £2390, respectively. Improved remission rates attributed to oral and topical mesalazine resulted in moderate improvements in quality-adjusted life years (QALYs) compared to oral mesalazine alone. Disaggregation of medical costs indicated that medical consultations and diagnostic costs were similar for both treatment arms. An abbreviated analysis which considered costs up to steroid-refractory patients in subacute UC indicated that combination therapy offered a cost-savings of £285 over 16 weeks of therapy compared with monotherapy.ConclusionsThe results indicate that the addition of 1 g topical mesalazine results in significant cost-savings and moderate quality of life improvements. We have also shown that irrespective of which treatment modality is used in steroid-refractory patients (eg, infliximab, azathioprine, ciclosporine) that topical mesalazine is cost-saving.