Risk of gastrointestinal complications associated to NSAIDs, low-dose aspirin and their combinations: Results of a pharmacovigilance reporting system.

Gastrointestinal (GI) complications are one of the most limiting cause of use of NSAIDs. Beyond others well defined factors, history of peptic ulcer, older age, Helicobacter pylori infection and use of gastrotoxic drugs may affect their GI safety profile. In particular, the risk of GI complications associated to the use of antiplatelet drugs, especially low-dose acetylsalicylic acid (LDA) should deserve much attention. However, only few studies have focused on the effect of combination LDA/NSAIDs on the GI tract compared with the monotherapy and much less studies assessed this effect with multiple NSAIDs use. We aimed to characterize the GI safety profile of NSAIDs and LDA as monotherapy or their combinations in real-life conditions by analysing spontaneous adverse drug reactions (ADRs) reporting system in a Southern Italy. We used the case/non-case method in the Italian Pharmacovigilance Network (RNF). Cases were reports of GI events in the RNF between January 2007 and December 2011. Non-cases were all other reports during the same period. The association between NSAID and suspected GI ADRs was calculated using the reporting odds ratio (ROR) with 95% confidence intervals as a measure of disproportionality while adjusting for age, and concomitant use of antineoplastic agents or drugs for cardiovascular diseases. Sub-analysis were performed within the NSAID class. Among the 2816 adverse drug reactions recorded, we identified 374 (13.3%) cases of GI complications. Upper GI complications were the most frequently reported type of events. The highest associations were found for the combined use of NSAIDs and/or LDA, whilst the lowest associations were for their respective monotherapy. Looking at individual NSAIDs the highest association with GI events was observed for ketorolac exposure followed by nimesulide, diclofenac, aspirin, ketoprofen, and ibuprofen. This study highlights the primary role of the national spontaneous reporting system to bring out potential signals, such as the inappropriate drug use pattern, which however, have to be furtherly studied in-depth with ad hoc population-based studies.

Oral prolonged release beclomethasone dipropionate and prednisone in the treatment of active ulcerative colitis: results from a double-blind, randomized, parallel group study.

OBJECTIVES: Double-blind study comparing efficacy and safety of the topically acting corticosteroid beclomethasone dipropionate (BDP) to prednisone (PD) in patients with active, mild-to-moderate ulcerative colitis (UC). METHODS: Overall, 282 patients were randomized to receive BDP-prolonged release tablets 5 mg once daily for 4 weeks and then every other day for an additional 4 weeks or oral PD 40 mg once daily for the initial 2 weeks tapered of 10 mg every 2 weeks during the 8-week study period. Efficacy end point was the non-inferiority of BDP vs. PD in terms of Disease Activity Index (DAI) score <3 or reduction by at least 3 points for patients with a baseline DAI ≥7 at week 4. Safety end point was the proportion of patients with steroid-related adverse events (AEs) and cortisol <150 nmol/l at week 4. RESULTS: DAI response rates at week 4 were 64.6% and 66.2% with BDP and PD, respectively, demonstrating non-inferiority of BDP vs. PD (delta: -1.56; 95% confidence interval (CI) -13.00-9.88, P=0.78). Patients with steroid-related AEs and cortisol <150 nmol/l at week 4 were 38.7% in the BDP group and 46.9% in the PD group (P=0.17 between groups). No safety signals were observed in both the groups. CONCLUSIONS: BDP was non-inferior to PD in the treatment of active UC, with a good safety profile in both the groups.

Hypoxic hepatitis occurring in cirrhosis after variceal bleeding: still a lethal disease.

BACKGROUND: Hypoxic hepatitis (HH) occurring after gastrointestinal bleeding in cirrhotic patients has been scarcely studied and is reported as a rare occurrence carrying a severe prognosis. The management of bleeding from esophageal varices (BEV) and similarly the prognosis has improved in the last decades. GOALS: To evaluate retrospectively the incidence, clinical features, risk factors, and outcome of HH occurring in cirrhotic patients with BEV treated with the current standard therapy. Cirrhotics with BEV consecutively admitted from 2004 to 2008 were considered. Standard therapy consisted of intensive care support, somatostatin, antibiotics, and band ligation. HH was diagnosed if an elevation of alanine aminotransferase >10-fold from basal occurred. RESULTS: Among 349 patients admitted for BEV, 24 (6.8%) had HH. Most patients were over 60 years old and had advanced liver disease; 41.7% had hepatocellular carcinoma, and 29.2% had portal vein thrombosis (PVT). Hypovolemic shock occurred in 16 (66.7%) patients, and failure to control initial bleeding in 12 (50%) patients. The 6-week mortality rate was 83.3% in HH compared with 24.6% in non-HH patients. Causes of death were massive bleeding in 4, hepatic encephalopathy in 7, and renal failure in 9. Binary logistic regression analysis showed that failure to control initial bleeding, diabetes, and PVT were factors independently associated with the development of HH. CONCLUSIONS: HH occurring in cirrhosis with gastrointestinal bleeding still carries an ominous prognosis. The severity of hemorrhage as expressed by failure to control bleeding contributes heavily to HH; in addition, the presence of PVT and diabetes further compromising the hepatic circulatory reserve may favor hypoxic damage.

Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis.

BACKGROUND: Treatment of portal vein thrombosis (PVT) in patients with liver cirrhosis is not well established. AIM: We intended to assess the safety and efficacy of low molecular weight heparin (LMWH) to treat PVT in cirrhotic patients. STUDY: All 39 patients diagnosed with non-neoplastic PVT and cirrhosis from June 2005 to December 2006 were evaluated for anticoagulation therapy (AT). PVT was occludent in 15.4%, partial in 64.1%, and portal cavernoma presented in 20.5%. Twenty-eight patients received 200 U/kg/d of enoxaparin for at least 6 months. In 39.3% of patients PVT was an occasional finding, in 10.7% presented with acute abdominal pain, in 50% with bleeding from gastroesophageal varices. In this last group LMWH was started after endoscopic eradication of varices by band ligation. RESULTS: Complete recanalization of portal vein occurred in 33.3%, partial recanalization in 50% and no response in 16.7% of patients. Further 12 patients who continued AT obtained complete recanalization at a median time of 11 months (range 7 to 17 mo). Overall, a complete response was obtained in 75% of patients. No significant side effects, particularly bleeding complications, were observed during the treatment. CONCLUSIONS: LMWH demonstrated safe and effective in the treatment of PVT in patients with liver cirrhosis.

Hospital admission for digestive diseases: Gastroenterology units offer a more effective and efficient care.

BACKGROUND: Digestive diseases imply a substantial burden for health care systems. Effectiveness of specialized gastroenterology care has been demonstrated in a few real life surveys. AIMS: To perform an in-depth analysis of Hospital Discharge Records (HDRs) of patients admitted for digestive diseases (DDs) from all Italian regions over the years 2010-2014. METHODS: Data on National HDRs were provided by the Italian Health Ministry. RESULTS: During the years 2010-2014, a mean of 949,830 patients with DDs were admitted to hospital per year, representing 10.0% of all admissions in Italy. Only 7.4% of patients with DDs were admitted to Gastroenterology units due to the limited number of the specialty-focused beds (3.4/100,000 inhabitants). DDs urgent admissions in Gastroenterology units represented 33% of admissions. The mean length of stay was 8.1 days in Gastroenterology units, as opposed to 8.3 in other units. Mortality rate for DDs altogether, for urgent admissions, and for urgent admissions with bleeding were 2.2%, 1.7%, 2.2% in Gastroenterology units, and 3.1%, 3.9%, 3.5% in other units, respectively. DDs admissions were appropriate in 81.3% in Gastroenterology units as opposed to 66.6% in all other units. CONCLUSIONS: Gastroenterology units offer a better specific care in terms of length of hospital stay and mortality even for patients admitted for emergent conditions.

In-hospital mortality in non-variceal upper gastrointestinal bleeding Forrest 1 patients.

OBJECTIVE: Non-variceal upper gastrointestinal bleeding (NVUGIB) is recognized world-wide as a common cause of emergency hospitalization, and it often represents a life-threatening event. The purpose of this prospective study was to assess in-hospital mortality in NVUGIB Forrest 1 patients admitted to the emergency unit owing to active bleeding. MATERIAL AND METHODS: We enrolled all patients consecutively admitted to the emergency unit for NVUGIB, acutely bleeding at endoscopy (spurting or oozing). Demographic characteristics, clinical and biochemical parameters, endoscopic findings and treatments were evaluated. RESULTS: Of a total of 142 patients (98 M (69%), mean age+/-SD=66+/-14 years), spurting (16 (11.3%)) and oozing (126 (88.7%)) were identified. All patients received endoscopic treatment within 6 h of admission and were managed according to the guidelines. Seventeen (12%) patients suffered rebleeding, 4 patients (2.8%) required surgery to stop the bleeding, and 8 (5.6%) died during hospitalization (4 within 5 days and the remainder within 24 days of admission) - 3 as a consequence of bleeding (2.1%) and 5 of non-surgical complications (3.5%). Cox regression analysis showed that the lesions in more than one segment of the esophagogastroduodenal tract (p=0.008, hazard ratio (95% CI)=7.623 (1.680-34.600)) and the number of blood units transfused during the first 48 h of hospitalization (p=0.038, 2.075 (1.041-4.135)) were predictive of in-hospital death. CONCLUSIONS: In Forrest 1 patients given rapid endoscopic treatment, in-hospital mortality seems to be related to the contemporaneous presence of bleeding and non-bleeding lesions in more than one segment of the esophagogastroduodenal tract and the number of blood units transfused during the first 48 h of hospitalization.

Surgical treatment of non-variceal upper gastrointestinal bleeding: our experience with 1482 patients.

We retrospectively evaluated the medical records of patients admitted to the U.O.C. of General and Emergency Surgery with Surgical and Polyspecialistic Observation of the Emergency Unit of A.O.R.N. A. Cardarelli of Naples for non-variceal upper gastrointestinal bleeding from 2003 to 2006. All data regarding patients submitted to surgery for non-variceal upper gastrointestinal bleeding were collected including the number of patients submitted to surgery after failure of the endoscopic procedure, the diseases most frequently requiring surgery, the endoscopic and surgical procedures most frequently used, and the reasons that prompted the surgical procedure. Of 1482 patients admitted for non-variceal upper gastrointestinal bleeding the lesions that most frequently required surgery were peptic ulcer disease complicated by bleeding in 31 patients (70.5%) and cancer in 13 (29.5%). The most frequent surgical procedure was subtotal gastrectomy (17 patients [38.6%]), followed by direct haemostasis of the ulcer (13 patients [29.5%]), total gastrectomy (11 patients [25%]), and ulcer excision (3 patients [6.9%]). Subtotal or total gastrectomy is the surgical procedure of choice in patients with non-variceal upper gastrointestinal bleeding after failure of endoscopic treatment. The indication for gastrectomy should be determined on the basis of the patient's haemodynamic condition.

Contrast-free endoscopic stent insertion in malignant biliary obstruction.

AIM: To present a case series of MRCP-guided endoscopic biliary stent placement, performed entirely without contrast injection. METHODS: Contrast-free endoscopic biliary drainage was attempted in 20 patients with malignant obstruction, unsuitable for resection on the basis of tumor extent or medical illness. MRCP images were used to confirm the diagnosis of tumor, to exclude other biliary diseases and to demonstrate the stenoses as well as dilation of proximal liver segments. The procedure was carried out under conscious sedation. Patients were placed in the left lateral decubitus position. The endoscope was inserted, the papilla identified and cannulated by a papillotome. A guide wire was inserted and guided deeply into the biliary tree, above the stenosis, by fluoroscopy. A papillotomy approximately 1 cm. long was performed and the papillotome was exchanged with a guiding-catheter. A 10 Fr, Amsterdam-type plastic stent, 7 to 15 cm long, was finally inserted over the guide wire/guiding catheter by a pusher tube system. RESULTS: Successful stent insertion was achieved in all patients. There were no major complications. Successful drainage, with substantial reduction in bilirubin levels, was achieved in all patients. CONCLUSION: This new method of contrast-free endoscopic stenting in malignant biliary obstruction is a safe and effective method of palliation. However, a larger, randomized study comparing this new approach with the standard procedure is needed to confirm the findings of the present study.

The corner of the gastroenterologist: what colonoscopy can do, what to ask to radiologist.

Colonoscopy is the diagnostic technique of choice for most colonic diseases and allows to explore the entire colonic mucosal surface and to visualize the mucosa of terminal ileum. When it is done with appropriate indications, significantly more clinically relevant diagnoses are made. Moreover, colonoscopy keeps an operative role in the treatment of some acute and chronic colonic diseases and it is the most effective colorectal cancer screening modality. The endoscopic exploration of colon is not infallible and presents rare complications. Programs of endoscopic training and practice, monitoring of quality indicators and continuous technological development are improving endoscopic diagnostic and therapeutic role. Appropriate indications for colonoscopy, its limits and complications and questions for the radiologist are discussed.

Increased plasma prothrombin concentration in cirrhotic patients with portal vein thrombosis and prothrombin G20210A mutation.

It was the aim of the present study to investigate factor II levels in liver cirrhosis (LC) patients with portal vein thrombosis (PVT) carrying the heterozygous G20210A prothrombin (PT) mutation. Plasma concentrations of factor II, VII, X, V, protein C (PC) total protein S (tPS) antithrombin (AT) and D-dimers (DD) were measured in 13 LC patients with PVT heterozygous for PT G20210A, in 13 LC patients with PVT without PT G20210A and in 13 LC controls matched by age, sex and Child-Pugh score. Crude factor II and factor II/DD ratio were highest in LC patients with PVT heterozygous for PT G20210A (p = 0.03 and p = 0.02 respectively). The factor II/PC ratio, expression of a procoagulant/anticoagulant imbalance was highest in the same group (p = 0.0008). Plasma factor II levels are elevated in LC patients heterozygous for PT G20210A and may favour PVT.

Acute portal and mesenteric thrombosis: unusual presentation of cytomegalovirus infection.

Cytomegalovirus infection is a benign disease in immunocompetent patients. In-vitro and in-vivo studies show that cytomegalovirus may cause arterial and venous thrombosis through different mechanisms. We describe two cases of acute cytomegalovirus infection complicated by portal and mesenteric vein thrombosis leading to intestinal ischemia. Both patients carried the heterozygous prothrombin G20210A mutation. The presence of this unusual complication should be searched for in patients with acute cytomegalovirus infection and abdominal symptoms in order to start early anticoagulation. The necessity for full thrombophilic screening is also pointed out.

Hepatic vein thrombosis leading to fulminant hepatic failure in a case of acute non-promyelocytic myelogenous leukemia.

Budd-Chiari syndrome is a rare disease due to occlusion of the hepatic veins often presenting with acute liver failure. Common causes of Budd-Chiari syndrome are chronic myeloproliferative disorders, while acute leukemia has been associated with hepatic vein thrombosis in only two cases in the literature to date. We report a case of Budd-Chiari syndrome complicating a non-promyelocytic acute myelogenous leukemia leading to fulminant hepatic failure.

Tinidazole: from protozoa to Helicobacter pylori--the past, present and future of a nitroimidazole with peculiarities.

Tinidazole (Fasigyn, Pfizer Ltd), like metronidazole - to which it is structurally related - was initially introduced for treating protozoal infections. However, both of these nitroimidazole compounds are active against most clinically important obligate anaerobes. In the last few years, the discovery of Heliobacter pylori and of its susceptibility to nitroimidazoles focused new attention on these drugs. Tinidazole, as a part of this class of drugs, shares the characteristics and indications of other nitroimidazoles. However, it has a number of desirable features that could potentially make it very successful: a better pharmacokinetic and pharmacodynamic profile, a better safety and tolerability spectrum, and a preserved activity against some bacteria that are resistant to metronidazole.

Hospital care services for digestive diseases in Italy: the first quantitative assessment.

The scarcity of human and structural resources for specialized gastroenterology care is a problem in many Western countries. Data regarding the resources for Italian Gastroenterology, so far lacking, have been thus searched and evaluated. Based on an agreement protocol between the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO) and the Ministry of Health, national data regarding all Institutions providing gastroenterological care were analysed. Hospital beds in Gastroenterology units are presented by region, regimen of stay and per million inhabitants as of January 2011. Association of Hospital Gastroenterologists and Endoscopists also performed a survey of gastroenterology units in all Italian regions regarding number of ordinary/day hospital beds and the number of staff gastroenterologists. The Ministry data showed a total of 174 Gastronterology Units in Italy, a total of 2062 hospital beds for the discipline, for a proportion of 34.2 beds per million inhabitants. The Association of Hospital Gastroenterologists and Endoscopists survey showed a total of 1425 gastroenterologists in Italy. These data should represent a key reference for appropriate planning of specialized care for digestive diseases.

Antiphospholipid antibodies and antiphospholipid syndrome: role in portal vein thrombosis in patients with and without liver cirrhosis.

UNLABELLED: The antiphospholipid syndrome (APS) has been associated with portal vein thrombosis (PVT). This study explored the contribution of antiphospholipid antibodies (aPL) to PVT in cirrhotic and noncirrhotic patients. PATIENTS AND METHODS: A total of 50 patients with liver cirrhosis and PVT, 50 patients with liver cirrhosis without PVT, 50 consecutive PVT without liver cirrhosis, and 50 controls. aPL tests: lupus anticoagulants (LAs), immunoglobulin G (IgG) anti-cardiolipin antibodies (aCL), IgG anti-beta-2-glycoprotein-I (ß(2)GPI), and IgG ß( 2)GPI-complexed with oxidized low-density lipoprotein antibodies (ox-LDL). RESULTS: Lupus anticoagulants were negative in all patients. A titre of IgG aCL >40 IgG phospholipid units (GPL) was present in 2% of patients with liver cirrhosis and in none of the other groups. In all, 4% of patients with PVT without cirrhosis were positive for IgG ß(2)GPI in the absence of any other positive aPL and labelled as primary APS. CONCLUSIONS: aPL play no role in PVT associated with liver cirrhosis but can be tested in idiopathic PVT.

Helicobacter pylori infection in bleeding peptic ulcer patients after non-steroidal antiinflammatory drug consumption.

AIM: To establish the prevalence of Helicobacter pylori (H. pylori) infection in patients with a bleeding peptic ulcer after consumption of non-steroidal antiinflammatory drugs (NSAIDs). METHODS: A very early upper endoscopy was performed to find the source of upper gastrointestinal bleeding and to take biopsy specimens for analysis of H. pylori infection by the rapid urease (CLO) test, histological examination, and bacterial culture. IgG anti-CagA were also sought. The gold standard for identifying H. pylori infection was positive culture of biopsy specimens or contemporary positivity of the CLO test and the presence of H. pylori on tissue sections. RESULTS: Eighty patients, 61 males (76.3%), mean age 61.2 ± 15.9 years, were consecutively enrolled. Forty-seven (58.8%) patients occasionally consumed NSAIDs, while 33 (41.3%) were on chronic treatment with low-dose aspirin (LD ASA). Forty-four (55.0%) patients were considered infected by H. pylori. The infection rate was not different between patients who occasionally or chronically consumed NSAIDs. The culture of biopsy specimens had a sensitivity of 86.4% and a specificity of 100%; corresponding figures for histological analysis were 65.9% and 77.8%, for the CLO test were 68.2% and 75%, for the combined use of histology and the CLO test were 56.8% and 100%, and for IgG anti-CagA were 90% and 98%. The highest accuracy (92.5%) was obtained with the culture of biopsy specimens. CONCLUSION: Patients with a bleeding peptic ulcer after NSAID/LD ASA consumption frequently have H. pylori infection. Biopsy specimen culture after an early upper gastrointestinal tract endoscopy seems the most efficient test to detect this infection.