OntoPharma: ontology based clinical decision support system to reduce medication prescribing errors.

BACKGROUND: Clinical decision support systems (CDSS) have been shown to reduce medication errors. However, they are underused because of different challenges. One approach to improve CDSS is to use ontologies instead of relational databases. The primary aim was to design and develop OntoPharma, an ontology based CDSS to reduce medication prescribing errors. Secondary aim was to implement OntoPharma in a hospital setting. METHODS: A four-step process was proposed. (1) Defining the ontology domain. The ontology scope was the medication domain. An advisory board selected four use cases: maximum dosage alert, drug-drug interaction checker, renal failure adjustment, and drug allergy checker. (2) Implementing the ontology in a formal representation. The implementation was conducted by Medical Informatics specialists and Clinical Pharmacists using Protégé-OWL. (3) Developing an ontology-driven alert module. Computerised Physician Order Entry (CPOE) integration was performed through a REST API. SPARQL was used to query ontologies. (4) Implementing OntoPharma in a hospital setting. Alerts generated between July 2020/ November 2021 were analysed. RESULTS: The three ontologies developed included 34,938 classes, 16,672 individuals and 82 properties. The domains addressed by ontologies were identification data of medicinal products, appropriateness drug data, and local concepts from CPOE. When a medication prescribing error is identified an alert is shown. OntoPharma generated 823 alerts in 1046 patients. 401 (48.7%) of them were accepted. CONCLUSIONS: OntoPharma is an ontology based CDSS implemented in clinical practice which generates alerts when a prescribing medication error is identified. To gain user acceptance OntoPharma has been designed and developed by a multidisciplinary team. Compared to CDSS based on relational databases, OntoPharma represents medication knowledge in a more intuitive, extensible and maintainable manner.

Pancreatic Insufficiency in Patients Under Sorafenib Treatment for Hepatocellular Carcinoma.

GOALS: To describe the occurrence of malabsorption (MA) in hepatocellular carcinoma (HCC) patients under sorafenib, the potential relationship with pancreatic insufficiency (PI), and the role of pancreatic enzymes supplementation. BACKGROUND: With the increasing options of second-line systemic therapies for HCC, the recognition of drug intolerance using practical tools is crucial. It has been proposed that a MA syndrome could be due to sorafenib-induced pancreatic dysfunction. STUDY: All sorafenib-treated patients with suspicion of MA (defined as decreased stool consistency lasting >4 wk or presenting ≥10% body weight loss without HCC progression) were prospectively evaluated by serum markers, endoscopy, and imaging techniques. RESULTS: We evaluated 81 sorafenib-treated patients and 21 developed MA suspicion (85.7% male, 81.5% Child-Pugh A, 52.4% BCLC-B, and 47.6% BCLC-C) within a median 5.9 months after starting sorafenib. The median treatment duration, follow-up, and overall survival after MA suspicion were 5.9, 20.3, and 20.3 months, respectively. Nine of them (42.9%) presented hyperparathyroidism secondary to vitamin D deficiency and 8 with PI. A gradual decrease in pancreatic volume of up to 19% was observed among patients with PI. Six of the 8 patients with PI received pancreatic enzymes, with complete recovery from MA symptoms and stabilization of pancreatic volume. CONCLUSIONS: We validated the association between MA and PI in 10% of sorafenib-treated patients. Pancreatic enzymes supplementation successfully led to symptomatic recovery. Awareness of this adverse event can help in the management of sorafenib irrespective of cancer type and likely, of other tyrosine kinase inhibitors for HCC patients.

Heterogeneity of clinical management of low-grade gastric lymphoma of mucosa-associated lymphoid tissue. An audit of 198 patients in Spain.

INTRODUCTION: Cure of Helicobacter pylori infection in patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT) leads to long-term clinical remission in the initial stages. As it is a rare disease, its management in clinical practice remains largely unknown and heterogeneity of care remains a concern. The aim was to audit the management and evolution of a large series of low-grade gastric MALT lymphomas from thirteen Spanish hospitals. MATERIALS AND METHODS: Multicentre retrospective study including data on the diagnosis and follow-up of patients with gastric low-grade MALT lymphoma from January 1998 to December 2013. Clinical, biological and pathological data were analyzed and survival curves were drawn. RESULTS: One-hundred and ninety-eight patients were included. Helicobacter pylori was present in 132 (69%) patients and 103 (82%) in tumors confined to the stomach (stage EI) and was eradicated in 92% of patients. Chemotherapy was given in 90 (45%) patients and 43 (33%) with stage EI. Marked heterogeneity in the use of diagnostic methods and chemotherapy was observed. Five-year overall survival was 86% (89% in EI). Survival was similar in EI patients receiving aggressive treatment and in those receiving only antibiotics (p=0.577). DISCUSSION: Gastric MALT lymphoma has an excellent prognosis. We observed, however, a marked heterogeneity in the use of diagnostic methods or chemotherapy in early-stage patients.

Autologous Haematopoietic Stem Cell Transplantation for Refractory Crohn's Disease: Efficacy in a Single-Centre Cohort.

BACKGROUND: Haematopoietic stem cell transplantation [HSCT] is considered a therapeutic option for patients with severe Crohn's disease [CD] unresponsive to currently available therapies. METHODS: Autologous HSCT was considered for CD patients with active disease, unresponsive or intolerant to approved medications and unsuitable for surgery. After HSCT, patients were closely followed up every 6 weeks during the first 2 years and every 6 months thereafter up to 5 years. Colonoscopy and/or magnetic resonance imaging were performed at Months 6, 12, 24, and 48 after HSCT. RESULTS: From December 1, 2007 to December 31, 2015, 37 CD patients were assessed for HSCT. Of these, 35 patients [13 within the ASTIC trial] underwent mobilisation. Six patients did not complete the transplant for various reasons and 29 patients were finally transplanted. Patients were followed up during a median of 12 months [6-60]. At 6 months, 70% of patients achieved drug-free clinical remission (Crohn's Disease Index of Severity [CDAI] < 150). The proportion of patients in drug-free remission (CDAI < 150, Simple Endoscopic activity Score [SES]-CD < 7] was 61% at 1 year, 52% at 2 years, 47% at 3 years, 39% at 4 years, and 15% at 5 years. Patients who relapsed were re-treated and 80% regained clinical remission. Six out of the 29 [21%] required surgery. One patient died due to systemic cytomegalovirus infection 2 months after transplant. CONCLUSIONS: HSCT is a salvage therapy for patients with extensive and refractory CD. Although relapse occurs in a majority of patients within 5 years after transplant, drug responsiveness is regained and clinical remission achieved in 80% of cases.

Long-Term Follow-Up of Patients Treated with Infliximab for Ulcerative Colitis: Predictive Factors of Response-An Observational Study.

AIM: To evaluate the early and long-term efficacy of infliximab in ulcerative colitis and to determine predictors of response and colectomy. METHODS: This is an ambidirectional cohort study in a tertiary referral center including patients who started infliximab within 2005 and 2008 and monitored until 2014. Efficacy was evaluated by partial Mayo scores at weeks 2, 4, 8, 30, and 54. Long-term treatment maintenance with infliximab and colectomy requirements were recorded. RESULTS: Fifty-three patients were included with a median follow-up of 69.5 months. Clinical remission at the time point assessments was 40.8, 47.2, 54.7, 54.7, and 49.1 %. At the time of maximal follow-up, the proportion of patients under infliximab maintenance was 24.5 %. A higher level of albumin (OR 1.4, CI 95 % 1.06-1.8; p = 0.017) was predictive of a higher remission rate at week 8. Concomitant immunomodulators beyond 6 months were predictive of infliximab's long-term maintenance (OR 15.8, CI 95 % 1.8-135.4; p = 0.012). Colectomy was required in 41.5 %. Factors associated with a higher rate of colectomy at week 54 were previous treatment with cyclosporine (OR 3.4, CI 95 % 1.2-9.7; p = 0.012), absence of response at week 8 (OR 10.3, CI 95 % 3.3-31.7; p < 0.001), and not receiving concomitant immunomodulators (OR 4.1, CI 95 % 1.8-9; p = 0.002). Colectomy rates within the first 54 weeks were closely dependent on the number of variables present: none (0 %), 1 (26.3 %), 2 (71.4 %), or 3 (100 %) of them (log rank <0.0001). CONCLUSIONS: Low albumin, previous treatment with cyclosporine, absence of a concomitant immunomodulator, and lack of response at week 8 negatively affected the efficacy of infliximab in ulcerative colitis.

Improving safety of autologous haematopoietic stem cell transplantation in patients with Crohn's disease.

OBJECTIVE: To evaluate the feasibility and toxicity of autologous haematopoietic stem cell transplantation (HSCT) for the treatment of refractory Crohn's disease (CD). DESIGN: In this prospective study, patients with refractory CD suffering an aggressive disease course despite medical treatment, impaired quality of life and in whom surgery was not an acceptable option underwent HSCT. Toxicity and complications during the procedure and within the first year following transplantation were evaluated, along with the impact of the introduction of supportive measures on safety outcomes. RESULTS: 26 patients were enrolled. During mobilisation, 16 patients (62%) presented febrile neutropaenia, including one bacteraemia and two septic shocks. Neutropaenia median time after mobilisation was 5 days. 5 patients withdrew from the study after mobilisation and 21 patients entered the conditioning phase. Haematopoietic recovery median time for neutrophils (>0.5×10(9)/L) was 11 days and for platelets (>20×10(9)/L) 4 days. Twenty patients (95%) suffered febrile neutropaenia and three patients (27%) presented worsening of the perianal CD activity during conditioning. Among non-infectious complications, 6 patients (28.5%) presented antithymocyte globulin reaction, 12 patients (57%) developed mucositis and 2 patients (9.5%) had haemorrhagic complications. Changes in supportive measures over the study, particularly antibiotic prophylaxis regimes during mobilisation and conditioning, markedly diminished the incidence of severe complications. During the first 12-month follow-up, viral infections were the most commonly observed complications, and one patient died due to systemic cytomegalovirus infection. CONCLUSIONS: Autologous HSCT for patients with refractory CD is feasible, but extraordinary supportive measures need to be implemented. We suggest that this procedure should only be performed in highly experienced centres.

Can the vicious cycle of obscure or intractable gastrointestinal bleeding be broken in patients with atrial fibrillation subject to anticoagulant therapy?

Gastrointestinal bleeding of obscure origin or with an intractable cause is particularly common in patients with atrial fibrillation subject to oral anticoagulant therapy. This condition is highly recurrent and therefore gives rise to high morbidity and mortality rates, thus entailing a vicious cycle that is difficult to solve.Percutaneous left atrial appendage closure has become a therapeutic alternative for patients with atrial fibrillation and a contraindication for oral anticoagulation. This technique would allow the discontinuation of oral anticoagulants, thus helping to reduce the risk for gastrointestinal bleeding, and would also be protective against embolic events in this group of patients, thereby eventually breaking this vicious cycle.We report our experience with percutaneous left atrial appendage closure in the management of patients with atrial fibrillation who are subject to oral anticoagulation therapy and suffer from obscure or intractable gastrointestinal bleeding.

Outcomes of peptic ulcer bleeding following treatment with proton pump inhibitors in routine clinical practice: 935 patients with high- or low-risk stigmata.

OBJECTIVE: To assess rates of further bleeding, surgery and mortality in patients hospitalized owing to peptic ulcer bleeding. MATERIALS AND METHODS: Consecutive patients hospitalized for peptic ulcer bleeding and treated with a proton pump inhibitor (PPI) (esomeprazole or pantoprazole) were identified retrospectively in 12 centers in Spain. Patients were included if they had high-risk stigmata (Forrest class Ia-IIb, underwent therapeutic endoscopy and received intravenous PPI ≥120 mg/day for ≥24 h) or low-risk stigmata (Forrest class IIc-III, underwent no therapeutic endoscopy and received intravenous or oral PPI [any dose]). RESULTS: Of 935 identified patients, 58.3% had high-risk stigmata and 41.7% had low-risk stigmata. After endoscopy, 88.3% of high-risk patients and 22.1% of low-risk patients received intravenous PPI therapy at doses of at least 160 mg/day. Further bleeding within 72 h occurred in 9.4% and 2.1% of high- and low-risk patients, respectively (p < 0.001). Surgery to stop bleeding was required within 30 days in 3.5% and 0.8% of high- and low-risk patients, respectively (p = 0.007). Mortality at 30 days was similar in both groups (3.3% in high-risk and 2.3% in low-risk patients). CONCLUSION: Among patients hospitalized owing to peptic ulcer bleeding and treated with PPIs, patients with high-risk stigmata have a higher risk of further bleeding and surgery, but not of death, than those with low-risk stigmata.

Effect of proton pump inhibitors on the outcomes of peptic ulcer bleeding: comparison of event rates in routine clinical practice and a clinical trial.

OBJECTIVE: To assess clinical outcomes in patients treated with proton pump inhibitors (PPIs) after endoscopic hemostasis in routine clinical care, and to compare these outcomes to those seen in a randomized controlled trial (RCT) of i.v. esomeprazole. MATERIALS AND METHODS: Patients with peptic ulcer bleeding and endoscopic stigmata of recent hemorrhage, who were treated with i.v. esomeprazole or pantoprazole ≥120 mg/day following therapeutic endoscopy, were identified from 12 hospitals in Spain (n = 539). Outcomes assessed included further bleeding, all-cause mortality and surgery. The results were compared to those of the RCT. RESULTS: Overall, 9.1% (95% confidence interval [CI]: 6.7-11.5) of patients experienced further bleeding within 72 h following initial endoscopy, 14.3% (95% CI: 11.3-17.2) of patients had further bleeding within 30 days and 3.3% (95% CI: 1.8-4.9) of patients died within 30 days. In the RCT, the rate of rebleeding within 72 h was significantly lower in the esomeprazole arm (5.9%) than in the placebo arm (10.3%; p = 0.026). The further bleeding rate in patients treated with esomeprazole in routine clinical practice (7.8%; 95% CI: 4.6-11.1) was between these two values. Similar results were seen with the other outcomes studied. CONCLUSIONS: The proportion of patients treated with i.v. esomeprazole in routine clinical practice who experienced further bleeding following endoscopic treatment for peptic ulcer bleeding was between the rates observed in the esomeprazole group and the placebo group in the RCT.

Risk of developing tuberculosis under anti-TNF treatment despite latent infection screening.

BACKGROUND: In patients treated with TNF-antagonists, incident cases of tuberculosis (TB) after a negative screening have been reported, leading to the suggestion that improved TB testing is necessary. AIM: The aim of the current study is to establish the incidence of TB and its characteristics in patients with inflammatory bowel disease (IBD) under TNF antagonists to design improved prevention strategies. METHODS: IBD patients from a single center treated with anti-TNF therapy between January 2000 and September 2011 were identified through a database that prospectively records clinical data, treatments and adverse events. RESULTS: During the study period 423 patients received anti-TNF therapy. Screening for latent TB infection (LTBI) previous to anti-TNF treatment was positive in 30 patients (6.96%). Seven patients (1.65%) developed TB while under anti-TNF treatment. Six patients (five under immunosuppressant treatment) had a negative LTBI screening. TST was positive in one patient not receiving immunosuppressants, and was treated with isoniazid before starting anti-TNF therapy. In 4 patients TB was diagnosed within the first 16 weeks after starting anti-TNF therapy. Three cases had pulmonary TB and 4 extrapulmonary disease. CONCLUSIONS: In the IBD population under study, incidence of TB infection associated with anti-TNF therapy is higher than that reported in controlled trials and occurs early after treatment initiation. False negative results of LTBI despite appropriate measures may occur, suggesting that more effective screening strategies are needed.

Diagnostic accuracy of magnetic resonance colonography for the evaluation of disease activity and severity in ulcerative colitis: a prospective study.

OBJECTIVE: The aim of this study was to determine the diagnostic accuracy of magnetic resonance colonography (MRC) for the evaluation of disease activity and severity in patients with ulcerative colitis (UC) using endoscopy as the reference standard. METHODS: Fifty patients with UC underwent colonoscopy and MRC for the evaluation of disease activity. All patients were prospectively and consecutively included. Endoscopic activity was evaluated globally and on a segment basis using the modified Baron score (MBS), and also classified as absent, mild to moderate (inflammation without ulcers) or severe (presence of ulceration). MRC parameters evaluated in each segment were: wall thickness, pre- and post-contrast wall signal intensity, relative contrast enhancement (RCE), mural oedema, ulcers, enlarged lymph nodes and the comb sign. RESULTS: Independent predictors for endoscopic activity on a segment basis were RCE (p=0.006), presence of oedema (p=0.003), enlarged lymph nodes (p<0.001) and the comb sign (p<0.001). A segmental simplified MRC index (MRC-S) ≥ 1 detected endoscopic inflammation with high diagnostic accuracy (sensitivity 87%, specificity 88%, area under the curve (AUC) 0.95; p<0.001). MRC-S index ≥ 2 detected severe lesions with high sensitivity (83%) and specificity (82%) with an AUC of 0.91 (p<0.001). The MRC-S index strongly correlated with the MBS (r=0.81, p<0.001) and with the subjective assessment of the radiologists for the evaluation of disease severity (r=0.77, p<0.001). CONCLUSIONS: MRC has a high accuracy for the diagnosis of disease activity and severity in UC.

[Current management of nonvariceal upper gastrointestinal bleeding in Spain]. / Situación actual del manejo de la hemorragia digestiva alta no varicosa en España.

BACKGROUND: Mortality related to nonvariceal upper gastrointestinal bleeding (NVUGIB) has not changed. More information is needed to improve the management of this entity. The aims of this study were: a) to determine the characteristics of bleeding episodes, b) to describe the clinical approaches routinely used in NVUGIB, and c) to identify adverse outcomes related to endoscopic or medical treatments in Spain. METHODS: The European survey of nonvariceal upper GI bleeding (ENERGiB) was an observational, retrospective cohort study on NVUGIB with endoscopic evaluation carried out across Europe. The present study focused on Spanish patients in the ENERGiB study. The patients were managed according to routine care. The mean and standard deviation were calculated for quantitative variables and absolute and relative frequencies were calculated for categorical variables. RESULTS: Patients (n=403) were mostly men (71%), with a mean age of 65 years, and co-morbidities (62.5%). Most of the patients were managed by gastroenterologists (57.1%) or internal medicine teams (25.1%). A proton pump inhibitor was used empirically in 80% before endoscopy. Bleeding persistence occurred in 6.4% and recurrence in 6.7%. The mortality rate at 30 days was 3.5%. CONCLUSIONS: This study contributes to the characterization of Spanish patients and NVUGIB episodes in a real clinical setting and identifies the routine management of this entity, which is in line with the standards proposed by recent clinical practice guidelines. A notable finding was that age and the number of comorbidities in NVUGIB patients were increasing. These factors could explain the persistent mortality rate, despite the evident advances in the management of this entity.

[Malignancy predictive factors in pancreatic intraductal papillary mucinous neoplasm]. / Factores predictivos de malignidad en la neoplasia mucinosa papilar intraductal de páncreas.

BACKGROUND AND OBJECTIVE: Intraductal papillary mucinous neoplasm (IPMN) is a premalignant lesion of the pancreas. Its natural history is not well known. We evaluated the characteristics and predictor factors of malignancy of IPMN. PATIENTS AND METHOD: A retrospective analysis was performed in 88 patients diagnosed with IPMN between January 1997 and December 2008. The diagnosis was done by abdominal computed tomography (CT), pancreatic-magnetic resonance imaging (MRI) and/or endoscopic ultrasound (EUS). Gender, age, symptoms, origin, location, CA 19.9 serum levels, size of tumours and nodules by imaging techniques, type of surgery, malignancy and survival were evaluated. Nine pre-surgical variables were selected, and univariate and multivariate analysis to identify independent prognostic factors of malignancy were performed. RESULTS: The mean age was 64 years and 53% were men. 39% of tumours were incidental. 50% had their origin on the main pancreatic duct, 37% on collateral branchs and 13% were multifocal. 68% patients were operated: 42% had malignant neoplasms (32% carcinoma in situ and 68% invasive). Twelve patients died (1 benign, 1 in situ and 10 invasive). Univariate and multivariate analysis identified the symptoms and the tumour size (≥ 22 mm [median of our serie] and ≥ 30 mm [size accepted in literature]) as independent predictor factors of malignancy. CONCLUSIONS: Many IPMN are incidental findings. The presence of symptoms and size of the tumour are independent prognostic factors of malignancy and they should be considered to decide therapeutic actions.

Has H. pylori prevalence in bleeding peptic ulcer been underestimated? A meta-regression.

OBJECTIVES: It has been suggested that prevalence of Helicobacter pylori (Hp) in peptic ulcer bleeding (PUB) is lower than that in non-complicated ulcers. As Hp infection is elusive in PUB, we hypothesized that this low prevalence could be related to an insufficiently intensive search for the bacteria. The aim of the study was to evaluate whether the prevalence of Hp in PUB depends on the diagnostic methods used in a given study. METHODS: A systematic review was performed of studies assessing the prevalence of Hp infection in patients with PUB. Data were extracted in duplicate. Univariate and multivariate random-effects meta-regression analyses were performed to determine the factors that explained the differences in Hp prevalence between studies. RESULTS: The review retrieved 71 articles, including 8,496 patients. The mean prevalence of Hp infection in PUB was 72%. The meta-regression analysis showed that the most significant variables associated with a high prevalence of Hp infection were the use of a diagnostic test delayed until at least 4 weeks after the PUB episode-odds ratio: 2.08, 95% confidence interval: 1.10-3.93, P=0.024-and a lower mean age of patients-odds ratio: 0.95 per additional year, 95% confidence interval: 0.92-0.99, P=0.008. CONCLUSIONS: Studies that performed a delayed test and those including younger patients found a higher prevalence of Hp, approaching that recorded in cases of non-bleeding ulcers. These results suggest that the low prevalence of Hp infection described in PUB may be related to the methodology of the studies and to patients' characteristics, and that the true prevalence of Hp in PUB is still to be determined. Our data also support the recent recommendations of the International Consensus on Non-Variceal Upper Gastrointestinal Bleeding regarding the performance of a delayed diagnostic test when Hp tests carried out during the acute PUB episode are negative.

[Whipple's disease. Analysis of 6 cases]. / Enfermedad de Whipple. Estudio de 6 casos.

BACKGROUND AND OBJECTIVE: Whipple's disease (WD) is an infrequent multisystemic process, with a bacterial etiology and with a marked variability in relation to its clinical manifestations. The diagnosis is established by histopathologic study or by polymerase chain reaction (PCR) test. Our objective was to analyze the clinical characteristics and evolution of these patients. PATIENTS AND METHOD: We have reviewed the patients diagnosed with WD in our hospital during the last 20 years (1987-2007). RESULTS: We describe 6 patients with WD (5 men and one woman), with a mean age of 47 years. Most patients presented articular symptoms (n = 5), in 3 cases with intermittent rheumatism. The mean period of time previous to diagnosis was 59 months. All patients developed a chronic diarrheic syndrome, constitutional syndrome and polyadenopathies at the time of diagnosis. Laboratory studies showed increased erythrocyte sedimentation rate and C-reactive protein values, ferropenic microcytic anemia and low serum levels of cholesterol. The clinical diagnosis was confirmed by pathologic study in 5 patients, and by means of PCR study of spleen tissue in one patient. All patients were treated with cotrimoxazole for 2 years, with resolution of the symptoms. After a mean follow-up of 98 months, no recurrence of the symptoms has been observed in any case. CONCLUSIONS: Articular symptoms in the form of intermittent rheumatism are the most common form of presentation of WD. Diarrheic and constitutional syndrome, which are observed later in all patients, as well as the presence of adenopathies, oblige us to discard this process.