The mystery behind the apprehensions of the selective cannabinoid receptor type-2 agonist BZO-HEXOXIZID (MDA-19) as a drug of abuse.

PURPOSE: MDA-19 or BZO-HEXOXIZID (N'-[(3Z)-1-(1-hexyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-benzohydrazide), in a more recent nomenclature, was first synthesized in 2008 as a selective type-2 cannabinoid receptor (CB2) agonist due to its potential to treat neuropathic pain. In Brazil, this substance was identified in a series of 53 apprehensions between September 2021 and February 2022. Nevertheless, what intrigues toxicologists is that BZO-HEXOXIZID does not exert significant type-1 cannabinoid receptor (CB1) agonism-which is responsible for the well-known psychoactivity of Δ-9-tetrahydrocannabinol. Thus, the objective of this work is to report the first apprehension and identification of BZO-HEXOXIZID in Brazil and to discuss pharmacologically the possible reasons why a CB2 agonist has been incorporated to the illicit market. METHODS: Suspected seized samples were sent to the Laboratory of the Scientific Police of the State of Sao Paulo. After the screening, samples were confirmed for the presence of BZO-HEXOXIZID using chromatography gas-mass spectrometry, Fourier-transform infrared spectroscopy and nuclear magnetic resonance techniques. RESULTS: Of the 53 samples analyzed, 25 contained only BZO-HEXOXIZID and 28 with mixtures, of which 11 with the CB1 agonist ADB-BUTINACA. Other substances were found in association such as cocaine and caffeine. CONCLUSIONS: BZO-HEXOXIZID was detected in a series of seized materials for the first time in Brazil. Nevertheless, there are still unanswered questions regarding the use of this selective CB2 agonist as a drug of abuse.

Synthetic cannabinoid receptor agonists profile in infused papers seized in Brazilian prisons.

PURPOSE: Synthetic cannabinoid receptor agonists (SCRAs) are a class of varied compounds that mimic the effects of natural cannabinoids found in cannabis. Because they have a wide range of diverse structures, they vary widely in their potency. The abuse of new psychoactive substances (NPS) in prisons was reported in many European countries and in the USA. In the present study, we have described the identification of SCRAs in 56 infused paper sheet samples, seized mainly in Brazilian prisons between 2016 and 2020. METHODS: The materials were seized by local or federal law enforcement and analyzed by São Paulo State Police or Brazilian Federal Police using gas chromatography-mass spectrometry, attenuated total reflection-Fourier transform infrared spectroscopy, liquid chromatography-high-resolution mass spectrometry or nuclear magnetic resonance spectrometry. RESULTS: Most of these samples (87.5%) were seized in 2019-2020; seven different SCRAs were identified in samples, and the most frequently identified substances were MDMB-4en-PINACA (23.6%) and 5F-MDMB-PICA (36.4%), the newest SCRAs emerging recently. CONCLUSIONS: As observed in Europe and the USA, Brazil also shows the prevalence of indazole-3-carboxamides and indole-3-carboxamides among SCRAs seizures in the prison system. This phenomenon is spreading all over the world at this moment. These data on the prevalence could help to alert judicial authorities to shutting down the introduction of NPS, including SCRAs, into prisons to ensure safety and security for avoiding health risks of prisoners and staff, leading to positive effects in this population. To our knowledge, this is the first demonstration of SCRAs smuggling into prisons in Latin America.

Lucy is back in Brazil with a new dress.

Lucy in the Sky with Diamonds, a John Lennon song that was a hit in the 1960s, was born amidst a social context enlightened by lysergic acid diethylamide (LSD). In Brazil, both the drug and the song were very popular at the time, although it gradually mitigated. Nevertheless, while the song remains out of the spotlight, LSD derivatives are currently gaining attention with the rising of the new psychoactive substances (NPS). With this new presentation, the drug is returning to Brazil after a few decades and herein we report and discuss the first cases of an LSD prodrug seized in our country. Nine suspected blotter paper samples were seized by the Sao Paulo State Police in different cities of the State. Gas chromatography-mass spectrometry (GC-MS), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and liquid chromatography coupled with electrospray ionization-mass spectrometry (LC-ESI-MS) analyses were utilized to confirm the identity of the LSD derivative. The compound was identified as 4-acetyl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (ALD-52 or 1A-LSD) and no other active substance was detected in all samples. The identity of the unknown compound found in seized blotter papers has been successfully confirmed as an LSD prodrug, ALD-52, which was not controlled by Brazilian legislation. The arrival of a new type of designer drug in Brazil is in support by other reports, although those are still scarce and should not be overlooked. Altogether, these findings indicate the rising of a new NPS strategy that merits proper discussion.

Detection of cocaine crystals dispersed on non- Erythroxylum herbs.

This case report deals with an unusual seized drugs case, in which cocaine, more commonly found in powder form or as crack cocaine, was found in herbs similar to those used to deliver synthetic cannabinoids. A comparison with expected physical appearance and chemical results for a genuine coca leaf is also presented.

Determination of the alcohol biomarker phosphatidylethanol 16:0/18:1 and 33 compounds from eight different drug classes in whole blood by LC-MS/MS.

INTRODUCTION: Most bioanalytical LC-MS/MS methods are developed for determination of single drugs or classes of drugs, but a multi-compound LC-MS/MS method that can replace several methods could reduce both analysis time and costs. The aim of this study was to develop a high-throughput LC-MS/MS method for determination of the alcohol biomarker phosphatidylethanol 16:0/18:1 (PEth 16:0/18:1) and 33 other compounds from eight different drug classes in whole blood. METHODS: Whole-blood samples were prepared by 96-well supported liquid extraction (SLE). Chromatographic separations were performed on a biphenyl core shell column with a mobile phase consisting of 10 mM ammonium formate, pH 3.1 and methanol. Each extract was analyzed twice by LC-MS/MS, injecting 0.4 µL and 2 µL, in order to obtain narrow and symmetrical peaks and good sensitivity for all compounds. Stable isotope-labeled internal standards were used for 31 of the 34 compounds. RESULTS: A 96-well SLE reversed phase LC-MS/MS method for determination of PEth 16:0/18:1 and 33 other compounds from eight different drug classes was developed and validated. By using an organic solvent mixture of isopropanol/ methyl tert-butyl ether (1:5, v:v), all compounds, including the polar and ampholytic compounds pregabalin, gabapentin and benzoylecgonine, was extracted by 96-well SLE. DISCUSSION/CONCLUSION: For the first time an LC-MS/MS method for the determination of alcohol biomarker PEth 16:0/18:1 and drugs and metabolites from several different drug classes was developed and validated. The developed LC-MS/MS method can be used for high-throughput analyses and sensitive determinations of the 34 compounds in whole blood.

Alcohol Consumption and Violent Deaths in the City of Sao Paulo in 2015.

Background: Excessive alcohol consumption is a serious public health issue, because drunkenness affects critical judgment and self-control, making people more vulnerable to violence and accidents, with thus a potential association between alcohol consumption and violent deaths. Objective: To assess the association between alcohol consumption and violent deaths in the city of Sao Paulo, Brazil, in 2015, and its relationship with gender, age, cause of death and blood alcohol concentration (BAC) of victims. Methods: A cross-sectional retrospective study was conducted by collection of data from 2,882 victims of violent deaths subjected to examination of BAC from the archives of the Institute of Legal Medicine of the State of Sao Paulo, Brazil. Results: Alcohol was detected in blood samples of 27.06% of the victims and mean BAC levels were 1.92 ± 1.24 g/L. The mean age of the victims was 33.49 ± 15.19 years. The majority of the victims were male (84.14%) and the prevalence of positive BAC was higher amongst men (28.74%) than women (18.16%). Homicide was the most prevalent cause of death in the sample (36.57%), but there were a higher proportion of traffic accidents victims with positive BAC (32.01%), as well as higher BAC levels in these victims (46.77% in the range of 1.6-2.5 g/L). Conclusions: The results obtained in this study support a potential association between alcohol consumption and violent deaths in the city of Sao Paulo, mainly in traffic accidents victims.

Heterogeneity of clinical management of low-grade gastric lymphoma of mucosa-associated lymphoid tissue. An audit of 198 patients in Spain / Heterogeneidad en el tratamiento clínico del linfoma gástrico de tejido linfoide asociado a mucosas de bajo grado. Una auditoría de 198 pacientes en España

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

Introducción: La cura de la infección por Helicobacter pylori (H. pylori) en pacientes con linfoma gástrico de tejido linfoide asociado mucosas (mucosa-associated lymphoid tissue [MALT]) conduce a la remisión clínica a largo plazo en los estadios iniciales. Al tratarse de una enfermedad rara, su tratamiento en la práctica clínica en muchas ocasiones se desconoce y la heterogeneidad de la atención sigue siendo motivo de preocupación. El objetivo es auditar el tratamiento y la evolución de una gran serie de linfomas gástricos MALT de bajo grado procedentes de 13 hospitales españoles. Materiales y métodos: Estudio retrospectivo y multicéntrico que incluye datos sobre el diagnóstico y el seguimiento de pacientes con linfoma MALT gástrico de bajo grado desde enero de 1998 hasta diciembre del 2013. Se analizaron los datos clínicos, biológicos y patológicos, y se trazaron las curvas de supervivencia. Resultados: Se incluyó a 198 pacientes. El H. pylori estaba presente en 132 (69%) de los pacientes y en 103 (82%) tumores confinados al estómago (estadio EI) y se erradicó en el 92% de los pacientes. Se administró quimioterapia a 90 (45%) de los pacientes y a 43 (33%) en estadio EI. Se observó una marcada heterogeneidad en el uso de los métodos de diagnóstico y de la quimioterapia. La supervivencia global a los 5 años fue del 86% (89% en estadio EI). La supervivencia fue similar en los pacientes en estadio EI que recibieron tratamiento agresivo y en los que recibieron solo antibióticos (p=0,577). Discusión: El linfoma MALT gástrico presenta un pronóstico excelente. Sin embargo, se observó una marcada heterogeneidad en el uso de los métodos de diagnóstico o la quimioterapia en pacientes en estadio inicial

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.

Drink driving and speeding in Sao Paulo, Brazil: empirical cross-sectional study (2015-2018).

OBJECTIVES: To evaluate the prevalence of drink driving and speeding during 2015-2018 in Sao Paulo, Brazil. DESIGN: Cross-sectional observational study. SETTING: Roads representing the five main regions of the city of Sao Paulo in Brazil, one of the world's largest urban areas. PARTICIPANTS: Drivers (N=10 294) stopped at routine roadside breath testing checkpoints and those driving in selected roads for speeding measurement (N=414 664). PRIMARY AND SECONDARY OUTCOME MEASURES: Microwave radar guns were used to measure the speed of vehicles, while the prevalence of drivers under the influence of alcohol was observed in police checkpoints. Data were collected during three consecutive years (2016-2018) following a baseline study established in 2015 using a city-level representative sample of observational data representing all days of the week. RESULTS: Alcohol-related fatalities kept at a constantly high percentage, with 39% of road traffic deaths involving alcohol in 2016. Drivers testing above the legal breath alcohol concentration limit showed a decreasing trend, from 4.1% (95% CI 2.9% to 5.5%) at baseline to 0.6% (95% CI 0.2% to 1.2%) in the end of 2018 (p<0.001); however, more than half of drivers refused breath tests at checkpoints despite steep legal penalties. The prevalence of speeding among all vehicles decreased from 8.1% (95% CI 7.9% to 8.2%) to 4.9% (95% CI 4.7% to 5.1%) by the end of 2016 (p<0.001), but then increased again to 13.5% (95% CI 13.2% to 13.9%) at the end of the study period (p<0.001). CONCLUSIONS: Drink driving rates have reduced, likely due to an increase in drivers refusing breath alcohol tests, while speeding rates have increased significantly by the end of the study period, particularly among motorcycles. Future strategies aiming at reducing road traffic injuries in the major Brazilian city should tailor drink driving and speeding enforcement based on the new evidence provided here.

Comparison of traffic data and blood alcohol concentration among fatally injured drivers in Norway and Sao Paulo, Brazil, 2005-2015.

Objective: Road traffic crashes (RTCs) are responsible for a large number of deaths worldwide, but low- and middle-income countries frequently present higher rates of deaths; for example, Norway, a high-income country, has a rate of 2.0 drivers killed per 100,000 inhabitants, whereas Brazil, a middle-income country, has a rate of 18.4. A significant fraction of RTCs are related to use of psychoactive substances, especially alcohol, due to its availability, legality, and relatively low price. The aim of the present study was to evaluate differences in alcohol-related fatal RTCs in Sao Paulo, the largest city in Brazil, and Norway during an 11-year period (2005-2015). Methods: The authors compared databases of drivers killed in RTCs in Sao Paulo and in Norway, a country renowned for its success in reducing traffic fatalities and keeping them at a low level. Results: In total, 772 victims from Norway (11 years, 2005 to 2015) and 584 victims from Sao Paulo (2 years, 2005 and 2015) were analyzed. Sao Paulo presented higher proportions of motorcycle drivers, men involved in RTCs, and blood alcohol concentration (BAC)-positive cases. The mean BAC for alcohol-positive cases was similar in both sites. For both regions, the percentage of alcohol-positive cases decreased during the study period (from 45.6% to 35.3% in Sao Paulo and from 24.4% to 15.8% in Norway) but remained higher for Sao Paulo. Conclusions: The study shows a different profile of RTC victims and higher alcohol consumption among drivers in Sao Paulo. The differences between the sites can possibly be attributed to public policies regarding traffic safety and alcohol control, which could be further improved by following the Norwegian model in Sao Paulo.

Loaded dice: A game theory analysis of drunk driving laws in Brazil.

OBJECTIVE: The aim of the study was to evaluate whether the current legislation would encourage drunk drivers to refrain from taking a breathalyzer and thus avoid jail time. METHOD: Brazilian traffic laws currently have 3 possible punishments for drivers suspected of driving under the influence: A fine and suspension of license for 12 months if the breathalyzer result is under 0.3 mg/L (by law; a result up to 0.33 mg/L would receive the same punishment due to a later regulatory document) but positive; the same punishment for refusal to take a breathalyzer test; and up to 3 years of jail time and license cancellation if over 0.3 mg/L. Analysis was done using decision tree analysis as well as game theory to evaluate the rational choice for drunk drivers according to possible financial loss. RESULTS: The authors have found that the rational choice for a drunk driver is not taking the breathalyzer test to avoid heavier penalties. This, in turn, contributes to the inefficacy of the law. CONCLUSION: The authors have also calculated that the fine for refusing should be around 2.5 times higher so that the economic equilibrium would shift toward encouraging drivers to take the test. This should also be accompanied by other incentives to promote safe behavior while driving.

Alcohol use by suicide victims in the city of Sao Paulo, Brazil, 2011-2015.

Excessive alcohol consumption is a serious public health issue, because drunkenness affects critical judgment and self-control which could trigger violent and self-harm behavior, with thus a potential association between alcohol consumption and suicide deaths. The objective of the present study was to assess the association between alcohol consumption and suicide deaths in the city of Sao Paulo, Brazil, from 2011 to 2015, and its relationship with socio-demographic characteristics of the victims and the circumstances of the suicide. A cross-sectional retrospective study was conducted by collection of data from 1,700 suicide victims subjected to examination of blood alcohol concentration (BAC) from toxicology reports from the Institute of Legal Medicine of the State of Sao Paulo, Brazil. Alcohol was detected in blood samples of 30.2% of the victims and mean BAC levels were 1.73 ± 0.08 g/L. The mean age of the victims was 39.90 ± 0.75 years. The majority of the victims were male (74.6%) and the prevalence of positive BAC was higher amongst men (34.7%) than women (17.1%), p<0.05. The majority of the victims were white skinned (64.7%), but there was a higher proportion of victims with positive BAC among mulatto and black individuals, p<0.05. Hanging was the most prevalent suicide method in the sample (48.7%) and amongst men (55.4%), but amongst women it was jumping from a height (35%), p < 0.05.

Accuracy of the Ultra-Rapid Urease Test for diagnosis of Helicobacter pylori infection / Exactitud del test Ultra-Rapido de la Ureasa para el Diagnóstico de la infección por Helicobacter pylori

Background: Rapid Urease Test (RUT) is a simple, cheap and relatively fast method for diagnosing Helicobacter pylori infection. It is therefore the preferred method used for patients undergoing gastroscopy. Most kits require 24h to give results. The new Ultra-Rapid Urease Test (URUT) kit by Biohit(R) requires less than 1h. Objective: To determine URUT's diagnostic accuracy. Method: Prospective, blind, multi-centre study involving dyspeptic patients. One corpus biopsy and three antral biopsies were obtained during gastroscopy for standard histological analysis, RUT and URUT. The URUT result was checked after 1min, 5min, 30min and 60min and the RUT was checked over the course of 24h. Histology was used as the gold standard test. Results: 144 patients were included, 68% female, with a mean age of 49 years old; 50% were H. pyloripositive. RUT and URUT diagnoses were correct in 85.9% and 90% of the cases, respectively. The mean waiting time for a positive RUT result was 6h. The sensitivity, specificity, and positive and negative predictive values for RUT were, respectively, 82%, 90%, 89% and 84%. The URUT's results were similar (85%, 94%, 94% and 87%). These figures improved when patients taking PPIs were excluded (RUT: 86%, 91%, 93% and 83%; URUT: 91%, 94%, 96% and 89%). No statistically significant differences were found when comparing RUT and URUT distributions of correct diagnoses (McNemar's Test, p=0.3) but there was a tendency towards better results with the URUT. Conclusion: The URUT is equivalent to (or slightly better than) the traditional RUT in diagnosing H. pyloriinfection, and provides results in less than an hour (AU)

Introducción: El test de la ureasa (TRU) es un método simple, barato y relativamente rápido para el diagnóstico de la infección por Helicobacter pylori (H. pylori). Por tanto, es el método de elección en pacientes sometidos a gastroscopia. La mayoría de los kits requieren 24 h para obtener un resultado. En nuevo test ultrarrápido de la ureasa (TURU) de Biohit requiere menos de una hora. Objetivo: Determinar la exactitud diagnóstica del TURU. Método: Estudio multicéntrico, prospectivo y ciego, en el que se incluyó a pacientes dispépticos. Se obtuvieron 3 biopsias de antro y una de corpus durante la gastroscopia para análisis histológico estándar, TRU y TURU. El resultado del TURU se comprobó a los 1, 5, 30 y 60 min, mientras que el TRU se evaluó a lo largo de 24 h. La histología se utilizó como patrón oro. Resultados: Se incluyó a 144 pacientes, 68% mujeres, edad media 49 años, el 50% fueron positivos para H. pylori. TRU y TURU diagnosticaron correctamente el 85,9% y 90,0% de los casos, respectivamente. La duración media de espera para un resultado positivo del TRU fue 6 h. La sensibilidad, la especificidad y los valores predictivos negativo y positivo para el TRU fueron, respectivamente, del 82, el 90, el 89 y el 84%. Los resultados del TURU fueron equivalentes (el 85, el 94, el 94 y el 87%). Estos resultados mejoraron al excluir los pacientes que tomaban IBP (TRU: 86, 91, 93 y 83%; TURU: 91, 94, 96 y 89%). La comparación de distribución de diagnósticos correctos entre TRU y TURU no encontró diferencias estadísticamente significativas (test de McNemar p=0,3) pero existe una tendencia a mejores resultados con el TURU. Conclusión: El TURU es equivalente (o algo superior) al TRU tradicional en el diagnóstico de la infección por H. pylori y obtiene los resultados en menos de una hora (AU)

Accuracy of the Ultra-Rapid Urease Test for diagnosis of Helicobacter pylori infection.

BACKGROUND: Rapid Urease Test (RUT) is a simple, cheap and relatively fast method for diagnosing Helicobacter pylori infection. It is therefore the preferred method used for patients undergoing gastroscopy. Most kits require 24h to give results. The new Ultra-Rapid Urease Test (URUT) kit by Biohit® requires less than 1h. OBJECTIVE: To determine URUT's diagnostic accuracy. METHOD: Prospective, blind, multi-centre study involving dyspeptic patients. One corpus biopsy and three antral biopsies were obtained during gastroscopy for standard histological analysis, RUT and URUT. The URUT result was checked after 1min, 5min, 30min and 60min and the RUT was checked over the course of 24h. Histology was used as the gold standard test. RESULTS: 144 patients were included, 68% female, with a mean age of 49 years old; 50% were H. pylori positive. RUT and URUT diagnoses were correct in 85.9% and 90% of the cases, respectively. The mean waiting time for a positive RUT result was 6h. The sensitivity, specificity, and positive and negative predictive values for RUT were, respectively, 82%, 90%, 89% and 84%. The URUT's results were similar (85%, 94%, 94% and 87%). These figures improved when patients taking PPIs were excluded (RUT: 86%, 91%, 93% and 83%; URUT: 91%, 94%, 96% and 89%). No statistically significant differences were found when comparing RUT and URUT distributions of correct diagnoses (McNemar's Test, p=0.3) but there was a tendency towards better results with the URUT. CONCLUSION: The URUT is equivalent to (or slightly better than) the traditional RUT in diagnosing H. pylori infection, and provides results in less than an hour.

Decreased Esophageal Sensitivity to Acid in Morbidly Obese Patients: A Cause for Concern?

BACKGROUND/AIMS: To evaluate esophageal sensitivity to acid between morbidly obese (MO) patients and non-MO controls with abnormal esophageal acid exposure. METHODS: We conducted a cross-sectional study of 58 patients: 30 MO (cases) and 28 non-MO (controls). Esophageal symptoms and esophageal sensitivity to 0.1 M hydrochloric acid solution (Bernstein test) were compared between MO and non-MO patients with a prior diagnosis of abnormal esophageal acid exposure. RESULTS: MO patients were less symptomatic than non-MO controls (14% vs 96%; odds ratio [OR], 0.006; 95% confidence interval [CI], 0.001 to 0.075; p=0.000). MO patients were more likely to present with decreased esophageal sensitivity to the instillation of acid than non-MO controls (57% vs 14%; OR, 8; 95% CI, 1.79 to 35.74; p=0.009). Subgroup analysis revealed no differences in esophageal sensitivity in MO patients with and without abnormal esophageal acid exposure (43% vs 31%; p=0.707). CONCLUSIONS: Silent gastroesophageal reflux disease (GERD) is common among MO individuals, likely due to decreased esophageal sensitivity to acid. The absence of typical GERD symptoms in these patients may delay discovery of precancerous conditions, such as Barrett's esophagus. We believe that these patients may require a more aggressive diagnostic work-up to rule out the presence of silent GERD.

Prevalence of severe esophagitis in Spain. Results of the PRESS study (Prevalence and Risk factors for Esophagitis in Spain: A cross-sectional study).

BACKGROUND: *N.P. and M.P. contributed equally to this study.The current prevalence of esophagitis in southern Europe is unknown. In addition, the risk factors for reflux esophagitis are not fully understood. OBJECTIVE: The objective of this article is to assess the prevalence and risk factors for esophagitis in Spain. METHODS: A prospective, observational, cross-sectional, multicenter study (PRESS study) was conducted among 31 gastrointestinal endoscopy units throughout Spain. A total of 1361 patients undergoing upper gastrointestinal endoscopy were enrolled. Sociodemographic, clinical and treatment data were recorded. RESULTS: A total of 95% of patients were Caucasian and 52% were male (mean age: 53 ± 17 years). The most frequent symptoms prompting endoscopy were heartburn (40%), regurgitation (26%) and dysphagia (15%). Fifty-four percent of patients undergoing endoscopy were receiving proton pump inhibitor (PPI) treatment. Esophagitis (mainly mild-moderate) was present in 154 (12.4%) patients. The severe form was recorded in only 11 (0.8%) patients. Multivariate analysis results indicated that the likelihood of esophagitis was higher in men (OR = 1.91, 95% CI = 1.31-2.78), in patients with high GERD-Q scores (OR = 1.256, 95% CI = 1.176-1.343), weight increase (OR = 1.014, 95% CI = 1.003-1.025) and high alcohol consumption (OR = 2.49, 95% CI = 1.16-5.36). CONCLUSION: Severe esophagitis is a rare finding in the Spanish population. Male gender, high GERD-Q score, weight increase and high alcohol consumption are main risk factors for its appearance.

Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants.

BACKGROUND & AIMS: Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin is associated with increased risk of upper gastrointestinal bleeding. There is little evidence on the risk of lower gastrointestinal bleeding with NSAIDs, antiplatelet agents (APAs), or anticoagulants. We aimed to quantify the relative risk (RR) of upper and lower gastrointestinal bleeding associated with use of NSAIDs, APAs, or anticoagulants. METHODS: We performed a case-control study that used data collected from consecutive patients hospitalized for gastrointestinal bleeding (563 upper, mean age, 63.6 ± 16.7 years and 415 lower, mean age, 70.8 ± 13.8 years), confirmed by endoscopy or other diagnostic procedures. Unhospitalized patients were used as controls (n = 1008) and matched for age, hospital, and month of admission. Drug use was considered current when taken within 7 days or less before hospitalization. RRs and 95% confidence intervals (CIs) were estimated by unconditional logistic regression analysis. RESULTS: Use of anticoagulants, low-dose aspirin, and other drugs (non-aspirin-APA, 82.3% thienopiridines) was associated with upper and lower gastrointestinal bleeding; the risk was 2-fold higher for anticoagulants (RR, 4.2; 95% CI, 2.9-6.2) than for low-dose aspirin (RR, 2.1; 95% CI, 1.4-3.3) or other non-aspirin-APA drugs (RR, 2.0; 95% CI, 1.6-2.6). NSAID use was also associated with increased risk of gastrointestinal bleeding and greater for upper (RR, 2.6; 95% CI, 2.0-3.5) than lower gastrointestinal bleeding (RR, 1.4; 95% CI, 1.0-1.9). Use of proton pump inhibitors was associated with reduced risk of upper, but not lower, gastrointestinal bleeding. CONCLUSIONS: Anticoagulants, low-dose aspirin, NSAIDs, and other non-aspirin-APA drugs are associated with increased risk of upper and lower gastrointestinal bleeding. Use of anticoagulants appears to be the strongest risk factor for gastrointestinal bleeding.

Small intestinal bacterial overgrowth in inactive Crohn's disease: influence of thiopurine and biological treatment.

AIM: To investigate the influence of thiopurines and biological drugs on the presence of small intestinal bacterial overgrowth (SIBO) in patients with inactive Crohn's disease (CD). METHODS: This was a prospective study in patients with CD in remission and without corticosteroid treatment, included consecutively from 2004 to 2010. SIBO was investigated using the hydrogen glucose breath test. RESULTS: One hundred and seven patients with CD in remission were included. Almost 58% of patients used maintenance immunosuppressant therapy and 19.6% used biological therapy. The prevalence of SIBO was 16.8%. No association was observed between SIBO and the use of thiopurine Immunosuppressant (12/62 patients), administration of biological drugs (2/21 patients), or with double treatment with an anti-tumor necrosis factor drugs plus thiopurine (1/13 patients). Half of the patients had symptoms that were suggestive of SIBO, though meteorism was the only symptom that was significantly associated with the presence of SIBO on univariate analysis (P < 0.05). Multivariate analysis revealed that the presence of meteorism and a fistulizing pattern were associated with the presence of SIBO (P < 0.05). CONCLUSION: Immunosuppressants and/or biological drugs do not induce SIBO in inactive CD. Fistulizing disease pattern and meteorism are associated with SIBO.

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.

Prevalencia y características de la anemia y ferropenia en pacientes hospitalizados por enfermedades digestivas en España / Prevalence and characteristics of anemia and iron deficiency in patients hospitalized for gastrointestinal diseases in Spain

OBJETIVO: Evaluar la prevalencia y el abordaje terapéutico de la anemia y ferropenia en pacientes hospitalizados por enfermedades gastrointestinales. MÉTODOS: Estudio epidemiológico, multicéntrico, con diseńo mixto (retrospectivo de revisión de historias clínicas aleatorizadas y prospectivo con visita de control) realizado entre febrero de 2010 y marzo de 2011 en 22 servicios de aparato digestivo espańoles. Se consideró anemia grave Hb < 10 g/dl y leve/moderada Hb ≥ 10 g/dl, y ferropenia (ferritina < 30 ng/ml o IST < 16%). RESULTADOS: Se incluyeron 379 pacientes. La edad media ± DE fue de 57 ± 19 ańos y el 47% eran hombres. La prevalencia de anemia al ingreso fue del 60% (IC 95%: 55-65), siendo grave en la mitad de ellos, y la prevalencia del déficit de hierro del 54% (IC 95%: 47-61). El 39% ingresaron por sangrado digestivo, de los cuales el 83% (121/146) tenían anemia. La prevalencia de anemia al alta no cambió (del 60% pasó al 58%) (IC 95%: 53-63): 17% grave y 41% leve/moderada, y la ferropenia se situó en el 41% (IC 95%: 32-50). A los 3-6 meses del ingreso, la prevalencia de anemia fue del 28% (IC 95%: 23-32): 5% grave y 23% leve/moderada; la prevalencia de ferropenia fue del 44% (IC 95%: 39-50). Durante el ingreso, el 50% de los pacientes con anemia no recibió tratamiento, y al alta al 55% de los pacientes que tenían anemia tampoco se les pautó tratamiento. CONCLUSIÓN: La prevalencia de anemia en pacientes hospitalizados por enfermedades gastroenterológicas es muy alta. En la visita de control, en más de la cuarta parte de los pacientes persiste la anemia. Únicamente la mitad de los ingresados recibieron tratamiento para la anemia, aun tratándose de pacientes graves

OBJECTIVE: To determine the prevalence and characteristics of anemia and iron deficiency inpatients hospitalized for gastrointestinal diseases. METHODS: An epidemiological, multicenter, mixed design study (retrospective review of randomized clinical records and prospective visits) conducted between February 2010 and March2011 in 22 Spanish gastroenterology departments. Severe anemia was defined as Hb < 10 g/dL, mild/moderate as Hb≥10 g/dL, and iron deficiency as ferritin < 30 ng/ml or transferrin saturation< 16%.RESULTS: We included 379 patients. The mean ±SD age was 57±19 years and 47% were men.The prevalence of anemia at admission was 60% (95% CI 55 to 65), and anemia was severe (Hb<10 g/dl) in half the patients. The prevalence of iron deficiency was 54% of evaluable patients(95% CI 47 to 61). Gastrointestinal bleeding at admission was found in 39% of the patients, of whom 83% (121/146) were anemic. At discharge, the proportion of anemic patients was unchanged (from 60% at admission to 58% at discharge) (95% CI 53 to 63) and iron deficiency was found in 41% (95% CI 32 to 50): anemia was severe in 17% and mild/moderate in 41%. During follow-up, at 3-6 months after admission, 44% (95% CI 39 to 50) of evaluable patients continued to have iron deficiency and 28% (95% CI 23 to 32) were still anemic: 5% severe and 23% mild/moderate. The prevalence of iron deficiency was 44% (95% CI: 39-50). During admission, 50% of patients with anemia did not receive treatment. At discharge, 55% were untreated. CONCLUSION: The prevalence of anemia in patients hospitalized for gastroenterological diseases was very high. Anemia persisted in over a quarter of patients at the follow-up visit. Only half of hospitalized patients received treatment for anemia, even when the anemia was severe