The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study.

Purpose: To investigate whether interindividual variability in the CYP2C9 (*2 and *3 alleles) and VKORC1 (rs9923231) genes is associated with increased risk of upper gastrointestinal bleeding (UGIB) in users of non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA). Methods: A full case-control study including 200 cases of patients diagnosed with UGIB and 706 controls was conducted in a Brazilian hospital complex. To perform an analysis of NSAIDs dose-effect, the defined daily dose (DDD) for NSAIDs was calculated in the 7-day etiologic window preceding the data index. Three categories of DDD, considering the genotypes of the genetic variants, were established: non-users of NSAIDs (DDD = 0), DDD ≤0.5, and DDD >0.5. Genetic variants and LDA or NSAIDs use synergism was estimated through Synergism Index (SI) and Relative Excess Risk Due To Interaction (RERI). Results: For DDDs of NSAIDs upward of 0.50, a risk of UGIB was identified in carriers of the *3 allele (OR: 15,650, 95% CI: 1.41-174.10) and in carriers of the variant homozygous genotype (TT) of rs9923231 (OR: 38,850, 95% CI: 2.70-556.00). In LDA users, the risk of UGIB was observed to be similar between carriers of the wild type homozygous genotype and carriers of the variant alleles for the CYP2C9 and VKORC1 genes. No synergism was identified. Conclusion: Our findings suggest an increased risk of UGIB in carriers of the variant allele of rs9923231 and in carriers of the *3 allele associated with doses of NSAIDs greater than 0.5. Hence, the assessment of these variants might reduce the incidence of NSAIDs-related UGIB and contribute to the safety of the NSAIDs user.

Genetic polymorphisms associated with upper gastrointestinal bleeding: a systematic review.

Non-variceal upper gastrointestinal bleeding (non-variceal UGIB) is a frequent and severe adverse drug reaction. Idiosyncratic responses due to genetic susceptibility to non-variceal UGIB has been suggested. A systematic review was conducted to assess the association between genetic polymorphisms and non-variceal UGIB. Twenty-one publications and 7134 participants were included. Thirteen studies evaluated genetic polymorphism in patients exposed to non-steroidal anti-inflammatory drugs, low-dose aspirin, and warfarin. Eight studies present at least one methodological problem. Only six studies clearly defined that the outcome evaluated was non-variceal UGIB. Genetic polymorphisms involved in platelet activation and aggregation, angiogenesis, inflammatory process, and drug metabolism were associated with risk of non-variceal UGIB (NOS3, COX-1; COX-2; PLA2G7; GP1BA; GRS; IL1RN; F13A1; CDKN2B-AS1; DPP6; TBXA2R; TNF-alpha; VKORC1; CYP2C9; and AGT). Further well-designed studies are needed (e.g., clear restriction to non-variceal UGIB; proper selection of participants; and adjustment of confounding factors) to provide strong evidence for pharmacogenetic and personalized medicine.

Traditional Lectures Actually Improve the Body of Knowledge, Skills, and Attitudes of Health Care Professional for Health Incident Reporting System.

Introduction: A solid patient safety culture lies at the core of an effective event reporting system in a health care setting requiring a professional commitment for event reporting identification. Therefore, health care settings should provide strategies in which continuous health care education comes up as a good alternative. Traditional lectures are usually more convenient in terms of costs, and they allow us to disseminate data, information, and knowledge through a large number of people in the same room. Taking in consideration the tight money budgets in Brazil and other countries, it is relevant to investigate the impact of traditional lectures on the knowledge, skills, and attitudes to incident reporting system and patient safety culture. Objective: The study aim was to assess the traditional lecture impact on the improvement of health care professional competency dimensions (knowledge, skills, and attitudes) and on the number of health care incident reports for better patient safety culture. Participants and Methods: An open-label, nonrandomized trial was conducted in ninety-nine health care professionals who were assessed in terms of their competencies (knowledge, skills, and attitudes) related to the health incident reporting system, before and after education intervention (traditional lectures given over 3 months). Results: All dimensions of professional competencies were improved after traditional lectures (P < .05, 95% confidence interval). Conclusions: traditional lectures are helpful strategy for the improvement of the competencies for health care incident reporting system and patient safety.

In vitro effects of extracellular hypercapnic acidification on the reactivity of rat aorta: Rat aorta vasodilation during hypercapnic acidification.

The mechanisms by which pH influences vascular tone are not entirely understood, but evidence suggests that the endothelium is involved. Here, we aimed to study the in vitro vascular responses induced by extracellular hypercapnic acidification (HA), as well as the endothelium-dependent mechanisms that are involved in the responses. We bubbled a mixture of CO2 (40%)/O2 (60%) in an organ bath; we constructed a pH-response curve (pH range 7.4-6.6) and registered isometric force simultaneously. Aortic rings from rats were pre-contracted with phenylephrine (10-6 M) and incubated for 30 min in the presence of different chemicals. The relaxations induced by HA occurred in rings with endothelium were: 1) Partially inhibited by indomethacin (10-5 M) (PGI2 pathway inhibitor); 2) Strongly inhibited by NO pathways: L-NAME (10-4 M) and L-NMMA (10-4 M) (no specific NO synthase inhibitors); L-Nil (10-3 M) (specific iNOS inhibitor); ODQ (10-4 M) (specific guanylate cyclase inhibitor), and; 4) Inhibit by tetraethylammonium (10-3 M) (non-specific potassium channel inhibitor), glibenclamide (10-5 M) (specific KATP inhibitor), aminopyridine (10-3 M) (specific Kv inhibitor) and apamin (10-6 M) (specific SKCa inhibitor). IN CONCLUSION: 1) HA causes endothelium-dependent relaxation; 2) Indomethacin failed in blocking this relaxation, but the method limitation does not allow ruling out some prostanoid role; 3) The HA vessel relaxation is mediated via cGMP/NO, and; 4) The hyperpolarization occurs by the action of potassium SKCa, KATP and Kv channels without relying on BKCa channels.

In vitro effects of the organophosphorus pesticide malathion on the reactivity of rat aorta.

BACKGROUND AND PURPOSE: There is a remarkable paucity of studies analyzing the role of the endothelium-derived relaxing factors on the vascular effects of organophosphates. This study was carried out to evaluate the vascular effects of malathion and the role of nitric oxide (NO) and prostacyclin (PGI2). METHODS: Vascular reactivity measuring isometric forces in vitro ('organ chambers') and flow cytometry (cells loaded with DAF-FM DA) were used. RESULTS: In rat thoracic aorta segments contracted with phenylephrine (Phe) (10(-7) mol/l), malathion (10(-10) to 10(-5) mol/l) induced concentration-dependent relaxation in arteries with intact endothelium (n = 7; p < 0.05). Malathion-mediated relaxation was blocked by N-nitro-L-arginine methyl ester (L-NAME; 10(-4) mol/l), a nonspecific NO synthase inhibitor, and/or indomethacin (10(-5) mol/l), a nonspecific cyclooxygenase inhibitor (n = 10, p < 0.05). In thoracic aorta rings, with and without endothelium, Phe (10(-10) to 10(-5) mol/l) evoked concentration-dependent contraction, which was reduced in the presence of malathion. In rings with or without endothelium, incubated with malathion, L-NAME and indomethacin, the Phe-induced contraction was restored. The role of NO was confirmed using flow cytometry. Malathion evokes endothelium-dependent relaxation through the M1 muscarinic receptor, since this relaxation was clearly blocked by atropine (M1 and M2 blocker) and pirenzepine (M1 blocker), but was less blocked by gallamine (M2 blocker) or 4-DAMP (M3 blocker). CONCLUSIONS: These findings suggest that the organophosphate compound effects on vascular reactivity depend of NO and PGI2.

A Rare Case of Right-Sided Chylothorax Following Thoracoscopic Sympathectomy Due to an Anomalous Thoracic Duct.

Chylothorax, despite being a common complication after thoracic surgery, is rare after thoracic sympathectomy, especially on the right side of the thorax. We present a case of a patient who developed a right chylothorax after a thoracoscopic sympathectomy due to the presence of an anomalous thoracic duct located on the right side of the patient's chest. A 37-year-old woman underwent a bilateral video-assisted thoracic sympathectomy for the treatment of primary focal axillary hyperhidrosis. During the postoperative period, there was an excessive discharge of a white, milky fluid through the chest drain, with an average daily output of 350-500 mL/day. Chylothorax was confirmed after laboratory analysis, which revealed a triglyceride level of 146 mg/dL. Due to the worsening appearance of the pleural fluid and the increased drainage volume, reaching 1,000 mL, the patient underwent exploratory videothoracoscopy. During the procedure, a lymphatic fistula was visualized in the region of the sympathetic chain, allowing the identification of an anomalous thoracic duct on the right side of the patient's thorax. The anomalous thoracic duct was dissected, with inferior and superior clipping of the duct. The patient remained stable and was discharged three days after the procedure. This case report describes an especially rare presentation, being one of the few cases of right chylothorax after thoracoscopic sympathectomy described in the literature to date. This study points out that, despite thoracic sympathectomy being considered a safe surgical procedure, unusual complications, such as chylothorax, and anatomical variations of the thoracic duct must be considered.

Look-Locker T1 relaxometry and high-resolution T2 in the evaluation of lung lesions: a single-center prospective study.

Objective: To explore the feasibility of two magnetic resonance imaging (MRI) sequences-high-resolution T2-weighted (HR T2) and Look-Locker T1 (LL T1) relaxometry-for the investigation focal lung lesions (FLLs). As a secondary objective, we analyzed the diagnostic accuracy of these sequences. Materials and Methods: This was a prospective observational study involving 39 subjects with FLLs scanned in a 1.5-T MRI system with LL T1 relaxometry and HR T2 sequences focused on the FLL region, in addition to a conventional protocol. All images were evaluated by two radiologists, working independently, who were blinded to other findings. Results: Most of the examinations (31 of the LL T1 relaxometry sequences and 36 of the HR T2 sequences) were of adequate diagnostic quality. Nondiagnostic examinations were considered so mainly because of limited coverage of the sequences. Of the FLLs studied, 19 were malignant, 17 were benign, and three were excluded from the accuracy analysis because there was no definitive diagnosis. Although LL T1 relaxometry could not distinguish between benign and malignant lesions, the signal intensity at its first inversion time (160 ms) differed between the two groups. The HR T2 sequence was considered the best sequence for assessing specific morphological characteristics, especially pseudocavities and pleural tags. We found that MRI showed better accuracy than did computed tomography (86% vs. 74%). Conclusion: Both MRI sequences are feasible for the evaluation of FLLs. Images at 160 ms of the LL T1 relaxometry sequence helped distinguish between benign and malignant lesions, and the HR T2 sequence was considered the best sequence for evaluating specific morphological characteristics.

Objetivo: Explorar a viabilidade de imagens de alta resolução T2 (T2 AR) e relaxometria T1 Look-Locker (T1 LL) para lesões pulmonares focais (LPFs). Como objetivo secundário, analisamos a precisão diagnóstica dessas sequências. Materiais e Métodos: Este é um estudo observacional prospectivo com 39 sujeitos com LPFs examinados em um sistema de ressonância magnética 1.5T com imagens T1 LL e T2 AR focadas na região das LPFs, além de um protocolo convencional. As imagens foram avaliadas por dois radiologistas independentes e cegos para o estudo. Imagens de tomografia computadorizada estavam disponíveis, mas foram avaliadas sem conhecimento dos outros resultados. Resultados: A maioria dos exames apresentou qualidade diagnóstica adequada em ambas as sequências (T1 LL em 31 exames e T2 AR em 36). Exames considerados não diagnósticos estavam principalmente relacionados à cobertura limitada das sequências. Das LPFs estudadas, 19 eram malignas, 17 eram benignas e três casos foram excluídos da análise de precisão de malignidade por falta de um diagnóstico definitivo. A relaxometria T1 LL não conseguiu distinguir entre lesões benignas e malignas, mas a análise da intensidade do sinal do primeiro tempo de inversão (160 ms) diferiu entre os grupos. A T2 AR foi considerada a melhor sequência para avaliar características morfológicas específicas, especialmente pseudocavidades e apêndices pleurais. A ressonância magnética teve melhor precisão em comparação com a tomografia computadorizada (86% e 74%, respectivamente). Conclusão: Ambas as sequências são viáveis na avaliação de LPFs. Imagens a 160 ms da sequência T1 LL ajudaram a distinguir lesões benignas de malignas, e a T2 AR foi considerada a melhor sequência na avaliação de algumas características morfológicas específicas.

Rib myelolipoma: a case report.

BACKGROUND: Myelolipoma is an uncommon benign tumor composed of mature adipose tissue and hematopoietic elements. These tumors generally affect the adrenal glands, with anomalous presentations being rare and with few cases described in the literature. Most myelolipomas are asymptomatic and discovered incidentally, either through imaging tests or at autopsies. However, depending on the location and size of the lesion, myelolipomas can cause symptoms of mass effect. This article aims to report a very rare presentation of a symptomatic primary myelolipoma affecting the ribs. CASE PRESENTATION: A 21-year-old white female patient presented with a complaint of burning chest pain over 3 months, with gradual worsening in intensity, accompanied by a progressively growing bulge in the right thoracic wall. The patient underwent thoracotomy of the fifth and sixth ribs with complete excision of the lesion with a safety margin. Thoracic wall reconstruction was performed using a polypropylene mesh. The patient had a good postoperative course and was discharged on postoperative day 3. Histopathological examination revealed a histological image consistent with myelolipoma. CONCLUSIONS: This report underscores the importance of considering a myelolipoma diagnosis for tumor masses in the ribs.

Use of Antidepressants and the Risk of Upper Gastrointestinal Tract Bleeding: A Case-control Study.

PURPOSE: To investigate the association between the use of antidepressants and the risk of upper gastrointestinal tract bleeding (UGIB). METHODS: A Case-control study was conducted in a Brazilian hospital complex. Cases were defined as patients with a diagnosis of UGIB and controls as patients admitted for reasons unrelated to gastrointestinal bleeding, gastric concerns, or complications associated with low-dose aspirin (LDA) or nonsteroidal anti-inflammatory drugs (NSAIDs) use. Sociodemographic and clinical data, comorbidities, drug therapy in use (long-term use and self-medication), and lifestyle habits were recorded through face-to-face interviews. Two groups were defined: use of antidepressants in general and use of antidepressants according to their affinity for serotonin transporters. The presence of synergism between the concomitant use of antidepressants and LDA or NSAIDs on the risk of UGIB was also explored. FINDINGS: A total of 906 participants were recruited (200 in the case group and 706 in the control group). The use of antidepressants was not associated with the risk of UGIB (odds ratio [OR] = 1.503; 95% CI, 0.78-2.88) or the use of antidepressants with high affinity for serotonin receptors (OR = 1.983; 95% CI, 0.81-4.85). An increased risk of UGIB was observed in concomitant users of antidepressants and LDA (OR = 5.489; 95% CI, 1.60-18.81) or NSAIDs (OR = 18.286; 95% CI, 3.18-105.29). Despite the lack of significance, the use of antidepressants appears to be a positive modifier of UGIB risk in LDA and NSAID users. IMPLICATIONS: These findings indicate an increased risk of UGIB in concomitant users of antidepressants and LDA or NSAIDs, suggesting the need to monitor antidepressant users, especially those most likely to develop UGIB. In addition, further studies with larger sample sizes are needed to confirm these findings.

Cost of Illness in Patients With COVID-19 Admitted in Three Brazilian Public Hospitals.

OBJECTIVES: The severity and transmissibility of COVID-19 justifies the need to identify the factors associated with its cost of illness (CoI). This study aimed to identify CoI, cost predictors, and cost drivers in the management of patients with COVID-19 from hospital and Brazil's Public Health System (SUS) perspectives. METHODS: This is a multicenter study that evaluated the CoI in patients diagnosed of COVID-19 who reached hospital discharge or died before being discharged between March and September 2020. Sociodemographic, clinical, and hospitalization data were collected to characterize and identify predictors of costs per patients and cost drivers per admission. RESULTS: A total of 1084 patients were included in the study. For hospital perspective, being overweight or obese, being between 65 and 74 years old, or being male showed an increased cost of 58.4%, 42.9%, and 42.5%, respectively. From SUS perspective, the same predictors of cost per patient increase were identified. The median cost per admission was estimated at US$359.78 and US$1385.80 for the SUS and hospital perspectives, respectively. In addition, patients who stayed between 1 and 4 days in the intensive care unit (ICU) had 60.9% higher costs than non-ICU patients; these costs significantly increased with the length of stay (LoS). The main cost driver was the ICU-LoS and COVID-19 ICU daily for hospital and SUS perspectives, respectively. CONCLUSIONS: The predictors of increased cost per patient at admission identified were overweight or obesity, advanced age, and male sex, and the main cost driver identified was the ICU-LoS. Time-driven activity-based costing studies, considering outpatient, inpatient, and long COVID-19, are needed to optimize our understanding about cost of COVID-19.

VNTR Polymorphism in Intron 4 of the eNOS Gene and the Risk of Gastrointestinal Bleeding: A Case-control Study.

BACKGROUND AND AIMS: Considering the lack of knowledge regarding the influence of the variable number of repeats of 27 pb in intron 4 (4b/4a VNTR - rs61722009) of the endothelial nitric oxide synthase (eNOS) on the drug response, we assessed the influence of this polymorphism for the risk of upper gastrointestinal bleeding (UGIB). METHODS: A case-control study, including 200 cases and 706 controls, was conducted in a Brazilian hospital complex. Cases were participants with UGIB diagnosis. Controls were participants admitted to surgical procedures not related to gastrointestinal problems. The 4b/4a VNTR was determined through polymerase chain reaction followed by fragment analysis. Conditional logistic regression models were designed. The additive interaction between the presence of the 4b/4a VNTR variant and the use of low-dose aspirin (LDA) and nonsteroidal anti-inflammatory drugs (NSAIDs) was calculated by fitting the Cox regression model through the parameters of Synergism index (S) and Relative Excess Risk Due To Interaction (RERI). RESULTS: The presence of the 4b/4a VNTR variant did not increase the risk of UGIB: carriers of the 4a/4a genotype (OR=0.37, 95%CI: 0.09-1.45) and of the variant allele "4a" (OR=0.91, 95%CI: 0.55-1.51). The risk of UGIB in LDA users carriers of the wild genotype (OR=4.96, 95%CI: 2.04- 2.06) and the variant allele "4a" (OR=3.49, 95%CI: 1.18-10.38) is similar, as well as for NSAID users carriers of the wild genotype (OR=5.73, 95%CI: 2.61-12.60) and variant allele "4a" (OR=5.51, 95%CI: 1.42-15.82). No additive interaction was identified between the presence of the genetic variant and the use of LDA [RERI: -1.44 (95%CI: -6.02-3.14; S: 0.63 (95%CI: -1.97-1.15)] and NSAIDs [RERI: -0.13 (95%CI: -6.79-6.53; S: 0.97 (95%CI: -0.23-4.19)] on the UGIB risk. CONCLUSION: Our data suggests that there is no increase in the magnitude of UGIB risk in LDA and NSAIDs users' carrying the variant allele "4a".

Extemporaneous Compounding: A Possible Trigger Tool to Detect Potential Health Incidents.

BACKGROUND: Extemporaneous compounding (EC) involves the preparation of a therapeutic product for specific patient need. However, there is a potential relationship between this procedure and the occurrence of health incidents (HI). The use of trigger tools increases HI identification. OBJECTIVE: This study assessed the performance of EC as a trigger to detect potential health incidents arising from this procedure. METHODS: A one-month observational and cross-sectional study was performed in internal medicine ward and intensive care unit of medium-sized hospital. Data collection was carried out in 5 stages: all triggered patients with dysphagia or enteral feeding tube with prescription of EC were included; EC executed in prescribed standardized drugs was observed; the procedure was compared with the hospital guide and scientific literature; HI monitoring and their evaluation using WHO and NCC MERP algorithms; a search for pharmaceutical alternatives (PA) that would avoid the observed EC. RESULTS: 197 patients were recruited. Almost half of them were triggered by EC from 84 standardized drugs. 48 patients met the inclusion criteria. 28 adverse drug reactions, 01 therapeutic ineffectiveness, and 29 medication errors were identified. EC as a trigger tool showed a PPV value of 0.38. Only 24 drugs have PA available in the market, which could avoid one third of all observed EC. CONCLUSION: It was possible to detect potentially HI in one of two patients with enteral feeding tubes using EC as a trigger tool. The use of EC as a trigger tool contributes to identifying potential HI arising from drugs, which have not gotten pharmaceutical alternatives to be administered via enteral feeding tube.

Genetic Variants in PTGS1 and NOS3 Genes Increase the Risk of Upper Gastrointestinal Bleeding: A Case-Control Study.

Objective: To assess the association between PTGS1 and NOS3 variant alleles and the risk to develop upper gastrointestinal bleeding (UGIB) secondary to complicated peptic disease. Methods: A case-control study was conducted in a Brazilian complex hospital from July 2016 to March 2020. Case: Patients with UGIB diagnosis. Control: Patients admitted for surgery not related to gastrointestinal disorders. Variables: UGIB (outcome), genetic variants in PTGS1 and NOS3 genes (independent), and sex, age, schooling, ethnicity, previous history of gastrointestinal disorders, Helicobacter pylori serology, comorbidity, drug therapy, and lifestyle (confounding). The single-nucleotide polymorphisms (SNPs) of the PTSG1 gene (rs1330344, rs3842787, rs10306114, and rs5788) and NOS3 gene (rs2070744 and rs1799983) were determined using the real-time polymerase chain reaction. Helicobacter pylori serology was determined through the chemiluminescence technique. Logistic regression models were built and deviations of allelic frequencies from Hardy-Weinberg equilibrium were verified. Results: 200 cases and 706 controls were recruited. Carriers of the AG genotype of rs10306114 (OR: 2.55, CI 95%: 1.13-5.76) and CA + AA genotypes of rs5788 (OR: 2.53, CI 95%: 1.14-5.59) were associated with an increased risk for the UGIB development. In nonsteroidal anti-inflammatory drugs (NSAIDs) users, the six variants evaluated modified the magnitude of the risk of UGIB, whereas in low-dose aspirin (LDA) users, an increased risk of UGIB was observed for four of them (rs1330344, rs10306114, rs2070744, and rs1799983). Personal ulcer history (p-value: < 0.001); Helicobacter pylori infection (p-value: < 0.011); NSAIDs, LDA, and oral anticoagulant use (p-value: < 0.001); and alcohol intake (p-value: < 0.001) were also identified as independent risk factors for UGIB. Conclusion: This study presents two unprecedented analyses within the scope of the UGIB (rs10306114 and rs2070744), and our findings showing an increased risk of UGIB in the presence of the genetic variants rs10306114 and rs5788, regardless of the drug exposure. Besides, the presence of the evaluated variants might modify the magnitude of the risk of UGIB in LDA/NSAIDs users. Therefore, our data suggest the need for a personalized therapy and drug use monitoring in order to promote patient safety.

Potential Adverse Drug Events and Nephrotoxicity Related to Prophylaxis With Omeprazole for Digestive Disorders: A Prospective Cohort Study.

PURPOSE: The purpose of this study was to assess whether prophylaxis for digestive disorders with omeprazole is a risk factor for adverse drug events (ADEs) and kidney impairment. METHODS: This was a 9-month, prospective, double-blinded cohort study performed in a Brazilian public hospital. All inpatients 18 years or older admitted during the period of data collection were divided into 2 cohorts. The first group comprised 200 patients receiving prophylaxis for digestive disorders with omeprazole. A total of 54 inpatients who received treatment with omeprazole and whose indication was not approved by the Brazilian Sanitary Agency and the US Food and Drug Administration were excluded. The second group comprised 219 inpatients without a prescription for omeprazole. Follow-up was performed until discharge and included assessment of medical records, medical prescriptions, laboratory data, and pharmaceutical anamnesis. The primary end point was kidney impairment. The variables monitored were kidney function (serum creatinine and urea levels as well as glomerular filtration rate), hepatic function (alanine aminotransferase and aspartate aminotransferase levels), pharmacotherapy, magnesium levels, and imputation of ADEs. With the aid of algorithms of World Health Organization and the National Coordinating Council for Medication Error Reporting and Prevention, we assessed the causality of adverse drug reactions (ADRs) and the seriousness of medication errors (ADEs), respectively. FINDINGS: Prophylaxis for digestive disorders with omeprazole (P = 0.019) and sex (P = 0.010) were considered risk factors for increased serum creatinine level via multivariate logistic regression even with concomitant use of nephrotoxic drugs (P = 0.252). Six ADEs related to omeprazole were identified: 2 ADRs (1 possible and 1 definite), 2 medication errors (nonserious), 1 therapeutic failure, and 1 drug-drug interaction. IMPLICATIONS: Prophylaxis for digestive disorders with omeprazole and male sex may contribute to the development of kidney impairment because both result in increased serum creatinine levels. Therefore, pharmacotherapeutic follow-up of male patients diagnosed with kidney disorders should be considered to identify potential drug-drug interactions early. This follow-up can prevent worsening clinical conditions and/or contraindicate prophylactic use of omeprazole. ClinicalTrials.gov identifier: NCT02278432.

Clavicle Kirschner Wire Migration into Left Lung: A Case Report.

BACKGROUND Kirschner wires are often used to perform osteosynthesis. Migration through tissue of these wires is a rare but well-known occurrence. CASE REPORT A 65-year-old female presented with light intensity pain complaints in the upper left chest area; personal history included left clavicle fracture 20 years ago that was treated surgically with fixation using a K-wire. Chest radiography showed the presence of metallic foreign body in the left pulmonary apex. An exploratory axillary thoracotomy was performed, and the foreign body was extracted by a pneumotomy. CONCLUSIONS To obtain satisfactory results with a K-wire, some peculiarities in their application should be respected. The time from orthopedic surgery of the collarbone to migration into the chest of the metal rod used can vary from one day to nearly 20 years. Although the migration mechanism remains unclear, it is likely that it involves shoulder movements, breathing movements, negative intrathoracic pressure, gravitational force, or local bone resorption. Caution should be exercised when orthopedic pins and wires are used for the fixation of fractures and dislocations of the shoulder girdle. If there is migration of the wire, it should be removed immediately to avoid sudden and fatal complications.

Confounding Variables and the Performance of Triggers in Detecting Unreported Adverse Drug Reactions.

PURPOSE: This study explored the performance of trigger in detecting adverse drug reactions (ADRs), the confounding variables impairing the causal association of the ADRs, and the underreporting rate by hospital health professionals. METHODS: A 6-month cross-sectional study was conducted in a public general hospital. Data collection was conducted in 2 stages: (1) screening of patient hospitalizations to identify suspected ADRs with 9 triggers developed by the Institute of Healthcare Improvement; and (2) chart review to perform the causality assessment of the suspected ADRs identified, to describe the confounding variables associated with detection of suspected ADRs that were not drug induced, and to analyze the positive predictive value of triggers in recognizing ADRs. To estimate the underreporting rate, ADRs detected by using the tool were compared with ADRs reported by health professionals during the same period. FINDINGS: During the study period, 3318 hospitalizations were analyzed. A total of 837 suspected ADRs were identified. However, after causality assessment, 356 were definite ADRs. Confounding variables associated with the detection-suspected ADRs were related to the clinical conditions of inpatients. The use of triggers contributed to increased ADR detection by 10.5%. The performance ranged from 0.00 to 0.75, with an overall positive predictive value of 0.43. Six ADRs were spontaneously reported, of which just 1 was also detected by using the trigger tool. Only 1 of 356 potential ADRs was reported by health professionals. IMPLICATIONS: Findings show that the use of triggers contributes to detecting ADRs underreported by health professionals. However, confounding variables impaired the performance of the tool because they underestimated the causal association. Furthermore, both methods are complementary to early recognition of drug-induced harm and should be applied together in health institutions to contribute to policies of risk management, drug safety, and optimization of pharmacotherapy.

Dorsal raphe nucleus and locus coeruleus neural networks and the elaboration of the sweet-substance-induced antinociception.

In order to investigate the effects of monoaminergic neurons of the dorsal raphe nucleus (DRN) and locus coeruleus (LC) on the elaboration and control of sweet-substance-induced antinociception, male albino Wistar rats weighing 180-200 g received sucrose solution (250 g/L) for 7-14 days as their only source of liquid. After the chronic consumption of sucrose solution, each animal was pretreated with unilateral microinjection of ibotenic acid (1.0 microg/0.2 microL) in the DRN or in the LC. The tail withdrawal latencies of the rats in the tail-flick test were measured immediately before and 7 days after this treatment. The neurochemical lesion of locus coeruleus, but not of DRN neural networks with ibotenic acid, after the chronic intake of sweetened solution, decreased the sweet-substance-induced antinociception. These results indicate the involvement of noradrenaline-containing neurons of the LC in the sucrose-induced antinociception. We also consider the possibility of DRN serotonergic neurons exerting some inhibitory effect on the LC neural networks involved with the elaboration of the sweet-substance-induced antinociception.

Impacto de intervenção educativa sobre segurança do paciente no conhecimento e atitude de estudantes de medicina / Impact of educational intervention about patient safety on the knowledge and attitudes of medical students

Introdução: a segurança é considerada um pilar da qualidade dos cuidados à saúde e seu sucesso depende do comprometimento individual e coletivo, porém, seu ensino é incipiente nas faculdades de medicina brasileiras. Objetivo: avaliar o impacto de intervenção sobre segurança do paciente no conhecimento e atitude dos alunos de medicina. Metodologia: conduziu-se o estudo do tipo pré-pós intervenção de janeiro a novembro de 2017. Todos os estudantes de graduação de medicina do 6° ano que realizaram estágio no hospital sob estudo foram incluídos. A intervenção compreendeu acolhimento, aula expositiva, estágio e aplicação de questionário para avaliar conhecimento e atitude sobre erro humano e segurança do paciente, que foi aplicado em 3 momentos: antes da aula e do estágio, imediatamente após a aula e após 15 dias da aula e término do estágio. As notificações de incidentes foram analisadas. Resultados: participaram 98 (100%) estudantes, dos quais 62% eram do sexo masculino, com média de idade de 25,8 anos. Após a intervenção, observou-se melhora significativa no conhecimento sobre a inevitabilidade do erro em saúde e a caracterização do profissional envolvido no incidente. As atitudes autorreferidas melhoraram significativamente em relação à necessidade de apoio institucional, abordagem sistêmica e adoção de práticas seguras para prevenção de erros; comunicação sobre riscos e erros para superiores, paciente e familiares e que apenas os médicos podem analisar os incidentes. Conclusão: a intervenção foi efetiva para aumentar o conhecimento dos estudantes sobre cultura de segurança, porém limitou-se na mudança de atitude, pois não evidenciou a notificação de incidentes em saúde.

Background: safety is considered a pillar of the quality of health care and its success depends on individual and collective commitment. However, in Brazilian medical schools there are fewer approaches to teaching this subject. Objective: To evaluate the impact of educational intervention about patient safety on the knowledge and attitude of medical students. Methodology: a pre-post intervention study was conducted from January to November 2017. All 6th year medical students who underwent an internship at the hospital under study were included. The intervention comprised reception, lecture, internship and application of a questionnaire to assess knowledge and attitude about human error and patient safety, which was applied in 3 moments: before class and internship, immediately after class and before of internship and in the end of the internship. Adverse drug reports were assessed. Results: 98 (100%) students participated, of which 62% were male, with an average age of 25.8 years. After intervention, there was a significant improvement in knowledge about the inevitability of health errors and the characterization of the professional involved in the incident. Self-reported attitudes have significantly improved in relation to the need for institutional support, a systemic approach and the adoption of safe practices to prevent errors; communication about risks and errors to superiors, patient and family and that only doctors can analyze the incidents. Conclusion: the intervention was effective in increasing students' knowledge of safety culture, but was limited to changing attitudes, as it did not show the notification of health incidents.

Toxoplasma gondii pseudocyst in a transbronchial biopsy: a case report.

BACKGROUND: We herein present a case in which a Toxoplasma cyst was found in a transbronchial biopsy specimen from an immunocompetent patient with negative serology for the parasite. CASE PRESENTATION: An 18-year-old Brazilian man presented with a 1-week history of dyspnea and fever and was diagnosed with right lower lobe pneumonia. He began inpatient treatment with intravenous antibiotics. During treatment, a bronchoscopy with bronchoalveolar lavage and transbronchial biopsy was performed. Anatomopathological examination of the transbronchial biopsy showed a small fragment of lung parenchyma with discrete septal thickening and a rounded structure, suggestive of a pseudocyst containing Toxoplasma gondii bradyzoites. However, serological tests were negative for immunoglobulin G and immunoglobulin M. CONCLUSIONS: Bronchoscopy is a minimally invasive, effective diagnostic and therapeutic method. Despite the fact that the Toxoplasma pseudocyst in the present case was not the cause of the patient's comorbidities, bronchoscopy with transbronchial biopsy allowed for an incidental diagnosis of a Toxoplasma pseudocyst with minimal invasiveness.

Self-perception of knowledge and adherence reflecting the effectiveness of antiretroviral therapy.

OBJECTIVES: To evaluate which indirect method for assessing adherence best reflects highly active antiretroviral therapy (HAART) effectiveness and the factors related to adherence. METHOD: This descriptive, cross-sectional study was performed in 2012 at a reference center of the state of São Paulo. Self-report (simplified medication adherence questionnaire [SMAQ]) and drug refill parameters were compared to the viral load (clinical parameter of the effectiveness of pharmacotherapy [EP]) to evaluate the EP. The "Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral" (CEAT-VIH) was used to evaluate factors related to adherence and the EP and, complementarily, patient self-perception of adherence was compared to the clinical parameter of the EP. RESULTS: Seventy-five patients were interviewed, 60 of whom were considered as adherent from the clinical parameter of the EP and ten were considered as adherent from all parameters. Patient self-perception about adherence was the instrument that best reflected the EP when compared to the standardized self-report questionnaire (SMAQ) and drug refill parameter. The level of education and the level of knowledge on HAART were positively correlated to the EP. Forgetfulness, alcohol use, and lack of knowledge about the medications were the factors most frequently reported as a cause of nonadherence. CONCLUSION: A new parameter of patient self-perception of adherence, which is a noninvasive, inexpensive instrument, could be applied and assessed as easily as self-report (SMAQ) during monthly drug refill, since it allows monitoring adherence through pharmaceutical assistance. Therefore, patient adherence to HAART could be evaluated using self-perception (CEAT-VIH) and the viral load test.