The accuracy of the Global Trigger Tool is higher for the identification of adverse events of greater harm: a diagnostic test study.

Global Trigger Tool (GTT) of the Institute for Healthcare Improvement (IHI) has been used as a measurement strategy for patient safety by several institutions and national programs. Although the greater ability of the GTT to identify adverse events (AEs) compared to other methods has already been demonstrated, there are few data on its accuracy, and studies suggest lower sensitivity for minor AEs. This study aimed to assess the accuracy of the GTT for identifying AEs in adult inpatients for all AEs and for the subgroup of AEs with greater harm to the patient, classified as F-I on the IHI-GTT adapted version of the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) Index for Categorizing Errors. In this diagnostic test study, GTT is the index test and identification of AEs (yes/no) represents the condition of interest. Due to the lack of a gold standard test, a composite reference standard method was developed. Reference standard method combined real-time (during hospitalizations) and retrospective search of medical records and administrative data for screening criteria and AEs. Both tests were applied to a random sample of 211 hospitalizations of adult inpatients during October-November 2016 in a large public hospital in Belo Horizonte, Brazil. The accuracy of the GTT was evaluated using sensitivity, specificity, and global accuracy. A total of 176 AEs were identified in 67 admissions using reference standard method and 129 AEs in 76 admissions using GTT, resulting in rates of 126 and 93 AEs/1000 patient-days, respectively. Sensitivity, specificity, and global accuracy of the GTT for the identification of individual AEs were, respectively, 0.41 (95% confidence interval [CI] 0.34; 0.49), 0.68 (95% CI 0.60; 0.74), and 0.54 (95% CI 0.49; 0.60) for all AEs, regardless of the harm categorization, and 0.85 (95% CI 0.72; 0.93), 0.88 (95% CI 0.82; 0.92), and 0.87 (95% CI 0.82; 0.91) for the subgroup of AEs categorized as harm F-I. Among the main AEs missed by the GTT are AEs related to nursing care, such as those related to peripheral venous access and gastric/enteric catheters. GTT proved to be a valid method for identifying AEs in adult inpatients. Its accuracy increases when minor harm AEs are not counted. Among the main AEs missed by the GTT are those related to nursing care. Therefore, the GTT should be used in conjunction with other measurement strategies to achieve results that are representative of the quality profile of the care provided and, thus, guide the best improvement strategies.

Pregnancy Outcomes in Wilson's Disease Women: Single-Center Case Series.

OBJECTIVES: To evaluate and compare pregnancy outcomes in women with Wilson's disease (WD) undergoing different therapies during pregnancy. MATERIAL AND METHODS: Retrospective review of medication in WD patients during pregnancy and the outcomes. RESULTS: Of 26 pregnancies, zinc was used in 14 (53.8%), D-penicillamine in 4 (15.4%) patients, and 8 (30.8%) were untreated. Spontaneous abortion was observed in 8 (30.8%) pregnancies - untreated patients (4/8 pregnancies), zinc (2/14 pregnancies) and D-penicillamine (2/4 pregnancies) -, healthy outcome in 12 (46.1%) and birth defects in 6 (23.1%). All cases of birth defects occurred in patients using zinc therapy (6/14 pregnancies). CONCLUSIONS: A remarkably high frequency of fetal complications shed lights on the potentially harmful effect of WD drugs during childbearing age. Zinc's safety profile may have to be better evaluated during pregnancy, as all of birth defects occurred with zinc therapy.

Assessment of the reliability of the IHI Global Trigger Tool: new perspectives from a Brazilian study.

OBJECTIVE: To assess the reliability of the Institute for Healthcare Improvement's Global Trigger Tool (IHI-GTT) between nurses and medical students as primary reviewers to measure adverse events (AEs). DESIGN: Interrater reliability study. SETTING: A 500-bed general public hospital in Belo Horizonte, Brazil. PARTICIPANTS: A randomly selected sample of 220 hospital admissions of adults (≥18 years) from Oct-Nov, 2016. INTERVENTION: Two 4th-5th year-medical students and two experienced nurses applied a Portuguese-translated version of the IHI-GTT to medical records. The role of medical reviewer was performed by two senior physicians specialists in Internal Medicine. MAIN OUTCOME MEASURES: Ability to identify AEs was compared between pairs and against medical reviewer through percentage inter-examiner agreement and Kappa coefficient (K). Two outcomes -- "AE identification" and "category of harm" -- were evaluated according to two different denominators -- "admissions" (the total number of admissions evaluated in the sample; reflects the presence or not of at least one AE in each admission) and "all possibilities of agreement" (obtained by adding each identified AE to the admissions without events; allows agreement assessment to be performed for each AE individually). RESULTS: Were identified 199 adverse events in 90 hospitalizations, with rates of 40.9% of admissions with AEs, 76.1 AEs/1,000 patient-days and 90.5 AEs/100 admissions. Comparing student-pair and nurse-pair, we found K = 0.76 (95% IC 0.62-0.88) and K = 0.17 (95% IC 0.06-0.27) for "AE identification" outcome and K = 0.28 (95% IC 0.01-0.55) and K = 0.46 (95% IC 0.28-0.64) for "category of harm" outcome to denominators "admission" and "all possibilities of agreement", respectively. There was no significant difference between the performances of the different primary reviewers composed in any analyses. CONCLUSION: IHI-GTT reliability varies considerably depending on the denominator used to calculate agreement. As the purpose of the tool is, in addition to measuring, promoting opportunities for quality of care improvement, the individual analysis of the AEs seems more appropriate. Further studies are needed to assess the implications of the slight agreement reached between primary reviewers on the test's overall accuracy. Moreover, advanced medical students may be considered for primary review in settings where unavailability of staff is a barrier to IHI-GTT adoption.

Persistent fever after pacemaker lead extraction.

The implant indication of cardiac electronic devices continues to expand; therefore, we have observed increasing complications related to their removal. We describe the case of a patient who presented with prolonged bloodstream infection after having undergone removal of a pacemaker. After extensive workup for fever of unknown origin and antibiotic therapy without any improvement, it was possible to demonstrate a foreign body in the right subclavian vein and superior vena cava corresponding to the distal part of the right ventricular lead. Endovascular removal of the foreign body and prolonged antibiotic administration was followed by complete resolution of the clinical picture. We ascribed the difficulty in diagnosing the source of the infection especially to the lack of local manifestations.

Impact of Neurological Complications on Long-Term Outcomes in Patients with Infective Endocarditis.

Neurological complications are frequent during the active course of infective endocarditis (IE), and they are associated with high in-hospital mortality rates. However, limited data exist on the prognostic value of these complications for late outcomes. This study aimed to assess the long-term impact of neurological complications in patients surviving an IE episode. A total of 263 consecutive IE patients admitted to a tertiary care center between 2007 and 2022 were prospectively included. Neurological complications at admission included transient ischemic attack (TIA), ischemic stroke, hemorrhagic stroke, intracerebral abscess, and meningitis. The primary outcome was a composite of overall mortality or heart valve surgery. Of the patients, 34.2% died in the hospital, leaving 173 survivors for long-term follow-up. Over a median of 3.5 years, 29 patients died, and 13 (9%) underwent cardiac surgery, resulting in an overall adverse event rate of 30%. Neurological complications independently predicted long-term adverse outcomes (hazard ratio (HR) 2.237; 95% CI 1.006-4.976), after adjusting for age, chronic kidney disease (CKD), and heart failure (HF) development. In an IE patient cohort, neurological complications at admission, which is a complication directly related to the IE process, were independent predictors of long-term outcomes.

Effectiveness of unsedated transnasal endoscopy with white-light, flexible spectral imaging color enhancement, and lugol staining for esophageal cancer screening in high-risk patients.

BACKGROUND AND AIMS: Transnasal endoscopy (TNE) has been proposed to screen for esophageal squamous cell cancer (ESCC) in Asia. This study aimed to assess the feasibility and tolerance of Brazilian patients to undergo unsedated TNE for screening, the prevalence of ESCC in this population, and the effectiveness of white-light endoscopy (WLE) and digital chromoendoscopy [flexible spectral imaging color enhancement (FICE)] to diagnose esophageal neoplasia. PATIENTS AND METHODS: This was a diagnostic test study that enrolled patients with head and neck squamous cell cancer (HNSCC) referred to ESCC screening. Patients' tolerance was rated by a numeric pain intensity scale. Interventions included unsedated TNE with WLE and FICE examination of the esophagus, in a tandem manner with blinded operators, followed by lugol chromoscopy. Performance of WLE and FICE for neoplasia detection was compared with the reference standard (lugol chromoscopy plus histology). RESULTS: A total of 106 patients were recruited. TNE was feasible in 99.1%, and 92% of the patients rated the discomfort as absent or minimal. Thirteen ESCC were detected (12.3%), with 10 early cancers (77%). The tests showed an excellent performance and there was no difference between WLE (sensitivity 92.3%, specificity 98.9%, accuracy 98.1%, area under curve 0.995) and FICE (sensitivity 100%, specificity 98.9%, accuracy 99%, area under curve 0.956) for esophageal neoplasia detection. CONCLUSIONS: Unsedated TNE is a feasible, well accepted, and efficient diagnostic tool for the screening of ESCC. The elevated rate of esophageal neoplasia strengthens the recommendations to screen patients with HNSCC. The yields of WLE and FICE were similar for ESCC detection.

Poor cardiorespiratory fitness may be an indicator of more severe liver inflammation in non-alcoholic fatty liver disease patients.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is related to cardiovascular disease. Cardiorespiratory fitness (CRF) is an important indicator of cardiovascular health. Therefore, we aimed to evaluate the CRF of NAFLD patients. METHODS: Cross-sectional study, including 32 patients with biopsy-proved NAFLD. The patients underwent ergometric test (ET) and six-minute walk test (6MWT) to determine CRF. The test results were compared to disease parameters and with each other. RESULTS: Considering the ET, 20 (62.5%) patients had very poor or poor CRF, and in 12 (37.5%), it was regular or good. In the 6MWT, 13 (40.6%) individuals had poor CRF, in 12 (37.5%), it was very poor, and in seven (21.9%), regular. NAFLD activity score (NAS) ≥5 was observed in 12 (37.5%) individuals. Twelve (37.5%) patients were sedentary, 11 (34.4%), insufficiently active, and nine (28.1%), active. Obesity and liver inflammation on biopsy were associated with very poor/poor CRF. NAS ≥5 and sedentary lifestyle were independently associated with very poor/poor CRF by ET. Although mean VO2max values determined by both tests were similar, no correlation of VO2max determined by ET and 6MWT was observed, as occurred for the distance walked in 6MWT and values of metabolic equivalent (MET) determined by ET. There was no reproducibility between CRF determined by ET and 6MWT. CONCLUSION: Most NAFLD patients had very poor or poor CRF. Severe liver injury (NAS ≥5) and sedentary lifestyle were independently associated with very poor/poor fitness, according to ET. No reproducibility was observed between the CRF defined by ET and 6MWT.

Occult hepatitis B virus infection in patients with chronic liver disease of different etiology in a Brazilian referral center: comparison of two different hepatitis B virus deoxyribonucleic acid amplification protocols: a cross-sectional study.

BACKGROUND: Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) in the liver of individuals with undetectable hepatitis B virus surface antigen (HBsAg) in the serum. The actual prevalence of OBI and its clinical relevance are not yet fully understood. OBJECTIVE: To evaluate the prevalence of HBV DNA in liver biopsies of HBsAg-negative patients with chronic liver disease of different etiologies in a referral center in Brazil and compare two different HBV DNA amplification protocols to detect HBV. DESIGN AND SETTING: This cross-sectional observational study was conducted at the Liver Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil, between January 2016 and December 2019. METHODS: HBV DNA was investigated in 104 liver biopsy samples from individuals with chronic liver disease of different etiologies, in whom HBsAg was undetectable in serum by nested-polymerase chain reaction (nested-PCR), using two different protocols. RESULTS: OBI, diagnosed by detecting HBV DNA using both protocols, was detected in 6.7% of the 104 individuals investigated. Both protocols showed a good reliability. CONCLUSION: In addition to the differences in the prevalence of HBV infection in different regions, variations in the polymerase chain reaction technique used for HBV DNA amplification may be responsible for the large variations in the prevalence of OBI identified in different studies. There is a need for better standardization of the diagnostic methods used to diagnose this entity.

Schistosome-Associated Pulmonary Arterial Hypertension: A Review Emphasizing Pathogenesis.

Schistosomiasis, especially due to Schistosoma mansoni, is a well-recognized cause of pulmonary arterial hypertension (PAH). The high prevalence of this helminthiasis makes schistosome-related PAH (Sch-PAH) one of the most common causes of this disorder worldwide. The pathogenic mechanisms underlying Sch-PAH remain largely unknown. Available evidence suggests that schistosome eggs reach the lung via portocaval shunts formed as a consequence of portal hypertension due to hepatosplenic schistosomiasis. Once deposited into the lungs, the eggs elicit an immune response resulting in periovular granuloma formation. Immune mediators drive transforming growth factor-ß (TGF-ß) release, which gives rise to pulmonary vascular inflammation with subsequent remodeling and development of angiomatoid and plexiform lesions. These mechanisms elicited by the eggs seem to become autonomous and the vascular lesions progress independently of the antigen. Portopulmonary hypertension, which pathogenesis is still uncertain, may also play a role in the genesis of Sch-PAH. Recently, there have been substantial advances in the diagnosis and treatment of PAH, but it remains a difficult condition to recognize and manage, and patients still die prematurely from right-heart failure. Echocardiography is used for screening, and the formal diagnosis requires right-heart catheterization. The experience in treating Sch-PAH is largely limited to the phosphodiesterase type 5 inhibitors, with evidence suggesting that these vasodilators improve symptoms and may also improve survival. Considering the great deal of uncertainty about Sch-PAH pathogenesis, course, and treatment, the aim of this review is to summarize current knowledge on this condition emphasizing its pathogenesis.

Cell-derived microvesicles in infective endocarditis: Role in diagnosis and potential for risk stratification at hospital admission.

OBJECTIVES: To characterize the plasmatic profile of cell-derived microvesicles (MVs) at diagnosis and during the treatment of patients with infective endocarditis (IE). METHODS: Blood samples from 57 patients with IE were obtained on 3 consecutive moments: upon admission (T0), at 2 weeks (T1), and at the end of treatment (T2), and were compared with 22 patients with other bacterial infections. MPs were measured by flow cytometry and labeled for specific cell markers of CD45 (leukocytes), CD66b (neutrophils), CD14 (monocytes), CD41a (platelets), CD51 (endothelial cells), CD3 (T lymphocyte) and CD235a (erythrocytes). RESULTS: MVs from platelets (pltMVs), leukocytes (leukMVs), neutrophils (neutMVs), monocytes (monoMVs) and lymphocytes (lymphMVs) were significantly more elevated in the patients with IE, compared to the patients with other bacterial infections, despite comparable age, sex, blood counts and C-reactive protein levels. MVs values revealed a relatively stable pattern over time in IE, except for a significant increase in leukMVs and neutMVs in T1. LeukMVs (p = 0.011), neutMVs (p = 0.010), monoMVs (p = 0.016) and lymphMVs (p = 0.020), measured at admission, were significantly higher in IE patients that died during hospitalization in comparison with those that survived. In a multivariable analyses, the levels of neutMVs remained as an independent factor associated with mortality (odds ratio 2.203; 95% confidence interval 1.217 - 3.988; p = 0.009), adjustment for heart failure during the treatment. CONCLUSIONS: Plasma levels of pltMVs, leukMVs, neutMVs, monoMVs and lymphMVs were significantly more elevated in patients with IE than in patients with other bacterial infections at hospital admission. Furthermore, neutMVs at admission have been identified as an independent predictor of mortality in patients with IE. Thus, cell derived MPs may become an important tool in the differential diagnosis and mortality risk assessment early in the course of IE suspected cases.

Occult hepatitis B virus infection in patients with chronic liver disease of different etiology in a Brazilian referral center: comparison of two different hepatitis B virus deoxyribonucleic acid amplification protocols: a cross-sectional study

ABSTRACT BACKGROUND: Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) in the liver of individuals with undetectable hepatitis B virus surface antigen (HBsAg) in the serum. The actual prevalence of OBI and its clinical relevance are not yet fully understood. OBJECTIVE: To evaluate the prevalence of HBV DNA in liver biopsies of HBsAg-negative patients with chronic liver disease of different etiologies in a referral center in Brazil and compare two different HBV DNA amplification protocols to detect HBV. DESIGN AND SETTING: This cross-sectional observational study was conducted at the Liver Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil, between January 2016 and December 2019. METHODS: HBV DNA was investigated in 104 liver biopsy samples from individuals with chronic liver disease of different etiologies, in whom HBsAg was undetectable in serum by nested-polymerase chain reaction (nested-PCR), using two different protocols. RESULTS: OBI, diagnosed by detecting HBV DNA using both protocols, was detected in 6.7% of the 104 individuals investigated. Both protocols showed a good reliability. CONCLUSION: In addition to the differences in the prevalence of HBV infection in different regions, variations in the polymerase chain reaction technique used for HBV DNA amplification may be responsible for the large variations in the prevalence of OBI identified in different studies. There is a need for better standardization of the diagnostic methods used to diagnose this entity.

Outcomes of infective endocarditis in the current era: Early predictors of a poor prognosis.

BACKGROUND: The early identification of patients at risk of complications of infective endocarditis (IE) using parameters obtained as part of routine practice is essential for guiding clinical decision-making. This study aimed to identify a parameter at hospital admission that predicts the outcome, adding value to other well-known factors of a poor prognosis in IE. METHODS: Two hundred and three patients with IE were included in this study. Clinical evaluation, echocardiography, blood cultures, and routine laboratory tests were performed at hospital admission. The endpoint was in-hospital mortality. RESULTS: The mean age of the patients was 48.2±16.6 years; 62% were male and 38% had rheumatic heart disease. During treatment, cardiac surgery was performed in 111 patients (55%), and the overall in-hospital mortality rate was 32%. In the multivariable analysis, the independent predictors of death were age (odds ratio (OR) 1.07, 95% confidence interval (CI) 1.02-1.13), C-reactive protein (CRP) at hospital admission (OR 1.12, 95% CI 1.04-1.21), length of the vegetation at diagnosis (OR 1.15, 95% CI 1.03-1.28), development of heart failure (OR 6.43, 95% CI 2.14-19.33), and embolic events during antimicrobial therapy (OR 12.14, 95% CI 2.11-71.89). CONCLUSIONS: An elevated CRP level at hospital admission and vegetation length at diagnosis were strong predictors of in-hospital mortality in IE, independent of other prognostic parameters, specifically taking into account patient characteristics and complications during therapy.

Successful treatment of a disseminated Sporothrix schenckii infection and in vitro analysis for antifungal susceptibility testing.

We report a case of a diabetic patient with localized osteoarticular sporotrichosis followed by widespread dissemination of the infection, which was successfully treated with amphotericin B. In addition, we evaluated the in vitro antifungal activity of 4 agents against both the mycelial and the yeast forms of the isolated fungus.

Cardiac manifestations of parasitic diseases.

The heart may be affected directly or indirectly by a variety of protozoa and helminths. This involvement may manifest in different ways, but the syndromes resulting from impairment of the myocardium and pericardium are the most frequent. The myocardium may be invaded by parasites that trigger local inflammatory response with subsequent myocarditis or cardiomyopathy, as occurs in Chagas disease, African trypanosomiasis, toxoplasmosis, trichinellosis and infection with free-living amoebae. In amoebiasis and echinococcosis, the pericardium is the structure most frequently involved with consequent pericardial effusion, acute pericarditis, cardiac tamponade or constrictive pericarditis. Chronic hypereosinophilia due to helminth infections, especially filarial infections, has been associated with the development of tropical endomyocardial fibrosis, a severe form of restrictive cardiomyopathy. Schistosomiasis-associated lung vasculature involvement may cause pulmonary hypertension (PH) and cor pulmonale Tropical pulmonary eosinophilia, which is characterised by progressive interstitial fibrosis and restrictive lung disease, may lead to PH and its consequences may occur in the course of filarial infections. Intracardiac rupture of an Echinococcus cyst can cause membrane or secondary cysts embolisation to the lungs or organs supplied by the systemic circulation. Although unusual causes of cardiac disease outside the endemic areas, heart involvement by parasites should be considered in the differential diagnosis especially of myocardial and/or pericardial diseases of unknown aetiology in both immunocompetent and immunocompromised individuals. In this review, we updated and summarised the current knowledge on the major heart diseases caused by protozoan and metazoan parasites, which either involve the heart directly or otherwise influence the heart adversely.

Development of an experimental model of schistosomal myeloradiculopathy.

Schistosomal myeloradiculopathy (SMR) is a severe form of presentation of schistosomiasis in which Schistosoma spp. affect the spinal cord. The aims of the present study were to develop an animal model of SMR caused by S. mansoni, to characterize both sensory and motor abnormalities in the infected animals, and to investigate the relationship of the sensory, motor and histological findings with the progression of the infection over time. Mechanical sensitivity and behavioral tests were performed followed by euthanasia in male Wistar rats divided into six groups of five animals each, on days 5, 10, 20 and 30 after infection of S. mansoni eggs. The controls were subjected to the same procedure but were administered phosphate-buffered saline (PBS). The spinal cord was removed and subjected to histological analysis. S. mansoni eggs were found in the spinal cord of 25% of the infected animals, which belonged to the groups that exhibited more significant reduction of the superficial mechanical sensitivity, thermal sensitivity and muscle strength. This model proved to be satisfactory to assess functional changes in Wistar rats and might be used in studies investigating the pathogenesis of SMR. To our knowledge, this is the first experimental model of SMR.

Intrathecal cytokines in spinal cord schistosomiasis.

We investigate the cytokine profile in the cerebrospinal fluid (CSF) and serum of patients with spinal cord schistosomiasis (SCS). Increased levels of IL-1beta, IL-4, IL-6 and IL-10 and low concentrations of TNF-alpha and IFN-gamma were observed in both CSF and serum. CSF showed higher levels of IL-4 and IL-6 when compared to the paired serum samples. A negative correlation between the concentrations of IL-10 and IFN-gamma was observed in the CSF. These findings suggest an inflammatory as well as a skewed type-2 immune response that probably occur both locally and systemically and may be involved in the pathogenesis of SCS.

Localized hepatic tuberculosis presenting as fever of unknown origin.

Localized hepatic tuberculosis is a rare clinical form of tuberculosis infection; it has signs and symptoms related only to hepatic injury, with minimal or no extrahepatic involvement. It frequently presents as a non-specific syndrome, with systemic manifestations, which can sometimes result in a diagnostic dilemma. A high index of suspicion is required and a definitive diagnosis can be very difficult. We report a case of localized hepatic tuberculosis that presented as fever of unknown origin.

Probiotics as a complementary therapeutic approach in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is currently recognized as one of the most common causes of chronic liver disease. It involves a spectrum of conditions that include pure steatosis without inflammation, steatohepatitis, fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes and, thus, oxidative stress, which is followed by inflammatory response. However, NAFLD pathogenesis is still largely unknown and has been extensively investigated. Although life style modification with the aim of losing weight has been advocated to treat this disorder, its effectiveness is limited; additionally, there is no specific pharmacologic treatment until nowadays. Recent evidence suggests that the gut microbiota may play a role in the development of insulin resistance, hepatic steatosis, necroinflammation and fibrosis. Differences in gut microbiota between NAFLD patients and lean individuals as well as presence of small intestinal bacterial overgrowth in NAFLD subjects have been demonstrated. Furthermore, some data indicate that the immunoregulatory effects of probiotics may be beneficial in NAFLD treatment as they modulate the intestinal microbiota; improve epithelial barrier function and strengthen the intestinal wall decreasing its permeability; reduce bacterial translocation and endotoxemia; improve intestinal inflammation; and reduce oxidative and inflammatory liver damage. In this article, we review the clinical trials on the use of probiotics in the treatment of NAFLD and discuss the effects of these agents and their efficacy as an emerging therapeutic resource to treat NAFLD patients.