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OBJECTIVE: To determine the prevalence of sicca symptoms, dry eye, and secondary Sjögren's syndrome and to evaluate the severity of dry eye in patients with mixed connective tissue disease. METHODS: In total, 44 consecutive patients with mixed connective tissue disease (Kasukawa's criteria) and 41 healthy controls underwent Schirmer's test, a tear film breakup time test, and ocular surface staining to investigate dry eye. In addition, the dry eye severity was graded. Ocular and oral symptoms were assessed using a structured questionnaire. Salivary gland scintigraphy was performed in all patients. Classification of secondary Sjögren's syndrome was assessed according to the American-European Consensus Group criteria. RESULTS: The patients and controls had comparable ages (44.7±12.4 vs. 47.2±12.2 years) and frequencies of female gender (93 vs. 95%) and Caucasian ethnicity (71.4 vs. 85%). Ocular symptoms (47.7 vs. 24.4%) and oral symptoms (52.3 vs. 9.7%) were significantly more frequent in patients than in controls. Fourteen (31.8%) patients fulfilled Sjögren's syndrome criteria, seven of whom (50%) did not have this diagnosis prior to study inclusion. A further comparison of patients with mixed connective tissue disease with or without Sjögren's syndrome revealed that the former presented significantly lower frequencies of polyarthritis and cutaneous involvement than did the patients without Sjögren's syndrome. Moderate to severe dry eye was found in 13 of 14 patients with mixed connective tissue disease and Sjögren's syndrome (92.8%). CONCLUSIONS: Sjögren's syndrome, particularly with moderate to severe dry eye, is frequent in patients with mixed connective tissue disease. These findings alert the physician regarding the importance of the appropriate diagnosis of this syndrome in such patients.

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OBJECTIVES: Drug safety problems can lead to hospital admission. In Brazil, the prevalence of hospitalization due to adverse drug events is unknown. This study aims to estimate the prevalence of hospitalization due to adverse drug events and to identify the drugs, the adverse drug events, and the risk factors associated with hospital admissions. METHOD: A cross-sectional study was performed in the internal medicine ward of a teaching hospital in São Paulo State, Brazil, from August to December 2008. All patients aged ≥18 years with a length of stay ≥24 hours were interviewed about the drugs used prior to hospital admission and their symptoms/complaints/causes of hospitalization. RESULTS: In total, 248 patients were considered eligible. The prevalence of hospitalization due to potential adverse drug events in the ward was 46.4%. Overprescribed drugs and those indicated for prophylactic treatments were frequently associated with possible adverse drug events. Frequently reported symptoms were breathlessness (15.2%), fatigue (12.3%), and chest pain (9.0%). Polypharmacy was a risk factor for the occurrence of possible adverse drug events. CONCLUSION: Possible adverse drug events led to hospitalization in a high-complexity hospital, mainly in polymedicated patients. The clinical outcomes of adverse drug events are nonspecific, which delays treatment, hinders causality analysis, and contributes to the underreporting of cases.

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OBJECTIVE: To determine the conjunctival bacterial flora present in patients with Stevens-Johnson syndrome. METHODS: A prospective study of the conjunctival bacterial flora was performed in 41 eyes of 22 patients with Stevens-Johnson syndrome. The information gathered included the patient's sex and age, the duration of disease, the cause of Stevens-Johnson syndrome, and treatments. Scrapings of the inferior conjunctival fornix were performed in both eyes. Fourteen days before scraping, the patients were asked to interrupt all topical medication and start using 0.5% nonpreserved methylcellulose. The microbiological evaluation included microorganism identification and determination of antibiotic sensitivity. RESULTS: Of 22 patients (41 eyes), 14 (64%) were females, and eight (36%) were males. The mean age was 33.2 years, and the mean duration of disease was 15.6 years. Visual acuity ranged from light perception to 20/25 (1.57 logMar). The treatment received by most patients consisted of tear substitutes, topical antibiotics, and contact lenses. Bacterial identification was positive in 39 eyes (95%) and negative in two eyes (5%). Gram-positive cocci accounted for 55.5% of the microorganisms, whereas gram-positive bacilli and gram-negative bacilli accounted for 19% and 25.5%, respectively. Half of the patients (54%) had multiple bacterial species in their flora, and only one bacterial species was identified in the other half. Resistant bacteria were isolated from four eyes. The antibiotic sensitivity results for the Streptococcus group showed the lowest sensitivity and the highest microbial resistance identified. CONCLUSION: Patients with Stevens-Johnson syndrome have a diverse conjunctival flora that includes many pathogenic species.

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OBJECTIVE: Veno-venous extracorporeal oxygenation for respiratory support has emerged as a rescue alternative for patients with hypoxemia. However, in some patients with more severe lung injury, extracorporeal support fails to restore arterial oxygenation. Based on four clinical vignettes, the aims of this article were to describe the pathophysiology of this concerning problem and to discuss possibilities for hypoxemia resolution. METHODS: Considering the main reasons and rationale for hypoxemia during veno-venous extracorporeal membrane oxygenation, some possible bedside solutions must be considered: 1) optimization of extracorporeal membrane oxygenation blood flow; 2) identification of recirculation and cannula repositioning if necessary; 3) optimization of residual lung function and consideration of blood transfusion; 4) diagnosis of oxygenator dysfunction and consideration of its replacement; and finally 5) optimization of the ratio of extracorporeal membrane oxygenation blood flow to cardiac output, based on the reduction of cardiac output. CONCLUSION: Therefore, based on the pathophysiology of hypoxemia during veno-venous extracorporeal oxygenation support, we propose a stepwise approach to help guide specific interventions.

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OBJECTIVES: We aimed to investigate whether glucocorticoid receptor gene polymorphisms are associated with clinical and metabolic profiles in patients with polycystic ovary syndrome. Polycystic ovary syndrome is a complex endocrine disease that affects 5-8% of women and may be associated with metabolic syndrome, which is a risk factor for cardiovascular disease. Cortisol action and dysregulation account for metabolic syndrome development in the general population. As glucocorticoid receptor gene (NR3C1) polymorphisms regulate cortisol sensitivity, we hypothesized that variants of this gene may be involved in the adverse metabolic profiles of patients with polycystic ovary syndrome. METHOD: Clinical, metabolic and hormonal profiles were evaluated in 97 patients with polycystic ovary syndrome who were diagnosed according to the Rotterdam criteria. The alleles of the glucocorticoid gene were genotyped. Association analyses were performed using the appropriate statistical tests. RESULTS: Obesity and metabolic syndrome were observed in 42.3% and 26.8% of patients, respectively. Body mass index was positively correlated with blood pressure, triglyceride, LDL-c, total cholesterol, glucose and insulin levels as well as HOMA-IR values and inversely correlated with HDL-c and SHBG levels. The BclI and A3669G variants were found in 24.7% and 13.4% of alleles, respectively. BclI carriers presented a lower frequency of insulin resistance compared with wild-type subjects. CONCLUSION: The BclI variant is associated with a lower frequency of insulin resistance in women with polycystic ovary syndrome. Glucocorticoid gene polymorphism screening during treatment of the syndrome may be useful for identifying subgroups of at-risk patients who would benefit the most from personalized treatment.

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OBJECTIVE: Minimally invasive methods are used as alternatives to treat leiomyomas and include uterine artery embolization, which has emerged as a safe, effective method. This study aims to evaluate the magnetic resonance imaging predictors for a reduction in leiomyoma volume in patients undergoing uterine artery embolization. METHODS: This prospective longitudinal study was performed at a university hospital. We followed 50 symptomatic premenopausal women with uterine leiomyomas who underwent uterine artery embolization. We examined 179 leiomyomas among these patients. Magnetic resonance imaging was performed one month before and six months after uterine artery embolization. Two radiologists who specialized in abdominal imaging independently interpreted the images. Main Outcome Measures: The magnetic resonance imaging parameters were the uterus and leiomyomas volumes, their localizations, contrast perfusion pattern and node-to-muscle ratio. RESULTS: Six months after treatment, the average uterine volume reduction was 38.91%, and the leiomyomas were reduced by 55.23%. When the leiomyomas were submucosal and/or had a higher node-to-muscle ratio in the T2 images, the volume reduction was even greater (greater than 50%). Other parameters showed no association. CONCLUSIONS: We conclude that symptomatic uterine leiomyomas in patients undergoing uterine artery embolization exhibit volume reductions greater than 50% by magnetic resonance imaging when the leiomyomas are submucosal and/or had a high node-to-muscle ratio in the T2 images.

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OBJECTIVES: Previous studies have demonstrated the role of inflammation in acute heart failure. The neutrophil-to-lymphocyte ratio was found to be a useful inflammatory marker for predicting adverse outcomes. We hypothesized that an elevated neutrophil-to-lymphocyte ratio would be associated with increased mortality in acute heart failure patients. METHODS: The study cohort consisted of 167 acute heart failure patients with an ejection fraction <50%. The primary endpoint was in-hospital mortality, and the patients were divided into two groups according to in-hospital mortality. RESULTS: In a multivariate regression analysis, including baseline demographic, clinical, and biochemical covariates, the neutrophil to lymphocyte ratio remained an independent predictor of mortality (OR 1.156, 95% CI 1.001 - 1.334, p= 0.048). CONCLUSION: In conclusion, an elevated neutrophil-to-lymphocyte ratio seems to be a predictor of short-term mortality in patients with acute heart failure and a reduced left ventricular ejection fraction.

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OBJECTIVES: Cognitive impairment in the elderly is frequently overlooked by general practitioners. The use of subjective memory complaints as a sign of cognitive impairment by the general practice is controversial. METHODS: Elderly individuals (N = 248) were asked whether they had memory complaints and underwent a cognitive impairment screening. Subjects classified as exhibiting “probable cognitive impairment” underwent a complete cognitive evaluation, and the final diagnoses were established by expert consensus. RESULTS: A total of 147 patients presented with subjective memory complaints, and 43 were further classified as demented or “cognitively impaired not demented”. Subjective memory complaints presented a sensitivity of 100% and a negative predictive value of 100%. CONCLUSION: Subjective memory complaints are an indicator for cognitive impairment screening.

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OBJECTIVE: Depression is the most important neuropsychiatric complication in chronic kidney disease because it reduces quality of life and increases mortality. Evidence demonstrating the association between dialysis shift and depression is lacking; thus, obtaining such evidence was the main objective of this study. METHOD: This cross-sectional study included patients attending a hemodialysis program. Depression was diagnosed using Beck's Depression Inventory. Excessive daytime sleepiness was evaluated using the Epworth Sleepiness Scale. RESULTS: A total of 96 patients were enrolled (55 males, age 48±14 years). Depression and excessive daytime sleepiness were observed in 42.7% and 49% of the patients, respectively. When comparing variables among the three dialysis shifts, there were no differences in age, dialysis vintage, employment status, excessive daytime sleepiness, hemoglobin, phosphorus levels, or albumin levels. Patients in the morning shift were more likely to live in rural areas (p<0.0001), although patients in rural areas did not have a higher prevalence of depression (p= 0.30). Patients with depression were more likely to be dialyzed during the morning shift (p= 0.008). Independent risk factors for depression were age (p<0.03), lower levels of hemoglobin (p<0.01) and phosphorus (p<0.01), and dialysis during the morning shift (p= 0.0009). The hospitalization risk of depressive patients was 4.5 times higher than that of nondepressive patients (p<0.008). CONCLUSION: These data suggest that depression is associated with dialysis shift, higher levels of phosphorus, and lower levels of hemoglobin. The results highlight the need for randomized trials to determine whether this association occurs by chance or whether circadian rhythm disorders may play a role.

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OBJECTIVES: This study investigated performance trends and the age of peak running speed in ultra-marathons from 50 to 3,100 miles. METHODS: The running speed and age of the fastest competitors in 50-, 100-, 200-, 1,000- and 3,100-mile events held worldwide from 1971 to 2012 were analyzed using single- and multi-level regression analyses. RESULTS: The number of events and competitors increased exponentially in 50- and 100-mile events. For the annual fastest runners, women improved in 50-mile events, but not men. In 100-mile events, both women and men improved their performance. In 1,000-mile events, men became slower. For the annual top ten runners, women improved in 50- and 100-mile events, whereas the performance of men remained unchanged in 50- and 3,100-mile events but improved in 100-mile events. The age of the annual fastest runners was approximately 35 years for both women and men in 50-mile events and approximately 35 years for women in 100-mile events. For men, the age of the annual fastest runners in 100-mile events was higher at 38 years. For the annual fastest runners of 1,000-mile events, the women were approximately 43 years of age, whereas for men, the age increased to 48 years of age. For the annual fastest runners of 3,100-mile events, the age in women decreased to 35 years and was approximately 39 years in men. CONCLUSION: The running speed of the fastest competitors increased for both women and men in 100-mile events but only for women in 50-mile events. The age of peak running speed increased in men with increasing race distance to approximately 45 years in 1,000-mile events, whereas it decreased to approximately 39 years in 3,100-mile events. In women, the upper age of peak running speed increased to approximately 51 years in 3,100-mile events.

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OBJECTIVES: This study investigated whether neurophysiologic responses (auditory evoked potentials) differ between typically developed children and children with phonological disorders and whether these responses are modified in children with phonological disorders after speech therapy. METHODS: The participants included 24 typically developing children (Control Group, mean age: eight years and ten months) and 23 children clinically diagnosed with phonological disorders (Study Group, mean age: eight years and eleven months). Additionally, 12 study group children were enrolled in speech therapy (Study Group 1), and 11 were not enrolled in speech therapy (Study Group 2). The subjects were submitted to the following procedures: conventional audiological, auditory brainstem response, auditory middle-latency response, and P300 assessments. All participants presented with normal hearing thresholds. The study group 1 subjects were reassessed after 12 speech therapy sessions, and the study group 2 subjects were reassessed 3 months after the initial assessment. Electrophysiological results were compared between the groups. RESULTS: Latency differences were observed between the groups (the control and study groups) regarding the auditory brainstem response and the P300 tests. Additionally, the P300 responses improved in the study group 1 children after speech therapy. CONCLUSION: The findings suggest that children with phonological disorders have impaired auditory brainstem and cortical region pathways that may benefit from speech therapy.