Evaluation of interventions to reduce catheter-associated bloodstream infection: Continuous tailored education versus one basic lecture

Background: This study evaluated the impact of 2 models of educational intervention on rates of central venous catheter-associated bloodstream infections (CVC-BSIs). Methods: This was a prospective observational study conducted between January 2005 and June 2007 in 2 medical intensive care units (designated ICU A and ICU B) in a large teaching hospital. The study was divided into in 3 periods: baseline (only rates were evaluated), preintervention (questionnaire to evaluate knowledge of health care workers [HCWs] and observation of CVC care in both ICUs), and intervention (in ICU A, tailored, continuous intervention; in ICU B, a single lecture). The preintervention and intervention periods for each ICU were compared. Results: During the preintervention period, 940 CVC-days were evaluated in ICUA and 843 CVC-days were evaluated in ICU B. During the intervention period, 2175 CVC-days were evaluated in ICUA and 1694 CVC-days were evaluated in ICU B. Questions regarding CVC insertion, disinfection during catheter manipulation, and use of an alcohol-based product during dressing application were answered correctly by 70%-100% HCWs. Nevertheless, HCWs` adherence to these practices in the preintervention period was low for CVC handling and dressing, hand hygiene (6%-35%), and catheter hub disinfection (45%-68%). During the intervention period, HCWs` adherence to hand hygiene was 48%-98%, and adherence to hub disinfection was 82%-97%. CVC-BSI rates declined in both units. In ICUA, this decrease was progressive and sustained, from 12CVC-BSIs/1000 CVC-days at baseline to 0 after 9 months. In ICU B, the rate initially dropped from 16.2 to 0 CVC-BSIs/1000 CVC-days, but then increased to 13.7 CVC-BSIs/1000 CVC-days. Conclusion: Personal customized, continuous intervention seems to develop a ""culture of prevention"" and is more effective than single intervention, leading to a sustained reduction of infection rates.

Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy

Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as `benign cytochrome c oxidase deficiency myopathy` is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T > C mt-tRNA(Glu) mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.

Health technology diffusion in developing countries: a case study of CT scanners in Brazil

Background The development of products and services for health care systems is one of the most important phenomena to have occurred in the field of health care over the last 50 years. It generates significant commercial, medical and social results. Although much has been done to understand how health technologies are adopted and regulated in developed countries, little attention has been paid to the situation in low- and middle-income countries (LMICs). Here we examine the institutional environment in which decisions are made regarding the adoption of expensive medical devices into the Brazilian health care system. Methods We used a case study strategy to address our research question. The empirical work relied on in-depth interviews (N = 16) with representatives of a wide range of actors and stakeholders that participate in the process of diffusion of CT (computerized tomography) scanners in Brazil, including manufacturers, health care organizations, medical specialty societies, health insurance companies, regulatory agencies and the Ministry of Health. Results The adoption of CT scanners is not determined by health policy makers or third-party payers of public and private sectors. Instead, decisions are primarily made by administrators of individual hospitals and clinics, strongly influenced by both physicians and sales representatives of the medical industry who act as change agents. Because this process is not properly regulated by public authorities, health care organizations are free to decide whether, when and how they will adopt a particular technology. Conclusions Our study identifies problems in how health care systems in LMICs adopt new, expensive medical technologies, and suggests that a set of innovative approaches and policy instruments are needed in order to balance the institutional and professional desire to practise a modern and expensive medicine in a context of health inequalities and basic health needs.

Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium

Background Sexual contact may be the means by which head and neck cancer patients are exposed to human papillomavirus (HPV). Methods We undertook a pooled analysis of four population-based and four hospital-based case-control studies from the International Head and Neck Cancer Epidemiology (INHANCE) consortium, with participants from Argentina, Australia, Brazil, Canada, Cuba, India, Italy, Spain, Poland, Puerto Rico, Russia and the USA. The study included 5642 head and neck cancer cases and 6069 controls. We calculated odds ratios (ORs) of associations between cancer and specific sexual behaviours, including practice of oral sex, number of lifetime sexual partners and oral sex partners, age at sexual debut, a history of same-sex contact and a history of oral-anal contact. Findings were stratified by sex and disease subsite. Results Cancer of the oropharynx was associated with having a history of six or more lifetime sexual partners [OR = 1.25, 95% confidence interval (CI) 1.01, 1.54] and four or more lifetime oral sex partners (OR = 2.25, 95% CI 1.42, 3.58). Cancer of the tonsil was associated with four or more lifetime oral sex partners (OR = 3.36, 95 % CI 1.32, 8.53), and, among men, with ever having oral sex (OR = 1.59, 95% CI 1.09, 2.33) and with an earlier age at sexual debut (OR = 2.36, 95% CI 1.37, 5.05). Cancer of the base of the tongue was associated with ever having oral sex among women (OR = 4.32, 95% CI 1.06, 17.6), having two sexual partners in comparison with only one (OR = 2.02, 95% CI 1.19, 3.46) and, among men, with a history of same-sex sexual contact (OR = 8.89, 95% CI 2.14, 36.8). Conclusions Sexual behaviours are associated with cancer risk at the head and neck cancer subsites that have previously been associated with HPV infection.

Type of Alcoholic Beverage and Risk of Head and Neck Cancer-025EFA Pooled Analysis Within the INHANCE Consortium

The authors pooled data from 15 case-control studies of head and neck cancer (9,107 cases, 14,219 controls) to investigate the independent associations with consumption of beer, wine, and liquor. In particular, they calculated associations with different measures of beverage consumption separately for subjects who drank beer only (858 cases, 986 controls), for liquor-only drinkers (499 cases, 527 controls), and for wine-only drinkers (1,021 cases, 2,460 controls), with alcohol never drinkers (1,124 cases, 3,487 controls) used as a common reference group. The authors observed similar associations with ethanol-standardized consumption frequency for beer-only drinkers (odds ratios (ORs) = 1.6, 1.9, 2.2, and 5.4 for <= 5, 6-15, 16-30, and > 30 drinks per week, respectively; P(trend) < 0.0001) and liquor-only drinkers (ORs = 1.6, 1.5, 2.3, and 3.6; P < 0.0001). Among wine-only drinkers, the odds ratios for moderate levels of consumption frequency approached the null, whereas those for higher consumption levels were comparable to those of drinkers of other beverage types (ORs = 1.1, 1.2, 1.9, and 6.3; P < 0.0001). Study findings suggest that the relative risks of head and neck cancer for beer and liquor are comparable. The authors observed weaker associations with moderate wine consumption, although they cannot rule out confounding from diet and other lifestyle factors as an explanation for this finding. Given the presence of heterogeneity in study-specific results, their findings should be interpreted with caution.

The awareness of chronic fatigue syndrome: A comparative study in Brazil and the United Kingdom

Objective: While in many Western affluent countries there is widespread awareness of chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), little is known about the awareness of CFS/ME in low- and middle-income countries. We compared the awareness of CFS in Brazil and the United Kingdom. Methods: Recognition and knowledge of CFS were assessed among 120 Brazilian specialist doctors in two major university hospitals using a typical case vignette of CFS. We also surveyed 3914 and 2435 consecutive attenders in Brazilian and British primary care clinics, respectively, concerning their awareness of CFS. Results: When given a typical case vignette of CFS, only 30.8% [95% confidence interval (CI), 22.7-39.9%] of Brazilian specialist doctors mentioned chronic fatigue or CFS as a possible diagnosis, a proportion substantially lower than that observed in Western affluent countries. Similarly, only 16.2% (95% CI, 15.1-17.4%) of Brazilian primary care attenders were aware of CFS, in contrast to 55.1% (95% CI, 53.1-57.1%) of their British counterparts (P <.001). This difference remained highly significant after controlling for patients` sociodemographic and socioeconomic characteristics (P <.001). Conclusions: The awareness of CFS was substantially lower in Brazil than the United Kingdom. The observed difference may influence patients` help-seeking behavior and both doctors` and patients` beliefs and attitudes in relation to fatigue-related syndromes. Attempts to promote the awareness of CFS should be considered in Brazil, but careful plans are required to ensure the delivery of sound evidence-based information. (c) 2008 Elsevier Inc. All rights reserved.

Bipolar disorder comorbid with alcoholism: A (1)H magnetic resonance spectroscopy study

Alcoholism is highly prevalent among bipolar disorder (BD) patients, and its presence is associated with a worse outcome and refractoriness to treatment of the mood disorder. The neurobiological underpinnings that characterize this comorbidity are unknown. We sought to investigate the neurochemical profile of the dorsolateral prefrontal cortex (DLPFC) of BD patients with comorbid alcoholism. A short-TE, single-voxel (1)H spectroscopy acquisition at 1.5T from the left DLFPC of 22 alcoholic BD patients, 26 non-alcoholic BD patients and 54 healthy comparison subjects (HC) were obtained. Absolute levels of N-acetyl aspartate, phosphocreatine plus creatine, choline-containing compounds, myo-inositol, glutamate plus glutamine (Glu + Gln) and glutamate were obtained using the water signal as an internal reference. Analysis of co-variance was used to compare metabolite levels among the three groups. In the primary comparison, non-alcoholic BD patients had higher glutamate concentrations compared to alcoholic BD patients. In secondary comparisons integrating interactions between gender and alcoholism, non-alcoholic BD patients presented significantly higher glutamate plus glutamine (Glu + Gln) than alcoholic BD patients and HC. These results appeared to be driven by differences in male subjects. Alcoholic BD patients with additional drug use disorders presented significantly lower myo-inositol than BD patients with alcoholism alone. The co-occurrence of BD and alcoholism may be characterized by neurochemical abnormalities related to the glutamatergic system and to the inositol second messenger system and/or in glial pathology. These abnormalities may be the neurochemical correlate of an increased risk to develop alcoholism in BD, or of a persistently worse clinical and functional status in BD patients in remission from alcoholism, supporting the clinical recommendation that efforts should be made to prevent or early diagnose and treat alcoholism in BD patients. (C) 2009 Elsevier Ltd. All rights reserved.

Individual risk prediction of nodal and distant metastasis for patients with typical bronchial carcinoid tumors

Objective: Bronchial typical carcinoid tumors are tow-grade malignancies. However, metastases are diagnosed in some patients. Predicting the individual risk of these metastases to determine patients eligible for a radical lymphadenectomy and patients to be followed-up because of distant metastasis risk is relevant. Our objective was to screen for predictive criteria of bronchial typical carcinoid tumor aggressiveness based on a logistic regression model using clinical, pathological and biomolecular data. Methods: A multicenter retrospective cohort study, including 330 consecutive patients operated on for bronchial typical carcinoid tumors and followed-up during a period more than 10 years in two university hospitals was performed. Selected data to predict the individual risk for both nodal and distant metastasis were: age, gender, TNM staging, tumor diameter and location (central/peripheral), tumor immunostaining index of p53 and Ki67, Bcl2 and the extracellular density of neoformed microvessels and of collagen/elastic extracellular fibers. Results: Nodal and distant metastasis incidence was 11% and 5%, respectively. Univariate analysis identified all the studied biomarkers as related to nodal metastasis. Multivariate analysis identified a predictive variable for nodal metastasis: neo angiogenesis, quantified by the neoformed pathological microvessels density. Distant metastasis was related to mate gender. Discussion: Predictive models based on clinical and biomolecular data could be used to predict individual risk for metastasis. Patients under a high individual risk for lymph node metastasis should be considered as candidates to mediastinal lymphadenectomy. Those under a high risk of distant metastasis should be followed-up as having an aggressive disease. Conclusion: Individual risk prediction of bronchial typical carcinoid tumor metastasis for patients operated on can be calculated in function of biomolecular data. Prediction models can detect high-risk patients and help surgeons to identify patients requiring radical lymphadenectomy and help oncologists to identify those as having an aggressive disease requiring prolonged follow-up. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Acute hyperglycemia rapidly stimulates VEGF mRNA translation in the kidney. Role of angiotensin type 2 receptor (AT2)

Angiotensin II (Ang II) and vascular endothelial growth factor (VEGF) are important mediators of kidney injury in diabetes. Acute hyperglycemia increased synthesis of intrarenal Ang I and Ang II and resulted in activation of both Ang II receptors, AT1 and AT2, in the kidney. Losartan (specific AT1 antagonist) or PD123319 (specific AT2 antagonist) did not affect hyperglycemia but prevented activation of renal AT1 and AT2, respectively. In murine renal cortex, acute hyperglycemia increased VEGF protein but not mRNA content after 24 h, which suggested translational regulation. Blockade of AT2, but not AT1, prevented increase in VEGF synthesis by inhibiting translation of VEGF mRNA in renal cortex. Acute hyperglycemia increased VEGF expression in wild type but not in AT2 knockout mice. Binding of heterogeneous nuclear ribonucleoprotein K to VEGF mRNA, which stimulates its translation, was prevented by blockade of AT2, but not AT1. The Akt-mTOR-p70(S6K) signaling pathway, involved in the activation of mRNA translation, was activated in hyperglycemic kidneys and was blocked by the AT2 antagonist. Elongation phase is an important step of mRNA translation that is controlled by elongation factor 1A (eEF1A) and 2 (eEF2). Expression of eEF1A and activity of eEF2 was higher in kidney cortex from hyperglycemic mice and only the AT2 antagonist prevented these changes. To assess selectivity of translational control of VEGF expression, we measured expression of fibronectin (FN) and laminin beta 1 (lam beta 1): acute hyperglycemia increased FN expression at both protein and mRNA levels, indicating transcriptional control, and did not affect the expression of lam beta 1. To confirm results obtained with PD123319, we induced hyperglycemia in AT2 knockout mice and found that in the absence of AT2, translational control of VEGF expression by hyperglycemia was abolished. Our data show that acute hyperglycemia stimulates Ang II synthesis in murine kidney cortex, this leads to AT2 activation and stimulation of VEGF mRNA translation, via the Akt-mTOR-p70(S6K) signaling pathway. Our data show that exclusive translational control of protein expression in the kidney by acute hyperglycemia is not a general phenomenon, but do not prove that it is restricted to VEGF. (C) 2010 Elsevier Inc. All rights reserved.

Noninvasive Brain Stimulation With High-Frequency and Low-Intensity Repetitive Transcranial Magnetic Stimulation Treatment for Posttraumatic Stress Disorder

Objective: We aimed to investigate the efficacy of 20 Hz repetitive transcranial magnetic stimulation (rTMS) of either right or left dorsolateral prefrontal cortex (DLPFC) as compared to sham rTMS for the relief of posttraumatic stress disorder (PTSD)-associated symptoms. Method: In this double-blind, placebo-controlled phase II trial conducted between October 2005 and July 2008, 30 patients with DSM-IV-diagnosed PTSD were randomly assigned to receive 1 of the following treatments: active 20 Hz rTMS of the right DLPFC, active 20 Hz rTMS of the left DLPFC, or sham rTMS. Treatments were administered in 10 daily sessions over 2 weeks. A blinded rater assessed severity of core PTSD symptoms, depression, and anxiety before, during, and after completion of the treatment protocol. In addition, a battery of neuropsychological tests was measured before and after treatment. Results: Results show that both active conditions-20 Hz rTMS of left and right DLPFC induced a significant decrease in PTSD symptoms as indexed by the PTSD Checklist and Treatment Outcome PTSD Scale; however, right rTMS induced a larger effect as compared to left rTMS. In addition, there was a significant improvement of mood after left rTMS and a significant reduction of anxiety following right rTMS. Improvements in PTSD symptoms were long lasting; effects were still significant at the 3-month follow-up. Finally, neuropsychological evaluation showed that active 20 Hz rTMS is not associated with cognitive worsening and is safe for use in patients with PTSD. Conclusions: These results support the notion that modulation of prefrontal cortex can alleviate the core symptoms of PTSD and suggest that high-frequency rTMS of right DLPFC might be the optimal treatment strategy. J an Psychiatry 2010;71(8):992-999 (C) Copyright 2009 Physicians Postgraduate Press, Inc.

Anterior genu corpus callosum and impulsivity in suicidal patients with bipolar disorder

Suicidality is a life-threatening symptom in patients with bipolar disorder (BD). Impulsivity and mood instability are associated with suicidality in mood disorders. Evidence suggests that gray and white matter abnormalities are linked with impulsivity in mood disorders, but little is known about the association between corpus callosum (CC) and impulsivity in BID. We examined the relationship between CC areas, impulsivity and suicidality in BID patients. We studied 10 female BD patients with a history of suicide attempt (mean +/- SD age 36.2 +/- 10.1 years), 10 female BD patients without suicide attempt history (44.2 +/- 12.5 years) and 27 female healthy subjects (36.9 +/- 13.8 years). Impulsivity was evaluated by the Barratt Impulsivity Scale (BIS). We traced MR images to measure the areas of the CC genu, anterior body, posterior body, isthmus and splenium. The genu was divided into anterior, middle and posterior regions. The suicidal and non-suicidal BID patients had significantly higher BIS total, attention and non-planning scores than the healthy subjects (ps < 0.01), and the suicidal BID patients had significantly higher BIS motor scores than the non-suicidal BD and healthy subjects (ps < 0.01). There were no significant differences among the three groups on any regional CC areas, although the suicidal BD patients had the smallest areas. The suicidal BD patients showed a significant inverse correlation between anterior genu area and the BIS total (r = -0.75, p = 0.04), motor (r = -0.79, p = 0.02) and non-planning scores (r = -0.79, p = 0.02). These correlations were not found in the non-suicidal BID patients or healthy subjects. The results suggest that the anterior medial frontal region may be involved in the pathophysiology of impulsive and suicidal behaviors in BD. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Normal metabolite levels in the left dorsolateral prefrontal cortex of unmedicated major depressive disorder patients: A single voxel (1)H spectroscopy study

Few proton magnetic resonance spectroscopy ((1)H spectroscopy) studies have investigated the dorsolateral prefrontal cortex (DLPFC), a key region in the pathophysiology of major depressive disorder (MDD). We used (1)H spectroscopy to verify whether MDD patients differ from healthy controls (HQ in metabolite levels in this brain area. Thirty-seven unmedicated DSM-IV MDD patients were compared with 40 HC. Subjects underwent a short echo-time (1)H spectroscopy examination at 1.5 T, with an 8-cm(3) single voxel placed in the left DLPFC. Reliable absolute metabolite levels of N-acetyl aspartate (NAA), phosphocreatine plus creatine (PCr+Cr), choline-containing compounds (GPC+PC), myo-inositol, glutamate plus glutamine (Glu+Gln), and glutamate were obtained using the unsuppressed water signal as an internal reference. Metabolite levels in the left DLPFC did not statistically differ between MDD patients and HC. We found an interaction between gender and diagnosis on PCr+Cr levels. Male MDD patients presented lower levels of PCr+Cr than male HC, and female MDD patients presented higher levels of PCr+Cr than female HC. Moreover, length of illness was inversely correlated with NAA levels. These findings suggest that there is not an effect of diagnosis on the left DLPFC neurochemistry. Possible effects of gender on PCr+Cr levels of MDD patients need to be further investigated. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Anterior cingulate volumes associated with trait impulsivity in individuals with bipolar disorder

Objective: Impulsivity is associated with the clinical outcome and likelihood of risky behaviors among bipolar disorder (BD) patients. Our previous study showed an inverse relationship between impulsivity and orbitofrontal cortex (OFC) volume in healthy subjects. We hypothesized that BD patients would show an inverse relationship between impulsivity and volumes of the OFC, anterior cingulate cortex (ACC), medial prefrontal cortex, and amygdala, which have been implicated in the pathophysiology of BD. Methods: Sixty-three BD patients were studied (mean +/- SD age = 38.2 +/- 11.5 years; 79% female). The Barratt Impulsiveness Scale (BIS), version 11A, was used to assess trait impulsivity. Images were processed using SPM2 and an optimized voxel-based morphometry protocol. We examined the correlations between BIS scores and the gray matter (GM) and white matter (WM) volumes of the prespecified regions. Results: Left rostral ACC GM volume was inversely correlated with the BIS total score (t = 3.95, p(corrected) = 0.003) and the BIS motor score (t = 5.22, p(corrected) < 0.001). In contrast to our hypothesis, OFC volumes were not significantly associated with impulsivity in BD. No WM volume of any structure was significantly correlated with impulsivity. No statistical association between any clinical variable and the rostral ACC GM volumes reached significance. Conclusions: Based on our previous findings and the current results, impulsivity may have a different neural representation in BD and healthy subjects, and the ACC may be involved in the pathophysiology of abnormal impulsivity regulation in BD patients.

An MRI-based approach for the measurement of the dorsolateral prefrontal cortex in humans

The dorsolateral prefrontal cortex (DLPFC) has been implicated in the pathophysiology of mental disorders. Previous region-of-interest MRI studies that attempted to delineate this region adopted various landmarks and measurement techniques, with inconsistent results. We developed a new region-of-interest measurement method to obtain morphometric data of this region from structural MRI scans, taking into account knowledge from cytoarchitectonic postmortem studies and the large inter-individual variability of this region. MRI scans of 10 subjects were obtained, and DLPFC tracing was performed in the coronal plane by two independent raters using the semi-automated software Brains2. The intra-class correlation coefficients between two independent raters were 0.94 for the left DLPFC and 0.93 for the right DLPFC. The mean +/- S.D. DLPFC volumes were 9.23 +/- 2.35 ml for the left hemisphere and 8.20 +/- 2.08 ml for the right hemisphere. Our proposed method has high inter-rater reliability and is easy to implement, permitting the standardized measurement of this region for clinical research applications. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been proposed as a possible candidate for involvement in the pathophysiology of bipolar disorder ( BD). To determine whether an association exists between the BDNF Val66Met genotype and morphometric abnormalities of the brain regions involved in memory and learning in BD and healthy subjects. Forty-two BD patients and 42 healthy subjects were studied. Interactions between BDNF Val66Met genotype and diagnosis in gray ( GM) volumes were analyzed using an optimized voxel-based morphometry technique. Declarative memory function was assessed with the California Verbal Learning Test II. Left and right anterior cingulate GM volumes showed a significant interaction between genotype and diagnosis such that anterior cingulate GM volumes were significantly smaller in the Val/Met BD patients compared with the Val/Val BD patients (left P = 0.01, right P = 0.01). Within-group comparisons revealed that the Val/Met carriers showed smaller GM volumes of the dorsolateral prefrontal cortex compared with the Val/Val subjects within the BD patient (P = 0.01) and healthy groups (left P = 0.03, right P = 0.03). The Val/Met healthy subjects had smaller GM volumes of the left hippocampus compared with the Val/Val healthy subjects (P<0.01). There was a significant main effect of diagnosis on memory function (P = 0.04), but no interaction between diagnosis and genotype was found (P = 0.48). The findings support an association between the BDNF Val66Met genotype and differential gray matter content in brain structures, and suggest that the variation in this gene may play a more prominent role in brain structure differences in subjects affected with BD. Neuropsychopharmacology (2009) 34, 1904-1913; doi: 10.1038/npp.2009.23; published online 18 March 2009