Drug-resistant tuberculosis in six hospitals in Rio de Janeiro, Brazil

SETTING: Tuberculosis (TB) drug resistance survey in six hospitals in Rio de Janeiro, Brazil. OBJECTIVE: To estimate resistance to at least one drug (DR) and multidrug resistance (MDR) and identify associated factors. DESIGN: One-year cross-sectional survey. Hospitals were included as a convenience sample. RESULTS: Of 595 patients investigated, 156 (26.2%) had previously undergone anti-tuberculosis treatment, 433 (72.8%) were not previously treated and information on the remaining 6 was not available. Overall, DR and MDR rates were high, at respectively 102 (17.1%, 95%CI 14.3-20.5) and 44 (7.4%, 95%CI 5.5-9.9) cases. Among individuals not previously treated, 17 had MDR (3.9%, 95%CI 2.4-6.3) and diagnosis in a TB reference hospital was independently associated with MDR (prevalence ratio [PR] 3.3, 95%CI 1.2-8.7) after multivariate analysis. Among previously treated individuals, 27 had MDR (17.3%, 95%CI 11.7-24.2). MDR-TB was independently associated with diagnosis in a TB reference hospital (PR 3.6, 95%CI 1.5-8.7), male sex (PR 2.3,95%CI 1.2-4.4) and dyspnoea (PR 0.3, 95%CI 0.1-0.7). CONCLUSION: We found high levels of DR- and MDR-TB. Our study design did not permit us to determine the contribution of community versus nosocomial transmission. Further studies are needed to establish this. Nevertheless, hospitals should be recognised as a potential source of transmission of resistant TB strains and urgent measures to avoid nosocomial TB transmission should be taken.

Access to tuberculosis diagnosis in Itaborai City, Rio de Janeiro, Brazil: the patient`s point of view

SETTING: Itaborai Municipality in Rio de Janeiro, Brazil. OBJECTIVE: To evaluate access to tuberculosis (TB) diagnosis for users of the Family Health Program (FHP) and Reference Ambulatory Units (RAUs). DESIGN : A cross-sectional study was conducted in Itaborai City, Rio de Janeiro, Brazil. Between July and October 2007, a sample of 100 TB patients registered consecutively with the TB Control Program was interviewed using the primary care assessment tool. The two highest scores, describing `almost always` and `always`, or `good` and `very good`, were used as a cut-off point to define high quality access to diagnosis. RESULTS: FHP patients were older and had less education than RAU interviewees. Sex and overcrowding did not differ in the two groups. Patient groups did not differ with regard to the number of times care was sought at a unit, transport problems, cost of attending units and availability of consultation within 24 h. Adequate access to diagnosis was identified by 62% of the FHP patients and 53% of the RAU patients (P = 0.01). CONCLUSION: In Itaborai, Rio de Janeiro, TB patients believe that the FHP units provide greater access to TB diagnosis than RAUs. These findings will be used by the Department of Health to improve access to diagnosis in Itaborai.

A Dynamical Modeling to Study the Adaptive Immune System and the Influence of Antibodies in the Immune Memory

Immunological systems have been an abundant inspiration to contemporary computer scientists. Problem solving strategies, stemming from known immune system phenomena, have been successfully applied to chall enging problems of modem computing. Simulation systems and mathematical modeling are also beginning use to answer more complex immunological questions as immune memory process and duration of vaccines, where the regulation mechanisms are not still known sufficiently (Lundegaard, Lund, Kesmir, Brunak, Nielsen, 2007). In this article we studied in machina a approach to simulate the process of antigenic mutation and its implications for the process of memory. Our results have suggested that the durability of the immune memory is affected by the process of antigenic mutation.and by populations of soluble antibodies in the blood. The results also strongly suggest that the decrease of the production of antibodies favors the global maintenance of immune memory.

Tuberculosis incidence among contacts of active pulmonary tuberculosis

BACKGROUND: Treatment of latent tuberculosis (TB) infection (LTBI) in Brazil is recommended only in the case of contacts of pulmonary smear-positive TB patients aged <= 15 years with a tuberculin skin test (TST) >= 10 mm and no previous bacille Calmette-Guerin (BCG) vaccination or with a TST >= 15 mm regardless of previous BCG vaccination. OBJECTIVE: To evaluate the 2-year incidence and predictors of TB among contacts who did not meet the Brazilian criteria for LTBI treatment. DESIGN: Retrospective cohort study. Contacts aged between 12 and 15 years and those aged >15 years who did not meet the Brazilian criteria for LTBI treatment were enrolled in the study. RESULTS: TB incidence was 3.2% (22/667), with an estimated TB rate of 1649 per 100000 population. Risk of TB was greater among the 349 contacts with TST >= 5 mm (5.4%) compared to the 318 contacts with TST <5 mm, (0.9%; RR 6.04, 95%CI 1.7-20.6). CONCLUSION: The high incidence of TB among contacts who did not meet the Brazilian criteria for LTBI treatment strongly suggests that these criteria should be reviewed. Furthermore, even among BCG-vaccinated contacts, TST induration >= 5 mm, was the only variable that predicted the development of TB disease within 2 years.

Two-step tuberculin skin test and booster phenomenon prevalence among Brazilian medical students

SETTING: Five medical schools in three cities in Rio de Janeiro State, Brazil, with different tuberculosis (TB) incidence rates. OBJECTIVE: To evaluate the prevalence of the booster phenomenon and its associated factors in a voting universally BCG-vaccinated TB-exposed population. DESIGN: A two-step tuberculin skin test (TST) was performed among undergraduate medical students. Boosting was defined as an induration >= 10 mm in the second TST (TST2), with an increase of at least 6 mm over the first TST (TST1). The association of boosting with independent variables was evaluated using multivariate analysis. RESULTS: Of the 764 participants (mean age 21.9 +/- 2.7 years), 672 (87.9%) had a BCG scar. The overall booster SUMMARY phenomenon prevalence was 8.4% (95%CI 6.5-10.6). Boosting was associated with TST1 reactions of 1-9 mm (aOR 2.5, 95%CI 1.04-5.9) and with BCG vaccination, mostly after infancy, i.e., after age two years (aOR 9.1, 95%,CI 1.2-70.7). CONCLUSION: The prevalence of the booster phenomenon was high. A two-step TST in young BCG-vaccinated populations, especially in those with TST1 reactions of 1-9 mm, can avoid misdiagnosis as a false conversion and potentially reduce unnecessary treatment for latent TB infection.

Study of the Discriminative Validity of the PHQ-9 and PHQ-2 in a Sample of Brazilian Women in the Context of Primary Health Care

PURPOSE. This study aimed to assess the discriminative validity of the Brazilian version of the Patient Health Questionnaire (PHQ-9) and of its reduced version (PHQ-2). DESIGN AND METHODS. The sample consisted of 177 women (60 cases of depression and 117 noncases). The SCID-IV was used as the gold standard. FINDINGS. For the PHQ-9, a cutoff score equal to or higher than 10 proved to be the most adequate for the screening of depression, whereas the best cutoff score for the PHQ-2 was found to lie between 3 and 4. PRACTICE IMPLICATIONS. The systematic use of these instruments in nursing and in the context of primary health care could favor the early detection of depression.

Modulation of Mediotemporal and Ventrostriatal Function in Humans by Delta 9-Tetrahydrocannabinol A Neural Basis for the Effects of Cannabis sativa on Learning and Psychosis

Context: Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms. Objectives: To investigate the effects of 2 main psychoactive constituents of C sativa, Delta 9-tetrahydrocannabinol (Delta 9-THC) and cannabidiol, on regional brain function during verbal paired associate learning. Design: Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of Delta 9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design. Setting: University research center. Participants: Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had used C sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime. Main Outcome Measures: Regional brain activation ( blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation. Results: Delta 9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of Delta 9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. Delta 9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, which was directly correlated with concurrently induced psychotic symptoms. In contrast, administration of cannabidiol had no such effect. Conclusion: The modulation of mediotemporal and ventrostriatal function by Delta 9-THC may underlie the effects of C sativa on verbal learning and psychotic symptoms, respectively.

Distinct Effects of Delta 9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing

Context: Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown. Objective: To investigate the effects of 2 main psycho-active constituents of Cannabis sativa (Delta 9-tetrahydrocannabinol [Delta 9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing. Design: Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta 9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design. Participants: Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life. Main Outcome Measures: Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety. Results: Delta 9-Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta 9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta 9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas. Conclusions: Delta 9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta 9-THC may be related to effects in other brain regions.

Electrophysiologic Activity of the Vestibular Fold

Objectives: To assess the vestibular fold muscle after cordectomy and laryngeal reconstruction, the pattern of motor unit recruitment during sound emission, and the morphologic characteristics of motor unit action potentials. Design: Prospective analysis. Setting: Tertiary academic hospital. Patients: We evaluated 11 men (mean age, 65.7 years; age range, 53-82 years) who underwent laryngofissure, cordectomy, and laryngeal reconstruction with a vestibular fold flap. Interventions: Laryngeal electromyography with the insertion of a needle electrode for the assessment of the electrophysiologic activity of thyroartenoid muscle fibers and of the cricothyroid muscle on the operated on and nonoperated on sides. The thyroarytenoid muscle was evaluated by introducing a needle electrode through the thyroid cartilage and the cricothyroid membrane. Main Outcome Measures: Activities of needle insertion, spontaneous muscle activity during rest, and pattern of motor unit recruitment. Results: Seven patients (64%) had vestibular fold muscle fiber, all of whom showed motor unit recruitment in response to sound emission. No neurogenic muscle injuries were observed except in 1 patient with evidence of chronic injury. Conclusion: After cordectomy and laryngeal reconstruction, thyroarytenoid muscle fibers are present in the vestibular fold, with motor unit recruitment during sound emission.

Efficacy of cidofovir in recurrent juvenile respiratory papillomatosis

The efficacy of cidofovir in juvenile recurrent respiratory papillomatosis (JRRP) remains uncertain due to the lack of published case-control studies. Aim: To establish factors affecting the progression of JRRP prognosis, and to evaluate cidofovir for eradicating JRRP. Study Design: Retrospective. Methods: 22 children with JRRP were evaluated at a referral center. All children underwent surgical debulking, followed by cidofovir injection (Group 2) or not (Group 1). Age at diagnosis was correlated with the Derkay score and disease outcome. Disease progression was compared between groups 1 and 2. Results: fifteen children were considered disease-free; 8 were in Group 2 and 7 in Group 1. Age and total and clinical scores (P<0.05) were negatively correlated. The mean number of surgeries required to control the disease was identical in both groups; the duration of treatment until remission was significantly higher in Group 1 (P<0,05). Conclusion: JRRP is more aggressive in earlier onset disease. The duration of treatment was significantly lower in patients treated with cidofovir until eradication of JRRP compared to patients treated with surgery only.

Maxillary sinuses microbiology from patients with chronic rhinosinusitis

There isn`t definitive and consistent data concerning the distribution of bacterial species in patients with Chronic Sinusitis (CS). The variability of the results from studies in CS may be due to the different techniques used as collection method, variations in culture methods, previous antibiotic use, and difficulty in distinguishing bacterial flora from pathogenic agents. Study design: Clinical prospective. Aim: To identify the incidence of microorganisms in patients with CRS by growing bacteria from the secretion of the maxillary sinus. Patients and Methods: Cross-sectional study in 62 patients that had undergone FESS for treatment of chronic sinusitis; cultures from the maxillary sinus were obtained. Results: 62 samples, 33 (53.2%) had no growth; 29 (45.2%) counts of aerobic bacteria; one case (1.6%) of fungus growth; we did not find anaerobic bacteria. Pseudomonas aeruginosa was the one more frequently found - 8 samples (27.6%), Staphylococcus aureus and Staphylococcus epidermidis in 4 samples each; Streptococcus pneumoniae in 3 samples (10.4%); other Gram negative agents in 17 samples (31%). Conclusion: In the present study we concluded that Pseudomonas aeruginosa, other Gram negatives bacteria and Staphylococcus spp were the representatives of the bacterial flora found in the paranasal sinuses of patients with CS.

A functional study on gentamicin-related cochleotoxicity in its conventional dose in newborns

The early identification of hearing impairment allows for an intervention still in the ""critical"" and ideal period of hearing and language stimulation. Pediatric ototoxicity is a very controversial topic. There have been variable percentages of ototoxicity cases in children with different aminoglycosides antibiotics. The main pediatric groups whom receive aminoglycosides are newborns with severe infections on the neonatal ICU. Aim: to check the functional aspect of the cochlear external hair cells and treatment regimens used to treat infections during the neonatal period. Study design: Experimental. Materials and Methods: we studied 26 albino guinea pigs, through distortion product otoacoustic emissions, before and after the use of gentamicin. Results: in all the assessments, the external hair cells functional status, studied by means of the distortion product otoacoustic emissions, proved preserved. Conclusion: In the present study, we did not notice changes in outer hair cell function in the albino guinea pigs treated with gentamicin in the doses of 4 mg/Kg/ day and 2.5 mg/Kg/day every 12 hours for 10 and 14 days.

Methotrexate Withdrawal at 6 vs 12 Months in Juvenile Idiopathic Arthritis in Remission A Randomized Clinical Trial

Context Novel therapies have improved the remission rate in chronic inflammatory disorders including juvenile idiopathic arthritis (JIA). Therefore, strategies of tapering therapy and reliable parameters for detecting subclinical inflammation have now become challenging questions. Objectives To analyze whether longer methotrexate treatment during remission of JIA prevents flares after withdrawal of medication and whether specific biomarkers identify patients at risk for flares. Design, Setting, and Patients Prospective, open, multicenter, medication-withdrawal randomized clinical trial including 364 patients (median age, 11.0 years) with JIA recruited in 61 centers from 29 countries between February 2005 and June 2006. Patients were included at first confirmation of clinical remission while continuing medication. At the time of therapy withdrawal, levels of the phagocyte activation marker myeloid-related proteins 8 and 14 heterocomplex (MRP8/14) were determined. Intervention Patients were randomly assigned to continue with methotrexate therapy for either 6 months (group 1 [n = 183]) or 12 months (group 2 [n = 181]) after induction of disease remission. Main Outcome Measures Primary outcome was relapse rate in the 2 treatment groups; secondary outcome was time to relapse. In a prespecified cohort analysis, the prognostic accuracy of MRP8/14 concentrations for the risk of flares was assessed. Results Intention-to-treat analysis of the primary outcome revealed relapse within 24 months after the inclusion into the study in 98 of 183 patients (relapse rate, 56.7%) in group 1 and 94 of 181 (55.6%) in group 2. The odds ratio for group 1 vs group 2 was 1.02 (95% CI, 0.82-1.27; P=.86). The median relapse-free interval after inclusion was 21.0 months in group 1 and 23.0 months in group 2. The hazard ratio for group 1 vs group 2 was 1.07 (95% CI, 0.82-1.41; P=.61). Median follow-up duration after inclusion was 34.2 and 34.3 months in groups 1 and 2, respectively. Levels of MRP8/14 during remission were significantly higher in patients who subsequently developed flares (median, 715 [IQR, 320-1110] ng/mL) compared with patients maintaining stable remission (400 [IQR, 220-800] ng/mL; P=.003). Low MRP8/14 levels indicated a low risk of flares within the next 3 months following the biomarker test (area under the receiver operating characteristic curve, 0.76; 95% CI, 0.62-0.90). Conclusions In patients with JIA in remission, a 12-month vs 6-month withdrawal of methotrexate did not reduce the relapse rate. Higher MRP8/14 concentrations were associated with risk of relapse after discontinuing methotrexate.