High incidence of adverse reactions to initial antiretroviral therapy in Brazil

A concurrent prospective study was conducted from 2001 to 2003 to assess factors associated with adverse reactions among individuals initiating antiretroviral therapy at two public referral HIV/AIDS centers in Belo Horizonte, MG, Brazil. Adverse reactions were obtained from medical charts reviewed up to 12 months after the first antiretroviral prescription. Cox proportional hazard model was used to perform univariate and multivariate analyses. Relative hazards (RH) were estimated with 95% confidence intervals (CI). Among 397 charts reviewed, 377 (95.0%) had precise information on adverse reactions and initial antiretroviral treatment. Most patients received triple combination regimens including nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. At least one adverse reaction was recorded on 34.5% (N = 130) of the medical charts (0.17 adverse reactions/100 person-day), while nausea (14.5%) and vomiting (13.1%) were the most common ones. Variables independently associated with adverse reactions were: regimens with nevirapine (RH = 1.78; 95% CI = 1.07-2.96), indinavir or indinavir/ritonavir combinations (RH = 2.05; 95% CI = 1.15-3.64), female patients (RH = 1.93; 95% CI = 1.31-2.83), 5 or more outpatient visits (RH = 1.94; 95% CI = 1.25-3.01), non-adherence to antiretroviral therapy (RH = 2.38; 95% CI = 1.62-3.51), and a CD4+ count of 200 to 500 cells/mm³ (RH = 2.66; 95% CI = 1.19-5.90). An independent and negative association was also found for alcohol use (RH = 0.55; 95% CI = 0.33-0.90). Adverse reactions were substantial among participants initiating antiretroviral therapy. Specially elaborated protocols in HIV/AIDS referral centers may improve the diagnosis, management and prevention of adverse reactions, thus contributing to improving adherence to antiretroviral therapy among HIV-infected patients.

Antiretroviral therapy-associated dyslipidemia in patients from a reference center in Brazil

The aim of this study was to determine the impact of antiretroviral therapy on the lipid profile of human immunodeficiency virus (HIV) patients before and after the initiation of highly active antiretroviral therapy (HAART). This was a cross-sectional analysis of patients receiving HAART at a reference center in Belo Horizonte, Brazil, on the basis of medical records from 2002 to 2006. Patients were included if they had at least one lipid test or a clinical or laboratory diagnosis of dyslipidemia/lipodystrophy. Among the 692 patients, 620 met the eligibility criteria. The majority were males (66.5%), middle age (average 39 years), had a low educational level (60.4%), and low income (51.0%). HAART duration ranged from 11 days to 4.6 years, with a mean of 28.6 months (SD = ± 470.19 days). The prevalence of dyslipidemia/lipodystrophy nearly tripled (11.3% pre- and 32.4% post-HAART). Dyslipidemia was associated with older age (P = 0.007), nucleoside reverse transcriptase inhibitor (NRTI) + protease inhibitor (PI) regimens (P = 0.04), NRTI + non-NRTI (NNRTI) regimens (P = 0.026), the use of stavudine (d4T) in any regimen (P = 0.002) or in NRTI-based regimens (P = 0.006), and longer exposure to HAART (P < 0.000). In addition, there was no correlation between dyslipidemia and gender (P = 0.084). Only 2.0% of the patients received treatment for dyslipidemia during the trial. These results show a need for continuous monitoring of patients under antiretroviral therapy, particularly those using NRTI-based regimens, especially when combined with d4T and PIs. Secondly, interventions should be developed to correct metabolic changes.

Relationship of inflammatory markers and pain in patients with head and neck cancer prior to anticancer therapy

Pain is a common symptom in patients with cancer, including those with head and neck cancer (HNC). While studies suggest an association between chronic inflammation and pain, levels of inflammatory cytokines, such as C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α), have not been correlated with pain in HNC patients who are not currently undergoing anticancer treatment. The purpose of this study was to examine the relationship between these inflammatory markers and perceived pain in HNC patients prior to anticancer therapy. The study group consisted of 127 HNC patients and 9 healthy controls. Pain was assessed using the Brief Pain Inventory (BPI), and serum levels of CRP and TNF-α were determined using the particle-enhanced turbidimetric immunoassay (PETIA) and ELISA techniques, respectively. Patients experiencing pain had significantly higher levels of CRP (P<0.01) and TNF-α (P<0.05) compared with controls and with patients reporting no pain. There were significantly positive associations between pain, CRP level, and tumor stage. This is the first study to report a positive association between perceived pain and CRP in HNC patients at the time of diagnosis. The current findings suggest important associations between pain and inflammatory processes in HNC patients, with potential implications for future treatment strategies.

Hormone therapy with tamoxifen reduces plasma levels of NT-B-type natriuretic peptide but does not change ventricular ejection fraction after chemotherapy in women with breast cancer

The objective of this study was to evaluate the effect of tamoxifen on the plasma concentration of NT-pro-B-type natriuretic peptide (NT-proBNP) in women undergoing chemotherapy for breast cancer and to correlate changes in NT-proBNP with the left ventricular ejection fraction (LVEF). Over a period of 12 months, we followed 60 women with a diagnosis of breast cancer. The patients were separated into a group that received only chemotherapy (n=23), a group that received chemotherapy + tamoxifen (n=21), and a group that received only tamoxifen (n=16). Plasma levels of NT-proBNP were assessed at 0 (T0), 6 (T6), and 12 (T12) months of treatment, and echocardiography data were assessed at T0 and T12. Plasma NT-proBNP levels were increased in the chemotherapy-only group at T6 and T12, whereas elevated NT-proBNP levels were only found at T6 in the chemotherapy + tamoxifen group. At T12, the chemotherapy + tamoxifen group exhibited a significant reduction in the peptide to levels similar to the group that received tamoxifen alone. The chemotherapy-only group exhibited a significant decrease in LVEF at T12, whereas the chemotherapy + tamoxifen and tamoxifen-only groups maintained levels similar to those at the beginning of treatment. Treatment with tamoxifen for 6 months after chemotherapy significantly reduced the plasma levels of NT-proBNP and did not change LVEF in women with breast cancer.

Dyad function-based cognitive behavioural therapy as a treatment for obsessive compulsive disorder in two school aged children with high functioning autism

Children with High-Functioning Autism (HF A) are more vulnerable to developing Obsessive Compulsive Disorder (OCD) than typically developing children and those with Low-Functioning Autism (Gadow et al., 2005). This study used a multiple baseline design across behaviours (Cooper, Heron, & Heward, 2007) to investigate if a two phase function-based Cognitive Behaviour Therapy (CBT) would decrease obsessive compulsive behaviours (OCBs) in two children ages 7 and 9 who met criteria for OCD and HF A. This multimodal treatment package consisted of treatment enhancements to meet the children's cognitive, linguistic, and social challenges associated with their HF A diagnosis, as well as a manual and accompanied children's workbook (Vause, Neil, & Feldman, in progress). In line with previous research conducted on CBT as a treatment for OCD in this population (e.g., Wood et at, 2009), the children in this study experienced clinically significant decreases in their OCBs as a result of receiving the CBT protocol.

Neurotrophic gene polymorphisms and response to psychological therapy

Therapygenetics, the study of genetic determinants of response to psychological therapies, is in its infancy. Here, we investigate whether single-nucleotide polymorphisms in nerve growth factor (NGF) (rs6330) and brain-derived neutrotrophic factor (BDNF) (rs6265) genes predict the response to cognitive behaviour therapy (CBT). Neurotrophic genes represent plausible candidate genes: they are implicated in synaptic plasticity, response to stress, and are widely expressed in brain areas involved in mood and cognition. Allelic variation at both loci has shown associations with anxiety-related phenotypes. A sample of 374 anxiety-disordered children with white European ancestry was recruited from clinics in Reading, UK, and in Sydney, Australia. Participants received manualised CBT treatment and DNA was collected from buccal cells using cheek swabs. Treatment response was assessed at post-treatment and follow-up time points. We report first evidence that children with one or more copies of the T allele of NGF rs6330 were significantly more likely to be free of their primary anxiety diagnosis at follow-up (OR=0.60 (0.42–0.85), P=0.005). These effects remained even when other clinically relevant covariates were accounted for (OR=0.62 (0.41–0.92), P=0.019). No significant associations were observed between BDNF rs6265 and response to psychological therapy. These findings demonstrate that knowledge of genetic markers has the potential to inform clinical treatment decisions for psychotherapeutic interventions.

Predicting outcomes following cognitive behavior therapy in child anxiety disorders: the influence of genetic, demographic and clinical information

Background. Within a therapeutic gene by environment (GxE) framework, we recently demonstrated that variation in the Serotonin Transporter Promoter Polymorphism; 5HTTLPR and marker rs6330 in Nerve Growth Factor gene; NGF is associated with poorer outcomes following cognitive behaviour therapy (CBT) for child anxiety disorders. The aim of this study was to explore one potential means of extending the translational reach of G×E data in a way that may be clinically informative. We describe a ‘risk-index’ approach combining genetic, demographic and clinical data and test its ability to predict diagnostic outcome following CBT in anxious children. Method. DNA and clinical data were collected from 384 children with a primary anxiety disorder undergoing CBT. We tested our risk model in five cross-validation training sets. Results. In predicting treatment outcome, six variables had a minimum mean beta value of 0.5: 5HTTLPR, NGF rs6330, gender, primary anxiety severity, comorbid mood disorder and comorbid externalising disorder. A risk index (range 0-8) constructed from these variables had moderate predictive ability (AUC = .62-.69) in this study. Children scoring high on this index (5-8) were approximately three times as likely to retain their primary anxiety disorder at follow-up as compared to those children scoring 2 or less. Conclusion. Significant genetic, demographic and clinical predictors of outcome following CBT for anxiety-disordered children were identified. Combining these predictors within a risk-index could be used to identify which children are less likely to be diagnosis free following CBT alone or thus require longer or enhanced treatment. The ‘risk-index’ approach represents one means of harnessing the translational potential of G×E data.

The treatment of child anxiety disorders via guided parent-delivered cognitive-behavioural therapy: a randomised controlled trial

Background Promising evidence has emerged of clinical gains using guided self-help cognitive-behavioural therapy (CBT) for child anxiety and by involving parents in treatment; however, the efficacy of guided parent-delivered CBT has not been systematically evaluated in UK primary and secondary settings. Aims To evaluate the efficacy of low-intensity guided parent-delivered CBT treatments for children with anxiety disorders. Method A total of 194 children presenting with a current anxiety disorder, whose primary carer did not meet criteria for a current anxiety disorder, were randomly allocated to full guided parent-delivered CBT (four face-to-face and four telephone sessions) or brief guided parent-delivered CBT (two face-to-face and two telephone sessions), or a wait-list control group (trial registration: ISRCTN92977593). Presence and severity of child primary anxiety disorder (Anxiety Disorders Interview Schedule for DSM-IV, child/parent versions), improvement in child presentation of anxiety (Clinical Global Impression-Improvement scale), and change in child anxiety symptoms (Spence Children’s Anxiety Scale, child/parent version and Child Anxiety Impact scale, parent version) were assessed at post-treatment and for those in the two active treatment groups, 6 months post-treatment. Results Full guided parent-delivered CBT produced superior diagnostic outcomes compared with wait-list at post-treatment, whereas brief guided parent-delivered CBT did not: at post-treatment, 25 (50%) of those in the full guided CBT group had recovered from their primary diagnosis, compared with 16 (25%) of those on the wait-list (relative risk (RR) 1.85, 95% CI 1.14-2.99); and in the brief guided CBT group, 18 participants (39%) had recovered from their primary diagnosis post-treatment (RR = 1.56, 95% CI 0.89-2.74). Level of therapist training and experience was unrelated to child outcome. Conclusions Full guided parent-delivered CBT is an effective and inexpensive first-line

Cognitive-behavior therapy for low self-esteem: a case example

Low self-esteem is a common, disabling, and distressing problem that has been shown to be involved in the etiology and maintenance of range of Axis I disorders. Hence, it is a priority to develop effective treatments for low self-esteem. A cognitive-behavioral conceptualization of low self-esteem has been proposed and a cognitive-behavioral treatment (CBT) program described (Fennell, 1997, 1999). As yet there has been no systematic evaluation of this treatment with routine clinical populations. The current case report describes the assessment, formulation, and treatment of a patient with low self-esteem, depression, and anxiety symptoms. At the end of treatment (12 sessions over 6 months), and at 1-year follow-up, the treatment showed large effect sizes on measures of depression, anxiety, and self-esteem. The patient no longer met diagnostic criteria for any psychiatric disorder, and showed reliable and clinically significant change on all measures. As far as we are aware, there are no other published case studies of CBT for low self-esteem that report pre- and posttreatment evaluations, or follow-up data. Hence, this case provides an initial contribution to the evidence base for the efficacy of CBT for low self-esteem. However, further research is needed to confirm the efficacy of CBT for low self-esteem and to compare its efficacy and effectiveness to alternative treatments, including diagnosis-specific CBT protocols.

Clinical predictors of response to cognitive-behavioural therapy in pediatric anxiety disorders: the Genes for Treatment (GXT) Study

Objective The Genes for Treatment study is an international, multisite collaboration exploring the role of genetic, demographic, and clinical predictors in response to cognitive-behavioral therapy (CBT) in pediatric anxiety disorders. The current article, the first from the study, examined demographic and clinical predictors of response to CBT. We hypothesized that the child’s gender, type of anxiety disorder, initial severity and comorbidity, and parents’ psychopathology would significantly predict outcome. Method A sample of 1,519 children 5 to 18 years of age with a primary anxiety diagnosis received CBT across 11 sites. Outcome was defined as response (change in diagnostic severity) and remission (absence of the primary diagnosis) at each time point (posttreatment, 3-, 6-, and/or 12-month follow-up) and analyzed using linear and logistic mixed models. Separate analyses were conducted using data from posttreatment and follow-up assessments to explore the relative importance of predictors at these time points. Results Individuals with social anxiety disorder (SoAD) had significantly poorer outcomes (poorer response and lower rates of remission) than those with generalized anxiety disorder (GAD). Although individuals with specific phobia (SP) also had poorer outcomes than those with GAD at posttreatment, these differences were not maintained at follow-up. Both comorbid mood and externalizing disorders significantly predicted poorer outcomes at posttreatment and follow-up, whereas self-reported parental psychopathology had little effect on posttreatment outcomes but significantly predicted response (although not remission) at follow-up. Conclusion SoAD, nonanxiety comorbidity, and parental psychopathology were associated with poorer outcomes after CBT. The results highlight the need for enhanced treatments for children at risk for poorer outcomes.

Enhanced visualization of histological samples with an adjustable RGB contrast system with application for tissue used in photodynamic therapy

The analysis of histological sections has long been a valuable tool in the pathological studies. The interpretation of tissue conditions, however, relies directly on visual evaluation of tissue slides, which may be difficult to interpret because of poor contrast or poor color differentiation. The Chromatic Contrast Visualization System (CCV) combines an optical microscope with electronically controlled light-emitting diodes (LEDs) in order to generate adjustable intensities of RGB channels for sample illumination. While most image enhancement techniques rely on software post-processing of an image acquired under standard illumination conditions, CCV produces real-time variations in the color composition of the light source itself. The possibility of covering the entire RGB chromatic range, combined with the optical properties of the different tissues, allows for a substantial enhancement in image details. Traditional image acquisition methods do not exploit these visual enhancements which results in poorer visual distinction among tissue structures. Photodynamic therapy (PDT) procedures are of increasing interest in the treatment of several forms of cancer. This study uses histological slides of rat liver samples that were induced to necrosis after being exposed to PDT. Results show that visualization of tissue structures could be improved by changing colors and intensities of the microscope light source. PDT-necrosed tissue samples are better differentiated when illuminated with different color wavelengths, leading to an improved differentiation of cells in the necrosis area. Due to the potential benefits it can bring to interpretation and diagnosis, further research in this field could make CCV an attractive technique for medical applications.

Different nutritional-state indicators of HIV-positive individuals undergoing antiretroviral therapy

This study aimed at learning about the nutritional profile of HIV-positive individuals undergoing antiretroviral therapy and at comparing the performance of nutritional-state indicators. A transversal study was performed on 94 patients attending the Tropical Diseases Outpatient Hospital of Botucatu Medical School (FMB)-UNESP. The body mass index (BMI) and the classification by Papini-Berto (PB) were used to evaluate nutritional state, aiming at detecting malnutrition and obesity. The waist-to-hips ratio (W/HR) and waist circumference (WC) were adopted for identification of abdominal obesity and lipodystrophy. According to BMI, most of the individuals were eutrophic, followed by 30.9% overweight and 6.4% malnourished. By using the PB classification, the frequency of malnourished increased (22.3%). The analysis of the PB classification in relation to BMI indicated that the former presented high sensitivity and good specificity for malnutrition diagnosis, namely 100% and 83%, respectively. The prevalence of abdominal obesity was 7.44% according to WC, and a higher prevalence (38.3%) was observed when taking W/HR into account. There was significant positive association between nutritional diagnosis according to PB and T CD4(+) lymphocyte. The results support the use of PB classification for malnutrition detection as well as that of BMI and W/HR for overweight and fat redistribution.

Potentially modifiable predictors of mortality in patients treated with long-term oxygen therapy

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Denture stomatitis treated with photodynamic therapy: five cases

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Use of computerized tomography for diagnosis and follow-up after endodontic surgery: clinical case report with 8 years of follow-up

Computerized tomography (CT) is a valuable tool for diagnosis and planning in conventional and surgical endodontic therapy. This case report describes the use of CT in the diagnosis of a periapical lesion undetected by periapical radiography in the mandibular molar area. The CT also showed a possible mesial root perforation associated with the lesion. Following CT, surgical planning, periradicular curettage, and sealing of the root perforation were performed. Eight years after surgery, cone beam CT revealed periapical bone repair. Computerized tomography can be an important resource for diagnosis and planning in conventional and surgical endodontic therapy, as well as for evaluation of post-treatment bone repair. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109: 629-633)