Consistency of FDG-PET Accuracy and Cost-Effectiveness in Initial Staging of Patients With Hodgkin Lymphoma Across Jurisdictions

Introduction: Two hundred ten patients with newly diagnosed Hodgkin`s lymphoma (HL) were consecutively enrolled in this prospective trial to evaluate the cost-effectiveness of fluorine-18 ((18)F)-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) scan in initial staging of patients with HL. Methods: All 210 patients were staged with conventional clinical staging (CCS) methods, including computed tomography (CT), bone marrow biopsy (BMB), and laboratory tests. Patients were also submitted to metabolic staging (MS) with whole-body FDG-PET scan before the beginning of treatment. A standard of reference for staging was determined with all staging procedures, histologic examination, and follow-up examinations. The accuracy of the CCS was compared with the MS. Local unit costs of procedures and tests were evaluated. Incremental cost-effectiveness ratio (ICER) was calculated for both strategies. Results: In the 210 patients with HL, the sensitivity for initial staging of FDG-PET was higher than that of CT and BMB in initial staging (97.9% vs. 87.3%; P < .001 and 94.2% vs. 71.4%, P < 0.003, respectively). The incorporation of FDG-PET in the staging procedure upstaged disease in 50 (24%) patients and downstaged disease in 17 (8%) patients. Changes in treatment would be seen in 32 (15%) patients. Cumulative cost for staging procedures was $3751/patient for CCS compared to $5081 for CCS + PET and $4588 for PET/CT. The ICER of PET/CT strategy was $16,215 per patient with modified treatment. PET/CT costs at the beginning and end of treatment would increase total costs of HL staging and first-line treatment by only 2%. Conclusion: FDG-PET is more accurate than CT and BMB in HL staging. Given observed probabilities, FDG-PET is highly cost-effective in the public health care program in Brazil.

Cost Effectiveness of Positron Emission Tomography in Patients With Hodgkin`s Lymphoma in Unconfirmed Complete Remission or Partial Remission After First-Line Therapy

Purpose To assess the cost effectiveness of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with Hodgkin`s lymphoma (HL) with unconfirmed complete remission (CRu) or partial remission (PR) after first-line treatment. Patients and Methods One hundred thirty patients with HL were prospectively studied. After treatment, all patients with CRu/PR were evaluated with FDG-PET. In addition, PET-negative patients were evaluated with standard follow-up, and PET-positive patients were evaluated with biopsies of the positive lesions. Local unit costs of procedures and tests were evaluated. Cost effectiveness was determined by evaluating projected annual economic impact of strategies without and with FDG-PET on HL management. Results After treatment, CRu/PR was observed in 50 (40.0%) of the 127 patients; the sensitivity, specificity, and positive and negative predictive values of FDG-PET were 100%, 92.0%, 92.3%, and 100%, respectively (accuracy of 95.9%). Local restaging costs without PET were $350,050 compared with $283,262 with PET, a 19% decrease. The incremental cost-effectiveness ratio is -$3,268 to detect one true case. PET costs represented 1% of total costs of HL treatment. Simulated costs in the 974 patients registered in the 2008 Brazilian public health care database showed that the strategy including restaging PET would have a total program cost of $56,498,314, which is $516,942 less than without restaging PET, resulting in a 1% cost saving. Conclusion FDG-PET demonstrated 95.9% accuracy in restaging for patients with HL with CRu/PR after first-line therapy. Given the observed probabilities, FDG-PET is highly cost effective and would reduce costs for the public health care program in Brazil.

The role of BPH, lower urinary tract symptoms, and PSA levels on erectile function of Brazilian men who undergo prostate cancer screening

Introduction. Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are common problems in middle-aged and older men. Recently, epidemiologic studies have shown significant associations between severity of LUTS and male sexual dysfunction. Aim. We analyzed the role of prostate enlargement, LUTS, and prostate specific antigen (PSA) levels in the erectile function of Brazilian men who underwent prostate cancer (PCa) screening. Method. We analyzed data from 1,008 consecutive patients enrolled in a PCa screening program. Benign prostatic hyperplasia (BPH) was defined as a prostate weight greater than 30 g as defined by digital rectal examination. For statistical analysis, we used the chi-squared and analysis of variance tests. The odds ratios (OR) for correlation of ED with prostate volume LUTS and PSA were estimated using logistic regression models. Main Outcome Measure. The American Urological Association (AUA) symptom score for LUTS and the International Index of Erectile Function. Results. Mean patient age was 61.2 years (45-87) and median PSA value was 1.9 ng/mL. BPH was identified in 48.5% of patients. Mild, moderate, and severe LUTS were found in 52.3%, 30.9%, and 16.8% of cases, respectively. ED was classified as absent, mild, mild to moderate, moderate, and severe in 18.6%, 23.1%, 18.6%, 15.2%, and 24.5%, respectively. While only 5.4% of the patients with no ED presented severe LUTS, this finding was observed in 27.1% of patients with severe ED (P<0.001). Univariate logistic regression analysis demonstrated that age, prostate volume, AUA symptom score, and PSA levels were significant predictors of ED. However, when controlled for patient age, only LUTS remained as an independent predictor of ED. Conclusions. Controlling for patient age, LUTS are independent risk factors for the development of ED among Brazilian men who undergo PCa screening.

Low DNA HTLV-2 proviral load among women in Sao Paulo city

Background: HTLV-2 infections are almost always asymptomatic, and diseases associated with the infection are rarely reported. Little information is available on the relationship between HTLV-2 proviral load and gender or expression of disease, especially among patients with HlV-1 co-infection. Methods: We studied 77 HTLV-2-infected subjects followed in our clinic for the last 9 years; 53 (69%) of them were co-infected with HIV-1. HTLV-2 DNA proviral load (PVL) was measured by real time PCR, a test with a sensitivity of 10 in 10(4) PBMCs. Results: Six of 53 HTLV-2/HIV-1 cases had a myelopathy (all of them had undetectable PVL of HTLV-2). Only 3 of 35 women (2 out of 3 co-infected with HIV) had a detectable PVL, whereas 10 of 42 men had a detectable PVL. Regardless of their HIV status women had significantly lower PVL than men (10 vs. 43 CopieS/10(4) PBMCs, p < 0.05). Conclusions: We noticed the occurrence of myelopathy in HTLV-2/HIV-1 co-infected patients, with undetectable HTLV-2 viral load. There was a sex difference in viral load for HTLV-2, what may be the result in mode of transmission or acquisition of the virus. (c) 2008 Elsevier B. V. All rights reserved.

Apoptosis induced by Oropouche virus infection in HeLa cells is dependent on virus protein expression

Oropouche (OROV) is a single-stranded RNA arbovirus of the family Bunyaviridae, genus Orthobunyavirus, which has caused over half a million cases of febrile illness in Brazil in the past 30 years. OROV fever has been registered almost exclusively in the Amazon region, but global warming, deforestation and redistribution of vectors and animal reservoirs increases the risk of Oropouche virus emergence in other areas. OROV causes a cytolytical infection in cultured cells with characteristic cytopathic effect 48 h post-infection. We have studied the mechanisms of apoptosis induced by OROV in HeLa cells and found that OROV causes DNA fragmentation detectable by gel electrophoresis and by flow cytometric analysis of the Sub-G1 population at 36 h post-infection. Mitochondrial release of cytochrome C and activation of caspases 9 and 3 were also detected by western blot analysis. Lack of apoptosis induced by UV-inactivated OROV reveals that virus-receptor binding is not sufficient to induce cell death. Results obtained in cells treated with chloroquine and cycloheximide indicated that viral uncoating and replication are required for apoptosis induction by OROV. Furthermore, treatment of the cells with pan-caspase inhibitor prevented OROV-induced apoptosis without affecting virus progeny production. The results show that OROV infection in vitro causes apoptosis by an intracellular pathway involving mitochondria, and activated by a mechanism dependent on viral replication and protein synthesis. (C) 2010 Elsevier B.V. All rights reserved.

Oropouche virus entry into HeLa cells involves clathrin and requires endosomal acidification

Oropouche virus (ORO), family Bunyaviridae, is the second most frequent cause of arboviral febrile illness in Brazil. Studies were conducted to understand ORO entry in HeLa cells. Chlorpromazine inhibited early steps of ORO replication cycle, consistent with entry/uncoating. The data indicate that ORO enters HeLa cells by clathrin-coated vesicles, by a mechanism susceptible to endosomal acidification inhibitors. Transmission electron microscopy and immunofluorescence indicated that ORO associates with clathrin-coated pits and can be found in association with late endosomes in a time shorter than 1 h. (C) 2008 Elsevier B.V. All rights reserved.

Oropouche virus experimental infection in the golden hamster (Mesocrisetus auratus)

Oropouche virus (OROV), of the family Bunyaviridae, is the second most frequent arbovirus causing febrile disease in Brazil. In spite of this, little is known about pathogenesis of OROV infection. This report describes an experimental model of OROV in golden hamster (Mesocricetus auratus). Following subcutaneous inoculation of OROV, over 50% of the animals developed disease characterized by lethargy, ruffled fur, shivering, paralysis, and approximately one third died. Animals were sacrificed on days 1, 3, 5, 8 and 11 post-inoculation to collect tissue samples from brain, heart, liver, lung, spleen, muscle and blood for virus titration, histology and OROV immunohistochemistry. OROV was detected in high titers in blood, liver and brain, but not in the other organs. Histopathology revealed meningoencephalitis and hepatitis, with abundant OROV antigen detected in liver and brain. Diffuse galectin-3 immunostaining in brain and liver supports microglial and Kupfer cells activation. This is the first description of an experimental model for OROV infection and should be helpful to study pathogenesis and possibly to test antiviral interventions such as drugs and vaccine candidates. (C) 2010 Elsevier B.V. All rights reserved.

Glutamine supplementation does not improve protein synthesis rate by the jejunal mucosa of the malnourished rat

It has been demonstrated that glutamine, a conditionally essential amino acid, improves nitrogen balance, acts as a stimulant of protein synthesis, and decreases proteolysis in myopathic children. In contrast, other studies have shown no beneficial effect of glutamine supplementation on burn victims or critically ill patients. Nonetheless, we hypothesized that glutamine supplementation would increase the fractional protein synthesis rate (FSR) in the jejunal mucosa of malnourished male Wistar rats. Thus, the objective of the present study was to test the effect of daily oral glutamine supplementation (0.42 g kg(-1) d(-1) for 14 days) on the FSR of the jejunal mucosa of healthy and malnourished rats. A 4-hour kinetic study with L-[1-(13)C]leucine was subsequently performed, and jejunal biopsies were obtained 1.5 cm from the Treitz angle and analyzed. Malnourished rats showed a 25% weight loss and increased urinary nitrogen excretion. Plasma amino acid concentration did not differ between groups. (13)C enrichment in plasma and jejunal cells was higher in the malnourished groups than in the healthy group. The FSR (percent per hour) was similar for the control and experimental groups (P > .05), with a mean range of 220%/h to 27%/h. Oral glutamine supplementation alone did not induce higher protein incorporation by the jejunal mucosa in malnourished rats, regardless of total food intake or the presence or absence of glutamine supplementation. (C) 2009 Elsevier Inc. All rights reserved.

Prevalence of trachoma in a population of the upper Rio Negro Basin and risk factors for active disease

Purpose: To determine the prevalence of trachoma in Sao Gabriel da Cachoeira (SGC), the only urban community of the upper Rio Negro Basin of the Amazon state in Brazil, near the Colombian border, and to investigate the risk factors associated with the active forms of the disease. Methods: A total of 1702 people (440 children up to 9 years and 1069 adults aged 15 years and above) were examined. The sample was selected from a probabilistic household sampling procedure based on census data and a previous study of trachoma prevalence in Sao Gabriel da Cachoeira. A two-stage probabilistic household cluster sample was drawn. Household units were randomly selected within each cluster. A variety of socioeconomic and hygiene variables were studied in order to determine the risk factors for active trachoma in a household. Results: The total prevalence of trachoma was 8.9%. Prevalence of active trachoma (TF and/or TI) in children aged 1-9 years was 11.1% and trachomatous trichiasis in adults aged 15 years and above was 0.19%. Trachomatous scarring reached a peak of 22.4% for subjects between 50 to 60 years of age. Corneal opacity occurred in subjects aged 50 years and older with a prevalence of 2.0%. No sex effect was found on the overall prevalence of trachoma in SGC. Risk factors associated with active trachoma were mainly related to poor socioeconomic indicators. Conclusions: Despite the ubiquitous presence of water, the analysis of the risk factors associated with the active forms of the disease supports the idea that a low personal standard of hygiene and not water availability per se, is the key factor associated with trachoma.