Stages I-III Inoperable Endometrial Carcinoma: A Retrospective Analysis by the Gynaecological Cancer GEC-ESTRO Working Group of Patients Treated with External Beam Irradiation and 3D-Image Guided Brachytherapy.

BACKGROUND/PURPOSE: Analyse the outcomes of stages I-III inoperable endometrial cancer (IEC) patients treated with external-beam-irradiation (EBRT) and 3D-image-guided-brachytherapy (IGBT). MATERIAL AND METHODS: Medical records of IEC patients receiving EBRT + IGBT in eight European and one Canadian centres (2004-2019) were examined, including: pelvic ± para-aortic EBRT and lymph node boost; anaesthetic procedure, applicators, BT-planning imaging, clinical target volume (CTV), brachytherapy schedule, and EQD2 to the CTV(α/ß=4.5Gy) and D2 cm3(α/ß=3Gy) for organs at risk. Complications are evaluated using CTCAEv4 scores. The 2- and 5-year survival probability according to stages was estimated (cancer-specific survival (CSS), disease-free survival (DFS), local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS)). STATISTICS: descriptive analysis and the Kaplan-Meier method. RESULTS: 103 patients (stages: I-44, II-14, III-44) were included. Median follow-up: 28 months (7-170). All patients received pelvic ± para-aortic EBRT. Median D90-EQD2(α/ß=4.5) to the CTV:73.3 Gy (44.6-132.7), 69.9 Gy (44.7-87.9 and 75.2 Gy (55.1-97) in stages I, II, and III, respectively. Thirty patients presented relapse (stages: 10-I, 3-II, 17-III): 24 uterine (stages: 7-I, 3-II, 14-III), 15 nodal (stages: 4-I, 1-II, 10-III), and 23 distant (stages: 6-I, 2-II, 15-III). Five year CSS was 71.2% (stages: 82%-I-II and 56%-III) and DFS, LRFS, LRRFS, and DMFS were 55.5%, 59%, 72%, and 67.2%, respectively. Late G3-G4 complications (crude): 1.3% small bowel, 2.5% rectum, and 5% bladder. CONCLUSION: In stages I-III of the IEC, EBRT + IGBT offer good 2- and 5-year CSS of 88.7% and 71.2%, respectively, with the best outcomes in stages I-II. Prospective studies are needed to determine how better outcomes can be achieved.

EQD2 Analyses of Vaginal Complications in Exclusive Brachytherapy for Postoperative Endometrial Carcinoma.

Background: To evaluate whether EQD2(α/ß = 3Gy) at 2 cm3 of the most exposed area of the vagina is related to late vaginal toxicity in postoperative endometrial cancer (PEC) patients (p) treated with exclusive brachytherapy (BT). Methods: From 2014 to 2017, 43p were included in this study. BT was administered: 3-fractions of 6Gy in 37p and 2-fractions of 7.5Gy in 6p. The dose was prescribed at a depth of 5 mm from the applicator surface with dose-point optimization based on distance. The active treatment length was 2.5 cm. CTV-D90 and the dose to the most exposed 2 cm3 of the vagina was calculated for each patient. Late toxicity of the bladder and rectum was assessed using Radiation Therapy Oncology Group (RTOG) criteria, and vaginal toxicity by objective Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) (LENT-SOMA) criteria. Statistics: frequency tables, mean, median, range, standard deviation, and box plot. Results: The median follow-up was 51 months (12-68). 20 p (46.5%) and 2 p (4.7%) developed G1 and G2 vaginal complications, respectively. Only 1/2 p-G2 receiving EQD2(α/ß = 3Gy) at 2 cm3 >68Gy presented vaginal shortening and 18/20 p-G1 received doses < 68Gy. Conclusions: PECp receiving exclusive brachytherapy with doses < 68Gy EQD2(α/ß = 3Gy) at 2 cm2 of the vagina presented only G0-G1 vaginal toxicity, except for one with bleeding telangiectasias. Larger prospective studies are necessary to confirm the present results.

Community-based approaches for malaria case management in remote communities in the Brazilian Amazon.

INTRODUCTION: Malaria case management is a pivotal intervention in malaria elimination. However, many remote areas in Brazil still lack access to basic health services. This study describes a community-based approach (CBA) for malaria case management in the large remote area of the Jaú National Park (JNP), Amazonas, Brazil. METHODS: In 2001, a general health CBA was initiated with a motor group (MG); a participative community health diagnosis (PCHD) was subsequently implemented between 2001 and 2005. In 2006, a CBA for malaria case management started with an expanded MG including all sectors with a stake in malaria control, from the local residents to the federal government. In 2008, community microscopists were selected and trained to diagnose hemoparasites. A full malaria strategy was implemented in 2009 with subsequent quality control follow-up. RESULTS: Two educational materials were co-created with local communities. The MG identified malaria as a major health problem and the malaria MG planned the control activities. Ten communities selected a resident to become malaria microscopists, and ten solar-operated health centers were built. The number of slide readings increased from 923 in 2006 to 1,900 in 2009, while malaria infections decreased from 354 cases in 2005 to 20 cases in 2015. The excess time (≥ 48 hours) between first symptoms and diagnosis/treatment decreased from 68.9% of cases in 2005 to 14.3% in 2010. CONCLUSIONS: While many factors were likely involved in the reduction of malaria transmission in the JNP, the CBA played an important role in the sustained success of the initiative.

Postoperative endometrial carcinoma treated with external beam irradiation plus vaginal-cuff brachytherapy. Is there a dose relationship with G2 vaginal complications?

AIM: To analyse the possible relationship between the EQD2(α/ß=3Gy) at 2 cm3 of the vagina and late toxicity in vaginal-cuff-brachytherapy (VBT) after external-beam-irradiation (EBRT) for postoperative endometrial carcinoma (EC). MATERIALS AND METHODS: From 2014 to 2016, 62 postoperative EC patients were treated with EBRT + VBT. The median EBRT dose was 45 Gy (44 Gy-50.4 Gy). VBT involved a single 7 Gy dose. Toxicity was prospectively evaluated using the RTOG score for the rectum and bladder and the objective LENT-SOMA criteria for the vagina. EQD2(α/ß = 3Gy) at 2 cm3 of the most exposed part of the vagina was calculated by the sum of the EBRT + VBT dose. Statistics: Boxplot, Student's t and Chi-square tests and ROC curves. RESULTS: Mean follow-up: 39.2 months (15-68). Late toxicity: bladder:0 patient; rectum:2 patients-G1; Vagina: 26 patients-17G1, 9G2; median EQD2(α/ß=3Gy) at 2 cm3 in G0-G1 patients was 70.4 Gy(SD2.36), being 72.5 Gy(SD2.94) for G2p. The boxplot suggested a cut-point identifying the absence of G2: 100 % of G2p received >68 Gy, ROC curves showed an area under the curve of 0.72 (sensitivity of 1 and specificity of 0.15). CONCLUSIONS: Doses >68 Gy EQD2(α/ß=3Gy) at 2 cm3 to the most exposed area of the vagina were associated with late G2 vaginal toxicity in postoperative EC patients treated with EBRT + VBT suggesting a very good dose limit to eliminate the risk of G2 late toxicity. The specificity obtained indicates the need for prospective analyses.

Economic impact of decreasing the fraction number in vaginal cuff brachytherapy: A direct cost analysis.

PURPOSE: The purpose of this study was to analyze the direct economic impact of two vaginal cuff brachytherapy (VBT) schedules in postoperative endometrial carcinoma (PEC) with similar vaginal control and toxicity results. MATERIALS AND METHODS: From 2006 to 2015, 397 PEC patients (p) were treated with VBT: mean 40p/year, 67.5% received external beam radiotherapy (EBRT)+VBT and 32.5% exclusive VBT. Schedule 1: 3 fractions (Fr) after EBRT and 6Fr (4-6 Gy/Fr) in exclusive VBT. Schedule 2: 7Gy × 1Fr + EBRT and 6Gy × 3Fr in exclusive VBT. Differential cost analysis of the two schedules was retrospectively performed. The direct costs in each schedule were (1) Personnel: radiotherapy technicians, nurses, radiation oncologists, medical physicists, administrative personnel, orderlies; time dedicated by each professional during CT planning acquisitions and delineation of vagina/organs at risk, dosimetric study and evaluation, autoradiography, procedure reporting time during/after treatment, removal of bladder/rectal tubes and applicators, material cleaning and transportation for sterilization; (2) Health care material (gels, gauzes, gloves, etc); (3) Equipment (time equipment used). The differential between the two schedules was estimated. Indirect costs and evaluation of quality of life-adjusted costs were not considered. RESULTS: The overall reduction in the number of Fr per year in Schedule 2 was 93. Cost savings included treatment time per year: 4,185 min (70 h); personnel: 221€ ($246)/p in EBRT + VBT and 331€ ($368)/p in exclusive VBT; and health care material and equipment: 40€ ($44.5)/p in EBRT + VBT and 90€ ($100.2)/p in exclusive VBT. The overall savings per patient was 261€ ($295) in combined treatment and 421€ ($475.7) in exclusive VBT. The total savings per year with Schedule 2 in 40p was 12,503€ ($13,915.8). CONCLUSIONS: A 41% reduction in the fractions number in VBT for PEC allowed economic savings of 261€ ($290.5)/p in combined treatment and 421€ ($475.7)/p in exclusive VBT. Other benefits include patient comfort and fewer treatment visits.

Community-based approaches for malaria case management in remote communities in the Brazilian Amazon

Abstract INTRODUCTION Malaria case management is a pivotal intervention in malaria elimination. However, many remote areas in Brazil still lack access to basic health services. This study describes a community-based approach (CBA) for malaria case management in the large remote area of the Jaú National Park (JNP), Amazonas, Brazil. METHODS In 2001, a general health CBA was initiated with a motor group (MG); a participative community health diagnosis (PCHD) was subsequently implemented between 2001 and 2005. In 2006, a CBA for malaria case management started with an expanded MG including all sectors with a stake in malaria control, from the local residents to the federal government. In 2008, community microscopists were selected and trained to diagnose hemoparasites. A full malaria strategy was implemented in 2009 with subsequent quality control follow-up. RESULTS Two educational materials were co-created with local communities. The MG identified malaria as a major health problem and the malaria MG planned the control activities. Ten communities selected a resident to become malaria microscopists, and ten solar-operated health centers were built. The number of slide readings increased from 923 in 2006 to 1,900 in 2009, while malaria infections decreased from 354 cases in 2005 to 20 cases in 2015. The excess time (≥ 48 hours) between first symptoms and diagnosis/treatment decreased from 68.9% of cases in 2005 to 14.3% in 2010. CONCLUSIONS While many factors were likely involved in the reduction of malaria transmission in the JNP, the CBA played an important role in the sustained success of the initiative.

A Model Based on the Combination of IFN-γ, IP-10, Ferritin and 25-Hydroxyvitamin D for Discriminating Latent From Active Tuberculosis in Children.

In recent years, pediatric research on tuberculosis (TB) has focused on addressing new biomarkers with the potential to be used as immunological non-sputum-based methods for the diagnosis of TB in children. The aim of this study was to characterize a set of cytokines and a series of individual factors (ferritin, 25-hydroxyvitamin D [25(OH)D], parasite infections, and nutritional status) to assess different patterns for discriminating between active TB and latent TB infection (LTBI) in children. The levels of 13 cytokines in QuantiFERON-TB Gold In-Tube (QFT-GIT) supernatants were analyzed in 166 children: 74 with active TB, 37 with LTBI, and 55 uninfected controls. All cytokines were quantified using Luminex or ELISA. Ferritin and 25(OH)D were also evaluated using CLIA, and Toxocara canis Ig-G antibodies were detected with a commercial ELISA kit. The combination of IP-10, IFN-γ, ferritin, and 25(OH)D achieved the best diagnostic performance to discriminate between active TB and LTBI cases in children in relation to the area under receiver operating characteristic (ROC) curve 0.955 (confidence interval 95%: 0.91-1.00), achieving optimal sensitivity and specificity for the development of a new test (93.2 and 90.0%, respectively). Children with TB showed higher ferritin levels and an inverse correlation between 25(OH)D and IFN-γ levels. The model proposed includes a combination of biomarkers for discriminating between active TB and LTBI in children to improve the accuracy of TB diagnosis in children. This combination of biomarkers might have potential for identifying the onset of primary TB in children.

Course of a major postpartum depressive episode: A prospective 2 years naturalistic follow-up study.

BACKGROUND: Survival methodology has not already been used in studies about postpartum depression (PPD) course. The aims of the present study were to estimate the duration of a Major Postpartum Depressive Episode (MPDE) during 2 years, as well as to explore factors associated with the course. METHOD: This was a prospective, naturalistic, longitudinal study with a cohort of 165 women with a MPDE (DSM-IV criteria). Potential predictors of prognosis were recorded at baseline. Follow-up was conducted using the Longitudinal Interval Follow-up Evaluation (LIFE). RESULTS: Of the total sample, 110 (66.7%) completed the 2 years follow-up. The mean time to full remission was 49.4 weeks (95% CI: 44.0-59.8). The probability of recovering was 30.2% (95% CI: 22.1%-37.4%) at 6 months of follow-up, 66.3% (95% CI: 57.4%-73.4%) at 12 months of follow-up, and 90.3% (95% CI: 79.8%-95.4%) at 24 months of follow-up. Mothers with financial difficulties, onset of depressive episode previous to birth, and those with prior treated depressive episodes took longer in achieving full remission. LIMITATIONS: Results are only generalizable to mothers with PPD treated in a psychiatric outpatient setting. Psychopharmacological treatment was uncontrolled and personality was not assessed. CONCLUSIONS: Our findings suggest that PPD could become a chronic disorder, particularly in mothers with an onset of the episode previous to birth, with a history of depression or with financial problems. Knowledge of these factors may help to improve the guidelines of depression management and treatment during the perinatal period.

Estrategia secuencial para el cribado de la ITBL en inmigrantes recién llegados en situación social vulnerable / Sequential strategy for the LTBI screening of newly-arrived immigrants in vulnerable social situations

INTRODUCCIÓN: Algunos estudios indican altas prevalencias de infección tuberculosa latente (ITBL) en población inmigrante, lo que es relevante, pues el 5-10% de los casos desarrollaran una tuberculosis activa. El objetivo de este estudio es describir los resultados de una estrategia secuencial en población inmigrante recién llegada para el diagnóstico de ITBL usando la prueba de tuberculina (PT) e IGRAs. MÉTODOS: Se realizó un estudio descriptivo retrospectivo con inmigrantes entre 6 y 35años de edad de centros de acogida, derivados a una unidad de salud internacional entre julio de 2013 y junio de 2016. Se realizó la PT, y cuando fue ≥ 5 mm, se determinaron los IGRAs. La ITBL se definió como aquellos con IGRAs ≥ 0,35 UI/ml y radiografía de tórax normal. RESULTADOS: De los 184 casos, 138 (75,0%) eran hombres, de 23,0años de edad. Las áreas geográficas de origen más frecuente fueron: 63 (34,2%) de Asia, 42 (22,8%) de Europa del Este y 41 (22,3%) del África subsahariana. La PT fue ≥10mm en 79 (42,9%). La prevalencia de ITBL usando la estrategia secuencial fue de 33/184 (17,9%). El índice kappa de Cohen (entre PT ≥ 10mm e IGRAs) fue de 0,226. CONCLUSIÓN: Basar el diagnóstico de la ITBL tan solo en la PT puede representar una sobreestimación. Algunos estudios demuestran que el cribado secuencial sería el más coste-efectivo, y ello parece más evidente en las poblaciones vacunadas con BCG

INTRODUCTION: Some studies indicate high prevalences of latent tuberculosis infection (LTBI) in the immigrant population, which is relevant because 5-10% of cases will develop active tuberculosis. The objective of this study is to describe the results of a sequential strategy in the newly-arrived immigrant population for the diagnosis of LTBI using the tuberculin skin test (TST) and IGRAs. METHODS: A retrospective descriptive study was carried out with immigrants between 6 and 35years of age from shelters, referred to an international health unit between July 2013 and June 2016. The TST was performed and when it was ≥ 5mm, IGRAs were conducted. LTBI was defined as an IGRA ≥ 0.35IU/ml and normal chest X-ray. RESULTS: Of the 184 cases, 138 (75.0%) were men, 23.0 years of age. The most common geographical areas were: 63 (34.2%) from Asia, 42 (22.8%) from Eastern Europe and 41 (22.3%) from sub-Saharan Africa. The TST was ≥ 10mm in 79 cases (42.9%). The prevalence of LTBI using the sequential strategy was 33/184 (17.9%). Cohen's Kappa index (between TST ≥ 10mm and IGRAs) was 0.226. CONCLUSION: Basing LTBI screening on the TST alone could give rise to an overestimation. Some studies show that sequential screening would be the most cost-effective; this seems most evident in BCG-vaccinated populations

Late G2 vagina toxicity in post-operative endometrial carcinoma is associated with a 68 Gy dose equivalent to 2 Gy per fraction(α/ß=3Gy) at 2 cm3 of vagina.

PURPOSE: To evaluate if the dose equivalent to 2 Gy per fraction (EQD2)(α/ß=3Gy) at 0.1 cm3, 1 cm3, and 2 cm3 of vagina in vaginal-cuff-brachytherapy (VBT) (high-dose-rate [HDR] 192Ir-source) ± external-beam-irradiation (EBRT) is associated with toxicity in post-operative endometrial carcinoma (P-EC). MATERIAL AND METHODS: From June 2014 till November 2015, 67 consecutive P-EC patients underwent VBT ± EBRT; 44 patients received EBRT (median, 45 Gy; range, 44-50.4) + VBT (7 Gy), and 23 exclusive-VBT (6 Gy x 3 fractions). The upper 2.5 cm of vagina was delineated on computed tomography (CT). The active-length source was 2.5 cm, and the brachytherapy dose was prescribed at 5 mm from the applicator. D90, V100, and EQD2(α/ß=3Gy) at 0.1 cm3, 1 cm3, and 2 cm3 of the most exposed part of the vagina were calculated. Vaginal toxicity assessment was completed with a LENT-SOMA-objective-criteria. Statistics were done with the use of χ2 and Student's-t test. RESULTS: The mean follow-up was 23.2 months (7.6-46.8). Median D90 was 7.8 Gy(α/ß=3Gy). Late toxicity: 8 G1 and 9 G2. Median EQD2(α/ß=3Gy) in vagina was 88.6 Gy (62.8-177.6) for 0.1 cm3, 72.4 Gy (57.1-130.4) for 1 cm3, and 69 Gy (53-113.4) for 2 cm3. Exclusive VBT vs. EBRT+VBT showed no differences in vaginal toxicity. There was no relationship between EQD2(α/ß=3Gy) at 0.1 cm3 and 1 cm3 of vagina with G1-G2 toxicity (p = 0.62 and p = 0.58, respectively). G2 toxicity was related to EQD2(α/ß=3Gy) at 2 cm3 (p = 0.03). EQD2(α/ß=3Gy) > 68 Gy caused G2 late toxicity in 20.5% patients. All patients presenting G2 toxicity received > 68 Gy EQD2(α/ß=3Gy). CONCLUSIONS: More than 68 Gy EQD2(α/ß=3Gy) at 2 cm3 was related to G2 toxicity in P-EC-VBT. Further studies including larger number of patients are needed to confirm these results. Patients receiving these doses should be informed of the risk of toxicity, with individualized treatment planning and follow-up to reduce G2 toxicity.

Health Status of Asylum Seekers, Spain.

The rising rate of conflicts and the unsafe situation caused by reasons of ethnicity, religion, gender, sexual orientation, political opinion, or nationality entail an increase in the number of migratory movements. The goal of this article is to describe the health status of asylum seekers visited in an international health center. We conducted a retrospective study of the asylum seekers visited between July 2013 and June 2016. A total of 303 cases were included. The median age was 28.0 years (interquartile range [IQR]: 21-35), and 203 (67.0%) were men. Of the total, 128 cases (42.2%) were from Asia, 82 (27.1%) from Eastern Europe, 42 (13.9%) from sub-Saharan Africa, 34 (11.2%) from America, and 17 (5.6%) from Maghreb. The majority, 287 (94.7%), were asymptomatic. Seventy of the 303 (23.1%) cases were diagnosed with at least one infection, this being more prevalent in men; migrants from sub-Saharan Africa; and in those who took a land-maritime migratory route. Eight of the 303 (2.6%) cases were referred to the transcultural psychiatric department. Two important challenges of the study were the communication barriers and the legal or social situation that condition the psychological symptoms. In 48 of the 303 (15.8%) cases, there was diagnosed a noncommunicable diseases. The process of care was completed by 82.5%; although 21.9% completed the vaccination for hepatitis B. The asylum seekers in this study were in general healthy young men, although special attention was given to infectious diseases with certain geoepidemiological backgrounds. Unstable living arrangements, linguistic, and cultural barriers could account for the failure of the course of care.

Sequential strategy for the LTBI screening of newly-arrived immigrants in vulnerable social situations. / Estrategia secuencial para el cribado de la ITBL en inmigrantes recién llegados en situación social vulnerable.

INTRODUCTION: Some studies indicate high prevalences of latent tuberculosis infection (LTBI) in the immigrant population, which is relevant because 5-10% of cases will develop active tuberculosis. The objective of this study is to describe the results of a sequential strategy in the newly-arrived immigrant population for the diagnosis of LTBI using the tuberculin skin test (TST) and IGRAs. METHODS: A retrospective descriptive study was carried out with immigrants between 6 and 35years of age from shelters, referred to an international health unit between July 2013 and June 2016. The TST was performed and when it was ≥5mm, IGRAs were conducted. LTBI was defined as an IGRA ≥0.35IU/ml and normal chest X-ray. RESULTS: Of the 184 cases, 138 (75.0%) were men, 23.0 years of age. The most common geographical areas were: 63 (34.2%) from Asia, 42 (22.8%) from Eastern Europe and 41 (22.3%) from sub-Saharan Africa. The TST was ≥10mm in 79 cases (42.9%). The prevalence of LTBI using the sequential strategy was 33/184 (17.9%). Cohen's Kappa index (between TST≥10mm and IGRAs) was 0.226. CONCLUSION: Basing LTBI screening on the TST alone could give rise to an overestimation. Some studies show that sequential screening would be the most cost-effective; this seems most evident in BCG-vaccinated populations.

Comparative results of three short brachytherapy schedules as exclusive treatment in postoperative endometrial carcinoma.

PURPOSE: To compare vaginal control and treatment toxicity of three different high-dose-rate brachytherapy schedules as exclusive treatment in postoperative endometrial carcinoma. METHODS AND MATERIALS: From 2003 to 2015, three different schedules were used as postoperative treatment for 146 patients (p) with intermediate-risk endometrial carcinoma. Group 1 (41 p): six fractions of 4-6 Gy, 3-4 fractions per week; Group 2 (59 p): four fractions of 5-6 Gy administered daily; Group 3 (46 p): 6 Gy × 3 fractions in three consecutive days. The dose was prescribed at 5 mm of applicator surface using an active treatment length of 2.5 cm. Toxicity scores were evaluated using the Radiation Therapy Oncology Group scores for bladder and rectum and the objective criteria of late effects of normal tissues-subjective, objective, management, analytic for vagina. Statistics used were group descriptions calculating their means, medians, and ranges. Bivariate analysis was evaluated using variance models and χ2 tests. RESULTS: The mean followup was as follows: Group 1: 88 months, Group 2: 75 months, and 41 months in Group 3. No vaginal relapses were found. Late toxicity ≥ G2: rectum: 0 p in the three groups (0%). Bladder: Group 1: 1 p (2.4%), Group 2: 0%, and Group 3: 0%. Vagina: Group 1: 4 p (9.5%); Group 2: 9 p (15.3%); and Group 3:10 p (21.8%). There were no differences in late toxicity among the three groups of patients for rectum (p = 0.83), bladder (p = 0.58), and vagina (p = 0.67); the expected global risk of complications for rectum, bladder, and vagina is 0.8%, 0.8%, and 28.8%, respectively. CONCLUSIONS: Similar results in vaginal control and complications were achieved with the three schedules. The use of three fractions of 6 Gy administered daily is the best option for patient comfort and convenience and use of resources. Nonetheless, specific studies are needed to demonstrate the best cost-efficacy regime.

A Bayesian approach to model the conditional correlation between several diagnostic tests and various replicated subjects measurements.

Two key aims of diagnostic research are to accurately and precisely estimate disease prevalence and test sensitivity and specificity. Latent class models have been proposed that consider the correlation between subject measures determined by different tests in order to diagnose diseases for which gold standard tests are not available. In some clinical studies, several measures of the same subject are made with the same test under the same conditions (replicated measurements), and thus, replicated measurements for each subject are not independent. In the present study, we propose an extension of the Bayesian latent class Gaussian random effects model to fit the data with binary outcomes for tests with replicated subject measures. We describe an application using data collected on hookworm infection carried out in the municipality of Presidente Figueiredo, Amazonas State, Brazil. In addition, the performance of the proposed model was compared with that of current models (the subject random effects model and the conditional (in)dependent model) through a simulation study. As expected, the proposed model presented better accuracy and precision in the estimations of prevalence, sensitivity and specificity. Copyright © 2017 John Wiley & Sons, Ltd.

Microscopic observation drug-susceptibility assay vs. Xpert® MTB/RIF for the diagnosis of tuberculosis in a rural African setting: a cost-utility analysis.

OBJECTIVE: To compare the cost-utility of microscopic observation drug-susceptibility assay (MODS) and Xpert® MTB/RIF implementation for tuberculosis (TB) diagnosis in rural northern Mozambique. METHODS: Stochastic transmission compartmental TB model from the healthcare provider perspective with parameter input from direct measurements, systematic literature reviews and expert opinion. MODS and Xpert® MTB/RIF were evaluated as replacement test of smear microscopy (SM) or as an add-on test after a negative SM. Costs were calculated in 2013 USD, effects in disability-adjusted life years (DALY). Willingness to pay threshold (WPT) was established at once the per capita Gross National Income of Mozambique. RESULTS: MODS as an add-on test to negative SM produced an incremental cost-effectiveness ratio (ICER) of 5647.89USD/DALY averted. MODS as a substitute for SM yielded an ICER of 5374.58USD/DALY averted. Xpert® MTB/RIF as an add-on test to negative SM yielded ICER of 345.71USD/DALY averted. Xpert® MTB/RIF as a substitute for SM obtained an ICER of 122.13USD/DALY averted. TB prevalence and risk of infection were the main factors impacting MODS and Xpert® MTB/RIF ICER in the one-way sensitivity analysis. In the probabilistic sensitivity analysis, Xpert® MTB/RIF was most likely to have an ICER below the WPT, whereas MODS was not. CONCLUSION: Our cost-utility analysis favours the implementation of Xpert® MTB/RIF as a replacement of SM for all TB suspects in this rural high TB/HIV prevalence African setting.

A new short daily brachytherapy schedule in postoperative endometrial carcinoma. Preliminary results.

PURPOSE: To evaluate the preliminary results of vaginal-cuff relapses (VCR) and complications of a short brachytherapy (BT) schedule in postoperative endometrial carcinoma. METHODS AND MATERIALS: From September 2011 to December 2014, 102 patients were treated with postoperative BT for endometrial carcinoma. Seventy-four patients received a single 7 Gy dose after external beam irradiation (Group 1), and 28 intermediate-risk patients received three daily fractions of 6 Gy (Group 2). The dose was prescribed at 5 mm from the applicator surface. Toxicity was prospectively evaluated after the objective late effects of normal tissues-subjective, objective, management, analytic scores for vagina and RTOG scores for rectum and bladder. STATISTICS: χ2 and Student's t tests. RESULTS: The mean followup was 28.85 months (9.6-58.5) in Group 1 and 31.19 months (7.7-62.3) in Group 2. No VCR was found during followup. Late toxicity: vagina toxicity was developed in 24.32% of the patients in Group 1 (G1-G2) and in 21.4% in Group 2 (G1-G2 but 1 G3). Rectal toxicity appeared in only 2.7% of patients in Group 1 (G1). Neither Group 1 nor Group 2 presented late bladder toxicity. No differences were found in late toxicity between Groups 1 and 2. CONCLUSIONS: The present short BT schedule was safe in relation to VCR and late toxicity for the followup period studied. These results are similar to those of two larger previous schedules performed in our center in relation to the same point of followup.

Prevalence and Diagnosis of Latent Tuberculosis Infection in Young Children in the Absence of a Gold Standard.

INTRODUCTION: For adequate disease control the World Health Organization has proposed the diagnosis and treatment of latent tuberculous infection (LTBI) in groups of risk of developing the disease such as children. There is no gold standard (GS) test for the diagnosis of LTBI. The objective of this study was to estimate the prevalence of LTBI in young children in contact with a household case of tuberculosis (TB-HCC) and determine the accuracy and precision of the Tuberculin Skin Test (TST) and QuantiFERON-TB Gold in-tube (QFT) used in the absence of a GS. METHODS: We conducted a cross-sectional study in children up to 6 years of age in Manaus/Brazil during the years 2009-2010. All the children had been vaccinated with the BCG and were classified into two groups according to the presence of a TB-HCC or no known contact with tuberculosis (TB). The variables studied were: the TST and QFT results and the intensity and length of exposure to the index tuberculosis case. We used the latent class model to determine the prevalence of LTBI and the accuracy of the tests. RESULTS: Fifty percent of the children with TB-HCC had LTBI, with the prevalence depending on the intensity and length of exposure to the index case. The sensitivity and specificity of TST were 73% [95% confidence interval (CI): 53-91] and 97% (95%CI: 89-100), respectively, versus 53% (95%CI: 41-66) and 81% (95%CI:71-90) for QFT. The positive predictive value of TST in children with TB-HCC was 91% (95%CI: 61-99), being 74% for QFT (95%CI: 47-95). CONCLUSIONS: This is one of the first studies to estimate the prevalence of LTBI in children and the parameters of the main diagnostic tests using a latent class model. Our results suggest that children in contact with an index case have a high risk of infection. The accuracy and the predictive value of the two tests did not significantly differ. Combined use of the two tests showed scarce improvement in the diagnosis of LTBI.

Evaluation of the paediatric dose of chloroquine in the treatment of Plasmodium vivax malaria.

BACKGROUND: Chloroquine (CQ) continues to be the first-line medication used worldwide in the treatment of Plasmodium vivax malaria. The dose recommended by the World Health Organization is 25 mg/kg independently of the age of the subject. Nonetheless, the pharmacokinetics and pharmacodynamics of drugs in children are different from those in adults and may influence the drug concentrations in blood and become risk factors for therapeutic failure and/o resistance to CQ. METHODS: This study is a secondary analysis of the data from a clinical trial in which children over 5 years of age were administered 25 mg/kg of CQ, and CQ concentrations in blood were measured at day 7 of follow-up. Models of regression and comparison were used to evaluate and compare the CQ dose taken per kg/body weight, the CQ dose calculated based on body surface area, CQ levels in blood on day 7 and the age of the population. RESULTS: The younger the study population the greater the difference between the dose per kg/body weight (real dose) and that calculated according to the BSA (theoretical dose). The difference between the two doses was -181.206 mg in the 5-9 years of age group (CI 95 % -195.39; -167.02 mg) and -71.39 mg (CI 95 % -118.61; -23.99 mg) in the 10-14-year-old group. The CQ concentrations in blood on day 7 differed in patients over and under 15 years (p = 0.008). A negative correlation was found between the real and theoretical dose (difference in dose) and the age in years (R2 = 0.529, p = 0.001). A negative correlation was also found between the difference in dose (mg) and CQ concentrations on day 7 (ng/ml) (r = -0.337, p = 0.001). Children under 15 years were found to have a higher rate of therapeutic failure than those over 15 (28 vs 4.2 %, respectively) (Kaplan-Meier p = 0.005). CONCLUSIONS: A CQ dose of 25 mg/kg for the treatment of P. vivax malaria may be too low in children as demonstrated by the reduction in CQ concentrations in blood at day 7 of follow-up. This under-dosage is probably associated with the higher rate of therapeutic failure found in children under 15 years (28 vs 4.3 %). These results suggest the need to review the paediatric doses of CQ currently used.

Prevalence of intestinal parasites and risk factors forspecific and multiple helminth infections in a remote city of the Brazilian Amazon.

INTRODUCTION: Few studies have described the risk factors of intestinal parasitic infections in the Amazon. METHODS: A cross-sectional survey was performed in a City of the State of Amazonas (Brazil) to estimate the prevalence of intestinal parasites and determine the risk factors for helminth infections. RESULTS: Ascaris lumbricoides was the most prevalent parasite. The main risk factors determined were: not having a latrine for A. lumbricoides infection; being male and having earth or wood floors for hookworm infection; and being male for multiple helminth infections. CONCLUSIONS: We reported a high prevalence of intestinal parasites and determined some poverty-related risk factors.

Infectious Diseases in Sub-Saharan Immigrants to Spain.

Immigrants may be carriers of infectious diseases because of the prevalence of these diseases in their country of origin, exposure during migration, or conditions during resettlement, with this prevalence being particularly high in sub-Saharan Africans. We performed a retrospective review of 180 sub-Saharan immigrants screened for infectious diseases at an International Health Center from January 2009 to December 2012. At least one pathogenic infectious disease was diagnosed in 72.8% patients: 60.6% latent tuberculosis infection, 36.8% intestinal parasites (intestinal protozoa or helminths), 28.1% helminths, 14.8% hepatitis B surface antigen positive, 1.2% anti-hepatitis C virus positive, 1.2% human immunodeficiency virus-positive, and 1.2% malaria. Coinfections were present in 28.4%. There was significant association between eosinophilia (absolute count or percentage) or hyper-IgE and the presence of helminths (P< 0.001). Relative eosinophilia and hyper-IgE were better indicators of helminth infection than absolute eosinophilia, particularly for schistosomiasis and strongyloidiasis. We found a high prevalence of infectious diseases in sub-Saharan immigrants, which could lead to severe health problems (in the absence of prompt treatment), representing a high cost to the public health system and possible transmission in the host country. Accurate screening and tailored protocols for infectious diseases are recommended in sub-Saharan immigrants.