Impact of an intervention program on drug adherence in patients with ulcerative colitis: Randomized clinical trial.

AIMS: Evaluate the impact of an intervention program in non-adherent patients with ulcerative colitis. METHODS: Parallel controlled randomized clinical trial (1:1), approved by the ethics committee (No. 3.068.511/2018) and registered at The Brazilian Clinical Trials Registry (No. RBR-79dn4k). Non-adherent ulcerative colitis patients according to the Morisky-Green-Levine-test were included. Recruitment began in August 2019 until August 2020, with 6-month follow-up. All participants received standard usual care, and additionally the intervention group received educational (video, educational leaflet, verbal guidance) and behavioral interventions (therapeutic scheme, motivational and reminder type short message services). Researchers were blinded for allocation prior to data collection at Visits 1 and 2 (0 and 6 months). Primary outcome: 180-day adherence rate, with relative risk 95%CI. Secondary outcome: 180-day quality of life according to SF-36 domains, using Student's t test. Variables with p<0.20 were selected for regression. Analysis included data from August/2019 to May/2021. RESULTS: Forty-six and 49 participants were allocated in control and intervention groups, respectively. Two were excluded due to intervention refusal, and 4 and 6 were lost to follow-up in control and intervention groups. There was no post-intervention adherence rate difference, even after adjustment for type of non-adherence (unintentional/both/intentional) as confounder, or if considered as adherent the intervention group participants lost in follow-up. Interventions promoted better quality of life scores even after multivariate analysis for "Pain", when adjusted for ulcerative colitis severity, sex, and marital status (ß = 18.352, p = 0.004), "Vitality", when adjusted for ulcerative colitis severity (ß = 10.568, p = 0.015) and "Emotional Aspects", when adjusted for disease severity, income, and education (ß = 24.907, p = 0.041). CONCLUSIONS: The intervention program was not able to produce a significant medication adherence rate difference between comparative groups, however, there was a significant improvement in quality of life. Study limitations may include: sample size calculated to identify differences of 30%, leading to a possible insufficient power; non blinded participants, exposing the results to the risk of performance bias; outcomes based on self-reported data.

Bilateral ictal EEG is associated with better memory outcome after hippocampal sclerosis surgery.

OBJECTIVE: To compare memory outcomes after surgery for unilateral hippocampal sclerosis (HS)-associated epilepsy in patients with unilateral and bilateral ictal electrographic involvement. METHODS: We prospectively evaluated HS patients, aged 18-55 years and IQ ≥70. Left (L) and right (R) surgical groups underwent noninvasive video-EEG monitoring and Wada test. We classified patients as Ipsilateral if ictal EEG was restricted to the HS side, or Bilateral, if at least one seizure onset occurred contralaterally to the HS, or if ictal discharge evolved to the opposite temporal region. Patients who declined surgery served as controls. Memory was evaluated on two occasions with Rey Auditory-Verbal Learning Test and Rey Visual-Design Learning Test. Baseline neuropsychological test scores were compared between groups. Pre- and postoperative scores were compared within each group. Reliable change index Z-scores (RCI) were obtained using controls as references, and compared between surgical groups. RESULTS: We evaluated 64 patients. Patients were classified as: L-Ipsilateral (9), L-Bilateral (15), L-Control (9), R-Ipsilateral (10), R-Bilateral (9), and R-Control (12). On preoperative evaluation, memory performance did not differ among surgical groups. Right HS patients did not present postoperative memory decline. L-Ipsilateral group presented postoperative decline on immediate (P = 0.036) and delayed verbal recall (P = 0.011), while L-Bilateral did not decline. L-Ipsilateral had lower RCI Z-scores, indicating delayed verbal memory decline compared to L-Bilateral (P = 0.012). SIGNIFICANCE: Dominant HS patients with bilateral ictal involvement presented less pronounced postoperative verbal memory decline compared to patients with exclusive ipsilateral ictal activity. Surgery was indicated in these patients regardless of memory impairment on neuropsychological testing, since resection of the left sclerotic hippocampus could result in cessation of contralateral epileptiform activity, and, therefore, improved memory function.

Epidemiological and molecular evidence of intrafamilial transmission through sexual and vertical routes in Bahia, the state with the highest prevalence of HTLV-1 in Brazil.

INTRODUCTION: Familial clustering of HTLV-1 and related diseases has been reported in Brazil. However, intrafamilial transmission of HTLV-1 based on molecular analysis has been studied only in a few communities of Japanese immigrants and African-Brazilians. OBJECTIVE: To investigate the familial clustering of HTLV-1 infection and to determine the likely routes of transmission through epidemiological and genetic analyzes. METHODS: Medical records of 1,759 HTLV-1+ patients from de the Center for HTLV in Salvador, Brazil, were evaluated to identify first-degree relatives previously tested for HTLV-1. Familial clustering was assumed if more than one member of the same family was HTLV-1+. LTR regions of HTLV-1 sequences were analyzed for the presence of intrafamilial polymorphisms. Family pedigrees were constructed and analyzed to infer the likely transmission routes of HTLV-1. RESULTS: In 154 patients at least one other family member had tested positive for HTLV-1 (a total of 182 first-degree relatives). Of the 91 couples (182 individuals), 51.6% were breastfed, and 67.4% reported never using a condom. Of the 42 mother-child pairs, 23.8% had a child aged 13 years or younger; all mothers reported breastfeeding their babies. Pedigrees of families with 4 or more members suggests that vertical transmission is a likely mode of transmission in three families. Three families may have had both vertical and sexual transmission routes for HTLV-1. The genetic signatures of the LTR region of 8 families revealed 3 families with evidence of vertical transmission, another 3 families (spouses) with sexual transmission, and one family with both transmission routes. HTLV-1 sequences belonged to Cosmopolitan subtype HTLV-1a Transcontinental subgroup A. CONCLUSION: Sexual and vertical transmission routes contribute to the intrafamilial spread of HTLV-1 in the state of Bahia.

Prevalence and characteristics of HTLV-associated uveitis in patients from Bahia, an endemic area for HTLV - 1 in Brazil.

BACKGROUND: HTLV-1-associated uveitis (HAU) is an inflammatory reaction of the choroid, retina, optic nerve and vitreous that can lead to vision impairment. The worldwide prevalence of HAU varies widely. OBJECTIVE: To determine the prevalence of HAU in patients from Salvador, Bahia-Brazil, and describe uveitis type and associated symptoms. METHODS: Cross-sectional analytical study to determine the prevalence of uveitis in HTLV-1-infected patients recruited in Bahia, Brazil, a region considered endemic for HTLV-1. Patients were enrolled at a local reference center for HTLV (infected) and at an outpatient ophthalmology clinic (noninfected group). All patients were examined by the same ophthalmologist following a single protocol. Prevalence ratios (PR) were calculated. RESULTS: A total of 168 consecutively examined HTLV-1-infected patients and 410 noninfected patients (randomly selected) were included. Females predominated (82.1%) in the HTLV-1-infected group (versus 64.4% in the uninfected group) (p < 0.001). The mean age of infected and uninfected patients was 53.2 and 62.8 years, respectively (p < 0.001). The prevalence of uveitis in HTLV-1+ and HTLV-1- patients was 7.14% and 0.73%, respectively (PR = 9.76; 95CI%:2.79-34.15; p < 0.01). Bilateral intermediate uveitis, associated with symptoms including visual disturbances and floaters, was most commonly identified in the HTLV-1-infected patients, whereas unilateral anterior uveitis, in association with symptoms such as blurring and ocular pain, was more common in the uninfected group. CONCLUSION: The prevalence of uveitis in patients with HTLV-1 was markedly higher than in uninfected subjects. HAU patients were mostly asymptomatic and exhibited bilateral presentation, with uveitis more frequently localized in the intermediate chamber.

Impaired flexibility in patients with tropical spastic paraparesis/HTLV-associated myelopathy: evaluation via pendulum fleximeter.

BACKGROUND: Flexibility is crucial to the harmonious execution of joint movements. While skeletal muscle dysfunction in patients with HTLV-1 can interfere with mobility, it is unclear whether these patients experience reduced flexibility. OBJECTIVE: To evaluate the differences in flexibility between HTLV-1-infected individuals with and without myelopathy compared with uninfected controls. We also investigated whether age, sex, body mass index (BMI), physical activity level, or lower back pain influence flexibility in HTLV-1-infected individuals. METHODS: The sample consisted of 56 adults, of which 15 did not have HTLV-1, 15 had HTLV-1 without myelopathy, and 26 had TSP/HAM. Their flexibility was assessed using the sit-and-reach test and a pendulum fleximeter. RESULTS: No differences in flexibility were observed between the groups with and without myelopathy and controls without HTLV-1 infection using the sit-and-reach test. The pendulum fleximeter results of individuals with TSP/HAM presented the lowest flexibility among the groups with respect to trunk flexion, hip flexion and extension, knee flexion, and ankle dorsiflexion, even after adjusting for age, sex, BMI, level of physical activity, and lower back pain using multiple linear regression models. Additionally, HTLV-1-infected individuals without myelopathy demonstrated reduced flexibility in movements: knee flexion, dorsiflexion, and ankle plantar flexion. CONCLUSIONS: Individuals with TSP/HAM demonstrated reduced flexibility in most of the movements evaluated by the pendulum fleximeter. Additionally, HTLV-1-infected individuals without myelopathy demonstrated reduced knee and ankle flexibility, potentially representing a marker of myelopathic development.

ANTECEDENTES: A flexibilidade é fundamental para a execução harmoniosa dos movimentos articulares. Embora a disfunção do músculo esquelético em pacientes com HTLV-1 possa interferir na mobilidade, não está claro se esses pacientes apresentam flexibilidade reduzida. OBJETIVO: Avaliar as diferenças de flexibilidade entre os indivíduos infectados com e sem mielopatia e o grupo controle sem infecção HTLV-1. Também investigamos se idade, sexo, índice de massa corporal (IMC), nível de atividade física ou dor lombar influenciam a flexibilidade em indivíduos infectados pelo HTLV-1. MéTODOS: A amostra foi composta por 56 adultos, dos quais 15 não possuíam HTLV-1, 15 possuíam HTLV-1 sem mielopatia e 26 possuíam TSP/HAM. A flexibilidade foi avaliada por meio do teste de sentar e alcançar e do flexímetro de pêndulo. RESULTADOS: Não foram observadas diferenças na flexibilidade entre os grupos com e sem mielopatia no teste de sentar e alcançar. Os resultados do flexímetro pendular dos indivíduos com TSP/HAM apresentaram a menor flexibilidade entre os grupos em relação à flexão do tronco, flexão e extensão do quadril, flexão do joelho e dorsiflexão do tornozelo, mesmo após ajuste para idade, sexo, IMC, nível de atividade física e dor lombar usando modelos de regressão múltipla linear. Além disso, os indivíduos infectados pelo HTLV-1 sem mielopatia demonstraram redução da flexibilidade nos movimentos de flexão do joelho, dorsiflexão e flexão plantar do tornozelo. CONCLUSãO: Indivíduos com TSP/HAM demonstraram redução da flexibilidade na maioria dos movimentos avaliados pelo flexímetro pendular. Além disso, indivíduos infectados pelo HTLV-1 sem mielopatia demonstraram redução da flexibilidade do joelho e tornozelo, representando potencialmente um marcador de desenvolvimento mielopático.

Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. METHODS: In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. FINDINGS: The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11 415 per quality-adjusted life-year (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian cost-effectiveness threshold ($18 107·74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. INTERPRETATION: HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide. FUNDING: None. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Vaginal dryness in women infected by human T-lymphotropic virus type 1: an exploratory study.

Background: Human T-lymphotropic virus type-1 (HTLV-1) causes a variety of sicca symptoms, including xeroderma, xerostomia, and xerophthalmia. Aim: We sought to evaluate vaginal dryness via the degree of perceived vaginal lubrication, vaginal hormonal cytology, and direct measurements of vaginal wetting. Methods: The research was designed as a cross-sectional study. Vaginal dryness was assessed by scores in the lubrication domain of the Female Sexual Function Index (FSFI) questionnaire and the Vaginal Maturation Index (VMI) determined by vaginal hormonal cytology, as well as the measurement of vaginal lubrication using Schirmer strips placed at the anterior vaginal wall. Medians (25th-75th percentiles) were calculated for each group and compared using a nonparametric Kruskal-Wallis test and the Dunn-Bonferroni post hoc method. Outcomes: Outcomes were detection of the presence of vaginal dryness in women who were infected or noninfected with HTLV-1. Results: HTLV-1-infected women (n = 72, 57 asymptomatic and 15 with HTLV-1-associated myelopathy/tropical spastic paraparesis [HAM/TSP]) and uninfected women (n = 49) were studied. Women with HAM/TSP had significantly lower FSFI lubrication scores than asymptomatic and uninfected women (P = .032). In addition, women with HAM/TSP had significantly lower VMI compared with the asymptomatic and uninfected groups (P = .027 and P = .039, respectively). Clinical Implications: The results of this study show a reduction in vaginal lubrication in HTLV-1-infected women diagnosed with HAM/TSP compared with asymptomatic and uninfected women. Strengths and Limitations: The lack of a gold standard test for the diagnosis of vaginal dryness and the fact that no assessment of vaginal pH was performed were limitations of this study. The strength of the study was the comprehensive assessment of vaginal dryness from several perspectives: subjective (perception of vaginal lubrication according to the vaginal lubrication domain of the FSFI), hormonal (vaginal hormonal cytology to assess local hormone status), and the degree of vaginal moisture (direct measurement of vaginal dryness with an instrument, the Schirmer strip, already used to measure the presence of dry eye). Conclusion: HTLV-1-infected women with HAM/TSP have decreased vaginal lubrication compared with asymptomatic and uninfected women after adjusting for age.

Impaired flexibility in patients with tropical spastic paraparesis/HTLV-associated myelopathy: evaluation via pendulum fleximeter / Flexibilidade prejudicada em pacientes com paraparesia espástica tropical/mielopatia associada ao HTLV: avaliação via flexímetro pendular

Abstract Background Flexibility is crucial to the harmonious execution of joint movements. While skeletal muscle dysfunction in patients with HTLV-1 can interfere with mobility, it is unclear whether these patients experience reduced flexibility. Objective To evaluate the differences in flexibility between HTLV-1-infected individuals with and without myelopathy compared with uninfected controls. We also investigated whether age, sex, body mass index (BMI), physical activity level, or lower back pain influence flexibility in HTLV-1-infected individuals. Methods The sample consisted of 56 adults, of which 15 did not have HTLV-1, 15 had HTLV-1 without myelopathy, and 26 had TSP/HAM. Their flexibility was assessed using the sit-and-reach test and a pendulum fleximeter. Results No differences in flexibility were observed between the groups with and without myelopathy and controls without HTLV-1 infection using the sit-and-reach test. The pendulum fleximeter results of individuals with TSP/HAM presented the lowest flexibility among the groups with respect to trunk flexion, hip flexion and extension, knee flexion, and ankle dorsiflexion, even after adjusting for age, sex, BMI, level of physical activity, and lower back pain using multiple linear regression models. Additionally, HTLV-1-infected individuals without myelopathy demonstrated reduced flexibility in movements: knee flexion, dorsiflexion, and ankle plantar flexion. Conclusions Individuals with TSP/HAM demonstrated reduced flexibility in most of the movements evaluated by the pendulum fleximeter. Additionally, HTLV-1-infected individuals without myelopathy demonstrated reduced knee and ankle flexibility, potentially representing a marker of myelopathic development.

Resumo Antecedentes A flexibilidade é fundamental para a execução harmoniosa dos movimentos articulares. Embora a disfunção do músculo esquelético em pacientes com HTLV-1 possa interferir na mobilidade, não está claro se esses pacientes apresentam flexibilidade reduzida. Objetivo Avaliar as diferenças de flexibilidade entre os indivíduos infectados com e sem mielopatia e o grupo controle sem infecção HTLV-1. Também investigamos se idade, sexo, índice de massa corporal (IMC), nível de atividade física ou dor lombar influenciam a flexibilidade em indivíduos infectados pelo HTLV-1. Métodos A amostra foi composta por 56 adultos, dos quais 15 não possuíam HTLV-1, 15 possuíam HTLV-1 sem mielopatia e 26 possuíam TSP/HAM. A flexibilidade foi avaliada por meio do teste de sentar e alcançar e do flexímetro de pêndulo. Resultados Não foram observadas diferenças na flexibilidade entre os grupos com e sem mielopatia no teste de sentar e alcançar. Os resultados do flexímetro pendular dos indivíduos com TSP/HAM apresentaram a menor flexibilidade entre os grupos em relação à flexão do tronco, flexão e extensão do quadril, flexão do joelho e dorsiflexão do tornozelo, mesmo após ajuste para idade, sexo, IMC, nível de atividade física e dor lombar usando modelos de regressão múltipla linear. Além disso, os indivíduos infectados pelo HTLV-1 sem mielopatia demonstraram redução da flexibilidade nos movimentos de flexão do joelho, dorsiflexão e flexão plantar do tornozelo. Conclusão Indivíduos com TSP/HAM demonstraram redução da flexibilidade na maioria dos movimentos avaliados pelo flexímetro pendular. Além disso, indivíduos infectados pelo HTLV-1 sem mielopatia demonstraram redução da flexibilidade do joelho e tornozelo, representando potencialmente um marcador de desenvolvimento mielopático.

Five-year performance analysis of a cystic fibrosis newborn screening program in northeastern Brazil

Abstract Objective: To analyze the performance of the cystic fibrosis (CF) newborn screening (NBS) program over its first five years in a Brazilian northeastern state. Methods: A population-based study using a screening algorithm based on immunoreactive trypsinogen (IRT)/IRT. Data were retrieved from the state referral screening center registry. The program performance was evaluated using descriptive indicators such as the results of an active search, coverage, newborn's age at the time of blood sampling, the time between sample collection and its arrival at the laboratory, and the child's age at diagnosis of disease. Results: The public CF screening program covered 82.6% of the 1,017,576 births that occurred, with an accumulated five-year incidence of 1:20,767 live births. The median (25th-75th) age at diagnosis was 3.5 (2.3-7.3) months. The sampling before 7 days of life for the first IRT (IRT1) increased between 2013 and 2017 from 42.2 to 48.3%. Around 5% of IRT1 samples and 30% of the second samples were collected after 30 days of life. In the first and second stages of screening, 23.6% and 19.9% of the infants, respectively, were lost to follow-up. In both stages of screening, the samples were retained at the health units for a median (25th-75th) of 9.0 (7.0-13.0) days. Conclusions: The coverage by the CF-NBS program was satisfactory as compared to other Brazilian state rates and the percentage of IRT1 samples collected within the first week of life increased progressively. However, time of samples retention at the health units, inappropriate sampling, inherent methodological problems, and loss of follow-up need to improve.

Human T Cell Lymphotropic Virus Type 1 Global Prevalence Associated with the Human Development Index: Systematic Review with Meta-Analysis.

In 2012, the number of people infected with human T cell lymphotropic virus type 1 (HTLV-1) was estimated to be 10 million worldwide. Prevalence varies according to geographic location, ethnic factors, sex, age, populations exposed to risk factors, income, and education, reaching countries with the worst socioeconomic scenarios. There is a need to determine the current global prevalence of HTLV-1 and examine its association with countries' human development index (HDI) to provide data for global health policy. Systematic review with meta-analysis is according to PRISMA 2020 recommendations. It was registered at PROSPERO, CRD42021223146. Prevalence or cross-sectional studies of HTLV-1 infection with at least 100 participants, screening, and confirmatory serologic testing were included. Studies with incomplete or unavailable results or with duplicate information were excluded. Data were selected by two independent investigators and analyzed using R software, a metapackage that generated the forest plots [95% confidence interval (CI)]. Heterogeneity was assessed using the I2 statistic, and funnel plot asymmetry was assessed using Egger's test. Countries were compared using an HDI cutoff ≥0.8. Methodological quality was assessed using Joanna Briggs Institute (JBI) criteria. The overall prevalence of HTLV-1 infection was 0.91% (95% CI: 0.80-1.02, p < .0001) and was higher in low HDI countries [1.18% (95% CI: 1.03-1.34)] than in high HDI countries [0.41% (95% CI: 0.27-0.57)]. Prevalence varied according to the populations studied: it was higher in the general population [1.65% (95% CI: 1.08-2.34)] compared to pregnant women [0.34% (95% CI: 0.17-0.57)] and blood donors [0.04% (95% CI: 0.01-0.08)]. Consistently, prevalence for each population group was higher in low HDI countries than in high HDI countries. The worldwide prevalence of HTLV-1 infection is highly heterogeneous, with a global prevalence of 0.91%. In high HDI countries, the observed prevalence is approximately three times lower than in low HDI countries. In the general population, the observed prevalence is about 5 times higher than in pregnant women and 41 times higher than in blood donors.

Five-year performance analysis of a cystic fibrosis newborn screening program in northeastern Brazil.

OBJECTIVE: To analyze the performance of the cystic fibrosis (CF) newborn screening (NBS) program over its first five years in a Brazilian northeastern state. METHOD: A population-based study using a screening algorithm based on immunoreactive trypsinogen (IRT)/IRT. Data were retrieved from the state referral screening center registry. The program performance was evaluated using descriptive indicators such as the results of an active search, coverage, newborn's age at the time of blood sampling, the time between sample collection and its arrival at the laboratory, and the child's age at diagnosis of disease. RESULTS: The public CF screening program covered 82.6% of the 1,017,576 births that occurred, with an accumulated five-year incidence of 1:20,767 live births. The median (25th-75th) age at diagnosis was 3.5 (2.3-7.3) months. The sampling before 7 days of life for the first IRT (IRT1) increased between 2013 and 2017 from 42.2 to 48.3%. Around 5% of IRT1 samples and 30% of the second samples were collected after 30 days of life. In the first and second stages of screening, 23.6% and 19.9% of the infants, respectively, were lost to follow-up. In both stages of screening, the samples were retained at the health units for a median (25th-75th) of 9.0 (7.0-13.0) days. CONCLUSIONS: The coverage by the CF-NBS program was satisfactory as compared to other Brazilian state rates and the percentage of IRT1 samples collected within the first week of life increased progressively. However, time of samples retention at the health units, inappropriate sampling, inherent methodological problems, and loss of follow-up need to improve.

Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model

Background Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. Methods In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. Findings The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11415 per quality-adjusted lifeyear (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian costeffectiveness threshold ($18 107·74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. Interpretation HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide. (AU)

Integrative and Multidisciplinary Care for People Living With Human T-Cell Lymphotropic Virus in Bahia, Brazil: 20 Years of Experience.

Brazil is home to the highest absolute number of human T-cell lymphotropic virus type-1 (HTLV-1)-infected individuals worldwide; the city of Salvador, Bahia, has the highest prevalence of HTLV-1 infection in Brazil. Due to the complex nature of several diseases associated with this retrovirus, a multidisciplinary health care approach is necessary to care for people living with HTLV-1. The Bahia School of Medicine and Public Health's Integrative Multidisciplinary HTLV Center (CHTLV) has been providing support to people living with HTLV and their families since 2002, striving to ensure physical and mental well-being by addressing biopsychosocial aspects, providing clinical care and follow-up, including to pregnant/postpartum women, as well as comprehensive laboratory diagnostics, psychological therapy, and counseling to family members. To date, CHTLV has served a total of 2,169 HTLV-infected patients. The average patient age is 49.8 (SD 15.9) years, 70.3% are female, most are considered low-income and have low levels of education. The majority (98.9%) are HTLV-1 cases, and approximately 10% have been diagnosed with tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM), while 2.2% have infective dermatitis and 1.1% have adult T-cell lymphoma. In all, 178 pregnant/postpartum women [mean age: 32.7 (±6.5) years] have received care at CHTLV. Regarding vertical transmission, 53% of breastfed infants screened for HTLV tested positive in their second year of life, nearly 18 times the rate found in non-breastfed infants. This article documents 20 years of experience in implementing an integrative and multidisciplinary care center for people living with HTLV in Bahia, Brazil. Still, significant challenges remain regarding infection control, and HTLV-infected individuals continue to struggle with the obtainment of equitable and efficient healthcare.

Comparison of General and Liver-Specific Prognostic Scores in Their Ability to Predict Mortality in Cirrhotic Patients Admitted to the Intensive Care Unit.

Introduction: Acute Physiology and Chronic Health Evaluation (APACHE) II and III and Sequential Organ Failure Assessment (SOFA) are prognostic scores commonly used in the intensive care unit (ICU). Their accuracy in predicting mortality has not been adequately evaluated in comparison to prognostic scores commonly used in critically ill cirrhotic patients with acute decompensation (AD) or acute-on-chronic liver failure (ACLF). Aims: This study was conducted to evaluate the performance of prognostic scores, including APACHE II, SOFA, Chronic Liver Failure Consortium (CLIF-C) SOFA, Child-Turcotte-Pugh (CPS), Model for End-Stage Liver Disease (MELD), MELD-Na, MELD to serum sodium ratio (MESO) index, CLIF-C organ failure (CLIF-C OF), CLIF-C ACLF, and CLIF-C AD scores, in predicting mortality of cirrhotic patients admitted to the ICU. Patients and Methods. A total of 382 patients (280 males, mean age 67.3 ± 10.6 years) with cirrhosis were retrospectively evaluated. All prognostic scores were calculated in the first 24 hours of ICU admission. Their ability to predict mortality was measured using the analysis of the area under the receiver operating characteristic curve (AUC). Results: Mortality was observed in 31% of the patients. Analysis of AUC revealed that CLIF-C OF (0.807) and CLIF-SOFA (0.776) had the best ability to predict mortality in all patients, but CLIF-C OF (0.749) had higher prognostic accuracy in patients with ACLF. CLIF-SOFA, SOFA, and CLIF-C AD had the highest AUC values in patients with AD, with no statistical difference (p=0.971). Conclusions: When compared to other general or liver-specific prognostic scores, CLIF-C OF, CLIF-SOFA, SOFA, and CLIF-C AD have good accuracy to predict mortality in critically ill patients with cirrhosis and patients with AD. According to the clinical scenario, different scores should be used to provide prognosis to patients with cirrhosis in the ICU.

Time until maximum flow rate uroflowmetry: A new parameter for predicting failure of transcutaneous electrical nerve stimulation (TENS) in treating children and adolescents with overactive bladder.

AIM: To analyze uroflowmetry as a predictor of the outcome of treatment with parasacral transcutaneous electrical nerve stimulation (TENS) in patients with pure overactive bladder. METHODS: Thirty-eight patients of 5-16 years of age were included in this prospective cohort study. All the patients had been seen at a referral clinic between 2006 and 2015. All had a diagnosis of pure overactive bladder and were treated with TENS. Parameters established at pretreatment uroflowmetry were evaluated, with patients then being separated into two groups based on their visual analogue scale (VAS) score immediately following TENS. The variables analyzed at uroflowmetry were: maximum flow rate, curve pattern (bell or tower-shaped), time until maximum flow and voided volume. RESULTS: The mean age of the children evaluated was 7.26 years (SD: 2.62) (95%CI: 6.4-8.13) and 73.7% were girls. No association was found between maximum flow rate, curve pattern (bell or tower-shaped) or voided volume and the complete resolution of symptoms following treatment. Nevertheless, a shorter time until maximum flow was associated with a greater likelihood of treatment failure. CONCLUSION: The time until maximum flow rate before treatment is a potential predictor of the outcome of TENS treatment.

METABOLIC CONTROL AND BODY COMPOSITION OF CHILDREN AND ADOLESCENTS WITH PHENYLKETONURIA.

OBJECTIVE: To characterize metabolic control and verify whether it has any relation with socioeconomic, demographic, and body composition variables in children and adolescents with phenylketonuria (PKU) diagnosed in the neonatal period. METHODS: This cohort study collected retrospective data of 53 phenylketonuric children and adolescents. Data on family income, housing, and mother's age and schooling level were collected, and anthropometric measures of body composition and distribution were taken. All dosages of phenylalanine (Phe) from the last five years (2015-2019) were evaluated and classified regarding their adequacy (cutoffs: 0-12 years: 2-6 mg/dL; 12-19 years: 2-10 mg/dL). Adequate metabolic control was considered if ≥7%) of the dosages were within desired ranges. RESULTS: The mean (±standard deviation) age in the last year was 10.1±4.6 years. Most of them were under 12 years old (33/53; 62.3%) and had the classic form of the disease (39/53; 73.6%). Better metabolic control was observed among adolescents (68.4 versus 51.4%; p=0.019). Overweight was found in 9/53 (17%) and higher serum Phe levels (p<0.001) were found in this group of patients. Metabolic control with 70% or more Phe level adequacy decreased along with the arm muscle area (AMA) (ptendency=0.042), being 70.0% among those with low reserve (low AMA), and 18.5% among those with excessive reserve (high AMA). CONCLUSIONS: Adequate metabolic control was observed in most patients. The findings suggest that, in this sample, the levels of phenylalanine may be related to changes in body composition.

Metabolic control and body composition of children and adolescents with phenylketonuria / Controle metabólico e composição corporal de crianças e adolescentes com diagnóstico neonatal de fenilcetonúria

ABSTRACT Objective: To characterize metabolic control and verify whether it has any relation with socioeconomic, demographic, and body composition variables in children and adolescents with phenylketonuria (PKU) diagnosed in the neonatal period. Methods: This cohort study collected retrospective data of 53 phenylketonuric children and adolescents. Data on family income, housing, and mother's age and schooling level were collected, and anthropometric measures of body composition and distribution were taken. All dosages of phenylalanine (Phe) from the last five years (2015-2019) were evaluated and classified regarding their adequacy (cutoffs: 0-12 years: 2-6 mg/dL; 12-19 years: 2-10 mg/dL). Adequate metabolic control was considered if ≥7%) of the dosages were within desired ranges. Results: The mean (±standard deviation) age in the last year was 10.1±4.6 years. Most of them were under 12 years old (33/53; 62.3%) and had the classic form of the disease (39/53; 73.6%). Better metabolic control was observed among adolescents (68.4 versus 51.4%; p=0.019). Overweight was found in 9/53 (17%) and higher serum Phe levels (p<0.001) were found in this group of patients. Metabolic control with 70% or more Phe level adequacy decreased along with the arm muscle area (AMA) (ptendency=0.042), being 70.0% among those with low reserve (low AMA), and 18.5% among those with excessive reserve (high AMA). Conclusions: Adequate metabolic control was observed in most patients. The findings suggest that, in this sample, the levels of phenylalanine may be related to changes in body composition.

RESUMO Objetivo: Caracterizar o controle metabólico e verificar se existe relação entre ele, variáveis socioeconômicas, demográficas e composição corporal de crianças e adolescentes com fenilcetonúria (FNC) diagnosticada no período neonatal. Métodos: Coorte com coleta retrospectiva de dados de 53 crianças e adolescentes fenilcetonúricos. Foram coletados dados de renda familiar, moradia, idade e escolaridade materna e realizaram-se medidas antropométricas de composição e distribuição corporal. Todas as dosagens de fenilalanina (Fal) dos últimos cinco anos (2015-2019) foram avaliadas e classificadas quanto à adequação (cortes: 0-12 anos: 2-6 mg/dL; 12-19 anos: 2-10 mg/dL). A proporção de dosagens adequadas ≥70% foi considerada como controle metabólico adequado. Resultados: A média (±desvio padrão) de idade, no último ano, foi de 10,1±4,6 anos. A maioria tinha menos de 12 anos (33/53; 62,3%) e apresentava a forma clássica da doença (39/53; 73,6%). Observou-se melhor controle metabólico entre os adolescentes (68,4 vs. 51,4%; p=0,019). Excesso de peso foi encontrado em 9/53 (17%) e maiores níveis séricos de Fal foram descritos nesse grupo (p<0,001). O percentual de controle metabólico com 70% ou mais de adequação dos níveis de Fal foi decrescente de acordo com a área muscular do braço (AMB; ptendência=0,042), sendo de 70% entre os de baixa reserva (AMB reduzida) e de 18,5% entre os com excesso (AMB elevada). Conclusões: Observou-se controle metabólico adequado na maioria dos avaliados e os achados sugerem que, nesta amostra, os níveis de fenilalanina podem estar relacionados com alterações da composição corporal.

Heightened Plasma Levels of Transforming Growth Factor Beta (TGF-ß) and Increased Degree of Systemic Biochemical Perturbation Characterizes Hepatic Steatosis in Overweight Pediatric Patients: A Cross-Sectional Study.

Nonalcoholic Fatty Liver Disease (NAFLD) is a common cause of chronic liver disease in childhood and strongly associated with obesity. Routine biochemical non-invasive tests remain with low accuracy for diagnosis of NAFLD. We performed a cross-sectional study to examine potential associations between anthropometric and biochemical parameters, specially TGF-ß, a prognosis marker for hepatic steatosis (HS). Between May and October 2019, seventy-two overweight adolescents were enrolled, of which 36 had hepatic steatosis. Hepatic, lipidic and glycemic profiles, and levels of vitamin D, ferritin and TGF-ß were analyzed. Hierarchical cluster and a discriminant model using canonical correlations were employed to depict the overall expression profile of biochemical markers and the biochemical degree of perturbation. Median values of alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), and TGF-ß were higher in the adolescents with HS. Values of body mass index (BMI)/age and ALT, but not of TGF-ß, were gradually increased proportionally to augmentation of steatosis severity. In a multivariate analysis, TGF-ß plasma concentrations were associated with occurrence of hepatic steatosis independent of other covariates. Discriminant analysis confirmed that TGF-ß concentrations can identify HS cases. Our data reveal that HS patients exhibit a distinct biosignature of biochemical parameters and imply TGF-ß as an important biomarker to evaluate risk of steatosis development.