Nutrition in Menopausal Women: A Narrative Review.

Among the various aspects of health promotion and lifestyle adaptation to the postmenopausal period, nutritional habits are essential because they concern all women, can be modified, and impact both longevity and quality of life. In this narrative review, we discuss the current evidence on the association between dietary patterns and clinical endpoints in postmenopausal women, such as body composition, bone mass, and risk markers for cardiovascular disease. Current evidence suggests that low-fat, plant-based diets are associated with beneficial effects on body composition, but further studies are needed to confirm these results in postmenopausal women. The Mediterranean diet pattern along with other healthy habits may help the primary prevention of bone, metabolic, and cardiovascular diseases in the postmenopausal period. It consists on the use of healthy foods that have anti-inflammatory and antioxidant properties, and is associated with a small but significant decrease in blood pressure, reduction of fat mass, and improvement in cholesterol levels. These effects remain to be evaluated over a longer period of time, with the assessment of hard outcomes such as bone fractures, diabetes, and coronary ischemia.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3-0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59-1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61-8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation. FUNDING: Coalition COVID-19 Brazil, Bayer SA.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3­0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59­1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61­8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation.

Rapid molecular diagnostics of COVID-19 by RT-LAMP in a centrifugal polystyrene-toner based microdevice with end-point visual detection.

Infection caused by the new coronavirus (SARS-CoV-2) has become a serious worldwide public health problem, and one of the most important strategies for its control is mass testing. Loop-mediated isothermal amplification (LAMP) has emerged as an important alternative to simplify the diagnostics of infectious diseases. In addition, an advantage of LAMP is that it allows for easy reading of the final result through visual detection. However, this step must be performed with caution to avoid contamination and false-positive results. LAMP performed on microfluidic platforms can minimize false-positive results, in addition to having potential for point-of-care applications. Here, we describe a polystyrene-toner (PS-T) centrifugal microfluidic device manually controlled by a fidget spinner for molecular diagnosis of COVID-19 by RT-LAMP, with integrated and automated colorimetric detection. The amplification was carried out in a microchamber with 5 µL capacity, and the reaction was thermally controlled with a thermoblock at 72 °C for 10 min. At the end of the incubation time, the detection of amplified RT-LAMP fragments was performed directly on the chip by automated visual detection. Our results demonstrate that it is possible to detect COVID-19 in reactions initiated with approximately 10-3 copies of SARS-CoV-2 RNA. Clinical samples were tested using our RT-LAMP protocol as well as by conventional RT-qPCR, demonstrating comparable performance to the CDC SARS-CoV-2 RT-qPCR assay. The methodology described in this study represents a simple, rapid, and accurate method for rapid molecular diagnostics of COVID-19 in a disposable microdevice, ideal for point-of-care testing (POCT) systems.

Exact sequential analysis for multiple weighted binomial end points.

Sequential analysis is used in clinical trials and postmarket drug safety surveillance to prospectively monitor efficacy and safety to quickly detect benefits and problems, while taking the multiple testing of repeated analyses into account. When there are multiple outcomes, each one may be given a weight corresponding to its severity. This paper introduces an exact sequential analysis procedure for multiple weighted binomial end points; the analysis incorporates a drug's combined benefit and safety profile. It works with a variety of alpha spending functions for continuous, group, or mixed group-continuous sequential analysis. The binomial probabilities may vary over time and do not need to be known a priori. The new method was implemented in the free R Sequential package for both one- and two-tailed sequential analysis. An example is given examining myocardial infarction and major bleeding events in patients who initiated non-steroidal antiinflammatory drugs.

Determinação de um ponto final humanitário em camundongos submetidos ao teste diagnóstico do vírus da raiva / Determination of a humanitarian endpoint in mice submitted to the rabies virus diagnostic test

A raiva é uma antropozoonose, uma doença infecciosa aguda causada por vírus do gênero Lyssavírus e espécie Rabies vírus. A organização Mundial da Saúde reco-menda que sejam realizados dois testes para diagnóstico da raiva: a imunofluores-cência direta (IFD) e o isolamento viral que pode ser realizado em cultura de células ou em camundongos. A técnica de IVC preconiza que os animais inoculados sejam observados diariamente e que a eutanásia seja realizada quando os animais estive-rem prostrados, apresentando sintomas severos da doença, tais como paralisia de membros, o que acarreta sofrimento animal. Sendo assim, o objetivo principal deste trabalho foi determinar um ponto final humanitário dos animais que adoecem na rotina de diagnóstico da raiva, de modo a reduzir o sofrimento sem que o diagnóstico seja prejudicado. Para tanto, foram utilizadas 20 amostras positivas da rotina laboratorial de diferentes variantes do vírus da raiva. Cada amostra foi inoculada em 5 camundon-gos recém-desmamados, sendo que cada animal foi observado e pesado em balança analítica diariamente. Os animais foram eutanasiados em 3 diferentes momentos: fase 1-no início dos sintomas da doença, quando o animal apresenta perda de peso e sin-tomas inespecíficos (piloereção, apatia); fase 2-aparecimento de sintomas neurológi-cos (incoordenação, alterações de comportamento) e fase 3-fase terminal (dificuldade locomotora, tremores, paralisia de membros). O SNC dos animais eutanasiados foram coletados e submetidos a IFD utilizando anticorpo policlonal e monoclonal, que foi classificada de acordo com a sua intensidade 1 (+) a 4 (+) e para fins de comparação da carga viral obtida em diferentes momentos da doença, foi realizada a titulação viral em cultivo de células N2a para as 3 fases de 4 amostras escolhidas aleatoriamente. Todos os animais foram positivos na IFD e apresentaram intensidade de fluorescência na maioria das amostras entre 2 (+) e 4(+), o que demonstra que não há comprome-timento do diagnóstico pela IFD mesmo que o animal seja eutanasiado em fase inicial da doença. Em relação a titulação viral, não foi observado um aumento do título em relação à evolução da doença. A técnica de IFD apresentou resultados relevantes a partir da primeira fase com vários campos com inclusões. A titulação viral obteve títu-los semelhantes em todas as fases, corroborando que é possível identificar a infecção já no início dos sintomas. Assim, a determinação de um endpoint precoce no diagnós-tico da raiva ou intervenções oportunas deve ser estabelecida, aplicando-se o mais cedo possível, prevenindo, melhorando ou minimizando dores ou angústia desneces-sárias. A observação dos sintomas em fase inicial pode demandar um pouco mais de tempo e pessoal habilitado, podendo ser inviável. A partir da fase 2, a qual os sintomas neurológicos são evidentemente observáveis, pode-se fazer a eutanásia sem a ne-cessidade de esperar a fase terminal, sem causar prejuízo ao diagnóstico como pode ser evidenciado nos resultados obtidos (AU),

Rabies is an anthropozoonosis, an acute infectious disease caused by viruses of the genus Lyssavirus and Rabies virus species. The World Health Organization recom-mends that two tests be performed for rabies diagnosis: direct fluorescence antibody (DFA) and viral isolation that can be carried out in cell culture or in mice. The mouse inoculation test (MIT) recommends daily observation of inoculated animals and eutha-nasia when the animals are prostrate, presenting severe symptoms of the disease, such as limb paralysis, which causes animal suffering. Therefore, the main objective of this work was to determine a humanitarian end point for animals that become ill in the routine of rabies diagnosis, in order to reduction suffering without the diagnosis being harmed. For this purpose, 20 positive samples from the laboratory routine of different rabies virus variants were used. Each sample was inoculated into 5 weaned mice, each animal was observed and weighed on an analytical balance daily. The an-imals were euthanized at 3 different times: phase 1 - at the beginning of the disease symptoms, when the animal shows weight loss and nonspecific symptoms (piloerec-tion, apathy); phase 2 - appearance of neurological symptoms (incoordination, behav-ioral changes) and phase 3 - terminal phase (locomotor difficulties, tremors, limb pa-ralysis). The CNS of the euthanized animals were collected and submitted to DFA us-ing polyclonal and monoclonal antibodies, which were classified according to their in-tensity 1 (+) to 4 (+) and for the purpose of comparing the viral load obtained in different moments of the disease, viral titration was performed in N2a cell culture for the 3 phases of 4 samples chosen at random. All animals were positive in IFD and showed fluorescence intensity in most samples between 2 (+) and 4 (+), which demonstrates that there is no impairment of diagnosis by IFD even if the animal is euthanized in the initial phase of disease. Regarding the viral titration, there was no increase in the titre in relation to the evolution of the disease. The DFA technique showed relevant results from the first phase with several fields with inclusions. Viral titration obtained similar titers in all phases, corroborating that it is possible to identify the infection early in the symptoms. Thus, the determination of an early endpoint in the diagnosis of rabies or timely interventions should be established, applying as soon as possible, preventing, improving or minimizing unnecessary pain or distress. The observation of symptoms in the initial phase can demand a little more time and qualified personnel, which may not be viable. From phase 2, which neurological symptoms are clearly observable, euthanasia can be performed without the need to wait for the terminal phase, without causing damage to the diagnosis as can be seen in the results obtained (AU).

Single and Combined Effects of Zinc and Manganese on the Bivalve Anodontites trapesialis: Complementary Endpoints to Support the Hypothesis of Manganese Promoting Metabolic Suppression in Gills.

Manganese (Mn) might stimulate the valve closure reflex in the freshwater bivalve Anodontites trapesialis, leading to metabolic suppression, whereas zinc (Zn) is not able to modify this behavior. To investigate this particular response, we exposed A. trapesialis specimens to Mn (0.5 mg L-1 ) and Zn (1.0 mg L-1 ) alone, and to their mixture, to measure further endpoints in different clam tissues: glycogen level in gills, and calcium (Ca2+ ), sodium (Na+ ), and chloride (Cl- ) concentrations in the hemolymph. Furthermore, we used cutting-edge technology, proteomics, to evaluate modifications in protein patterns under the 3 exposure tests. The main results highlighted that only Mn caused a clear drop in glycogen levels in gills, an increase in Ca2+ and Na+ , and a simultaneous decrease in Cl- concentration in the hemolymph. The proteomic analysis confirmed that Mn promoted more effects in A. trapesialis than the other tested conditions, because the number of proteins modulated was higher than the results obtained after exposure to Zn and the mixture. Moreover, 11 of the 12 modulated proteins were down-expressed. These results consolidate the hypothesis that Mn might suppress gill metabolic rate in A. trapesialis. Environ Toxicol Chem 2019;38:2480-2485. © 2019 SETAC.

The TyG index cutoff point and its association with body adiposity and lifestyle in children / Ponto de corte do índice TyG e sua associação com a adiposidade corporal e estilo de vida em crianças

Abstract Objective: To investigate the factors associated with insulin resistance in children aged 4-7 years, and to identify the cutoff point of the triglyceride-glucose index for the prediction of insulin resistance in this population. Methods: A cross-sectional study was conducted with 403 children from a retrospective cohort. Insulin resistance was also evaluated in a sub-sample using the HOMA index. Four indicators of body adiposity were assessed: body mass index, waist-to-height ratio, and the percentages of total and central body fat. Food habits were evaluated by the identification of dietary patterns, using principal component analysis. Information was also collected on lifestyle, socioeconomic status, and breastfeeding time. Results: The median index observed in the sample was 7.77, which did not differ between the genders. The shorter the time spent in active activities, the higher the triglyceride-glucose value; and increase in the values of body adiposity indicators was positively associated with triglyceride-glucose. The cutoff point with the best balance between sensitivity and specificity values was 7.88 (AUC = 0.63, 95% CI: 0.51-0.74). Conclusion: The present study identified that total and central body adiposity and shorter time spent in lively activities was positively associated with insulin resistance, evaluated through the triglyceride-glucose index. The cutoff point of 7.88 may be used in this population for insulin resistance risk screening, but caution is required when using it in other populations.

Resumo Objetivo: Investigar os fatores associados à resistência à insulina em crianças de 4 a 7 anos, e identificar o ponto de corte do índice triglicerídeos-glicemia (TyG) para predição da RI nessa população. Métodos: Estudo transversal, com 403 crianças pertencentes a uma coorte retrospectiva. A resistência à insulina foi avaliada pelo índice triglicerídeos-glicemia e também pelo índice HOMA, este em uma subamostra. Avaliou-se quatro indicadores de adiposidade corporal: o índice de massa corporal, a relação cintura-estatura e os percentuais de gordura corporal total e central. O hábito alimentar foi avaliado pela identificação dos padrões alimentares, utilizando-se a análise de componentes principais. Foram coletadas também informações sobre estilo de vida, condição socioeconômica e tempo de aleitamento materno. Resultados: A mediana observada do índice triglicerídeos-glicemia na amostra foi de 7,77 e não diferiu entre os sexos. Quanto menor o tempo diário em atividades ativas, maior o valor de triglicerídeos-glicemia; e o aumento nos valores dos indicadores de adiposidade corporal associou-se positivamente com o triglicerídeos-glicemia. O ponto de corte com melhor equilíbrio entre os valores de sensibilidade e especificidade foi o de 7,88 (AUC = 0,63; IC 95% 0,51 - 0,74). Conclusão: O presente estudo identificou que a adiposidade corporal total e central e o menor tempo diário em atividades ativas associou-se positivamente com a resistência à insulina, avaliada pelo índice triglicerídeos-glicemia. O ponto de corte de 7,88 pode ser utilizado nessa população para triagem do risco de resistência à insulina, mas é necessário cautela na sua utilização em outras populações.

Establishment of an objective endpoint in mice model for caseous lymphadenitis vaccine trials.

For a long time, the scientific community has described the need for a continued update in practices that ensure the welfare of animals undergoing experimentation. In addition to approaches on principles of care and use of animals, there is a more current emerging concern: defining an appropriate end point in experiments that use animals for research, teaching and testing. The term "endpoint" is defined as the point at which an experimental animal's pain and/or distress is terminated, minimized, or reduced humanely. In the present study, we established an endpoint in Balb/C mice for caseous lymphadenitis vaccine trials, which can be considered as a highly important parameter since several studies are being developed to control the disease efficiently. Mice were monitored daily until the 30th day after infection with pathogenic strain of C. pseudotuberculosis MIC-6 using the most relevant parameters for the appearance of clinical signs of caseous lymphadenitis (CLA), such as abscesses, lethargy, and loss of weight and hair. The endpoint was found to be a weight loss of 0.2167 g after five days or 10% weight loss in less than five days. In conclusion, the findings reported here will help improve animal's well-being during vaccine trials for CLA and consequently represent significant contribution to animal's welfare.

The TyG index cutoff point and its association with body adiposity and lifestyle in children.

OBJECTIVE: To investigate the factors associated with insulin resistance in children aged 4-7 years, and to identify the cutoff point of the triglyceride-glucose index for the prediction of insulin resistance in this population. METHODS: A cross-sectional study was conducted with 403 children from a retrospective cohort. Insulin resistance was also evaluated in a sub-sample using the HOMA index. Four indicators of body adiposity were assessed: body mass index, waist-to-height ratio, and the percentages of total and central body fat. Food habits were evaluated by the identification of dietary patterns, using principal component analysis. Information was also collected on lifestyle, socioeconomic status, and breastfeeding time. RESULTS: The median index observed in the sample was 7.77, which did not differ between the genders. The shorter the time spent in active activities, the higher the triglyceride-glucose value; and increase in the values of body adiposity indicators was positively associated with triglyceride-glucose. The cutoff point with the best balance between sensitivity and specificity values was 7.88 (AUC=0.63, 95% CI: 0.51-0.74). CONCLUSION: The present study identified that total and central body adiposity and shorter time spent in lively activities was positively associated with insulin resistance, evaluated through the triglyceride-glucose index. The cutoff point of 7.88 may be used in this population for insulin resistance risk screening, but caution is required when using it in other populations.

A protocol update for the Selenium Treatment and Chagasic Cardiomyopathy (STCC) trial.

Several studies evaluating clinical forms of chronic Chagas disease show that about one-third of patients present cardiac involvement. Heart failure, sudden death and cardioembolic stroke are the main mechanisms of death in Chagas heart disease. The impact of specific etiologic treatment on the prognosis of patients with chronic Chagas heart disease is very limited regardless of the presence or absence of heart failure. Patients with symptomatic Chagas heart disease present serum selenium (Se) levels lower than patients without Chagas heart disease. Moreover, Se supplementation in animal models showed promising results. The aim of this trial is to estimate the effect of Se treatment on prevention of heart disease progression in patients with Chagas cardiomyopathy. However, we had to introduce some protocol modifications in order to keep trial feasibility, as follows: the primary outcome was restricted to left ventricular ejection fraction as a continuous variable, excluding disease progression; the follow-up period was decreased from 5 years to 1 year, an adjustment that might increase the participation rate of our study; the superior age limit was increased from 65 to 75 years; and diabetes mellitus was no longer considered an exclusion criterion. All of these protocol modifications were extensively debated by the research team enrolled in the design, recruitment and conduction of the clinical trial to guarantee a high scientific quality. TRIAL REGISTRATION: Clinical Trials.gov, NCT00875173 . Registered on 20 October 2008.

Efectividad del programa de control de tuberculosis en las entidades estatales. Departamento de Córdoba, Colombia 2015 / Effectiveness of the tuberculosis control program in state entities. Department of Cordoba, Colombia 2015

Objetivo. Medir la efectividad del Programa de Control de Tuberculosis en las diferentes entidades estatales del departamento de Córdoba. Materiales y métodos.Estudio descriptivo, retrospectivo, utilizando datos de las fuentes secundarias relacionados con aspectos sociales y demográficos, epidemiológicos, clínicos, de laboratorio, tratamiento y evolución y diagnostico final, analizando el comportamiento de la atención y el grado de adherencia terapéutica de la Tuberculosis. Resultados. En 2015 la prevalencia de Tuberculosis fue de 17 casos por 100000 habitantes; en cuatro de las seis zonas geográficas sujetos de este estudio las prevalencias superaban la media nacional. Las regiones con prevalencias más altas corresponden al Alto Sinú y Alto San Jorge y las más bajas las zonas costaneras y de sabanas. El 79.2% de los casos fueron incidentes, 18.8% recaídas y 2.1% abandono del tratamiento. En 68.7% de las historias revisadas no se encontró evidencia de actividades realizadas a contactos. Los pacientes acuden a la consulta inicial tras un periodo entre 31 a 60 días de síntomas; 12.5% fueron diagnosticados después de 15 días de la consulta inicial, en 14.6% de los casos el tratamiento se inició después de 16 días de la consulta inicial. 41.7% culminaron con baciloscopia negativa, a 37.5% de quienes terminaron su tratamiento no se les realizó Baciloscopia al final, 2.1% de los casos fracasó y 14.6% falleció. Conclusiones. Existen factores de gestión del programa que se manifiestan en demoras para identificar los casos probables e iniciar tratamiento oportunamente

Objective. To measure the effectiveness of the Tuberculosis Control Program in the different entities of the department of Córdoba. Materials and methods. This is a descriptive and retrospective study. The researchers used data from the secondary sources relating to social, demographic, epidemiological, clinical, laboratory, treatment, final evolution, and diagnosis to analyze the behavior of the attention and the degree of therapeutic adherence to tuberculosis. Results. In 2015, the prevalence of disease was 17 cases per 1000 inhabitants. In four of the six geographic target areas, the prevalence exceeded the national average. The regions with the highest incidence were the Alto Sinú and Alto San Jorge. The lowest was the coastal and savanna areas. 79.2% of the cases were incidents, 18.8%, relapses, and 2.1%, treatment withdrawal. In 68.7% of the reviewed histories of the cases attended in the public network, no institutional evidence of activities performed to contacts was found. Patients go for the initial consultation after a period between 31 to 60 days of symptoms. 12.5% of the cases were diagnosed after 15 days of the initial consultation. In 14.6% of the cases, the tuberculosis treatment started after 16 days of the patient's initial meeting. In 41.7%, negative sputum smear microscopy was achieved. 37.5% of those who completed their treatment but did not undergo BK at the end. 2.1% of the cases failed, and 14.6% died. The process ended with positive bacilloscopy. Conclusions. There are program management factors that delay in identifying the probable instances and initiate treatment promptly.

N-of-1 trials in the clinical care of patients in developing countries: a systematic review.

BACKGROUND: N-of-1 trials have a potential role in promoting patient-centered medicine in developing countries. However, there is limited academic literature regarding the use of N-of-1 trials in the clinical care of patients in resource-poor settings. OBJECTIVE: To assess the extent of use, purpose and treatment outcome of N-of-1 trials in developing countries. METHOD: A systematic review of clinical N-of-1 trials was conducted between 1985 and September 2015 using PubMed, Embase, CINAHL, Web of Science and the Cochrane Central Register of Controlled Trials. Grey literature databases and clinical trial registers were also searched. This review included randomized, multi-cycle, crossover within individual patient trials involving drug intervention. Quality assessment and data extraction were conducted by two independent reviewers. RESULT: Out of 131 N-of-1 trials identified, only 6 (4.5%) were conducted in developing countries. The major reason that N-of-1 trials were used was to provide evidence on feasibility, effectiveness and safety of therapies. A total of 72 participants were involved in these trials. Five of the studies were conducted in China and all evaluated Chinese traditional medicine. The remaining study was conducted in Brazil. The completion rate was 93%. More than half, 46 (69%) of subjects made medication changes consistent with trial results after trial completion. A number of threats to the validity of the included evidence limited the validity of the evidence. In particular, the estimated overall effect in four of the included studies could have been affected by the "carry over" of the previous treatment effect as no adequate pharmacokinetic evidence regarding traditional medicines was presented. CONCLUSION: The prevalence and scope of N-of-1 trials in developing countries is low. A coordinated effort among government, clinicians, researchers and sponsor organizations is needed to increase their uptake and quality in developing countries. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015026841 .

A fatal and metabolic experimental hemorrhagic shock in immature swine

Abstract Purpose: To use blood lactate (BL) as an end-point metabolic marker for the begin resuscitation of volume replacement in experimental hemorrhagic shock. Methods: Group I (n=7) was not bled (Control). Animals in Group II (n=7) were bled to a MAP of 30mmHg in thirty minutes. Hemodynamic and metabolic data were recorded at Baseline, at 30, 60 and 120 minutes after Baseline. The animals were intubated in spontaneous breathing (FIO2=0.21) with halothane. Results: Group I all survived. In Group II all died; no mortality occurred before a BL<10mM/L. Beyond the end-point all animals exhibited severe acidemia, hyperventilation and clinical signs of shock. Without treatment all animals died within 70.43±24.51 min of hypotension shortly after reaching an average level of BL 17.01±3.20mM/L. Conclusions: Swine's breathing room air spontaneously in hemorrhagic shock not treated a blood lactate over 10mM/L results fatal. The predictable outcome of this shock model is expected to produce consistent information based on possible different metabolic and hemodynamic patterns as far as the type of fluid and the timing of resuscitation in near fatal hemorrhagic shock.

Assessment and Impact of Phase Angle and Sarcopenia in Palliative Cancer Patients.

Sarcopenia has been evaluated as a separate condition in cancer patients and as an important indicator of adverse outcomes. Muscle mass and phase angle are usually quantified by bioelectrical impedance analysis, due to its lower cost, and availability. The aim of this study was to assess the impact of sarcopenia, phase angle, and other characteristics on overall survival (OS) in palliative cancer patients at the National Cancer Institute of Mexico. We enrolled 628 patients (female, 59%). The most frequent disease was gastric cancer (39.5%). Kaplan-Meier analysis showed a significant survival disadvantage for patients with sarcopenia compared to patients without sarcopenia (p = 0.02). Sarcopenia univariably predicted OS [HR 1.4 (95% CI, 1.1-1.8), p = 0.001], but was not significant in multivariable Cox-regression analysis (p = 0.08). Significant predictors for sarcopenia in multivariable Cox-regression analysis were sex, age, body mass index, phase angle, clinical symptoms, and Karnofsky. Our results corroborate the reliability of sarcopenia and phase angle in Mexican population, showing that the measurement of these parameters might also be useful in early-stage cancer patients as prognostic markers.

Efficacy and Safety of Diacerein in Patients With Inadequately Controlled Type 2 Diabetes: A Randomized Controlled Trial.

OBJECTIVE: To assess, in a randomized, double-blind, and placebo-controlled trial, the efficacy and safety of diacerein, an immune modulator anti-inflammatory drug, in improving glycemic control of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Eighty-four patients with HbA1c between 7.5 and 9.5% (58-80 mmol/mol) were randomized to 48-week treatment with placebo (n = 41) or diacerein 100 mg/day (n = 43). The primary outcome was the difference in mean HbA1c changes during treatment. Secondary outcomes were other efficacy and safety measurements. A general linear regression with repeated measures, adjusted for age, sex, diabetes duration, and each baseline value, was used to estimate differences in mean changes. Both intention-to-treat (ITT) analysis and per-protocol analysis (excluding 10 patients who interrupted treatment) were performed. RESULTS: Diacerein reduced HbA1c compared with placebo by 0.35% (3.8 mmol/mol; P = 0.038) in the ITT analysis and by 0.41% (4.5 mmol/mol; P = 0.023) in the per-protocol analysis. The peak of effect occurred at the 24th week of treatment (-0.61% [6.7 mmol/mol; P = 0.014] and -0.78% [8.5 mmol/mol; P = 0.005], respectively), but it attenuated toward nonsignificant differences at the 48th week. No significant effect of diacerein was observed in other efficacy and safety measures. Diarrhea occurred in 65% of patients receiving diacerein and caused treatment interruption in 16%. Seven patients in the diacerein group reduced insulin dosage, whereas 10 in the placebo group increased it; however, mild hypoglycemic events were equally observed. CONCLUSIONS: Diacerein reduced mean HbA1c levels, with peak of effect at the 24th week of treatment. The drug was well tolerated and may be indicated as adjunct treatment in patients with type 2 diabetes, particularly in those with osteoarthritis.

Rickettsia amblyommatis infecting ticks and exposure of domestic dogs to Rickettsia spp. in an Amazon-Cerrado transition region of northeastern Brazil.

This study was performed in Maranhão state, a transition area two Brazilian biomes, Amazon and Cerrado. During 2011-2013, 1,560 domestic dogs were sampled for collection of serum blood samples and ticks in eight counties (3 within the Amazon and 5 within the Cerrado). A total of 959 ticks were collected on 150 dogs (9.6%). Rhipicephalus sanguineus sensu lato (s.l.) was the most abundant tick (68% of all collected specimens), followed by Amblyomma cajennense sensu lato (s.l.) (12.9%), Amblyomma parvum (9.2%), and Amblyomma ovale (5.2%). Other less abundant species (<1%) were Amblyomma oblongoguttatum, Rhipicephalus microplus, Haemaphysalis juxtakochi, and Amblyomma rotundatum. Females of A. cajennense s.l. ticks were morphologically identified as A. cajennense sensu stricto (s.s.) or A. sculptum. Molecular analyses of 779 canine ticks revealed three Rickettsia species: Rickettsia amblyommatis in 1% (1/100) A. cajennense s.l., 'Candidatus Rickettsia andeanae' in 20.7% (12/58) A. parvum, Rickettsia bellii in 6.8% (3/44) A. ovale and 100% (1/1) A. rotundatum ticks. An additional collection of A. sculptum from horses in a Cerrado area, and A. cajennense s.s. from pigs in an Amazon area revealed R. amblyommatis infecting only the A. cajennense s.s. ticks. Serological analysis of the 1,560 canine blood samples revealed 12.6% canine seroreactivity to Rickettsia spp., with the highest specific seroreactivity rate (10.2%) for R. amblyommatis. Endpoint titers to R. amblyommatis were significantly higher than those for the other Rickettsia antigens, suggesting that most of the seroreactive dogs were exposed to R. amblyommatis-infected ticks. Highest canine seroreactivity rates per locality (13.1-30.8%) were found in Amazon biome, where A. cajennense s.s. predominated. Lowest seroreactivity rates (1.9-6.5%) were found in Cerrado localities that were further from the Amazon, where A. sculptum predominated. Multivariate analyses revealed that canine seroreactivity to Rickettsia spp. or R. amblyommatis was statistically associated with rural dogs, exposed to Amblyomma ticks.

Clinical Trials in Veterinary Medicine: A New Era Brings New Challenges.

Randomized clinical trials (RCTs) are among the most rigorous ways to determine the causal relationship between an intervention and important clinical outcome. Their use in veterinary medicine has become increasingly common, and as is often the case, with progress comes new challenges. Randomized clinical trials yield important answers, but results from these studies can be unhelpful or even misleading unless the study design and reporting are carried out with care. Herein, we offer some perspective on several emerging challenges associated with RCTs, including use of composite endpoints, the reporting of different forms of risk, analysis in the presence of missing data, and issues of reporting and safety assessment. These topics are explored in the context of previously reported veterinary internal medicine studies as well as through illustrative examples with hypothetical data sets. Moreover, many insights germane to RCTs in veterinary internal medicine can be drawn from the wealth of experience with RCTs in the human medical field. A better understanding of the issues presented here can help improve the design, interpretation, and reporting of veterinary RCTs.

Preoperative carbohydrate load and intraoperatively infused omega-3 polyunsaturated fatty acids positively impact nosocomial morbidity after coronary artery bypass grafting: a double-blind controlled randomized trial.

BACKGROUND: A strategy of limited preoperative fasting, with carbohydrate (CHO) loading and intraoperative infusion of omega-3 polyunsaturated fatty acids (ω-3 PUFA), has seldom been tried in cardiovascular surgery. Brief fasting, followed by CHO intake 2 h before anesthesia, may improve recovery from CABG procedures and lower perioperative vasoactive drug requirements. Infusion of ω-3 PUFA may reduce occurrences of postoperative atrial fibrillation (POAF) and shorten hospital stays. The aim of this study was to assess morbidity (especially POAF) in ICU patients after coronary artery bypass grafting (CABG)/cardiopulmonary bypass (CPB) in combination, if preoperative fasts are curtailed in favor of CHO loading, and ω-3 PUFA are infused intraoperatively. METHODS: Fifty-seven patients undergoing CABG were randomly assigned to receive 12.5% maltodextrin (200 ml, 2 h before anesthesia), without infusing ω-3 PUFA (CHO, n = 14); water (200 ml, 2 h before anesthesia), without infusing ω-3 PUFA (controls, n = 14); 12.5% maltodextrin (200 ml, 2 h before anesthesia) plus intraoperative ω-3 PUFA (0.2 mcg/kg) (CHO + W3, n = 15); or water (200 ml, 2 h before anesthesia) plus intraoperative ω-3 PUFA (0.2 mcg/kg) (W3, n = 14). Perioperative clinical variables and mortality were analyzed, examining the incidence of POAF, as well as the need for inotropic vasoactive drugs during surgery and in ICU. RESULTS: Two deaths occurred (3.5%), but there were no instances of bronchoaspiration and mediastinitis. Neither ICU stays nor total postoperative stays differed by group (P > 0.05). Patients given preoperative CHO loads (CHO and CHO + W3 groups) experienced fewer instances of hospital infection (RR = 0.29, 95%CI 0.09-0.94; P = 0.023) and were less reliant on vasoactive amines during surgery (RR = 0.60, 95% CI 0.38-0.94; P = 0.020). Similarly, the number of patients requiring vasoactive drugs while recovering in ICU differed significantly by group (P = 0.008), showing benefits in patients given CHO loads. The overall incidence of POAF was 29.8% (17/57), differing significantly by group (P = 0.009). Groups given ω-3 PUFA (W3 and CHO + W3 groups) experienced significantly fewer instances of POAF (RR = 4.83, 95% CI 1.56-15.02; P = 0.001). CONCLUSION: Preoperative curtailment of fasting was safe in this cohort. When implemented in conjunction with CHO loading and infusion of ω-3 PUFA during surgery, expedited recovery from CABG with CPB was observed. TRIAL REGISTRATION: NCT: 03017001.

Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis: Subgroup analysis of Latin American patients in the phase 3 randomized UNCOVER-3 study.

BACKGROUND AND OBJECTIVES: Ixekizumab demonstrated greater efficacy than placebo and etanercept in UNCOVER-3. Subgroup analysis of Latin American patients was performed. We report 12-week and 60-week data. PATIENTS AND METHODS: Analysis included 102 Latin American patients randomized to receive placebo (n=14), etanercept 50mg twice weekly (n=30), or ixekizumab 160-mg starting dose followed by 80mg every 2 weeks (Q2W; n=29) or every 4 weeks (Q4W; n=29). At week 12, patients maintaining efficacy response and adequate overall safety were assigned, at the discretion of the investigator, to long-term extension with ixekizumab Q4W. RESULTS: At week 12, Psoriasis Area and Severity Index (PASI) 100 scores were 0%, 20.0% (p=0.075 vs placebo), 62.1% (p<0.001 vs placebo; p=0.001 vs etanercept), and 48.3% (p=0.002 vs placebo; p=0.023 vs etanercept) for placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. Among patients who continued therapy up to week 60 (n=97), PASI 100 scores were 71.4%, 60.0%, 77.8%, and 57.7% for patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively (non-responder imputation). By week 60, ≥1 serious adverse event was experienced by 7.1% (n=1/14), 3.3% (n=1/30), 14.8% (n=4/27), and 0% (n=0/26) of patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. There were no cases of active tuberculosis with ixekizumab treatment through 60 weeks. CONCLUSIONS: In Latin American patients, both ixekizumab dosing regimens demonstrated greater efficacy than etanercept for treating psoriasis over 12 weeks. The safety profile of ixekizumab through 60 weeks was well tolerated and consistent with the overall profile.