World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy : a systematic review and meta-analysis

Altres ajuts: Maria Lazo-Porras is funded by the Swiss Goverment Excellence Scholarship (2018.0698).To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed

Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design

Abstract Background: Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30%. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question. Methods/design: We will conduct systematic reviews to update the searches of 210 truncated RCTs to identify similar trials ongoing at the time of publication, or started subsequently, to the truncated trials ('subsequent RCTs'). Reviewers will determine in duplicate the similarity between the truncated and subsequent trials. We will analyze the epidemiology, distribution, and predictors of subsequent RCTs. We will also contact authors of subsequent trials to determine reasons for beginning, continuing, or prematurely discontinuing their own trials, and the extent to which they rely on the estimates from truncated trials. Discussion: To the extent that investigators begin or continue subsequent trials they implicitly disagree with the decision to stop the truncated RCT because of an ethical mandate to administer the experimental treatment. The results of this study will help guide future decisions about when to stop RCTs early for benefit

Antifibrinolytic therapy to reduce haemoptysis from any cause

BACKGROUND: Haemoptysis is a common pathology around the world, occurring with more frequency in low-income countries. It has different etiologies, many of which have infectious characteristics. Antifibrinolytic agents are commonly used to manage bleeding from different sources, but their usefulness in pulmonology is unclear. OBJECTIVES: To evaluate the effectiveness and safety of antifibrinolytic agents in reducing the volume and duration of haemoptysis in adult and paediatric patients. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library, EMBASE and LILACS for publications that describe randomized controlled trials (RCTs) of antifibrinolytic therapy in patients presenting with haemoptysis. We also performed an independent search in MEDLINE for relevant trials not yet included in CENTRAL or DARE. Searches are up to date to the 19th September 2016. We conducted electronic and manual searches of relevant national and international journals. We reviewed the reference lists of included studies to locate relevant randomized controlled trials (RCTs). An additional search was carried out to find unpublished RCTs. SELECTION CRITERIA: We included RCTs designed to evaluate the effectiveness and safety of antifibrinolytic agents in reducing haemoptysis in adult and paediatric patients of both genders presenting with haemoptysis of any etiology and severity. The intervention of interest was the administration of antifibrinolytic agents compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: All reviewers independently assessed methodological quality and extracted data tables pre-designed for this review. MAIN RESULTS: The electronic literature search identified 1 original study that met the eligibility criteria. One unpublished study was also identified through manual searches. Therefore two randomized controlled trials met the inclusion criteria: Tscheikuna 2002 (via electronic searches) and Ruiz 1994 (via manual searches). Tscheikuna 2002, a double-blind RCT performed in Thailand, evaluated the effectiveness of tranexamic acid (TXA, an antifibrinolytic agent) administered orally in 46 hospital in- and outpatients with haemoptysis of various etiologies. Ruiz 1994, a double-blind RCT performed in Peru, evaluated the effectiveness of intravenous TXA in 24 hospitalised patients presenting with haemoptysis secondary to tuberculosis.Pooled together, results demonstrated a significant reduction in bleeding time between patients receiving TXA and patients receiving placebo with a weighted mean difference (WMD) of -19.47 (95% CI -26.90 to -12.03 hours), but with high heterogeneity (I² = 52%). TXA did not affect remission of haemoptysis evaluated at seven days after the start of treatment. Adverse effects caused by the drug\u27s mechanism of action were not reported. There was no significant difference in the incidence of mild side effects between active and placebo groups (OR 3.13, 95% CI 0.80 to 12.24). AUTHORS\u27 CONCLUSIONS: There is insufficient evidence to judge whether antifibrinolytics should be used to treat haemoptysis from any cause, though limited evidence suggests they may reduce the duration of bleeding

Rabdomiolisis y miopatía como únicas manifestaciones de hipotiroidismo severo secundario a tiroiditis de Hashimoto

Hashimoto’s thyroiditis is the most frequent cause of hypothyroidism. In the regions with no iodine deficiency, it is more frequent in women and oftentimes has a familial association. The symptoms and signs of hypothyroidism are systemic and depend on the duration and intensity of the thyroid hormone deficiency. Neuromuscular manifestations are seldom the only symptoms and signs present. We present the case of a young patient with severe myopathy, where rhabdomyolysis was the sole manifestation of severe hypothyroidism secondary to Hashimoto’s thyroiditis.La tiroiditis de Hashimoto constituye la causa más frecuente de hipotiroidismo en las regiones sin deficiencia de yodo, es más frecuente en mujeres y muchas veces tiene asociación familiar. Los síntomas y signos del hipotiroidismo son sistémicos y dependen de la duración e intensidad de la deficiencia de la hormona tiroidea. Las manifestaciones neuromusculares, son excepcionalmente los únicos signos clínicos. Se presenta el caso de un paciente joven con una miopatía severa con rabdomiolisis como la única manifestación de hipotiroidismo severo debido a tiroiditis de Hashimoto

Rabdomiolisis y miopatía como únicas manifestaciones de hipotiroidismo severo secundario a tiroiditis de Hashimoto

Hashimoto’s thyroiditis is the most frequent cause of hypothyroidism. In the regions with no iodine deficiency, it is more frequent in women and oftentimes has a familial association. The symptoms and signs of hypothyroidism are systemic and depend on the duration and intensity of the thyroid hormone deficiency. Neuromuscular manifestations are seldom the only symptoms and signs present. We present the case of a young patient with severe myopathy, where rhabdomyolysis was the sole manifestation of severe hypothyroidism secondary to Hashimoto’s thyroiditis.La tiroiditis de Hashimoto constituye la causa más frecuente de hipotiroidismo en las regiones sin deficiencia de yodo, es más frecuente en mujeres y muchas veces tiene asociación familiar. Los síntomas y signos del hipotiroidismo son sistémicos y dependen de la duración e intensidad de la deficiencia de la hormona tiroidea. Las manifestaciones neuromusculares, son excepcionalmente los únicos signos clínicos. Se presenta el caso de un paciente joven con una miopatía severa con rabdomiolisis como la única manifestación de hipotiroidismo severo debido a tiroiditis de Hashimoto

Rabdomiolisis y miopatía como únicas manifestaciones de hipotiroidismo severo secundario a tiroiditis de Hashimoto Rhabdomyolysis and myopathy as the only manifestations of severe hypothyroidism secondary to Hashimoto’s thyroiditis

La tiroiditis de Hashimoto constituye la causa más frecuente de hipotiroidismo en las regiones sin deficiencia de yodo, es más frecuente en mujeres y muchas veces tiene asociación familiar. Los síntomas y signos del hipotiroidismo son sistémicos y dependen de la duración e intensidad de la deficiencia de la hormona tiroidea. Las manifestaciones neuromusculares, son excepcionalmente los únicos signos clínicos. Se presenta el caso de un paciente joven con una miopatía severa con rabdomiolisis como la única manifestación de hipotiroidismo severo debido a tiroiditis de Hashimoto<br>Hashimoto’s thyroiditis is the most frequent cause of hypothyroidism. In the regions with no iodine deficiency, it is more frequent in women and oftentimes has a familial association. The symptoms and signs of hypothyroidism are systemic and depend on the duration and intensity of the thyroid hormone deficiency. Neuromuscular manifestations are seldom the only symptoms and signs present. We present the case of a young patient with severe myopathy, where rhabdomyolysis was the sole manifestation of severe hypothyroidism secondary to Hashimoto’s thyroiditi

Rhabdomyolysis and myopathy as the only manifestations of severe hypothyroidism secondary to Hashimoto's thyroiditis

Hashimoto's thyroiditis is the most frequent cause of hypothyroidism. In the regions with no iodine deficiency, it is more frequent in women and oftentimes has a familial association. The symptoms and signs of hypothyroidism are systemic and depend on the duration and intensity of the thyroid hormone deficiency. Neuromuscular manifestations are seldom the only symptoms and signs present. We present the case of a young patient with severe myopathy, where rhabdomyolysis was the sole manifestation of severe hypothyroidism secondary to Hashimoto's thyroiditis

Precisión de la taquipnea y las retracciones subcostales como signos clínicos para diagnóstico de neumonía adquirida en la comunidad en niños: revisión sistemática y metaanálisis Identification of tachypnea and subcostal retractions as clinical signs for the diagnosis of community-acquired pneumonia among children: systematic review and meta-analysis

Objetivos. Evaluar si la taquipnea y las retracciones subcostales son predictoras eficientes para el diagnóstico de neumonía adquirida en la comunidad (NAC) en niños. Materiales y métodos. Se revisaron las bases de datos: PubMed, LILACS, The African Journal Database y The Cochrane Central Library. Se incluyeron estudios originales que evaluaron el rendimiento diagnóstico de los criterios clínicos de taquipnea o retracciones subcostales, definidos según los criterios de la Organización Mundial de la Salud (OMS) para el diagnóstico de NAC en niños de hasta cinco años de edad con tos y fiebre. Se estimaron las razones de probabilidades (LR), el odds ratio diagnostico (DOR) y sus respectivos intervalos de confianza al 95% (IC95%) para cada prueba clínica evaluada. Resultados. Se encontraron 975 estudios, incluyendo ocho en la revisión. Se enrolaron 4740 pacientes y analizaron 3584 (75%), de los cuales 916 (19%) tuvieron el diagnóstico de NAC. Al combinar los datos, la taquipnea obtuvo una LR positiva de 3,16, (IC95% 2,11-4,73) y una LR negativa de 0,36 (IC95% 0,23-0,57). El DOR fue de 10,63 (IC95% 4,4-25,66, I2=93%). Al realizar el análisis para retracciones subcostales se obtuvo un LR positivo de 2,49 (IC95% 1,41-4,37) y un LR negativo de 0,59 (IC95% 0,4-0,87). El DOR fue de 5,32 (IC95% 1,88-15,05, I2=89%). Conclusiones. Se puede tomar en cuenta la presencia o ausencia de taquipnea y retracciones subcostales en el diagnóstico de NAC, cabe considerar la incertidumbre relativa en su poder diagnóstico y los LR relativamente modestos. La confianza en estos resultados es baja por la inadecuada calidad de la evidencia en este tema<br>Objectives. Determine whether tachypnea and subcostal retractions can be efficient predictors for the diagnosis of Community-Acquired Pneumonia (CAP) among children. Materials and methods. These were the databases used: PubMed, LILACS, The African Journal Database and The Cochrane Central Library. Original studies were included which assessed the diagnostic performance of the clinical criteria for tachypnea or subcostal retraction defined in accordance with the criteria of the World Health Organization (OMS) for CAP diagnosis in children &#8804; 5 with cough and fever. The likelihood ratio (LR), the diagnosis odds ratio (DOR), and their respective confidence intervals at 95% (IC95%) were estimated for each clinical test. Results. 975 studies were found, eight were included in the review. 4740 patients were enrolled and 3584 (75%) were analyzed, 916 (19%) of which had a CAP diagnosis. When data were combined, tachypnea had a positive LR of 3.16, (95% CI 2.11-4.73) and a negative LR of 0.36 (95% CI 0.23-0.57). The DOR was 10.63 (95% CI 4.4-25.66, I2=93%). When subcostal retractions were analyzed, a positive LR of 2.49 (95%CI 1.41-4.37) and a negative LR of 0.59 (95%CI 0.4-0.87) were obtained. The DOR was 5.32 (95%CI 1.88-15.05, I2=89%). Conclusions. The presence or absence of tachypnea and subcostal retractions can be used in CAP diagnosis; it is worth considering the relative uncertainty in its diagnostic power and relatively modest LR. The confidence of these results is low due to the inadequate quality of the related evidenc

Influenza vaccines licensed in the United States in healthy children: a systematic review and network meta-analysis (Protocol)

Abstract Background Influenza is an acute respiratory illness caused by influenza viruses, which occurs in epidemics worldwide every year. Children are an important target for prevention methods, including vaccination. While evidence about the decision on whether to vaccinate healthy children is robust, evidence supporting the decision of which of available vaccines to use remains unclear. This review will summarize the evidence about the efficacy and safety of the available vaccines for seasonal influenza licensed in the United States for use in healthy children. Methods/design An umbrella systematic review (SR) and network meta-analysis will be conducted of randomized controlled trials (RCTs). We will search for SRs to identify parallel RCTs evaluating inactive and/or live attenuated influenza vaccines licensed in the United States for use in healthy children to prevent influenza. Subsequently, we will update the literature search of the selected SRs to the present time to capture recent controlled studies. To complement the work focused on harms, we will also select observational studies focusing on post marketing retrospective studies. Inclusion will not be limited by language, publication date or publication status. To identify additional candidate studies, we will review the reference lists of the eligible primary studies and narrative reviews; we will query the expert members of the Advisory Committee on Immunization Practices and review references from their previous statement. Additionally, we will review the reports from the Institute of Medicine on the adverse effects of vaccines. Two reviewers will independently determine study eligibility and will extract descriptive, methodological (using the Cochrane risk of bias tool for RCTs and the Newcastle–Ottawa scale for observational studies) and efficacy data. When possible, we will conduct meta-analyses and network meta-analyses by combining indirect and direct comparisons. We will evaluate heterogeneity using the I2 statistic and the agreement of indirect comparisons and direct evidence. We will report the Cochrane Q test to determine the statistical significance of heterogeneity. The overall quality of evidence will be assessed following the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) approach. Discussion Our systematic review will allow patients, clinicians, guideline developers and policy makers to make evidence-based choices between the two available vaccine options, by providing information regarding benefits and harms of these types of vaccines.</p

Precisión de la taquipnea y las retracciones subcostales como signos clínicos para diagnóstico de neumonía adquirida en la comunidad en niños: revisión sistemática y metaanálisis

Objectives. Determine whether tachypnea and subcostal retractions can be efficient predictors for the diagnosis of Community-Acquired Pneumonia (CAP) among children. Materials and methods. These were the databases used: PubMed, LILACS, The African Journal Database and The Cochrane Central Library. Original studies were included which assessed the diagnostic performance of the clinical criteria for tachypnea or subcostal retraction defined in accordance with the criteria of the World Health Organization (OMS) for CAP diagnosis in children ≤ 5 with cough and fever. The likelihood ratio (LR), the diagnosis odds ratio (DOR), and their respective confidence intervals at 95% (IC95%) were estimated for each clinical test. Results. 975 studies were found, eight were included in the review. 4740 patients were enrolled and 3584 (75%) were analyzed, 916 (19%) of which had a CAP diagnosis. When data were combined, tachypnea had a positive LR of 3.16, (95% CI 2.11-4.73) and a negative LR of 0.36 (95% CI 0.23-0.57). The DOR was 10.63 (95% CI 4.4-25.66, I2=93%). When subcostal retractions were analyzed, a positive LR of 2.49 (95%CI 1.41-4.37) and a negative LR of 0.59 (95%CI 0.4-0.87) were obtained. The DOR was 5.32 (95%CI 1.88-15.05, I2=89%). Conclusions. The presence or absence of tachypnea and subcostal retractions can be used in CAP diagnosis; it is worth considering the relative uncertainty in its diagnostic power and relatively modest LR. The confidence of these results is low due to the inadequate quality of the related evidence.Objetivos. Evaluar si la taquipnea y las retracciones subcostales son predictoras eficientes para el diagnóstico de neumonía adquirida en la comunidad (NAC) en niños. Materiales y métodos. Se revisaron las bases de datos: PubMed, LILACS, The African Journal Database y The Cochrane Central Library. Se incluyeron estudios originales que evaluaron el rendimiento diagnóstico de los criterios clínicos de taquipnea o retracciones subcostales, definidos según los criterios de la Organización Mundial de la Salud (OMS) para el diagnóstico de NAC en niños de hasta cinco años de edad con tos y fiebre. Se estimaron las razones de probabilidades (LR), el odds ratio diagnostico (DOR) y sus respectivos intervalos de confianza al 95% (IC95%) para cada prueba clínica evaluada. Resultados. Se encontraron 975 estudios, incluyendo ocho en la revisión. Se enrolaron 4740 pacientes y analizaron 3584 (75%), de los cuales 916 (19%) tuvieron el diagnóstico de NAC. Al combinar los datos, la taquipnea obtuvo una LR positiva de 3,16, (IC95% 2,11-4,73) y una LR negativa de 0,36 (IC95% 0,23-0,57). El DOR fue de 10,63 (IC95% 4,4-25,66, I 2 =93%). Al realizar el análisis para retracciones subcostales se obtuvo un LR positivo de 2,49 (IC95% 1,41-4,37) y un LR negativo de 0,59 (IC95% 0,4-0,87). El DOR fue de 5,32 (IC95% 1,88-15,05, I 2 =89%). Conclusiones. Se puede tomar en cuenta la presencia o ausencia de taquipnea y retracciones subcostales en el diagnóstico de NAC, cabe considerar la incertidumbre relativa en su poder diagnóstico y los LR relativamente modestos. La confianza en estos resultados es baja por la inadecuada calidad de la evidencia en este tema