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1.
PLoS One ; 14(11): e0224448, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31693680

RESUMO

BACKGROUND: The mechanisms explaining multimorbidity between asthma, dermatitis and rhinitis (allergic multimorbidity) are not well known. We investigated these mechanisms and their specificity in distinct cell types by means of an interactome-based analysis of expression data. METHODS: Genes associated to the diseases were identified using data mining approaches, and their multimorbidity mechanisms in distinct cell types were characterized by means of an in silico analysis of the topology of the human interactome. RESULTS: We characterized specific pathomechanisms for multimorbidities between asthma, dermatitis and rhinitis for distinct emergent non-eosinophilic cell types. We observed differential roles for cytokine signaling, TLR-mediated signaling and metabolic pathways for multimorbidities across distinct cell types. Furthermore, we also identified individual genes potentially associated to multimorbidity mechanisms. CONCLUSIONS: Our results support the existence of differentiated multimorbidity mechanisms between asthma, dermatitis and rhinitis at cell type level, as well as mechanisms common to distinct cell types. These results will help understanding the biology underlying allergic multimorbidity, assisting in the design of new clinical studies.

2.
Cochrane Database Syst Rev ; 6: CD003506, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31194882

RESUMO

BACKGROUND: Standard androgen suppression therapy (AST) using surgical or medical castration is considered a mainstay of advanced hormone-sensitive prostate cancer treatment. AST can be initiated early when disease is asymptomatic or deferred when patients suffer symptoms of disseminated prostate cancer. OBJECTIVES: To assess the effects of early versus deferred standard AST for advanced hormone-sensitive prostate cancer. SEARCH METHODS: For this Cochrane Review update, we performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase, Web of Science; last searched November 2018) and two clinical trial registers, with no restrictions on the language of publication or publication status. We also searched bibliographies of included studies and conference proceedings (last searched January 2019). SELECTION CRITERIA: We included all randomised controlled trials (RCTs) with a direct comparison of early versus deferred standard AST. We excluded all other study designs. Participants included had advanced hormone-sensitive prostate cancer receiving surgical or medical castration. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data. The primary outcomes were time to death of any cause and serious adverse events. Secondary outcomes were time to disease progression, time to death from prostate cancer, adverse events and quality of life. We performed statistical analyses using a random-effects model and assessed the certainty of evidence according to GRADE. We performed subgroup analyses for advanced but non-metastatic disease (T2-4/N+ M0), metastatic disease (M1), and prostate-specific antigen (PSA) relapse. MAIN RESULTS: We identified seven new RCTs since publication of the original review in 2002. In total, we included 10 RCTs.Primary outcomesEarly AST probably reduces the risk of death from any cause over time (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90; moderate-certainty evidence; 4767 participants). This corresponds to 57 fewer deaths (95% CI 80 fewer to 31 fewer) per 1000 participants at 5 years for the moderate risk group and 23 fewer deaths (95% CI 32 fewer to 13 fewer) per 1000 participants at 5 years in the low risk group. We downgraded for study limitations. Early versus deferred AST may have little or no effect on serious adverse events (risk ratio (RR) 1.05, 95% CI 0.95 to 1.16; low-certainty evidence; 10,575 participants) which corresponds to 6 more serious adverse events (6 fewer to 18 more) per 1000 participants. We downgraded the certainty of evidence for study limitations and selective reporting.Secondary outcomesEarly AST probably reduces the risk of death from prostate cancer over time (HR 0.69, 95% CI 0.57 to 0.84; moderate-certainty evidence). This corresponds to 62 fewer prostate cancer deaths per 1000 (95% CI 87 fewer to 31 fewer) at 5 years for the moderate risk group and 24 fewer death from prostate cancer (95% CI 34 fewer to 12 fewer) per 1000 men at 5 years in the low risk group. We downgraded the certainty of evidence for study limitations.Early AST may decrease the rate of skeletal events (RR 0.37, 95% CI 0.17 to 0.80; low-certainty evidence) corresponding to 23 fewer skeletal events per 1000 (95% CI 31 fewer to 7 fewer). We downgraded for study limitations and imprecision. It may also increase fatigue (RR 1.41, 95% CI 1.23 to 1.62; low-certainty evidence), corresponding to 31 more men with this complaint per 1000 (95% CI 18 more to 48 more). We downgraded for study limitations and imprecision. It may increase the risk of heart failure (RR 1.90, 95% CI 1.09 to 3.33; low-certainty evidence) corresponding to 27 more events per 1000 (95% CI 3 more to 69 more). We downgraded the certainty of evidence for study limitations and imprecision.Global quality of life is probably similar after two years as assessed with the EORTC QLQ-C30 (version 3.0) questionnaire (mean difference -1.56, 95% CI -4.50 to 1.38; moderate-certainty evidence) with higher scores reflecting better quality of life. We downgraded the certainty of evidence for study limitations. AUTHORS' CONCLUSIONS: Early AST probably extends time to death of any cause and time to death from prostate cancer. It may slightly decrease the rate of skeletal events. Rates of serious adverse events and quality of life may be similar. It may increase fatigue and may increase the risk of heart failure. Better quality trials would be particularly important to better understand the outcomes related to possible treatment-related harm, for which we only found low-certainty evidence.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Progressão da Doença , Humanos , Masculino , Antígeno Prostático Específico/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Artigo em Espanhol | PAHO-IRIS | ID: phr-50724

RESUMO

[RESUMEN]. Objetivo. Esta revisión sintetiza la evidencia cuantitativa, general y desglosada por categorías tipológicas de la falta de respeto y maltrato en la atención institucional del parto y el aborto en América Latina y el Caribe. Métodos. Mediante búsquedas sistemáticas se identificaron 18 estudios primarios. Se calcularon Q e I2 y se realizaron metaanálisis, metarregresiones y análisis de subgrupos con la aplicación de un modelo de DerSimonian-Laird de efectos aleatorios agrupados con varianza inversa y la transformación arco-seno doble de Freeman-Tukey. Resultados. Se identificaron estudios realizados en cinco países de América Latina. No se identificaron estudios del Caribe. La prevalencia agregada de falta de respeto y maltrato durante el parto y el aborto fue de 39%. La medida agregada para este fenómeno durante el parto fue de 43% y la medida agregada en los casos de aborto fue de 29%. La heterogeneidad elevada no permitió generar medidas agregadas según categorías tipológicas. No obstante, se presentan las frecuencias de formas específicas del fenómeno agrupadas tipológicamente. Conclusiones. La evidencia sugiere que la falta de respeto y maltrato durante la atención del parto y el aborto son problemas de derechos humanos y salud pública prevalentes en algunos países de la Región. Es necesario lograr consenso internacional sobre la definición y operacionalización de este problema y desarrollar métodos estandarizados para su medición. Lo anterior es imprescindible para el alcance de las metas de la Agenda 2030 relacionadas con la reducción de la morbimortalidad maternoperinatal y la eliminación de todas las formas de violencia y discriminación contra la mujer.


[ABSTRACT]. Objective. This review synthesizes the evidence (quantitative, general, and by typological categories) of disrespect and abuse during childbirth and abortion in health facilities in Latin America and the Caribbean. Methods. Systematic searches identified 18 primary studies. Q and I2 were calculated, meta-analyses and meta-regressions were performed, and subgroups were analyzed using a DerSimonian and Laird random-effects model grouped by inverse variance and the Freeman-Tukey double arcsine transformation. Results. Studies conducted in five Latin American countries were identified. No studies from the Caribbean were found. The aggregate prevalence of disrespect and abuse during childbirth and abortion was 39%. The aggregated prevalence of the phenomenon in childbirth was 43% and 29% during abortion. The high heterogeneity made it impossible to generate aggregate measures according to typological categories. Nevertheless, the frequencies of specific forms of the phenomenon were grouped typologically. Conclusions. The evidence suggests that disrespect and abuse during childbirth and abortion care are human-rights and public-health problems that are prevalent in some countries of the Region. It is necessary to reach international consensus on the definition and operationalization of this problem and to develop standardized methods for its measurement. Doing so is essential in order to achieve the targets of the 2030 Agenda related to reducing maternal and newborn morbidity and mortality and eliminating all forms of violence and discrimination against women.


[RESUMO]. Objetivo. Esta revisão sintetiza as evidências quantitativas, gerais e desagregadas por categorias tipológicas do desrespeito e maus-tratos na atenção institucional ao parto e ao aborto na América Latina e Caribe. Métodos. Dezoito estudos primários foram identificados por meio de buscas sistemáticas. Foi feito o cálculo de Q e I2 e realizadas meta-análises, metarregressões e análises de subgrupos com um modelo de DerSimonian e Laird de efeitos aleatórios agrupados com variância inversa e transformação de Freeman-Tukey (duplo arco-seno). Resultados. Foram identificados estudos realizados em cinco países da América Latina. Não foi identificado nenhum estudo no Caribe. Observou-se uma prevalência agregada de 39% de desrespeito e maus-tratos durante o parto e o aborto. A medida agregada para este fenômeno durante o parto foi 43% e a medida agregada nos casos de aborto foi 29%. Devido à alta heterogeneidade, não foi possível gerar medidas agregadas segundo categorias tipológicas. No entanto, são descritas as frequências de formas específicas do fenômeno agrupadas tipologicamente. Conclusões. As evidências indicam que o desrespeito e os maus-tratos na atenção ao parto e ao aborto são uma questão de direitos humanos e de saúde pública prevalente em alguns países da Região. É preciso chegar a um consenso internacional sobre a definição e a operacionalização deste problema e elaborar métodos padronizados para mensurá-lo. Isso é imprescindível para o alcance das metas da Agenda 2030 relativas à redução da morbidade e mortalidade materna e perinatal e à eliminação de todas as formas de violência e discriminação contra a mulher.


Assuntos
Violência contra a Mulher , Parto Humanizado , Serviços de Saúde da Mulher , Aborto , Parto , Violência contra a Mulher , Parto Humanizado , Serviços de Saúde da Mulher , Aborto , Parto , Violência contra a Mulher , Serviços de Saúde da Mulher
4.
Eur Respir J ; 53(4)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30765504

RESUMO

RATIONALE: We aimed to identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma and chronic obstructive pulmonary disease (COPD) across the life course. METHODS: We meta-analysed epigenome-wide data of 1688 children from five cohorts to identify cord blood DMRs and their annotated genes, in relation to forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) ratio and forced expiratory flow at 75% of FVC at ages 7-13 years. Identified DMRs were explored for associations with childhood asthma, adult lung function and COPD, gene expression and involvement in biological processes. RESULTS: We identified 59 DMRs associated with childhood lung function, of which 18 were associated with childhood asthma and nine with COPD in adulthood. Genes annotated to the top 10 identified DMRs were HOXA5, PAOX, LINC00602, ABCA7, PER3, CLCA1, VENTX, NUDT12, PTPRN2 and TCL1A. Differential gene expression in blood was observed for 32 DMRs in childhood and 18 in adulthood. Genes related with 16 identified DMRs were associated with respiratory developmental or pathogenic pathways. INTERPRETATION: Our findings suggest that the epigenetic status of the newborn affects respiratory health and disease across the life course.

5.
Am J Epidemiol ; 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30351340

RESUMO

International collaborations among birth cohorts to better understand asthma and allergies have increased in the last years. However, differences in definitions and methods preclude direct pooling of original individual participant data. We harmonized data from 14 birth cohorts, with three to 20 follow-ups, from nine European countries, as part of the Mechanisms of the Development of Asthma and Allergies (MeDALL) project. The harmonization process followed six steps: organization of the harmonization panel; identification of variables relevant to MeDALL objectives (candidate variables); proposal of a definition for each candidate variable (reference definition); assessment of the compatibility of each cohort variable to its reference definition (inferential equivalence) and classifications of this inferential equivalence as complete, partial, or impossible; workshop to agree on the reference definitions and classifications of inferential equivalence; and data preparation and delivery through a knowledge management portal. We agreed on 137 reference definitions. The inferential equivalence of 3,551 cohort variables to their corresponding reference definition was classified as complete, partial and impossible for 70%, 15% and 15% of the variables, respectively. A harmonized database was delivered. In birth cohorts of asthma and allergies, the harmonization of data for pooled analyses is feasible and may achieve high inferential comparability. The MeDALL harmonization approach can be used in other collaborative projects.

6.
Bull World Health Organ ; 96(6): 402-413D, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29904223

RESUMO

Objective: To conduct a systematic review to estimate the prevalence of asymptomatic Zika virus infection in the general population and in specific population groups. Methods: We searched PubMed®, Embase® and LILACS online databases from inception to 26 January 2018. We included observational epidemiological studies where laboratory testing was used to confirm positive exposure of participants to Zika virus and in which Zika virus symptom status was also recorded. We excluded studies in which having symptoms of Zika virus was a criterion for inclusion. The main outcome assessed was percentage of all Zika virus-positive participants who were asymptomatic. We used a quality-effects approach and the double arcsine transformation for the meta-analysis. Findings: We assessed 753 studies for inclusion, of which 23 were included in the meta-analysis, totalling 11 305 Zika virus-positive participants. The high degree of heterogeneity in the studies (I2 = 99%) suggests that the pooled prevalence of asymptomatic Zika virus-positive participants was probably not a robust estimate. Analysis based on subgroups of the population (general population, returned travellers, blood donors, adults with Guillain-Barré syndrome, pregnant women and babies with microcephaly) was not able to explain the heterogeneity. Funnel and Doi plots showed major asymmetry, suggesting selection bias or true heterogeneity. Conclusion: Better-quality research is needed, using standardized methods, to determine the true prevalence of asymptomatic Zika virus and whether it varies between populations or over time.


Assuntos
Infecção por Zika virus/epidemiologia , Adulto , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Prevalência , Estudos Soroepidemiológicos , Zika virus
7.
Genes Nutr ; 13: 12, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29736190

RESUMO

Background: The multidisciplinary nature of nutrition research is one of its main strengths. At the same time, however, it presents a major obstacle to integrate data analysis, especially for the terminological and semantic interpretations that specific research fields or communities are used to. To date, a proper ontology to structure and formalize the concepts used for the description of nutritional studies is still lacking. Results: We have developed the Ontology for Nutritional Studies (ONS) by harmonizing selected pre-existing de facto ontologies with novel health and nutritional terminology classifications. The ONS is the result of a scholarly consensus of 51 research centers in nine European countries. The ontology classes and relations are commonly encountered while conducting, storing, harmonizing, integrating, describing, and searching nutritional studies. The ONS facilitates the description and specification of complex nutritional studies as demonstrated with two application scenarios. Conclusions: The ONS is the first systematic effort to provide a solid and extensible formal ontology framework for nutritional studies. Integration of new information can be easily achieved by the addition of extra modules (i.e., nutrigenomics, metabolomics, nutrikinetics, and quality appraisal). The ONS provides a unified and standardized terminology for nutritional studies as a resource for nutrition researchers who might not necessarily be familiar with ontologies and standardization concepts.

8.
J Nutr ; 148(2): 285-297, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29490094

RESUMO

Background: Joint data analysis from multiple nutrition studies may improve the ability to answer complex questions regarding the role of nutritional status and diet in health and disease. Objective: The objective was to identify nutritional observational studies from partners participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) Consortium, as well as minimal requirements for joint data analysis. Methods: A predefined template containing information on study design, exposure measurements (dietary intake, alcohol and tobacco consumption, physical activity, sedentary behavior, anthropometric measures, and sociodemographic and health status), main health-related outcomes, and laboratory measurements (traditional and omics biomarkers) was developed and circulated to those European research groups participating in the ENPADASI under the strategic research area of "diet-related chronic diseases." Information about raw data disposition and metadata sharing was requested. A set of minimal requirements was abstracted from the gathered information. Results: Studies (12 cohort, 12 cross-sectional, and 2 case-control) were identified. Two studies recruited children only and the rest recruited adults. All studies included dietary intake data. Twenty studies collected blood samples. Data on traditional biomarkers were available for 20 studies, of which 17 measured lipoproteins, glucose, and insulin and 13 measured inflammatory biomarkers. Metabolomics, proteomics, and genomics or transcriptomics data were available in 5, 3, and 12 studies, respectively. Although the study authors were willing to share metadata, most refused, were hesitant, or had legal or ethical issues related to sharing raw data. Forty-one descriptors of minimal requirements for the study data were identified to facilitate data integration. Conclusions: Combining study data sets will enable sufficiently powered, refined investigations to increase the knowledge and understanding of the relation between food, nutrition, and human health. Furthermore, the minimal requirements for study data may encourage more efficient secondary usage of existing data and provide sufficient information for researchers to draft future multicenter research proposals in nutrition.


Assuntos
Dieta , Epidemiologia , Estado Nutricional , Estudos Observacionais como Assunto , Adulto , Biomarcadores/sangue , Glicemia/análise , Estudos de Casos e Controles , Criança , Doença Crônica , Estudos de Coortes , Estudos Transversais , Europa (Continente) , Genômica , Nível de Saúde , Humanos , Inflamação/sangue , Insulina/sangue , Estilo de Vida , Lipoproteínas/sangue , Estudos Longitudinais , Metabolômica , Estatística como Assunto/métodos
9.
EBioMedicine ; 26: 91-99, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29221963

RESUMO

BACKGROUND: Sensitization in early childhood may precede respiratory allergy in adolescence. METHODS: IgE reactivity against 132 allergen molecules was evaluated using the MeDALL microarray in sera obtained from a random sample of 786 children at the age of 4, 8 and 16years in a population based birth cohort (BAMSE). Symptoms were analyzed by questionnaire at ages 4, 8 and 16years. Clinically and independent relevant allergen molecules accounting for ≥90% of IgE reactivities in sensitized individuals and at all time-points were identified as risk molecules and used to predict respiratory allergy. The data was replicated in the Manchester Asthma and Allergy Study (MAAS) birth cohort by studying IgE reactivity with the use of a commercial IgE microarray. Sera were obtained from children at the ages of 3, 5, 8 and 11years (N=248) and the outcome was studied at 11years. FINDINGS: In the BAMSE cohort 4 risk molecules could be identified, i.e.: Ara h 1 (peanut), Bet v 1 (birch), Fel d 1 (cat), Phl p 1 (grass). For MAAS the corresponding number of molecules was 5: Der p 1 (dust mite), Der f 2 (dust mite), Phl p 1 (grass), Phl p 5 (grass), Fel d 1 (cat). In BAMSE, early IgE reactivity to ≥3 of 4 allergen molecules at four years predicted incident and persistent asthma and/or rhinitis at 16years (87% and 95%, respectively). The corresponding proportions in the MAAS cohort at 16years were 100% and 100%, respectively, for IgE reactivity to ≥3 of 5 risk molecules. INTERPRETATIONS: IgE reactivity to a few allergen molecules early in life identifies children with a high risk of asthma and/or rhinitis at 16years. These findings will be of importance for developing preventive strategies for asthma and rhinitis in children.


Assuntos
Alérgenos/efeitos adversos , Asma/imunologia , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Rinite Alérgica/imunologia , Alérgenos/imunologia , Antígenos de Dermatophagoides/efeitos adversos , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/efeitos adversos , Proteínas de Artrópodes/imunologia , Asma/sangue , Asma/etiologia , Criança , Pré-Escolar , Cisteína Endopeptidases/efeitos adversos , Cisteína Endopeptidases/imunologia , Feminino , Humanos , Hipersensibilidade/etiologia , Hipersensibilidade/patologia , Imunoglobulina E/sangue , Masculino , Rinite Alérgica/etiologia , Rinite Alérgica/patologia
11.
Cochrane Database Syst Rev ; 12: CD005067, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29192424

RESUMO

BACKGROUND: Cutaneous leishmaniasis, caused by a parasitic infection, is considered one of the most serious skin diseases in many low- and middle-income countries. Old World cutaneous leishmaniasis (OWCL) is caused by species found in Africa, Asia, the Middle East, the Mediterranean, and India. The most commonly prescribed treatments are antimonials, but other drugs have been used with varying success. As OWCL tends to heal spontaneously, it is necessary to justify the use of systemic and topical treatments. This is an update of a Cochrane Review first published in 2008. OBJECTIVES: To assess the effects of therapeutic interventions for the localised form of Old World cutaneous leishmaniasis. SEARCH METHODS: We updated our searches of the following databases to November 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We wrote to national programme managers, general co-ordinators, directors, clinicians, WHO-EMRO regional officers of endemic countries, pharmaceutical companies, tropical medicine centres, and authors of relevant papers for further information about relevant unpublished and ongoing trials. We undertook a separate search for adverse effects of interventions for Old World cutaneous leishmaniasis in September 2015 using MEDLINE. SELECTION CRITERIA: Randomised controlled trials of either single or combination treatments in immunocompetent people with OWCL confirmed by smear, histology, culture, or polymerase chain reaction. The comparators were either no treatment, placebo/vehicle, and/or another active compound. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias and extracted data. We only synthesised data when we were able to identify at least two studies investigating similar treatments and reporting data amenable to pooling. We also recorded data about adverse effects from the corresponding search. MAIN RESULTS: We included 89 studies (of which 40 were new to this update) in 10,583 people with OWCL. The studies included were conducted mainly in the Far or Middle East at regional hospitals, local healthcare clinics, and skin disease research centres. Women accounted for 41.5% of the participants (range: 23% to 80%). The overall mean age of participants was 25 years (range 12 to 56). Most studies lasted between two to six months, with the longest lasting two years; average duration was four months. Most studies were at unclear or high risk for most bias domains. A lack of blinding and reporting bias were present in almost 40% of studies. Two trials were at low risk of bias for all domains. Trials reported the causative species poorly.Here we provide results for the two main comparisons identified: itraconazole (200 mg for six to eight weeks) versus placebo; and paromomycin ointment (15% plus 10% urea, twice daily for 14 days) versus vehicle.In the comparison of oral itraconazole versus placebo, at 2.5 months' follow up, 85/125 participants in the itraconazole group achieved complete cure compared to 54/119 in the placebo group (RR 3.70, 95% CI 0.35 to 38.99; 3 studies; 244 participants). In one study, microbiological or histopathological cure of skin lesions only occurred in the itraconazole group after a mean follow-up of 2.5 months (RR 17.00, 95% CI 0.47 to 612.21; 20 participants). However, although the analyses favour oral itraconazole for these outcomes, we cannot be confident in the results due to the very low certainty evidence. More side effects of mild abdominal pain and nausea (RR 2.36, 95% CI 0.74 to 7.47; 3 studies; 204 participants) and mild abnormal liver function (RR 3.08, 95% CI 0.53 to 17.98; 3 studies; 84 participants) occurred in the itraconazole group (as well as reports of headaches and dizziness), compared with the placebo group, but again we rated the certainty of evidence as very low so are unsure of the results.When comparing paromomycin with vehicle, there was no difference in the number of participants who achieved complete cure (RR of 1.00, 95% CI 0.86, 1.17; 383 participants, 2 studies) and microbiological or histopathological cure of skin lesions after a mean follow-up of 2.5 months (RR 1.03, CI 0.88 to 1.20; 383 participants, 2 studies), but the paromomycin group had more skin/local reactions (such as inflammation, vesiculation, pain, redness, or itch) (RR 1.42, 95% CI 0.67 to 3.01; 4 studies; 713 participants). For all of these outcomes, the certainty of evidence was very low, meaning we are unsure about these results.Trial authors did not report the percentage of lesions cured after the end of treatment or speed of healing for either of these key comparisons. AUTHORS' CONCLUSIONS: There was very low-certainty evidence to support the effectiveness of itraconazole and paromomycin ointment for OWCL in terms of cure (i.e. microbiological or histopathological cure and percentage of participants completely cured). Both of these interventions incited more adverse effects, which were mild in nature, than their comparisons, but we could draw no conclusions regarding safety due to the very low certainty of the evidence for this outcome.We downgraded the key outcomes in these two comparisons due to high risk of bias, inconsistency between the results, and imprecision. There is a need for large, well-designed international studies that evaluate long-term effects of current therapies and enable a reliable conclusion about treatments. Future trials should specify the species of leishmaniasis; trials on types caused by Leishmania infantum, L aethiopica, andL donovani are lacking. Research into the effects of treating women of childbearing age, children, people with comorbid conditions, and those who are immunocompromised would also be helpful.It was difficult to evaluate the overall efficacy of any of the numerous treatments due to the variable treatment regimens examined and because RCTs evaluated different Leishmania species and took place in different geographical areas. Some outcomes we looked for but did not find were degree of functional and aesthetic impairment, change in ability to detect Leishmania, quality of life, and emergence of resistance. There were only limited data on prevention of scarring.


Assuntos
Antiprotozoários/uso terapêutico , Itraconazol/uso terapêutico , Leishmaniose Cutânea/terapia , Paromomicina/uso terapêutico , Adulto , Animais , Anti-Infecciosos/uso terapêutico , Antiprotozoários/administração & dosagem , Terapias Complementares/métodos , Crioterapia/métodos , Extremo Oriente , Feminino , Temperatura Alta/uso terapêutico , Humanos , Itraconazol/administração & dosagem , Terapia a Laser , Leishmania major , Leishmania tropica , Masculino , Pessoa de Meia-Idade , Oriente Médio , Bases para Pomadas/administração & dosagem , Paromomicina/administração & dosagem , Fotoquimioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Cochrane Database Syst Rev ; 11: CD005067, 2017 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-29149474

RESUMO

BACKGROUND: Cutaneous leishmaniasis, caused by a parasitic infection, is considered one of the most serious skin diseases in many low- and middle-income countries. Old World cutaneous leishmaniasis (OWCL) is caused by species found in Africa, Asia, the Middle East, the Mediterranean, and India. The most commonly prescribed treatments are antimonials, but other drugs have been used with varying success. As OWCL tends to heal spontaneously, it is necessary to justify the use of systemic and topical treatments. This is an update of a Cochrane Review first published in 2008. OBJECTIVES: To assess the effects of therapeutic interventions for the localised form of Old World cutaneous leishmaniasis. SEARCH METHODS: We updated our searches of the following databases to November 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We wrote to national programme managers, general co-ordinators, directors, clinicians, WHO-EMRO regional officers of endemic countries, pharmaceutical companies, tropical medicine centres, and authors of relevant papers for further information about relevant unpublished and ongoing trials. We undertook a separate search for adverse effects of interventions for Old World cutaneous leishmaniasis in September 2015 using MEDLINE. SELECTION CRITERIA: Randomised controlled trials of either single or combination treatments in immunocompetent people with OWCL confirmed by smear, histology, culture, or polymerase chain reaction. The comparators were either no treatment, placebo/vehicle, and/or another active compound. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias and extracted data. We only synthesised data when we were able to identify at least two studies investigating similar treatments and reporting data amenable to pooling. We also recorded data about adverse effects from the corresponding search. MAIN RESULTS: We included 89 studies (of which 40 were new to this update) in 10,583 people with OWCL. The studies included were conducted mainly in the Far or Middle East at regional hospitals, local healthcare clinics, and skin disease research centres. Women accounted for 41.5% of the participants (range: 23% to 80%). The overall mean age of participants was 25 years (range 12 to 56). Most studies lasted between two to six months, with the longest lasting two years; average duration was four months. Most studies were at unclear or high risk for most bias domains. A lack of blinding and reporting bias were present in almost 40% of studies. Two trials were at low risk of bias for all domains. Trials reported the causative species poorly.Here we provide results for the two main comparisons identified: itraconazole (200 mg for six to eight weeks) versus placebo; and paromomycin ointment (15% plus 10% urea, twice daily for 14 days) versus vehicle.In the comparison of oral itraconazole versus placebo, at 2.5 months' follow up, 85/125 participants in the itraconazole group achieved complete cure compared to 54/119 in the placebo group (RR 3.70, 95% CI 0.35 to 38.99; 3 studies; 244 participants). In one study, microbiological or histopathological cure of skin lesions only occurred in the itraconazole group after a mean follow-up of 2.5 months (RR 17.00, 95% CI 0.47 to 612.21; 20 participants). However, although the analyses favour oral itraconazole for these outcomes, we cannot be confident in the results due to the very low certainty evidence. More side effects of mild abdominal pain and nausea (RR 2.36, 95% CI 0.74 to 7.47; 3 studies; 204 participants) and mild abnormal liver function (RR 3.08, 95% CI 0.53 to 17.98; 3 studies; 84 participants) occurred in the itraconazole group (as well as reports of headaches and dizziness), compared with the placebo group, but again we rated the certainty of evidence as very low so are unsure of the results.When comparing paromomycin with vehicle, there was no difference in the number of participants who achieved complete cure (RR of 1.00, 95% CI 0.86, 1.17; 383 participants, 2 studies) and microbiological or histopathological cure of skin lesions after a mean follow-up of 2.5 months (RR 1.03, CI 0.88 to 1.20; 383 participants, 2 studies), but the paromomycin group had more skin/local reactions (such as inflammation, vesiculation, pain, redness, or itch) (RR 1.42, 95% CI 0.67 to 3.01; 4 studies; 713 participants). For all of these outcomes, the certainty of evidence was very low, meaning we are unsure about these results.Trial authors did not report the percentage of lesions cured after the end of treatment or speed of healing for either of these key comparisons. AUTHORS' CONCLUSIONS: There was very low-certainty evidence to support the effectiveness of itraconazole and paromomycin ointment for OWCL in terms of cure (i.e. microbiological or histopathological cure and percentage of participants completely cured). Both of these interventions incited more adverse effects, which were mild in nature, than their comparisons, but we could draw no conclusions regarding safety due to the very low certainty of the evidence for this outcome.We downgraded the key outcomes in these two comparisons due to high risk of bias, inconsistency between the results, and imprecision. There is a need for large, well-designed international studies that evaluate long-term effects of current therapies and enable a reliable conclusion about treatments. Future trials should specify the species of leishmaniasis; trials on types caused by Leishmania infantum, L aethiopica, andL donovani are lacking. Research into the effects of treating women of childbearing age, children, people with comorbid conditions, and those who are immunocompromised would also be helpful.It was difficult to evaluate the overall efficacy of any of the numerous treatments due to the variable treatment regimens examined and because RCTs evaluated different Leishmania species and took place in different geographical areas. Some outcomes we looked for but did not find were degree of functional and aesthetic impairment, change in ability to detect Leishmania, quality of life, and emergence of resistance. There were only limited data on prevention of scarring.


Assuntos
Leishmaniose Cutânea/terapia , Animais , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/uso terapêutico , Antiprotozoários/efeitos adversos , Antiprotozoários/uso terapêutico , Terapias Complementares , Crioterapia , Temperatura Alta/uso terapêutico , Humanos , Itraconazol/efeitos adversos , Itraconazol/uso terapêutico , Terapia a Laser , Leishmania major , Leishmania tropica , Paromomicina/efeitos adversos , Paromomicina/uso terapêutico , Fotoquimioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Adv Nutr ; 8(5): 639-651, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28916566

RESUMO

Pooled analysis of secondary data increases the power of research and enables scientific discovery in nutritional epidemiology. Information on study characteristics that determine data quality is needed to enable correct reuse and interpretation of data. This study aims to define essential quality characteristics for data from observational studies in nutrition. First, a literature review was performed to get an insight on existing instruments that assess the quality of cohort, case-control, and cross-sectional studies and dietary measurement. Second, 2 face-to-face workshops were organized to determine the study characteristics that affect data quality. Third, consensus on the data descriptors and controlled vocabulary was obtained. From 4884 papers retrieved, 26 relevant instruments, containing 164 characteristics for study design and 93 characteristics for measurements, were selected. The workshop and consensus process resulted in 10 descriptors allocated to "study design" and 22 to "measurement" domains. Data descriptors were organized as an ordinal scale of items to facilitate the identification, storage, and querying of nutrition data. Further integration of an Ontology for Nutrition Studies will facilitate interoperability of data repositories.


Assuntos
Dieta , Avaliação Nutricional , Estudos Observacionais como Assunto , Adiposidade , Antropometria , Bases de Dados Factuais , Estudos Epidemiológicos , Humanos , Projetos de Pesquisa
14.
PLoS One ; 12(7): e0180220, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28686621

RESUMO

INTRODUCTION: Given the severity and impact of the current Zika virus (ZIKV) outbreak in the Americas, numerous countries have rushed to develop research studies to assess ZIKV and its potential health consequences. In an effort to ensure that studies are comprehensive, both internally and externally valid, and with reliable results, the World Health Organization, the Pan American Health Organization, Institut Pasteur, the networks of Fiocruz, the Consortia for the Standardization of Influenza Seroepidemiology (CONSISE) and the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) have generated six standardized clinical and epidemiological research protocols and questionnaires to address key public health questions on ZIKV. METHODS: We conducted a systematic search of ongoing study protocols related to ZIKV research. We analyzed the content of protocols of 32 cohort studies and 13 case control studies for systematic bias that could produce erroneous results. Additionally we aimed to characterize the risks of bias and confounding in observational studies related to ZIKV and to propose ways to minimize them, including the use of six newly standardized research protocols. RESULTS: Observational studies of ZIKV face an array of challenges, including measurement of exposure and outcomes (microcephaly and Guillain-Barré Syndrome). Potential confounders need to be measured where known and controlled for in the analysis. Selection bias due to non-random selection is a significant issue, particularly in the case-control design, and losses to follow-up is equally important for the cohort design. CONCLUSION: Observational research seeking to answer key questions on the ZIKV should consider these restrictions and take precautions to minimize bias in an effort to provide reliable and valid results. Utilization of the standardized research protocols developed by the WHO, PAHO, Institut Pasteur, and CONSISE will harmonize the key methodological aspects of each study design to minimize bias at different stages of the study. Biases need to be considered by researchers implementing the standardized protocols as well as by users of observational epidemiological studies of ZIKV.


Assuntos
Síndrome de Guillain-Barré/epidemiologia , Microcefalia/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Surtos de Doenças , Feminino , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Microcefalia/etiologia , Microcefalia/fisiopatologia , Gravidez , Complicações Infecciosas na Gravidez/etiologia , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/virologia , Saúde Pública , Fatores de Risco , Organização Mundial da Saúde , Zika virus/patogenicidade , Infecção por Zika virus/complicações , Infecção por Zika virus/patologia , Infecção por Zika virus/virologia
15.
PLoS One ; 12(6): e0179125, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28598986

RESUMO

BACKGROUND: The mechanisms explaining the co-existence of asthma, eczema and rhinitis (allergic multimorbidity) are largely unknown. We investigated the mechanisms underlying multimorbidity between three main allergic diseases at a molecular level by identifying the proteins and cellular processes that are common to them. METHODS: An in silico study based on computational analysis of the topology of the protein interaction network was performed in order to characterize the molecular mechanisms of multimorbidity of asthma, eczema and rhinitis. As a first step, proteins associated to either disease were identified using data mining approaches, and their overlap was calculated. Secondly, a functional interaction network was built, allowing to identify cellular pathways involved in allergic multimorbidity. Finally, a network-based algorithm generated a ranked list of newly predicted multimorbidity-associated proteins. RESULTS: Asthma, eczema and rhinitis shared a larger number of associated proteins than expected by chance, and their associated proteins exhibited a significant degree of interconnectedness in the interaction network. There were 15 pathways involved in the multimorbidity of asthma, eczema and rhinitis, including IL4 signaling and GATA3-related pathways. A number of proteins potentially associated to these multimorbidity processes were also obtained. CONCLUSIONS: These results strongly support the existence of an allergic multimorbidity cluster between asthma, eczema and rhinitis, and suggest that type 2 signaling pathways represent a relevant multimorbidity mechanism of allergic diseases. Furthermore, we identified new candidates contributing to multimorbidity that may assist in identifying new targets for multimorbid allergic diseases.


Assuntos
Asma/epidemiologia , Rinite Alérgica/epidemiologia , Rinite/epidemiologia , Asma/etiologia , Asma/metabolismo , Biomarcadores , Comorbidade , Simulação por Computador , Bases de Dados Factuais , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Modelos Estatísticos , Modelos Teóricos , Proteoma , Proteômica/métodos , Rinite/etiologia , Rinite/metabolismo , Rinite Alérgica/etiologia , Rinite Alérgica/metabolismo , Transdução de Sinais
16.
Int Arch Allergy Immunol ; 172(4): 224-235, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28456795

RESUMO

BACKGROUND: A sex-related switch in the prevalence of asthma from childhood (male predominance) to adulthood (female predominance) has been described, but for allergic rhinitis this remains unclear. We aimed to examine sex- and age-group-specific differences in allergic rhinitis prevalence by systematically evaluating studies from across the globe. METHODS: A systematic search of MEDLINE and Embase for population-based cross-sectional studies was performed regardless of the language of publication. The search was restricted to the present millennium (2000 to June 2014). Study quality was defined by the sampling method, response rate, sample size, and data collection method. To assess sex differences in the prevalence of self- or parent-reported symptoms of rhinitis, calculated pooled estimates of the male-female ratio (MFR) were obtained using random-effects model meta-analyses due to heterogeneity. A meta-regression analysis was also performed. RESULTS: Out of 6,539 publications identified, 67 cross-sectional population-based studies (291,726 males and 301,781 females) were included in our meta-analysis. In children (<11 years of age) significantly more boys than girls had rhinitis symptoms (MFR 1.21, 95% CI 1.17-1.25), whereas in adolescents (11 to <18 years of age) males were significantly less often affected than females (MFR 0.90, 95% CI 0.85-0.95). No sex-specific prevalence difference was observed in adults (MFR 0.96, 95% CI 0.83-1.17). These findings were consistent in all continents except in Asia, where the male predominance remained beyond childhood. CONCLUSIONS: The male predominance of rhinitis prevalence in childhood changed towards a female predominance in adolescence across the globe, except in Asia. Longitudinal studies are needed to confirm these cross-sectional data and examine possible determinants and underlying mechanisms.


Assuntos
Rinite Alérgica/epidemiologia , Adulto , Criança , Feminino , Humanos , Masculino , Prevalência , Caracteres Sexuais
17.
Int J Infect Dis ; 58: 96-109, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28341436

RESUMO

OBJECTIVE: To compare the efficacy and safety of different pivmecillinam (PIV) regimes for uncomplicated lower urinary tract infections (UTIs). METHODS: The MEDLINE, Embase, and Cochrane Library databases were searched. Randomized controlled clinical trials (RCTs) involving adults or children with symptoms suggestive of uncomplicated UTI and that compared different PIV regimes or PIV versus other antibiotics were included. Meta-analyses were conducted to obtain direct and indirect efficacy estimates. PIV regimes were categorized into high total dosage, moderate total dosage, and low total dosage. The risk of bias was evaluated using the Cochrane tool. RESULTS: Twenty-four RCTs were identified. No difference in clinical cure was found for the high vs. moderate (short-term: risk ratio (RR) 1.01, p=0.813; long term: RR 1.09, p=0.174) or high vs. low dosage comparisons (mean difference 0, 95% confidence interval -0.44 to 0.45, p=1). For bacteriological cure, comparisons of high vs. moderate dosage (short term: RR 1.05, p=0.056; long term: RR 1.05, p=0.131) and high vs. low dosage (short term: RR 1.02, p=0.759; long term: RR 1.13, p=0.247) showed a trend in favor of the high dosage treatment. Results for relapse, re-infection, and failure were inconclusive and not statistically significant. Patients treated with high dosages were 40% (p=0.062) and 44% (p=0.293) more likely to report mild to moderate adverse events. CONCLUSIONS: There is insufficient evidence to support the use of an optimal combination of dosage, frequency, and duration of PIV therapy for the treatment of uncomplicated lower UTI. Evidence is limited due to the high risk of bias, poor reporting, and heterogeneous study data.


Assuntos
Andinocilina Pivoxil/administração & dosagem , Anti-Infecciosos Urinários/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos
18.
J Allergy Clin Immunol ; 139(2): 388-399, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28183433

RESUMO

Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non-IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), and transcriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.


Assuntos
Alérgenos/imunologia , Hipersensibilidade/imunologia , Adolescente , Animais , Criança , Estudos de Coortes , Comorbidade , Europa (Continente)/epidemiologia , Feminino , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/genética , Imunização , Imunoglobulina E/metabolismo , Fenótipo , Pesquisa Médica Translacional , Adulto Jovem
19.
JAMA ; 316(16): 1708-1709, 2016 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-27784078

RESUMO

Clinical Question: Which interventions are associated with highest efficacy and fewest adverse events for treating vitiligo? Bottom Line: Combination therapies, particularly those involving some form of light (ie, narrowband UV-B) were associated with more improved repigmentation than monotherapies. There was limited evidence to support the association of UV-A alone and UV-B alone with repigmentation for vitiligo. There was moderate evidence to support the association of UV-A and UV-B, when used in combination with psoralens, topical corticosteroids, vitamin D analogues, fluorouracil, azathioprine, and oral prednisolone with improved outcomes for vitiligo. However, combination therapies were associated with more adverse effects.


Assuntos
Glucocorticoides/uso terapêutico , Vitiligo/tratamento farmacológico , Terapia Combinada , Humanos , Resultado do Tratamento
20.
Int Arch Allergy Immunol ; 168(2): 110-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26657241

RESUMO

BACKGROUND: During the last decades, a large number of phenotypes and disease classifications of allergic diseases have been proposed. Despite the heterogeneity across studies, no systematic review has been conducted on phenotype classification and the criteria that define allergic diseases. We aimed to identify clinically expressed, population-based phenotypes of allergic diseases and their interrelationships, to explore disease heterogeneity and to evaluate the measurements employed in disease diagnosis. METHODS: We conducted a search of MEDLINE up to December 2012, to identify relevant original studies published in the English language that examine at least one objective of this systematic review in subjects aged 0-18 years. The screening of titles and abstracts and the extraction of data were conducted independently by two reviewers. RESULTS: From a total of 13,767 citations, 197 studies met the criteria for inclusion, with 54% being cohort studies. Allergic diseases were studied as a single entity in 55% (109/197) of the studies or in the context of multimorbidity in 45%. Asthma accounted for 81.7% of the studies examining single diseases. Overall, up to 33 different phenotypes of allergic disease were reported. Transient early, late-onset and persistent wheeze were the most frequently reported phenotypes. Most studies (78%) used questionnaires. The skin-prick test was the preferred measurement of sensitization (64%). Spirometry and bronchial hyperresponsiveness were assessed in one third of the studies, peak flow rate in 8.6% and disease severity in 35%. CONCLUSIONS: Studies reporting phenotypes of allergic diseases in children are highly heterogeneous and often lack objective phenotypical measures. A concerted effort to standardize methods and terminology is necessary.


Assuntos
Hipersensibilidade/classificação , Fenótipo , Criança , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/fisiopatologia
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