RESUMEN
BACKGROUND: Recent progesterone trials call for an update of previous syntheses of interventions to prevent preterm birth. OBJECTIVES: To compare the relative effects of different types and routes of administration of progesterone, cerclage, and pessary at preventing preterm birth in at-risk women overall and in specific populations. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL, and Web of Science up to 1 January 2018. SELECTION CRITERIA: We included randomised trials of progesterone, cerclage or pessary for preventing preterm birth in at-risk singleton pregnancies. DATA COLLECTION AND ANALYSIS: We used a piloted data extraction form and performed Bayesian random-effects network meta-analyses with 95% credibility intervals (CrI), as well as pairwise meta-analyses, rating the quality of the evidence using GRADE. MAIN RESULTS: We included 40 trials (11 311 women). In at-risk women overall, vaginal progesterone reduced preterm birth <34 (OR 0.43, 95% CrI 0.20-0.81) and <37 weeks (OR 0.51, 95% CrI 0.34-0.74), and neonatal death (OR 0.41, 95% CrI 0.20-0.83). In women with a previous preterm birth, vaginal progesterone reduced preterm birth <34 (OR 0.29, 95% CI 0.12-0.68) and <37 weeks (OR 0.43, 95% CrI 0.23-0.74), and 17α-hydroxyprogesterone caproate reduced preterm birth <37 weeks (OR 0.53, 95% CrI 0.27-0.95) and neonatal death (OR 0.39, 95% CI 0.16-0.95). In women with a short cervix (≤25 mm), vaginal progesterone reduced preterm birth <34 weeks (OR 0.45, 95% CI 0.24-0.84). CONCLUSIONS: Vaginal progesterone was the only intervention with consistent effectiveness for preventing preterm birth in singleton at-risk pregnancies overall and in those with a previous preterm birth. TWEETABLE ABSTRACT: In updated NMA, vaginal progesterone consistently reduced PTB in overall at-risk pregnancies and in women with previous PTB.
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Caproato de 17 alfa-Hidroxiprogesterona/administración & dosificación , Cerclaje Cervical/estadística & datos numéricos , Pesarios/estadística & datos numéricos , Nacimiento Prematuro/prevención & control , Progesterona/administración & dosificación , Administración Intravaginal , Administración Oral , Medición de Longitud Cervical , Cuello del Útero/patología , Femenino , Humanos , Recién Nacido , Metaanálisis en Red , Muerte Perinatal/prevención & control , Embarazo , Embarazo de Alto Riesgo , Nacimiento Prematuro/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Preterm birth (PTB) is the leading cause of infant death, but it is unclear which intervention is best to prevent it. OBJECTIVES: To compare progesterone, cerclage and pessary, determine their relative effects and rank them. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL and Web of Science (to April 2016), without restrictions, and screened references of previous reviews. SELECTION CRITERIA: We included randomised trials of progesterone, cerclage or pessary for preventing PTB in women with singleton pregnancies at risk as defined by each study. DATA COLLECTION AND ANALYSIS: We extracted data by duplicate using a piloted form and performed Bayesian random-effects network meta-analyses and pairwise meta-analyses. We rated evidence quality using GRADE, ranked interventions using SUCRA and calculated numbers needed to treat (NNT). MAIN RESULTS: We included 36 trials (9425 women; 25 low risk of bias trials). Progesterone ranked first or second for most outcomes, reducing PTB < 34 weeks [odds ratio (OR) 0.44; 95% credible interval (CrI) 0.22-0.79; NNT 9; low quality], <37 weeks (OR 0.58; 95% CrI 0.41-0.79; NNT 9; moderate quality), and neonatal death (OR 0.50; 95% CrI 0.28-0.85; NNT 35; high quality), compared with control, in women overall at risk. We found similar results in the subgroup with previous PTB, but only a reduction of PTB < 34 weeks in women with a short cervix. Pessary showed inconsistent benefit and cerclage did not reduce PTB < 37 or <34 weeks. CONCLUSIONS: Progesterone was the best intervention for preventing PTB in singleton pregnancies at risk, reducing PTB < 34 weeks, <37 weeks, neonatal demise and other sequelae. TWEETABLE ABSTRACT: Progesterone was better than cerclage and pessary to prevent preterm birth, neonatal death and more in network meta-analysis.
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Cerclaje Cervical/estadística & datos numéricos , Pesarios/estadística & datos numéricos , Nacimiento Prematuro/prevención & control , Progesterona/administración & dosificación , Progestinas/administración & dosificación , Administración Intravaginal , Adulto , Teorema de Bayes , Femenino , Edad Gestacional , Humanos , Recién Nacido , Metaanálisis en Red , Embarazo , Nacimiento Prematuro/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk. OBJECTIVES: To assess the evidence for the effectiveness of progesterone, cerclage, and pessary in twin pregnancies. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, up to 25 January 2016. SELECTION CRITERIA: Randomised controlled trials of progesterone, cerclage, or pessary for preventing preterm birth in women with twin pregnancies, without symptoms of threatened preterm labour. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data using a piloted form. Study quality was appraised with the Cochrane Risk of Bias tool. We performed pairwise inverse variance random-effects meta-analyses. MAIN RESULTS: We included 23 trials (all but three were considered to have a low risk of bias) comprising 6626 women with twin pregnancies. None of the interventions significantly reduced the risk of preterm birth overall at <34 or <37 weeks of gestation, or neonatal death, our primary outcomes, compared to a control group. In women receiving vaginal progesterone, the relative risk (RR) of preterm birth <34 weeks of gestation was 0.82 (95% CI 0.64-1.05, seven studies, I2 36%), with a significant reduction in some key secondary outcomes, including very low birthweight (<1500 g, RR 0.71, 95% CI 0.52-0.98, four studies, I2 46%) and mechanical ventilation (RR 0.61, 95% CI 0.45-0.82, four studies, I2 22%). CONCLUSION: In twin gestations, although no overarching intervention was beneficial for the prevention of preterm birth and its sequelae, vaginal progesterone improved some important secondary outcomes. TWEETABLE ABSTRACT: Vaginal progesterone may be beneficial in twin pregnancies, but not 17-OHPC, cerclage, or pessary.
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Cerclaje Cervical/estadística & datos numéricos , Pesarios/estadística & datos numéricos , Embarazo Gemelar , Nacimiento Prematuro/prevención & control , Progesterona/administración & dosificación , Progestinas/administración & dosificación , Administración Intravaginal , Femenino , Edad Gestacional , Humanos , Embarazo , Nacimiento Prematuro/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Resultado del TratamientoRESUMEN
Objective Malnutrition in children pervades all aspects of their health, growth, cognitive and social development and can lead to irreversible and lifelong effects. We examine the prevalence and determinants of malnutrition in children under 5 in the Ghanaian population. Methods Using data from the latest available Ghana Demographic and Health Survey (GDHS), we estimated and compared prevalence of malnutrition in children among the different subgroups of the population. We used multivariable logistic regression to identify potential factors associated with childhood malnutrition in Ghana. Results Overall, 35.6 % (95 % CI: 33.6, 37.6) of Ghanaian children under 5 years of age suffer from some form of malnutrition. Specifically, 27.5 % (95 % CI: 25.1, 28.7), 13.8 % (95 % CI: 12.5, 15.3), 8.9 % (95 % CI: 7.8, 10.2) were stunted, underweight and wasted, respectively. Results from the logistic regression indicate that gender and age of the child, educational and nutritional status of the mother, and financial status of the household are risk factors associated with childhood malnutrition in Ghana. Conclusions for Practice In view of the observed high rate of malnutrition among Ghanaian children despite the interventions that have been in place since the 1990s, there is a need for increased awareness and improved targeted interventions as well as knowledge translation tools including extensive education on infant and young child feeding practices.
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Lactancia Materna/métodos , Cuidado del Lactante/métodos , Desnutrición/epidemiología , Desnutrición/prevención & control , Madres/educación , Adulto , Factores de Edad , Preescolar , Femenino , Geografía , Ghana/epidemiología , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Prevalencia , Factores Sexuales , Factores SocioeconómicosRESUMEN
Thiopurine S-methyltransferase (TPMT) deficiency increases the risk of serious adverse events in persons receiving thiopurines. The objective was to synthesize reported sensitivity and specificity of TPMT phenotyping and genotyping using a latent class hierarchical summary receiver operating characteristic meta-analysis. In 27 studies, pooled sensitivity and specificity of phenotyping for deficient individuals was 75.9% (95% credible interval (CrI), 58.3-87.0%) and 98.9% (96.3-100%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 90.4% (79.1-99.4%) and 100.0% (99.9-100%), respectively. For individuals with deficient or intermediate activity, phenotype sensitivity and specificity was 91.3% (86.4-95.5%) and 92.6% (86.5-96.6%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 88.9% (81.6-97.5%) and 99.2% (98.4-99.9%), respectively. Genotyping has higher sensitivity as long as TPMT*2 and TPMT*3 are tested. Both approaches display high specificity. Latent class meta-analysis is a useful method for synthesizing diagnostic test performance data for clinical practice guidelines.The Pharmacogenomics Journal advance online publication, 24 May 2016; doi:10.1038/tpj.2016.37.
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Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Metiltransferasas/genética , Pruebas de Farmacogenómica/métodos , Variantes Farmacogenómicas/genética , Errores Innatos del Metabolismo de la Purina-Pirimidina/diagnóstico , Errores Innatos del Metabolismo de la Purina-Pirimidina/genética , Purinas/efectos adversos , Área Bajo la Curva , Hipersensibilidad a las Drogas/enzimología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/enzimología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Predisposición Genética a la Enfermedad , Humanos , Metiltransferasas/metabolismo , Fenotipo , Valor Predictivo de las Pruebas , Errores Innatos del Metabolismo de la Purina-Pirimidina/enzimología , Purinas/metabolismo , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
We evaluated single nucleotide polymorphisms (SNPs) associated with infection risk in children with newly diagnosed acute myeloid leukaemia (AML). We conducted a multicentre, prospective cohort study that included children aged ≤18 years with de novo AML. DNA was isolated from blood lymphocytes or buccal swabs, and candidate gene SNP analysis was conducted. Primary outcome was the occurrence of microbiologically documented sterile site infection during chemotherapy. Secondary outcomes were Gram-positive and -negative infections, viridans group streptococcal infection and proven/probable invasive fungal infection. Interpretation was guided by consistency in risk alleles and microbiologic agent with previous literature. Over the study period 254 children and adolescents with AML were enrolled. Overall, 190 (74.8%) had at least one sterile site microbiologically documented infection. Among the 172 with inferred European ancestry and DNA available, nine significant associations were observed; two were consistent with previous literature. Allele A at IL1B (rs16944) was associated with decreased microbiologically documented infection, and allele G at IL10 (rs1800896) was associated with increased risk of Gram-positive infection. We identified SNPs associated with infection risk in paediatric AML. Genotype may provide insight into mechanisms of infection risk that could be used for supportive-care novel treatments.
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Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/genética , Predisposición Genética a la Enfermedad , Interleucina-1beta/genética , Leucemia Mieloide Aguda/complicaciones , Polimorfismo de Nucleótido Simple , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios Prospectivos , Medición de RiesgoRESUMEN
Competing events (or risks) preclude the observation of an event of interest or alter the probability of the event's occurrence and are commonly encountered in transplant outcomes research. Transplantation, for example, is a competing event for death on the waiting list because receiving a transplant may significantly decrease the risk of long-term mortality. In a typical analysis of time-to-event data, competing events may be censored or incorporated into composite end points; however, the presence of competing events violates the assumption of "independent censoring," which is the basis of standard survival analysis techniques. The use of composite end points disregards the possibility that competing events may be related to the exposure in a way that is different from the other components of the composite. Using data from the Scientific Registry of Transplant Recipients, this paper reviews the principles of competing risks analysis; outlines approaches for analyzing data with competing events (cause-specific and subdistribution hazards models); compares the estimates obtained from standard survival analysis, which handle competing events as censoring events; discusses the appropriate settings in which each of the two approaches could be used; and contrasts their interpretation.
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Trasplante de Riñón/mortalidad , Modelos Estadísticos , Medición de Riesgo/métodos , Listas de Espera , Humanos , Análisis de SupervivenciaRESUMEN
Depression during pregnancy has been associated with an increased risk of adverse outcomes for the infant such as preterm birth. These risks are not reduced with pharmacological treatment, but the effect of non-pharmacological therapies is unknown. We performed a systematic review to assess the risk of adverse perinatal outcomes in non-pharmacologically treated depressed women compared to non-depressed women. We found no studies that met our inclusion criteria, highlighting a critical need for research on this topic.
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Depresión/terapia , Complicaciones del Embarazo/terapia , Psicoterapia , Depresión/diagnóstico , Depresión/psicología , Femenino , Humanos , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Embarazo , Complicaciones del Embarazo/psicología , Nacimiento Prematuro/prevención & control , Medición de RiesgoRESUMEN
Despite extensive research efforts over decades, the teratogenic profile of valproic acid (VPA) remains obscure. We performed cumulative and conventional meta-analyses of cohort studies to determine the time profiles of signal emergence of VPA-associated congenital malformations (CMs) and to define risk estimates of each of the CMs. Fifty-nine studies were identified and analyzed. We found that the significant risk signals began to emerge over the last 10-20 years even before large-scale studies were performed: neural tube defect (the significant risk signal emerged in 1992); genitourinary and musculoskeletal anomalies (2004); cleft lip and/or palate (2005); and congenital heart defects (2006). At present, the risks of VPA-associated CMs are 2-7-fold higher than other common antiepileptic drugs. VPA should not be used as a first-line therapy in women of childbearing age unless it is the only option for the patient.
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Anomalías Inducidas por Medicamentos/etiología , Anticonvulsivantes/efectos adversos , Exposición Materna/efectos adversos , Ácido Valproico/efectos adversos , Femenino , Humanos , Oportunidad Relativa , Embarazo , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
Morbidly obese (Class III, body mass index [BMI] ≥ 40 kg m(-2)) women constitute 8% of reproductive-aged women and are an increasing proportion; however, their pregnancy risks have not yet been well understood. Hence, we performed meta-analyses following the MOOSE (Meta-Analysis of Observational Studies in Epidemiology) guideline, searching Medline and Embase from their inceptions. To examine graded relationships, we compared Class III obesity to Class I and I/II, and separately to normal weight. We found important effects on all three primary outcomes in morbidly obese women: preterm birth <37 weeks was 31% higher compared with Class I (relative risk [RR] 1.31 [1.19, 1.43]) and 20% higher than Class I/II (RR 1.20 [1.13, 1.27]), large-for-gestational age was higher (RR 1.37 [1.29, 1.45] and RR 1.30 [1.24, 1.36] compared with Class I and I/II, respectively), while small-for-gestational age was lower (RR 0.89 [0.84, 0.93] compared with Class I, with nearly identical reductions for Class I/II). Morbidly obese women have higher risks of preterm birth, large-for-gestational age and numerous other adverse maternal and infant health outcomes, relative to not only normal weight but also Class I or I/II obese women. These findings have important implications for screening and care of morbidly obese pregnant women, to try to decrease adverse outcomes.
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Cesárea/estadística & datos numéricos , Macrosomía Fetal/etiología , Obesidad Mórbida/complicaciones , Complicaciones del Embarazo/etiología , Nacimiento Prematuro/etiología , Adulto , Índice de Masa Corporal , Femenino , Macrosomía Fetal/prevención & control , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Servicios de Salud Materno-Infantil , Obesidad Mórbida/fisiopatología , Obesidad Mórbida/prevención & control , Embarazo , Complicaciones del Embarazo/fisiopatología , Complicaciones del Embarazo/prevención & control , Resultado del Embarazo , Nacimiento Prematuro/prevención & controlRESUMEN
A systematic review was conducted to determine the risk of adverse pregnancy outcomes with gestational weight gain (GWG) below the 2009 Institute of Medicine guidelines compared with within the guidelines in obese women. MEDLINE, Embase, Cochrane Register, CINHAL and Web of Science were searched from 1 January 2009 to 31 July 2014. Quality was assessed using a modified Newcastle-Ottawa scale. Three primary outcomes were included: preterm birth, small for gestational age (SGA) and large for gestational age (LGA). Eighteen cohort studies were included. GWG below the guidelines had higher odds of preterm birth (adjusted odds ratio [AOR] 1.46; 95% confidence interval [CI] 1.07-2.00) and SGA (AOR 1.24; 95% CI 1.13-1.36) and lower odds of LGA (AOR 0.77; 95% CI 0.73-0.81) than GWG within the guidelines. Across the three obesity classes, the odds of SGA and LGA did not show any notable gradient and remained unexplored for preterm birth. Decreased odds were noted for macrosomia (AOR 0.64; 95% CI 0.54-0.77), gestational hypertension (AOR, 0.70; 95% CI 0.53-0.93), pre-eclampsia (AOR 0.90; 95% CI 0.82-0.99) and caesarean (AOR 0.87; 95% CI 0.82-0.92). GWG below the guidelines cannot be routinely recommended but might occasionally be individualized for certain women, with caution, taking into account other known risk factors.
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Madres/estadística & datos numéricos , Obesidad/prevención & control , Preeclampsia/epidemiología , Complicaciones del Embarazo/epidemiología , Aumento de Peso , Adulto , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Recién Nacido Pequeño para la Edad Gestacional , Obesidad/complicaciones , Obesidad/epidemiología , Oportunidad Relativa , Proyectos Piloto , Guías de Práctica Clínica como Asunto , Preeclampsia/etiología , Preeclampsia/prevención & control , Embarazo , Complicaciones del Embarazo/etiología , Complicaciones del Embarazo/prevención & control , Resultado del Embarazo , Factores de RiesgoRESUMEN
We conducted a nested case-control study from a cohort of adult kidney transplant recipients to assess the risk of transplant glomerulopathy (TG) as a function of donor and recipient HLA-DR and -DQ incompatibility at the eplet level. Cases (n = 52) were defined as patients diagnosed with transplant glomerulopathy based on biopsies showing glomerular basement membrane duplication without immune complex deposition. Controls (n = 104) with a similar follow-up from transplantation were randomly selected from the remaining cohort. HLAMatchmaker was used to ascertain the number of DRB1/3/4/5, DQA1 and DQB1 related eplet mismatches (eplet load). Multivariable conditional logistic regression models demonstrated an increase in the odds of TG (odds ratios [OR] of 2.84 [95% confidence interval (CI): 1.03, 7.84] and 4.62 [95% CI: 1.51, 14.14]) in the presence of 27-43 and >43 HLA-DR + DQ related eplet mismatches versus <27 eplet mismatches, respectively. When the eplet load was modeled as a continuous variable, the OR for TG was 1.25 (95% CI: 1.04, 1.50) for every 10 additional HLA-DR + DQ eplet mismatches. Our study suggests that minimization of HLA-DR + DQ eplet mismatches may decrease the incidence of transplant glomerulopathy diagnosed by indication biopsies. The role of eplet immunogenicity/antigenicity as determinants of allograft outcomes requires further study.
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Glomerulonefritis Membranosa/etiología , Antígenos HLA-DQ/inmunología , Antígenos HLA-DR/inmunología , Histocompatibilidad/inmunología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Adulto , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Glomerulonefritis Membranosa/inmunología , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/inmunología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Factores de Riesgo , Receptores de Trasplantes , Trasplante HomólogoRESUMEN
BACKGROUND/OBJECTIVES: In the absence of consistent clinical evidence, there are concerns that fructose contributes to non-alcoholic fatty liver disease (NAFLD). To determine the effect of fructose on markers of NAFLD, we conducted a systematic review and meta-analysis of controlled feeding trials. SUBJECTS/METHODS: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library (through 3 September 2013). We included relevant trials that involved a follow-up of ≥ 7 days. Two reviewers independently extracted relevant data. Data were pooled by the generic inverse variance method using random effects models and expressed as standardized mean difference (SMD) for intrahepatocellular lipids (IHCL) and mean difference (MD) for alanine aminotransferase (ALT). Inter-study heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). RESULTS: Eligibility criteria were met by eight reports containing 13 trials in 260 healthy participants: seven isocaloric trials, in which fructose was exchanged isocalorically for other carbohydrates, and six hypercaloric trials, in which the diet was supplemented with excess energy (+21-35% energy) from high-dose fructose (+104-220 g/day). Although there was no effect of fructose in isocaloric trials, fructose in hypercaloric trials increased both IHCL (SMD=0.45 (95% confidence interval (CI): 0.18, 0.72)) and ALT (MD=4.94 U/l (95% CI: 0.03, 9.85)). LIMITATIONS: Few trials were available for inclusion, most of which were small, short (≤ 4 weeks), and of poor quality. CONCLUSIONS: Isocaloric exchange of fructose for other carbohydrates does not induce NAFLD changes in healthy participants. Fructose providing excess energy at extreme doses, however, does raise IHCL and ALT, an effect that may be more attributable to excess energy than fructose. Larger, longer and higher-quality trials of the effect of fructose on histopathological NAFLD changes are required.
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Fructosa/administración & dosificación , Fructosa/efectos adversos , Enfermedad del Hígado Graso no Alcohólico/patología , Alanina Transaminasa/metabolismo , Bases de Datos Factuales , Humanos , Enfermedad del Hígado Graso no Alcohólico/etiología , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Objectives were to describe the reliability and validity of a new paediatric-specific mucositis scale, the Children's International Mucositis Evaluation Scale (ChIMES). METHODS: In a multi-centre prospective study, children aged 0 to ≤18 years were eligible if they were receiving any of the following: myeloablative stem cell transplantation (SCT), ≥60 mg m(-2) course(-1) doxorubicin or ≥12 g m(-2) methotrexate. Multiple measures of mucositis were included along with ChIMES. Respondents were parent proxy report for children aged <12 years, and child self-report for children aged 12-18 years and 8 to <12 years. Mucositis diaries were completed at baseline and on Days 7-17 following chemotherapy/conditioning. On Day 14, the respondent reported presence of mucositis and change since the previous day. RESULTS: The 185 respondents included parents (N=98), children aged 12-18 years (N=66) and children aged 8 to <12 years (N=21). Test-retest reliability was excellent for ChIMES Total Score and ChIMES Percentage Score with r>0.8 for all respondent types. Criteria for construct validation were met across all measures. ChIMES also demonstrated responsiveness with significant differences between baseline and Day 14. CONCLUSION: ChIMES is a paediatric-specific measure of mucositis with favourable psychometric properties. It exhibits reliability, construct validity and responsiveness. ChIMES should be incorporated into clinical trials of mucositis prevention and treatment in paediatric cancer and SCT.
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Mucositis/diagnóstico , Mucositis/etiología , Agonistas Mieloablativos/efectos adversos , Neoplasias/terapia , Índice de Severidad de la Enfermedad , Trasplante de Células Madre , Adolescente , Niño , Terapia Combinada/efectos adversos , Femenino , Humanos , Masculino , Mucosa Bucal , Mucositis/epidemiología , Agonistas Mieloablativos/uso terapéutico , Neoplasias/diagnóstico , Neoplasias/epidemiología , Trasplante de Células Madre/efectos adversos , Trasplante de Células Madre/métodos , Estomatitis/diagnóstico , Estomatitis/epidemiología , Estomatitis/etiología , Encuestas y Cuestionarios , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodosRESUMEN
Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in paediatric acute myeloid leukaemia (AML). This study describes risk factors for IFI and IFI-related sepsis in this population. We conducted a population-based, retrospective cohort study of children with AML in Canada. IFIs during chemotherapy and prior to haematopoietic stem cell transplantation, relapse, persistent disease or death were identified. Risk factors for proven or probable IFI were examined. Among courses complicated by IFI, risk factors for sepsis were also evaluated. There were 341 children with AML included of which 41 (12.0%) experienced 46 different episodes of IFI. Candida species accounted for 23 (50.0%) of IFIs and Aspergillus spp. accounted for 14 (30.4%). Days of broad-spectrum antibiotics, days of corticosteroids and neutropenia at start of the course were independently associated with IFI. Only days of fever were independently associated with IFI-related sepsis. Invasive fungal infections occurred in 12.0% of paediatric AML patients. Risk factors for IFI and IFI-related sepsis were identified. This knowledge may help to consider targeted strategies.
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Fungemia/epidemiología , Fungemia/microbiología , Huésped Inmunocomprometido , Leucemia Mieloide Aguda/complicaciones , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/microbiología , Adolescente , Canadá/epidemiología , Niño , Preescolar , Estudios de Cohortes , Femenino , Hongos/clasificación , Hongos/aislamiento & purificación , Humanos , Lactante , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Prevalencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Objectives were to compare systemic mould-active vs fluconazole prophylaxis in cancer patients receiving chemotherapy or haematopoietic stem cell transplantation (HSCT). METHODS: We searched OVID MEDLINE and the Cochrane Central Register of Controlled Trials (1948-August 2011) and EMBASE (1980-August 2011). Randomised controlled trials of mould-active vs fluconazole prophylaxis in cancer or HSCT patients were included. Primary outcome was proven/probable invasive fungal infections (IFI). Analysis was completed by computing relative risks (RRs) using a random-effects model and Mantel-Haenszel method. RESULTS: From 984 reviewed articles, 20 were included in this review. Mould-active compared with fluconazole prophylaxis significantly reduced the number of proven/probable IFI (RR 0.71, 95% CI 0.52 to 0.98; P=0.03). Mould-active prophylaxis also decreased the risk of invasive aspergillosis (IA; RR 0.53, 95% confidence interval (CI) 0.37-0.75; P=0.0004) and IFI-related mortality (RR 0.67, 95% CI 0.47-0.96; P=0.03) but is also associated with an increased risk of adverse events (AEs) leading to antifungal discontinuation (RR 1.95, 95% CI 1.24-3.07; P=0.004). There was no decrease in overall mortality (RR 1.0; 95% CI 0.88-1.13; P=0.96). CONCLUSION: Mould-active compared with fluconazole prophylaxis significantly reduces proven/probable IFI, IA, and IFI-related mortality in cancer patients receiving chemotherapy or HSCT, but increases AE and does not affect overall mortality. (PROSPERO Registration: CRD420111174).
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Antifúngicos/uso terapéutico , Antineoplásicos/efectos adversos , Fluconazol/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Micosis/prevención & control , Neoplasias/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Humanos , Lactante , Persona de Mediana EdadRESUMEN
BACKGROUND: There is no consensus on whether therapeutic intensity can be reduced safely in children with low-risk febrile neutropenia (FN). Our primary objective was to determine whether there is a difference in efficacy between outpatient and inpatient management of children with low-risk FN. Our secondary objective was to compare oral and parenteral antibiotic therapy in this population. METHODS: We performed electronic searches of Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled Trials, and limited studies to prospective pediatric trials in low-risk FN. Percentages were used as the effect measure. RESULTS: From 7,281 reviewed articles, 16 were included in the meta-analysis. Treatment failure, including antibiotic modification, was less likely to occur in the outpatient setting compared with the inpatient setting (15 % versus 28 %, P = 0.04) but was not significantly different between oral and parenteral antibiotic regimens (20 % versus 22 %, P = 0.68). Of the 953 episodes treated in the outpatient setting and 676 episodes treated with oral antibiotics, none were associated with infection-related mortality. CONCLUSION: Based on the combination of results from all prospective studies to date, outpatient and oral antibiotic management of low-risk FN are effective in children and should be incorporated into clinical care where feasible.
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Antibacterianos/administración & dosificación , Fiebre/tratamiento farmacológico , Neutropenia/tratamiento farmacológico , Administración Oral , Atención Ambulatoria , Niño , Fiebre/etiología , Humanos , Neoplasias/tratamiento farmacológico , Neutropenia/etiología , Factores de Riesgo , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
UNLABELLED: Inconsistent study findings of exercise on areal bone density highlight the need to include parameters of bone geometry and volumetric bone density measurements. Using a systematic review and meta-analysis, we found a decrease in bone loss through the maintenance of cortical and trabecular volumetric bone mineral density (BMD). Studies with longer exercise durations and larger sample sizes are needed. INTRODUCTION: Exercise has long been recommended to prevent age-related loss of bone mass in postmenopausal women. However, inconsistent study findings on the effect of exercise on BMD preservation have highlighted the importance of extending the evaluation of bone to include the parameters of bone geometry. We conducted both a systematic review and meta-analysis of the effects of exercise on bone geometry and volumetric BMD in postmenopausal women. METHODS: We searched MEDLINE, PubMed, and EMBASE from 1950 to April 2009 and included prospective, randomized controlled trials of healthy postmenopausal women where the intervention involved exercise or sport and outcomes included quantitative or peripheral quantitative computed tomography bone parameters. Outcome variables included: total volumetric BMD, cortical volumetric BMD (CvBMD), trabecular volumetric BMD (TrvBMD), total bone mineral content, cortical BMC, total bone area, cortical area, polar stress-strain index, and bone strength index. RESULTS: Six studies satisfied our inclusion and exclusion criteria. Lower extremity exercises resulted in small (â¼0.9%) but significant improvements in TrvBMD of the distal tibia (p = 0.0006) and in CvBMD of the tibial shaft (p = 0.0007). Studies with longer durations of exercise (12 months) and those in early postmenopausal women showed significant changes in CvBMD at the tibial shaft. CONCLUSIONS: We conclude that exercise in postmenopausal women may decrease bone loss by maintaining cortical and trabecular volumetric BMD. To better understand the effect of exercise on bone geometric structure and strength, more studies of longer duration and larger sample sizes are needed.
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Densidad Ósea/fisiología , Ejercicio Físico/fisiología , Osteoporosis Posmenopáusica/prevención & control , Femenino , Humanos , Osteoporosis Posmenopáusica/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Tibia/fisiología , Tomografía Computarizada por Rayos XRESUMEN
INTRODUCTION: Inherited bone marrow failure syndromes (IBMFSs) often have substantial phenotypic overlap, thus genotyping is often critical for establishing a diagnosis. OBJECTIVES AND METHODS: To determine the genetic characteristics and mutation profiles of IBMFSs, a comprehensive population-based study that prospectively enrols all typical and atypical cases without bias is required. The Canadian Inherited Marrow Failure Study is such a study, and was used to extract clinical and genetic information for patients enrolled up to May 2010. RESULTS: Among the 259 primary patients with IBMFS enrolled in the study, the most prevalent categories were Diamond-Blackfan anaemia (44 patients), Fanconi anaemia (39) and Shwachman-Diamond syndrome (35). The estimated incidence of the primary IBMFSs was 64.5 per 10(6) births, with Fanconi anaemia having the highest incidence (11.4 cases per 10(6) births). A large number of patients (70) had haematological and non-haematological features that did not fulfil the diagnostic criteria of any specific IBMFS category. Disease-causing mutations were identified in 53.5% of the 142 patients tested, and in 16 different genes. Ten novel mutations in SBDS, RPL5, FANCA, FANCG, MPL and G6PT were identified. The most common mutations were nonsense (31 alleles) and splice site (28). Genetic heterogeneity of most IBMFSs was evident; however, the most commonly mutated gene was SBDS, followed by FANCA and RPS19. CONCLUSION: From this the largest published comprehensive cohort of IBMFSs, it can be concluded that recent advances have led to successful genotyping of about half of the patients. Establishing a genetic diagnosis is still challenging and there is a critical need to develop novel diagnostic tools.
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Proteína del Grupo de Complementación A de la Anemia de Fanconi/genética , Hemoglobinuria Paroxística/genética , Mutación , Proteínas/genética , Proteínas Ribosómicas/genética , Alelos , Anemia Aplásica , Anemia de Diamond-Blackfan/genética , Enfermedades de la Médula Ósea/genética , Trastornos de Fallo de la Médula Ósea , Estudios de Cohortes , Insuficiencia Pancreática Exocrina/genética , Anemia de Fanconi/genética , Pruebas Genéticas , Humanos , Lipomatosis/genética , Estudios Prospectivos , Síndrome de Shwachman-DiamondRESUMEN
BACKGROUND: There is uncertainty whether low-risk episodes of febrile neutropaenia (FN) in adult cancer patients are best managed in the in- or outpatient setting. METHODS: A Monte Carlo cost-utility model was created to compare four treatment strategies for low-risk FN: (1) treatment in hospital with intravenous antibiotics (HospIV); (2) early discharge after 48 h in-patient observation, followed by oral outpatient treatment (EarlyDC); (3) outpatient management with IV antibiotics (HomeIV); and (4) outpatient management with oral antibiotics (HomePO). The model used a health-care payer perspective and a time horizon of one FN episode. Outcome measures were quality-adjusted FN episodes (QAFNE), costs (Canadian dollars) and incremental cost-effectiveness ratios (ICER). Parameter uncertainty was assessed with probabilistic sensitivity analyses. RESULTS: HomePO was cost saving ($3470 vs $4183), but less effective (0.65 QAFNE vs 0.72 QAFNE) than HomeIV. The corresponding ICER was $10,186 per QAFNE. Both EarlyDC ($6115; 0.66 QAFNE) and HospIV ($13,557; 0.62 QAFNE) were dominated strategies. At a willingness-to-pay (WTP) threshold of $4,000 per QAFNE, HomePO and HomeIV were cost effective in 54 and 38% of simulations, respectively. INTERPRETATION: For adult cancer patients with an episode of low-risk FN, treatment in hospital is more expensive and less effective than outpatient strategies.