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2.
Reprod Sci ; 27(2): 513-522, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31925771

RESUMO

The intrauterine environment can have a significant impact on fetal and maternal well-being, both during pregnancy and in later life. We aimed to identify how fetal sex and maternal body mass index (BMI) influence insulin resistance and metabolic function during pregnancy with maternal BMI > 25 kg/m2. This secondary analysis assessed data from the PEARS-randomized controlled trial that recruited pregnant women with body mass indexes 25-39.9 kg/m2. Longitudinal measurements of maternal and fetal insulin resistance and metabolic function were recorded throughout pregnancy. Regression models tested the effects of fetal sex and maternal BMI on markers of metabolic function and insulin regulation. A total of 484 women and their newborns (252 (52%) males vs. 232 (48%) females) were included in the analysis. A total of 333 (69%) women were overweight and 151 (31%) were obese. Male newborns were heavier and larger than females, and had a higher rate of instrumental delivery. Males had a lower LDL, but no other markers of insulin resistance or metabolic function were affected by fetal sex. Women with obesity had elevated markers of insulin resistance and metabolic dysfunction compared with women that were overweight, but maternal BMI did not impact these variables in the fetus. Fetal sex did not impact maternal and fetal metabolic parameters in women with BMI > 25 kg/m2. However, a higher BMI caused increasingly deranged maternal blood lipid concentrations and markers of insulin resistance as pregnancy progressed. Lipid monitoring and interventions to reduce lipids during pregnancy therefore require further evaluation.

3.
J Matern Fetal Neonatal Med ; 33(5): 707-711, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29996681

RESUMO

Objective: To determine if an elevated fetal umbilical artery Doppler pulsatility index is associated with abnormal respiratory function and atopy in children aged 12 years.Methods: This prospective case-control study compared children that had an elevated fetal umbilical artery Doppler pulsatility index (>90th centile) to those with a normal pulsatility index (<90th centile). All subjects were delivered at full-term and with appropriate growth for gestational age. Outcome measures included; (i) presence of asthma and/or atopy; (ii) spirometry measurements and (iii) serum C-reactive protein and leptin. Multiple regression was used to account for parental smoking, childhood age, gender and socioeconomic status.Results: 174 children with an average age of 12.1 (±0.6 SD), 48% of who were male were included in the analysis. Of the 174, 99 (57%) were in the normal umbilical artery Doppler pulsatility index group and 75 (43%) elevated umbilical artery Doppler pulsatility index groups. The overall proportion of subjects with asthma was 28% (48/174) and atopy 56% (98/174). No association was found between elevated fetal umbilical artery Doppler pulsatility index and asthma (p = .47) or atopy (p = .75) at age 12 years. Similarly there was no association between FEV1(%) (p = .96), forced vital capacity (FVC)(%) (p = .98), elevated serum C-reactive protein (p = .69) or leptin (p = .20) and an elevated fetal umbilical artery Doppler pulsatility index.Conclusions: An elevated umbilical artery Doppler at 28-weeks gestation in the absence of prematurity or fetal growth restriction is not associated with altered respiratory function or the presence of atopy in children aged 12 years. These findings support the theory that such disease has a multifactorial pathophysiology.

4.
Health Informatics J ; : 1460458219884195, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31702409

RESUMO

Demand for the use of mobile apps in mental health interventions has grown in recent years, particularly among adolescents who experience elevated levels of distress. However, there is a scarcity of evidence for the effectiveness of these tools within this population. The aim of this study was to test the effectiveness of CopeSmart, a mental health mobile app, using a multicentre cluster randomised controlled trial design. Participants were 15-18-years-olds (N = 560) recruited from 10 schools randomly assigned to an intervention or control condition. Intervention participants used the app over a 4-week period. Multi-level modelling analyses revealed no significant changes in the intervention group from pre-test to post-test, when compared to the control group, in terms of emotional distress, well-being, emotional self-awareness or coping strategies. Findings suggest that a 4-week app-based intervention may not be enough to elicit intra-personal changes in mental health outcomes in a general adolescent population.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31613323

RESUMO

BACKGROUND: Use of anticholinergic medication is associated with an increased risk of cognitive impairment and/or dementia. Despite this, the impact of continuing medication with anticholinergic properties in those diagnosed with Alzheimer Disease (AD) is not clear. METHODS: Analysis of data from NILVAD, an 18-month randomised controlled trial of Nilvadipine in AD. Effects of ongoing Anticholinergic Cognitive Burden (ACB) on cognition (ADAS-Cog: Alzheimer's Disease Cog Subsection) and dementia severity (CDR-sb: Clinical Dementia Rating - Sum of Boxes/DAD: Disability Assessment for Dementia) over 18 months was evaluated adjusting for important clinical covariates. RESULTS: Just over one-quarter (27.90%, n = 142/510) of patients with mild to moderate AD were prescribed a potential/definite anticholinergic. Whilst ACB score was not associated with greater progression on the ADAS-Cog/CDR-sb over time, a higher total ACB predicted greater dementia severity on the DAD, which persisted after robust covariate adjustment (ß Coef: -1.53 95% CI: -2.83 - -0.23, p = 0.021). There was a significant interaction between APOE ɛ4 status and ACB score, with carriers experiencing greater progression on both the CDR-Sb (ß Coef: 0.36 95% CI: 0.05 - 0.67, p = 0.021) and DAD (ß Coef: -3.84 95% CI: -7.65 - 0.03, p = 0.049). CONCLUSIONS: Ongoing use of anticholinergic medication was associated with greater dementia progression on the DAD, but not the CDR-sb. APOE ɛ4 carriers may be particularly vulnerable to the effect of ongoing anticholinergic medication on dementia severity, with significant APOE ɛ4 x ACB score interactions demonstrated on both the DAD and CDR-sb.

6.
BMJ Open ; 9(8): e025620, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31375602

RESUMO

OBJECTIVES: To identify if maternal educational attainment is a prognostic factor for gestational weight gain (GWG), and to determine the differential effects of lifestyle interventions (diet based, physical activity based or mixed approach) on GWG, stratified by educational attainment. DESIGN: Individual participant data meta-analysis using the previously established International Weight Management in Pregnancy (i-WIP) Collaborative Group database (https://iwipgroup.wixsite.com/collaboration). Preferred Reporting Items for Systematic reviews and Meta-Analysis of Individual Participant Data Statement guidelines were followed. DATA SOURCES: Major electronic databases, from inception to February 2017. ELIGIBILITY CRITERIA: Randomised controlled trials on diet and physical activity-based interventions in pregnancy. Maternal educational attainment was required for inclusion and was categorised as higher education (≥tertiary) or lower education (≤secondary). RISK OF BIAS: Cochrane risk of bias tool was used. DATA SYNTHESIS: Principle measures of effect were OR and regression coefficient. RESULTS: Of the 36 randomised controlled trials in the i-WIP database, 21 trials and 5183 pregnant women were included. Women with lower educational attainment had an increased risk of excessive (OR 1.182; 95% CI 1.008 to 1.385, p =0.039) and inadequate weight gain (OR 1.284; 95% CI 1.045 to 1.577, p =0.017). Among women with lower education, diet basedinterventions reduced risk of excessive weight gain (OR 0.515; 95% CI 0.339 to 0.785, p = 0.002) and inadequate weight gain (OR 0.504; 95% CI 0.288 to 0.884, p=0.017), and reduced kg/week gain (B -0.055; 95% CI -0.098 to -0.012, p=0.012). Mixed interventions reduced risk of excessive weight gain for women with lower education (OR 0.735; 95% CI 0.561 to 0.963, p=0.026). Among women with high education, diet based interventions reduced risk of excessive weight gain (OR 0.609; 95% CI 0.437 to 0.849, p=0.003), and mixed interventions reduced kg/week gain (B -0.053; 95% CI -0.069 to -0.037,p<0.001). Physical activity based interventions did not impact GWG when stratified by education. CONCLUSIONS: Pregnant women with lower education are at an increased risk of excessive and inadequate GWG. Diet based interventions seem the most appropriate choice for these women, and additional support through mixed interventions may also be beneficial.

7.
Cochrane Database Syst Rev ; 7: CD012764, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31323120

RESUMO

BACKGROUND: Mobilization of community first responders (CFRs) to the scene of an out-of-hospital cardiac arrest (OHCA) event has been proposed as a means of shortening the interval from occurrence of cardiac arrest to performance of cardiopulmonary resuscitation (CPR) and defibrillation, thereby increasing patient survival. OBJECTIVES: To assess the effect of mobilizing community first responders (CFRs) to out-of-hospital cardiac arrest events in adults and children older than four weeks of age, in terms of survival and neurological function. SEARCH METHODS: We searched the following databases for relevant trials in January 2019: CENTRAL, MEDLINE (Ovid SP), Embase (Ovid SP), and Web of Science. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov, and we scanned the abstracts of conference proceedings of the American Heart Association and the European Resuscitation Council. SELECTION CRITERIA: We included randomized and quasi-randomized trials (RCTs and q-RCTs) that compared routine emergency medical services (EMS) care versus EMS care plus mobilization of CFRs in instances of OHCA.Trials with randomization by cluster were eligible for inclusion, including cluster-design studies with intervention cross-over.In some communities, the statutory ambulance service/EMS is routinely provided by the local fire service. For the purposes of this review, this group represents the statutory ambulance service/EMS, as distinct from CFRs, and was not included as an eligible intervention.We did not include studies primarily focused on opportunistic bystanders. Individuals who were present at the scene of an OHCA event and who performed CPR according to telephone instruction provided by EMS call takers were not considered to be CFRs.Studies primarily assessing the impact of specific additional interventions such as administration of naloxone in narcotic overdose or adrenaline in anaphylaxis were also excluded.We included adults and children older than four weeks of age who had experienced an OHCA. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed all titles and abstracts received to assess potential eligibility, using set inclusion criteria. We obtained and examined in detail full-text copies of all papers considered potentially eligible, and we approached authors of trials for additional information when necessary. We summarized the process of study selection in a PRISMA flowchart.Three review authors independently extracted relevant data using a standard data extraction form and assessed the validity of each included trial using the Cochrane 'Risk of bias' tool. We resolved disagreements by discussion and consensus.We synthesized findings in narrative fashion due to the heterogeneity of the included studies. We used the principles of the GRADE system to assess the certainty of the body of evidence associated with specific outcomes and to construct a 'Summary of findings' table. MAIN RESULTS: We found two completed studies involving a total of 1136 participants that ultimately met our inclusion criteria. We also found one ongoing study and one planned study. We noted significant heterogeneity in the characteristics of interventions and outcomes measured or reported across these studies, thus we could not pool study results.One completed study considered the dispatch of police and fire service CFRs equipped with automatic external defibrillators (AEDs) in an EMS system in Amsterdam and surrounding areas. This study was an RCT with allocation made by cluster according to non-overlapping geographical regions. It was conducted between 5 January 2000 and 5 January 2002. All participants were 18 years of age or older and had experienced witnessed OHCA. The study found no difference in survival at hospital discharge (odds ratio (OR) 1.3, 95% confidence interval (CI) 0.8 to 2.2; 1 RCT; 469 participants; low-certainty evidence), despite the observation that all 72 incidences of defibrillation performed before EMS arrival occurred in the intervention group (OR and 95% CI - not applicable; 1 RCT; 469 participants; moderate-certainty evidence). This study reported increased survival to hospital admission in the intervention group (OR 1.5, 95% CI 1.1 to 2.0; 1 RCT; 469 participants; moderate-certainty evidence).The second completed study considered the dispatch of nearby lay volunteers in Stockholm, Sweden, who were trained to perform cardiopulmonary resuscitation (CPR). This represented a supplementary CFR intervention in an EMS system where police and fire services were already routinely dispatched to OHCA in addition to EMS ambulances. This study, an RCT, included both witnessed and unwitnessed OHCA and was conducted between 1 April 2012 and 1 December 2013. Participants included adults and children eight years of age and older. Researchers found no difference in 30-day survival (OR 1.34, 95% CI 0.79 to 2.29; 1 RCT; 612 participants; low-certainty evidence), despite a significant increase in CPR performed before EMS arrival (OR 1.49, 95% CI 1.09 to 2.03; 1 RCT; 665 participants; moderate-certainty evidence).Neither of the included completed studies considered neurological function at hospital discharge or at 30 days, measured by cerebral performance category or by any other means. Neither of the included completed studies considered health-related quality of life. The overall certainty of evidence for the outcomes of included studies was low to moderate. AUTHORS' CONCLUSIONS: Moderate-certainty evidence shows that context-specific CFR interventions result in increased rates of CPR or defibrillation performed before EMS arrival. It remains uncertain whether this can translate to significantly increased rates of overall patient survival. When possible, further high-quality RCTs that are adequately powered to measure changes in survival should be conducted.The included studies did not consider survival with good neurological function. This outcome is likely to be important to patients and should be included routinely wherever survival is measured.We identified one ongoing study and one planned trial whose results once available may change the results of this review. As this review was limited to randomized and quasi-randomized trials, we may have missed some important data from other study types.


Assuntos
Reanimação Cardiopulmonar/métodos , Serviços Médicos de Emergência , Socorristas , Parada Cardíaca Extra-Hospitalar/terapia , Adulto , Criança , Cardioversão Elétrica , Humanos , Parada Cardíaca Extra-Hospitalar/mortalidade , Qualidade da Assistência à Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida
8.
J Electromyogr Kinesiol ; 47: 49-56, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31121550

RESUMO

PURPOSE: This study investigated the effect of knee joint angle and age on torque steadiness of knee extensors (KE) at varying submaximal isometric contractions. METHODS: 22 young (24.0 ±â€¯2.6 years; 11 women) and 22 older (69.4 ±â€¯2.4 years; 10 women) healthy men and women participated. Maximal voluntary isometric contraction (MVIC) of the KE and flexors was examined at 90° and 60° of knee flexion (0°â€¯= full extension). At each angle, participants performed KE isometric contractions (20%, 50% and 80% MVIC) to evaluate torque steadiness, whereas surface EMG was concurrently acquired from the vastus lateralis and biceps femoris muscles. RESULTS: Age-related impairment in torque steadiness was observed only at 20% MVIC (p < 0.01). A lower level of steadiness (p < 0.001) with a higher level of agonist and antagonist activations (all p < 0.01) was observed at 90° of knee flexion in comparison with contractions at 60°. Young participants were less steady when performing contractions at 90° compared with contractions at 60° of flexion (p < 0.001), whereas there was no difference for older participants. Furthermore, a significant effect of agonist activation and antagonist co-activation on torque steadiness was observed, but only in young participants (all p < 0.05). CONCLUSIONS: These findings suggest that: (1) knee joint angle affects torque steadiness differently in young and older individuals; (2) an age-related impairment in steadiness was only presented at the lowest considered contraction intensity; and (3) the muscle activation responses were not associated with steadiness in older individuals.


Assuntos
Envelhecimento/fisiologia , Eletromiografia/métodos , Articulação do Joelho/fisiologia , Amplitude de Movimento Articular/fisiologia , Torque , Adulto , Idoso , Feminino , Músculos Isquiotibiais/fisiologia , Humanos , Contração Isométrica/fisiologia , Masculino , Músculo Esquelético/fisiologia , Músculo Quadríceps/fisiologia , Adulto Jovem
9.
J Proteome Res ; 18(6): 2613-2623, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31074629

RESUMO

Novel metabolomic profiling techniques combined with traditional biomarkers provide knowledge of mechanisms underlying metabolic health. Twin studies describe the impact of genes and environment on variation in traits. This study aims to identify relationships between traditional markers of metabolic health and the plasma metabolomic profile using a twin modeling approach and determine whether covariation is caused by shared genetic and environmental factors. Using a classic twin design, this study examined covariation between anthropometric, clinical chemistry, and metabolomic profiles. Cholesky decomposition modeling was used to determine the genetic and environmental path coefficients through successive anthropometric and clinical chemistry traits onto metabolomic derived metabolites. This study shows that WC, TAG, and a metabolomic signature composed of 7 metabolites are inter-related, and that covariation can be attributed to common genetic, shared and unique environmental factors as well as unique environmental factors specific to the metabolite. This quantitative modeling connecting the traditional anthropometry and clinical chemistry traits with the more recent and potentially more sensitive metabolomic profile approach may provide further insight on the pleiotropic genes or modifiable environmental factors influencing variation in metabolic health.

10.
Eur J Obstet Gynecol Reprod Biol ; 236: 121-126, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30904815

RESUMO

OBJECTIVE: It has been proposed that the Robson Ten-Group Classification System be used as a global standard for assessing, monitoring and comparing cesarean delivery (CD) rates within and between maternity services. Our objective was to compare the change of CD rates within the 10-Group Classification System in our institution over 10 years. STUDY DESIGN: From 2005-2014 inclusive data was collected prospectively and all women were classified using the obstetric concepts and parameters described in the Ten-Group Classification System. Linear regression and weighted Least Squares regression analyses were used to analyze trends over time. RESULTS: During 2005-2014 inclusive, 88,004 mothers delivered 89,649 babies ≥500 g. Over the 10 year period there was an increase in CD rate from 18.3% to 23.5%, with a linear increase in CD rate by 0.6% annually (95% CI:0.52, 0.75;p < 0.001). The main contribution to the increase in the CD rate was Group 2a (induced single cephalic nulliparous women at term), Group 2b (pre-labor single cephalic nulliparous women at term) and Group 5 (single cephalic multiparous women at term with a previous CD). No increase in CD rate was noted in Group 1 (single cephalic nulliparous women presenting in spontaneous labor at term). The percentage of women ≥35 years of age increased from 28.4% to 39.8% over the study period (0.98% per year; 95% CI:0.64, 1.33;p < 0.001). CONCLUSION: The driving force for the increase in CD in the National Maternity Hospital has been induction of labor and pre-labor CD in nulliparous women with a single cephalic pregnancy at term. This inevitably results in a larger population of women with a previous CD and therefore a secondary contribution to the increase in the overall CD rate.


Assuntos
Cesárea/tendências , Maternidades , Trabalho de Parto Induzido/tendências , Trabalho de Parto , Adulto , Feminino , Humanos , Irlanda , Gravidez , Nascimento a Termo
11.
J Matern Fetal Neonatal Med ; : 1-7, 2019 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-30614328

RESUMO

BACKGROUND: The growth of the fetus is a complex process, influenced by genetic and environmental factors. Longitudinal patterns of fetal growth are required to fully understand this process, however to date, a paucity of data exists in this area. OBJECTIVE: To identify fetal growth trajectories in-utero and to assess their association with maternal and child characteristics up to 5 years postnatal. METHODS: Data from 781 mother-child pairs from the ROLO longitudinal birth cohort study were analyzed. The ROLO study was a randomized control trial of a low glycemic index diet in pregnancy to prevent recurrence of macrosomia. Fetal ultrasound measurements were recorded at 20 and 34 weeks gestation, and birth weight was recorded. Abdominal circumference (AC), weight (fetal weight, or birth weight), a standardized proxy for length (femur length or birth length, individually standardized), and AC:length ratio were examined for trajectory classes using latent class trajectory mixture models. Two-, three-, four-, and five-class models were evaluated for fit, using a linear (first order) trajectory over three time-points. ANOVA and chi-square tests were applied to test associations between trajectory membership and maternal and child characteristics up to age 5. RESULTS: For AC, two fetal growth trajectories were identified, with 29% of participants on a "slow" trajectory and 71% on a "fast" trajectory. Those on a fast trajectory had higher rates of maternal impaired glucose tolerance (28.7 versus 16.5%, p<.001) and higher rates of mean child 5-year body mass index (BMI) centiles (64th versus 58th centile, p<.05) compared to those on the slow trajectory. For estimated fetal weight, four trajectories were identified, with 4% on a "very-slow" trajectory, 63% in a "moderate-slow" trajectory, 30% in a "moderate-fast" trajectory and 3% on a "very-fast" trajectory. Mothers with a fetus on the fastest trajectory had higher antenatal serum glucose levels (p<.05), and were more likely to deliver by cesarean section (59.1 versus 20%, p<.001). At 5 years of age, children on the fastest growth trajectory had the highest mean BMI centile (86th versus 60th centile, p<.05). CONCLUSIONS: This study shows that specific fetal growth trajectories may be associated with maternal serum glucose concentrations during pregnancy, mode of delivery and child BMI at 5 years of age. Diet and lifestyle measures that target maternal glucose levels during pregnancy may have lifelong benefits for children's BMI. Identifying those on an accelerated growth trajectory during fetal life provides a unique opportunity for antenatal and infant interventions that may have long-lasting health benefits.

12.
Br J Nutr ; 120(11): 1252-1261, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30484757

RESUMO

Infant protein intake has been associated with child growth, however, research on maternal protein intake during pregnancy is limited. Insulin-like growth factors (IGF) play a role in early fetal development and maternal protein intake may influence child body composition via IGF-1. The aim of this study was to investigate the association of maternal protein intake throughout pregnancy on cord blood IGF-1 and child body composition from birth to 5 years of age. Analysis was carried out on 570 mother-child dyads from the Randomised cOntrol trial of LOw glycaemic index diet study. Protein intake was recorded using 3-d food diaries in each trimester of pregnancy and protein intake per kg of maternal weight (g/d per kg) was calculated. Cord blood IGF-1 was measured at birth. Infant anthropometry was measured at birth, 6 months, 2 and 5 years of age. Mixed modelling, linear regression, and mediation analysis were carried out. Birth weight centiles were positively associated with early-pregnancy protein intake (g/d per kg), while weight centiles from 6 months to 5 years were negatively associated (B=-21·6, P<0·05). These associations were not mediated by IGF-1. Our findings suggest that high protein intake in early-pregnancy may exert an in utero effect on offspring body composition with a higher weight initially at birth but slower growth rates into childhood. Further research is needed to elucidate the exact mechanisms by which dietary protein modulates fetal growth.


Assuntos
Proteínas na Dieta , Índice Glicêmico , Fator de Crescimento Insulin-Like I/análise , Fenômenos Fisiológicos da Nutrição Materna , Adulto , Antropometria , Peso ao Nascer , Composição Corporal , Índice de Massa Corporal , Pré-Escolar , Registros de Dieta , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Idade Materna , Gravidez
13.
PLoS Med ; 15(9): e1002660, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30248105

RESUMO

BACKGROUND: This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated anti-inflammatory and anti-tau activity in preclinical studies, properties that could have disease-modifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease. METHODS AND FINDINGS: NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged >50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of ≥12 and <27. Participants were randomly assigned to 8 mg sustained-release nilvadipine or matched placebo. The a priori defined primary outcome was progression on the Alzheimer's Disease Assessment Scale Cognitive Subscale-12 (ADAS-Cog 12) in the modified intention-to-treat (mITT) population (n = 498), with the Clinical Dementia Rating Scale sum of boxes (CDR-sb) as a gated co-primary outcome, eligible to be promoted to primary end point conditional on a significant effect on the ADAS-Cog 12. The analysis set had a mean age of 73 years and was 62% female. Baseline demographic and Alzheimer disease-specific characteristics were similar between treatment groups, with reported mean of 1.7 years since diagnosis and mean SMMSE of 20.4. The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADAS-Cog 12 on placebo was 0.79 (95% CI, -0.07-1.64) at 13 weeks, 6.41 (5.33-7.49) at 52 weeks, and 9.63 (8.33-10.93) at 78 weeks and on nilvadipine was 0.88 (0.02-1.74) at 13 weeks, 5.75 (4.66-6.85) at 52 weeks, and 9.41 (8.09-10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid. CONCLUSIONS: The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease. TRIAL REGISTRATION: Clinicaltrials.gov NCT02017340, EudraCT number 2012-002764-27.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Nifedipino/análogos & derivados , Nootrópicos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/psicologia , Progressão da Doença , Método Duplo-Cego , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nifedipino/uso terapêutico , Resultado do Tratamento
14.
Int J Mol Sci ; 19(6)2018 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-29890775

RESUMO

Signal transducers and activator of transcription (STAT)-3 is activated in cancers, where it promotes growth, inflammation, angiogenesis, and inhibits apoptosis. Tissue microarrays were generated using tissues from 154 patients, with oesophageal adenocarcinoma (OAC) (n = 116) or squamous cell carcinoma (SCC) (n = 38) tumours. The tissues were stained for pSTAT3 and IL-6R using immunohistochemistry. The OE33 (OAC) and OE21 (SCC) cell lines were treated with the STAT3 inhibitor, STATTIC. The Univariate cox regression analysis revealed that a positive pSTAT3 in SCC was adversely associated with survival (Hazard ratio (HR) 6.382, 95% CI 1.266⁻32.184), while a protective effect was demonstrated with the higher pSTAT3 levels in OAC epithelium (HR 0.74, 95% CI 0.574⁻0.953). The IL-6R intensity levels were higher in the SCC tumours compared with the OAC tumours for the core and leading edge tumour tissue. The pSTAT3 levels correlated positively with the IL-6R levels in both the OAC and SCC. The treatment of OE21 and OE33 cells with the STAT3 inhibitor STATTIC in vitro resulted in decreased survival, proliferation, migration, and increased apoptosis. The pSTAT3 expression was associated with adverse survival in SCC, but not in the OAC patients. The inhibition of STAT3 in both of the tumour subtypes resulted in alterations in the survival, proliferation, migration, and apoptosis, suggesting a potential role for therapeutically targeting STAT3.


Assuntos
Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Fator de Transcrição STAT3/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Apoptose , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Humanos , Fosforilação , Modelos de Riscos Proporcionais , Receptores de Interleucina-6/metabolismo , Análise de Sobrevida , Análise Serial de Tecidos
15.
Obstet Gynecol ; 131(5): 818-826, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29630009

RESUMO

OBJECTIVE: To evaluate the effect of a healthy lifestyle package (an antenatal behavior change intervention supported by smartphone application technology) on the incidence of gestational diabetes mellitus (GDM) in overweight and obese women. METHODS: Women with body mass indexes (BMIs) 25-39.9 were enrolled into this randomized controlled trial. The intervention consisted of specific dietary and exercise advice that addressed behavior change supported by a tailor-designed smartphone application. Women in the control group received usual care. The primary outcome was the incidence of GDM at 28-30 weeks of gestation. To reduce GDM from 15% to 7.2%, we estimated that 506 women would be required to have 80% power to detect this effect size at a significance of .05, that is, 253 in each group. RESULTS: Between March 2013 and February 2016, 565 women were recruited with a mean BMI of 29.3 and mean gestational age of 15.5 weeks. The incidence of GDM did not differ between the two groups, 37 of 241 (15.4%) in the intervention group compared with 36 of 257 (14.1%) in the control group (relative risk 1.1, 95% CI 0.71-1.66, P=.71). CONCLUSIONS: A mobile health-supported behavioral intervention did not decrease the incidence of GDM. CLINICAL TRIAL REGISTRATION: ISRCTN registry, https://www.isrctn.com/, ISRCTN29316280.


Assuntos
Controle Comportamental/métodos , Diabetes Gestacional , Exercício/psicologia , Obesidade , Complicações na Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal/fisiologia , Smartphone , Adulto , Índice de Massa Corporal , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/prevenção & controle , Diabetes Gestacional/psicologia , Exercício/fisiologia , Feminino , Comportamentos Relacionados com a Saúde , Estilo de Vida Saudável , Humanos , Incidência , Aplicativos Móveis , Obesidade/diagnóstico , Obesidade/psicologia , Obesidade/terapia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/psicologia , Complicações na Gravidez/terapia , Resultado da Gravidez/epidemiologia , Cuidado Pré-Natal/métodos
16.
Eur J Obstet Gynecol Reprod Biol ; 224: 188-191, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29614445

RESUMO

BACKGROUND: The rate of caesarean sections at full cervical dilatation with their high risk of morbidity continues to rise mirroring the overall increase in caesarean section rates internationally. OBJECTIVES: The objectives of this study were to determine the rate of full dilatation caesarean section in a tertiary referral unit and evaluate key labour, maternal and fetal factors potentially linked to those deliveries. We also assessed maternal and fetal morbidity at full dilatation sections. Where possible, these were compared with successful operative vaginal deliveries carried out in theatre to determine key differences. STUDY DESIGN: Retrospective cohort study. We reviewed the rate of full dilatation caesarean section over a 10-year period. We analysed deliveries (caesarean sections or operative vaginal deliveries) in single cephalic pregnancies ≥34 weeks with contemporaneously collected data from our unit's electronic database for 2015. RESULTS: The rate of full dilatation caesarean section increased by over a third in the ten-year period (56/6947 (0.80%) vs 92/7378 (1.24%), p = 0.01). Of 84 full dilatation caesarean sections who met the inclusion criteria, 63 (75%) were nulliparous and the mean maternal age was 33 (±5) years. Oxytocin was used in the second stage in less than half of second stage caesarean sections (22 out of a recorded 57, 38.6%). There were more fetal head malposition (occipito-posterior, or occipito-transverse) at full dilatation caesarean section compared to successful operative vaginal deliveries (41/46 (89.1%) vs 2/21 (9.5), p < 0.001). The rate of significant postpartum haemorrhage (defined as estimated blood loss ≥1000 ml) was similar in both full dilatation caesarean section and operative vaginal deliveries. There was no difference in the mean birthweight at full dilatation caesarean sections compared to operative vaginal delivery (3.88 kg (2.80-5.33 kg) vs 3.48 kg (1.53-4.40 kg)). There was no difference in neonatal morbidity. CONCLUSION: Fetal head malposition is associated with a higher risk of full dilatation caesarean section. Interestingly, maternal and fetal morbidity were similar between full dilatation caesarean sections and anticipated difficult operative vaginal deliveries carried out in theatre. The management of labour in terms of the decision to use oxytocin judiciously in hope of correcting inefficient uterine contractions and continuous labour ward training, particularly the diagnosis of malposition and its correction may be beneficial in reducing the rate of full dilation caesarean sections.


Assuntos
Cesárea/estatística & dados numéricos , Segunda Fase do Trabalho de Parto , Adulto , Feminino , Humanos , Gravidez , Estudos Retrospectivos
17.
Trials ; 19(1): 194, 2018 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-29566744

RESUMO

BACKGROUND: Acceptance and Commitment Therapy (ACT) is a form of cognitive behavioural therapy, which may be beneficial for people with chronic pain. The approach aims to enhance daily functioning through increased psychological flexibility. Whilst the therapeutic model behind ACT appears well suited to chronic pain, there is a need for further research to test its effectiveness in clinical practice, particularly with regards to combining ACT with physical exercise. METHODS/DESIGN: This prospective, two-armed, parallel-group, single-centre randomised controlled trial (RCT) will assess the effectiveness of a combined Exercise and ACT programme, in comparison to supervised exercise for chronic pain. One hundred and sixty patients, aged 18 years and over, who have been diagnosed with a chronic pain condition by a physician will be recruited to the trial. Participants will be individually randomised to one of two 8-week, group interventions. The combined group will take part in weekly psychology sessions based on the ACT approach, in addition to supervised exercise classes led by a physiotherapist. The control group will attend weekly supervised exercise classes but will not take part in an ACT programme. The primary outcome will be pain interference at 12-week follow-up, measured using the Brief Pain Inventory-Interference Scale. Secondary outcomes will include self-reported pain severity, self-perception of change, patient satisfaction, quality of life, depression, anxiety and healthcare utilisation. Treatment process measures will include self-efficacy, pain catastrophising, fear avoidance, pain acceptance and committed action. Physical activity will be measured using Fitbit ZipTM activity trackers. Both groups will be followed up post intervention and again after 12 weeks. Estimates of treatment effects at follow-up will be based on an intention-to-treat framework, implemented using a linear mixed-effects model. Individual and focus group qualitative interviews will be undertaken with a purposeful sample of participants to explore patient experiences of both treatments. DISCUSSION: To our knowledge, this will be the first RCT to examine whether combining exercise with ACT produces greater benefit for patients with chronic pain, compared to a standalone supervised exercise programme. TRIAL REGISTRATION: www.ClinicalTrials.gov, ID: NCT03050528 . Registered on 13 February 2017.


Assuntos
Dor Crônica/terapia , Terapia Cognitivo-Comportamental/métodos , Terapia por Exercício/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Dor Crônica/psicologia , Coleta de Dados , Interpretação Estatística de Dados , Exercício , Humanos , Satisfação do Paciente , Qualidade de Vida , Tamanho da Amostra
18.
BMJ Open ; 8(2): e017013, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29463584

RESUMO

OBJECTIVE: The association of maternal pregnancy diet with offspring asthma risk have been reported. However, literature on longitudinal patterns of asthma risk relative to intrauterine nutrient exposure is limited. We aimed to establish whether vegetable, oily fish and vitamin D intake during pregnancy are associated with childhood asthma risk over a 10-year period in the Irish Republic. DESIGN: Mother-child pairs (n=897) from the Lifeways prospective birth cohort, with data on nutrient intake during pregnancy and asthma status, respectively, were eligible for inclusion in the analysis. Data on socioeconomic and morbidity indicators over 10 years of follow-up on mothers and the index child were collected through self-administered questionnaires. Asthma status as diagnosed by the general practitioner at any time point over 10 years was related to maternal vegetable, oily fish and vitamin D intake during pregnancy, while adjusting for gestational age, socioeconomic status, smoking at delivery, breast feeding, season of birth and supplement use. Data were modelled with a marginal model on correlated observations over time within individuals. RESULTS: In the fully adjusted model, asthma was inversely associated with higher daily average intake of oily fish (OR 0.23 per serving/day, 95% CI 0.04 to 1.41) and of vegetables (OR 0.96 per serving/day, 95% CI 0.88 to 1.05), but the confidence limits overlapped 1. A higher daily vitamin D intake was associated with reduced odds of asthma (OR 0.93 per µg/day, 95% CI 0.89 to 0.98). CONCLUSION: This analysis suggests higher daily average intake of vitamin D in pregnancy is associated with asthma risk in offspring over the first 10 years of life.


Assuntos
Asma/epidemiologia , Dieta , Mães , Asma/etiologia , Criança , Pré-Escolar , Suplementos Nutricionais , Feminino , Óleos de Peixe/administração & dosagem , Seguimentos , Humanos , Irlanda , Análise Multivariada , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Estudos Prospectivos , Fatores de Risco , Verduras , Vitamina D/administração & dosagem
19.
SSM Popul Health ; 4: 100-116, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29349279

RESUMO

Exposure to deprived socioeconomic conditions during the peri-conception and early childhood periods can have a negative long-term impact on individuals' health and that of their progeny. We aimed to examine whether relatives' birth period affected index-child (grand-child) birthweight status in the Lifeways Cross-Generation Cohort in the Republic of Ireland. Participants were 943 mothers and offspring, 890 fathers, 938 maternal grandmothers (MGM), 700 maternal grandfathers (MGF) 537 paternal grandmothers (PGM) and 553 paternal grandfathers (PGF). Index-child's birthweight was sex-for-gestational age standardised (UK1990 population), and then classified into low birthweight (≤10th percentile) and high-birthweight (≥90th percentile) and compared against normal-birthweight (>10th to <90th percentiles). Four adult birth periods were considered: The Free State (FS, 1916-1938); Emergency Act (EA, 1939-1946); Post-World War-II Baby-Boom (PWWII-BB, 1947-1964); and Modern Ireland (MI, 1964 onwards). Logistic regression was used to assess the crude and adjusted relationship between index-child's birthweight status and relatives' birth periods. Overall, there were 8.7% (n=82) index-children in the low-birthweight category, 77.9% (n=735) and 13.4% (n=126) within the normal and high birthweight groups respectively. Index-children whose mothers were born during the PWWII-BB had higher birthweight infants (Crude OR(COR)=1.81 (1.08-3.03) which remained the case only for male index-children when adjusted for co-variables (Adjusted OR(AOR)=4.61(1.71-12.42)). Parents' combined PWWII-BB birth period was positively associated with male index-child higher birthweight, even adjusted for maternal characteristics (AOR=4.60(1.69-12.50)). MGFs born during the EA were more likely to have grandchildren with low birthweight after adjustment for maternal characteristics (AOR=2.45(1.03-5.85)), particularly for female index-children (AOR=4.74(1.16-19.25)). Both PGMs and PGFs born during the FS period had higher birthweight grandchildren, adjusted for maternal-related co-variables (PGM, AOR=3.23(1.21-8.63); PGF, AOR=3.93(1.11-13.96)), with the effect of PGM more evident in her granddaughter (AOR=6.53(1.25-34.04)). In conclusion, there is some evidence that period of grandparental birth is associated with their grandchildren's birthweights, suggesting that transgenerational exposures may be particular to historical context, meriting further exploration.

20.
Phys Ther ; 98(2): 95-107, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29088437

RESUMO

Background: Provider training programs are frequently underevaluated, leading to ambiguity surrounding effective intervention components. Objective: The purpose of this study was to assess the effectiveness of a training program in guiding physical therapists to deliver the Self-management of Osteoarthritis and Low back pain through Activity and Skills (SOLAS) group education and exercise intervention (ISRCTN49875385), using a communication style underpinned by self-determination theory (SDT). Design: This was an assessment of the intervention arm training program using quantitative methods. Methods: Thirteen physical therapists were trained using mixed methods to deliver the SOLAS intervention. Training was evaluated using the Kirkpatrick model: (1) Reaction-physical therapists' satisfaction with training, (2) Learning-therapists' confidence in and knowledge of the SDT-based communication strategies and intervention content and their skills in applying the strategies during training, and (3) Behavior-8 therapists were audio-recorded delivering all 6 SOLAS intervention classes (n = 48), and 2 raters independently coded 50% of recordings (n = 24) using the Health Care Climate Questionnaire (HCCQ), the Controlling Coach Behavior Scale (CCBS), and an intervention-specific measure. Results: Reaction: Physical therapists reacted well to training (median [IRQ]; min-max = 4.7; [0.5]; 3.7-5.0). Learning: Physical therapists' confidence in the SDT-based communication strategies and knowledge of some intervention content components significantly improved. Behavior: Therapists delivered the intervention in a needs-supportive manner (median HCCQ = 5.3 [1.4]; 3.9-6.0; median CCBS = 6.6 ([0.5]; 6.1-6.8; median intervention specific measure = 4.0 [1.2]; 3.2-4.9). However, "goal setting" was delivered below acceptable levels by all therapists (median 2.9 [0.9]; 2.0-4.0). Limitations: The intervention group only was assessed as part of the process evaluation of the feasibility trial. Conclusions: Training effectively guided physical therapists to be needs-supportive during delivery of the SOLAS intervention. Refinements were outlined to improve future similar training programs, including greater emphasis on goal setting.


Assuntos
Atitude do Pessoal de Saúde , Competência Clínica , Educação de Pacientes como Assunto , Fisioterapeutas/educação , Modalidades de Fisioterapia/educação , Autoeficácia , Terapia por Exercício , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Aprendizagem , Dor Lombar/terapia , Osteoartrite/terapia , Fisioterapeutas/psicologia , Autocuidado
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