Biomedical subjects

Angie Wade

Publications and source records attributed to Angie Wade.

15 recordsLinked to original sources

PubMed2006

Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests.

BACKGROUND: Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from the multiple-breath inert gas washout (MBW) technique, has been shown to detect abnormal lung function more readily than spirometry in preschool children with cystic fibrosis, but whether this holds true during infancy is unknown. OBJECTIVES: To compare the extent to which parameters derived from the MBW and the raised lung volume rapid thoraco-abdominal compression (RVRTC) techniques identify diminished airway function in infants with cystic fibrosis when compared with healthy controls. METHODS: Measurements were performed during quiet sleep, with the tidal breathing MBW technique being performed before the forced expiratory manoeuvres. RESULTS: Measurements were obtained in 39 infants with cystic fibrosis (mean (SD) age 41.4 (22.0) weeks) and 21 controls (37.0 (15.1) weeks). Infants with cystic fibrosis had a significantly higher respiratory rate (38 (10) vs 32 (5) bpm) and LCI (8.4 (1.5) vs 7.2 (0.3)), and significantly lower values for all forced expiratory flow-volume parameters compared with controls. Girls with cystic fibrosis had significantly lower forced expiratory volume (FEV(0.5) and FEF(25-75 )) than boys (mean (95% CI girls-boys): -1.2 (-2.1 to -0.3) for FEV(0.5) Z score; FEF(25-75): -1.2 (-2.2 to -0.15)). When using both the MBW and RVRTC techniques, abnormalities were detected in 72% of the infants with cystic fibrosis, with abnormalities detected in 41% using both techniques and a further 15% by each of the two tests performed. CONCLUSIONS: These findings support the view that inflammatory and/or structural changes in the airways of children with cystic fibrosis start early in life, and have important implications regarding early detection and interventions. Monitoring of early lung disease and functional status in infants and young children with cystic fibrosis may be enhanced by using both MBW and the RVRTC.

Area Under Curve↗

PubMed2006

Behaviour change in perinatal care practices among rural women exposed to a women's group intervention in Nepal [ISRCTN31137309].

BACKGROUND: A randomised controlled trial of participatory women's groups in rural Nepal previously showed reductions in maternal and newborn mortality. In addition to the outcome data we also collected previously unreported information from the subgroup of women who had been pregnant prior to study commencement and conceived during the trial period. To determine the mechanisms via which the intervention worked we here examine the changes in perinatal care of these women. In particular we use the information to study factors affecting positive behaviour change in pregnancy, childbirth and newborn care. METHODS: Women's groups focusing on perinatal care were introduced into 12 of 24 study clusters(average cluster population 7000). A total of 5400 women of reproductive age enrolled in the trial had previously been pregnant and conceived during the trial period. For each of four outcomes (attendance at antenatal care; use of a boiled blade to cut the cord; appropriate dressing of the cord; not discarding colostrum) each of these women was classified as BETTER, GOOD, BAD or WORSE to describe whether and how she changed her pre-trial practice. Multilevel multinomial models were used to identify women most responsive to intervention. RESULTS: Among those not initially following good practice, women in intervention areas were significantly more likely to do so later for all four outcomes (OR 1.92 to 3.13). Within intervention clusters, women who attended groups were more likely to show a positive change than non-group members with regard to antenatal care utilisation and not discarding colostrum, but non-group members also benefited. CONCLUSION: Women's groups promoted significant behaviour change for perinatal care amongst women not previously following good practice. Positive changes attributable to intervention were not restricted to specific demographic subgroups.

Journal Article↗

PubMed2006

An investigation of minimisation criteria.

BACKGROUND: Minimisation can be used within treatment trials to ensure that prognostic factors are evenly distributed between treatment groups. The technique is relatively straightforward to apply but does require running tallies of patient recruitments to be made and some simple calculations to be performed prior to each allocation. As computing facilities have become more widely available, minimisation has become a more feasible option for many. Although the technique has increased in popularity, the mode of application is often poorly reported and the choice of input parameters not justified in any logical way. METHODS: We developed an automated package for patient allocation which incorporated a simulation arm. We here demonstrate how simulation of data can help to determine the input parameters to be used in a subsequent application of minimisation. RESULTS: Several scenarios were simulated. Within the selected scenarios, increasing the number of factors did not substantially adversely affect the extent to which the treatment groups were balanced with respect to the prognostic factors. Weighting of the factors tended to improve the balance when factors had many categories with only a slight negative effect on the factors with fewer categories. When interactions between factors were included as minimisation factors, there was no major reduction in the balance overall. CONCLUSION: With the advent of widely available computing facilities, researchers can be better equipped to implement minimisation as a means of patient allocation. Simulations prior to study commencement can assist in the choice of minimisation parameters and can be used to justify those selections.

Age Distribution↗

PubMed2006

Effects on neural function of repleting vitamin E-deficient rats with alpha-tocopherol.

A severe and chronic deficiency of vitamin E (alpha-tocopherol) is associated with a characteristic neurological syndrome with typical "clinical," neuropathological, and electrophysiological abnormalities in both humans and experimental animals. Repletion of vitamin E-deficient human subjects with alpha-tocopherol typically halts the progression of the neural signs and symptoms, and in some cases, can result in objective improvement. Electrophysiological parameters provide an objective measure of neural and visual function and improvement of some of these measures has been reported after repletion with vitamin E in humans. In this longitudinal study, the effects of repleting rats with a diet containing 36 mg/kg all-rac-alpha-tocopheryl acetate for 20 wk after they had been receiving a vitamin E-deficient diet for 38 wk was studied. We report significant improvements in growth and a number of electrophysiological parameters of both neural and visual function after repletion. These results confirm the validity of the vitamin E-deficient rat as a model of vitamin E deficiency in humans.

Animals↗

PubMed2005

Economic assessment of a women's group intervention to improve birth outcomes in rural Nepal.

We did a cost-effectiveness analysis alongside a cluster-randomised controlled trial of a participatory intervention with women's groups to improve birth outcomes in rural Nepal. The average provider cost of the women's group intervention was US0.75 dollars per person per year (0.90 dollars with health-service strengthening) in a population of 86,704. The incremental cost per life-year saved (LYS) was 211 dollars (251 dollars), and expansion could rationalise on start-up costs and technical assistance, reducing the cost per LYS to 138 dollars (179 dollars). Sensitivity analysis showed a variation from 83 dollars to 263 dollars per LYS for most variables. This intervention could provide a cost-effective way of reducing neonatal deaths.

Adult↗

PubMed2005

Determining the cost effectiveness of a smoke alarm give-away program using data from a randomized controlled trial.

BACKGROUND: In 2001, 486 deaths and 17,300 injuries occurred in domestic fires in the UK. Domestic fires represent a significant cost to the UK economy, with the value of property loss alone estimated at pounds 375 million in 1999. In 2001 in the US, there were 383 500 home fires, resulting in 3110 deaths, 15,200 injuries and dollar 5.5 billion in direct property damage. METHODS: A cluster RCT was conducted to determine whether a smoke alarm give-away program, directed to an inner-city UK population, is effective and cost-effective in reducing the risk of fire-related deaths/injuries. Forty areas were randomized to the give-away or control group. The number of injuries/deaths and the number of fires in each ward were collected prospectively. Cost-effectiveness analysis was undertaken to relate the number of deaths/injuries to resource use (damage, fire service, healthcare and give-away costs). Analytical methods were used which reflected the characteristics of the trial data including the cluster design of the trial and a large number of zero costs and effects. RESULTS: The mean cost for a household in a give-away ward, including the cost of the program, was pounds 12.76, compared to pounds 10.74 for the control ward. The total mean number of deaths and injuries was greater in the intervention wards then the control wards, 6.45 and 5.17. When an injury/death avoided is valued at pounds 1000, a smoke alarm give-away has a probability of being cost effective of 0.15. CONCLUSIONS: A smoke alarm give-away program, as administered in the trial, is unlikely to represent a cost-effective use of resources.

Cluster Analysis↗

PubMed2005

Maternal diet programs embryonic kidney gene expression.

Human epidemiological data associating birth weight with adult disease suggest that organogenesis is "programmed" by maternal diet. In rats, protein restriction in pregnancy produces offspring with fewer renal glomeruli and higher systemic blood pressures than controls. We tested the hypothesis that maternal diet alters gene expression in the metanephros, the precursor of the definitive mammalian kidney. We demonstrated that maternal low-protein diet initiated when pregnancy starts and maintained to embryonic day 13, when the metanephros consists of mesenchyme surrounding a once-branched ureteric bud, is sufficient to significantly reduce glomerular numbers in offspring by about 20%. As assessed by representational difference analyses and real-time quantitative polymerase chain reactions, low-protein diet modulated gene expression in embryonic day 13 metanephroi. In particular, levels of prox-1, the ortholog of Drosophila transcription factor prospero, and cofilin-1, a regulator of the actin cytoskeleton, were reduced. During normal metanephrogenesis, prox-1 protein was first detected in mesenchymal cells around the ureteric tree and thereafter in nascent nephron epithelia, whereas cofilin-1 immunolocalized to bud derivatives and condensing mesenchyme. Previously, we reported that low-protein diets increased mesenchymal apoptosis cells when metanephrogenesis began and thereafter reduced numbers of precursor cells. Collectively, these studies prove that the maternal diet programs the embryonic kidney, altering cell turnover and gene expression at a time when nephrons and glomeruli have yet to form. The human implication is that the maternal diet ingested between conception and 5- 6-wk gestation contributes to the variation in glomerular numbers that are known to occur between healthy and hypertensive populations.

Animals↗

PubMed2005

Inflammatory response in children after laparoscopic vs open Nissen fundoplication: randomized controlled trial.

UNLABELLED: We performed a randomized controlled trial to compare the inflammatory and immune responses to Nissen fundoplication in infants and children undergoing either open or laparoscopic surgery. METHODS: Forty children undergoing Nissen fundoplication were randomized to laparoscopy or open surgery using minimization with respect to age, neurologic status, and operating surgeon. Intraoperative and postoperative analgesias were standardized. Inflammatory markers (plasma malondialdehyde, nitrate plus nitrite level, and cytokines) and monocyte class II major histocompatibility complex expression were measured preoperatively, at end of surgery, 4, 24, and 48 hours postoperatively. Postoperative changes were compared between open and laparoscopic groups. RESULTS: There were no significant changes in circulating malondialdehyde, nitrates plus/ nitrite, interleukin-10, or tumor necrosis factor alpha in the postoperative period in either group. Interleukin-1 receptor antagonist (IL-1rA) and IL-6 were significantly increased in both groups, with a tendency for greater elevation of IL-1rA in the open group. Monocyte major histocompatibility complex expression fell significantly in both groups; however, this fall appeared to be slightly more marked in the open group. CONCLUSIONS: The postoperative cytokine response is similar in children undergoing open and laparoscopic Nissen fundoplication. This trial indicates that laparoscopy may partly reduce postoperative immune suppression.

Child↗

PubMed2004

The evolution of airway function in early childhood following clinical diagnosis of cystic fibrosis.

This study aimed to investigate the evolution of airway function in infants newly diagnosed with cystic fibrosis (CF). FEV(0.5) was measured soon after diagnosis (median age of 28 weeks) and 6 months later in subjects with CF and on two occasions 6 months apart (median ages of 7.4 and 33.7 weeks) in healthy infants, using the raised-volume technique. Repeated measurements were successful in 34 CF and 32 healthy subjects. After adjustment for age, length, sex, and exposure to maternal smoking, mean FEV(0.5) was significantly lower in infants with CF both shortly after diagnosis and at the second test, with no significant difference in rate of increase in FEV(0.5) with growth between the two groups. When compared with published reference data, FEV(0.5) was reduced by an average of two z scores on both test occasions in those with CF, with 72% of individuals having an FEV(0.5) of less than 1.64 z-scores (i.e., less than the fifth percentile) on one or both test occasions. On longitudinal analysis, subjects with CF experienced a mean (95% confidence interval) reduction in FEV(0.5) of 20% (11, 28). Airway function is diminished soon after diagnosis in infants with CF and does not catch up during infancy and early childhood. These findings have important implications for early interventions in CF.

Body Height↗

PubMed2003

Speech, language, and cognitive development in children with isolated sagittal synostosis.

This study investigated the occurrence, nature, and severity of speech, language, and cognitive impairment in 76 children (61 males, 15 females) with isolated sagittal synostosis (ISS) aged 9 months to 15 years 7 months. There was no increased prevalence of global cognitive impairment in the group but there was a high prevalence rate of speech and/or language impairment with 28 (37%) displaying impairment of whom 20 (71%) had moderate or severe impairments that fulfilled the criteria for specific impairments. Prevalence rates were only increased for children over two years of age. Expressive language impairment occurred most frequently. Raised intracranial pressure, peri-neonatal risk factors, otitis media, or being operated were not associated with impairment. Surgery at a later age and a family history of speech and language impairment were both associated with impairments but numbers were small. The findings suggest that children with ISS are at an increased risk of developing speech and language impairment.

Adolescent↗

PubMed2002

Relative ability of full and partial forced expiratory maneuvers to identify diminished airway function in infants with cystic fibrosis.

The tidal and raised volume rapid thoracoabdominal compression techniques are increasingly used to detect diminished airway function in infancy. The aim of this study was to assess the relative ability of parameters measured by these techniques to identify diminished airway function in infants newly diagnosed with cystic fibrosis (CF) with and without clinical evidence of prior lower respiratory illness. A cross-sectional, prospective study design was used in which maximal flow at functional residual capacity (VmaxFRC) from the tidal technique and FVC, FEV0.5, FEF75, and FEF25-75 from the raised volume technique were measured in 47 infants with CF and 187 healthy infants of similar body size, sex distribution, ethnic group, and exposure to maternal smoking. Multiple linear regression was used to assess group differences and to calculate SD scores for each parameter for the infants with CF. Airway function was also compared with clinical assessments of respiratory status made by pediatric pulmonologists. FEV0.5 was significantly diminished in 13 infants with CF, of whom 4 had been identified by clinicians as having normal respiratory status. Only one infant with CF had a VmaxFRC below the estimated normal range. Airway function is diminished in infants with CF irrespective of prior lower respiratory illness and in those whose respiratory status is considered normal by pediatric pulmonologists. In infants with CF, the raised volume technique identified diminished airway function more frequently than the tidal technique.

Age Factors↗

PubMed2002

Incidence of fires and related injuries after giving out free smoke alarms: cluster randomised controlled trial.

OBJECTIVE: To measure the effect of giving out free smoke alarms on rates of fires and rates of fire related injury in a deprived multiethnic urban population. DESIGN: Cluster randomised controlled trial. SETTING: Forty electoral wards in two boroughs of inner London, United Kingdom. PARTICIPANTS: Primarily households including elderly people or children and households that are in housing rented from the borough council. INTERVENTION: 20 050 smoke alarms, fittings, and educational brochures distributed free and installed on request. MAIN OUTCOME MEASURES: Rates of fires and related injuries during two years after the distribution; alarm ownership, installation, and function. RESULTS: Giving out free smoke alarms did not reduce injuries related to fire (rate ratio 1.3; 95% confidence interval 0.9 to 1.9), admissions to hospital and deaths (1.3; 0.7 to 2.3), or fires attended by the fire brigade (1.1; 0.96 to 1.3). Similar proportions of intervention and control households had installed alarms (36/119 (30%) v 35/109 (32%); odds ratio 0.9; 95% confidence interval 0.5 to 1.7) and working alarms (19/118 (16%) v 18/108 (17%); 0.9; 0.4 to 1.8). CONCLUSIONS: Giving out free smoke alarms in a deprived, multiethnic, urban community did not reduce injuries related to fire, mostly because few alarms had been installed or were maintained.

Burns↗

PubMed2002

Nocturnal oxygen saturation and painful sickle cell crises in children.

The pathogenesis of acute painful crisis in children with sickle cell disease is poorly understood; suggested risk factors include sickle cell type, severity of anemia, fetal hemoglobin concentration, and hypoxemia from upper airway obstruction. In a cohort study of 95 patients the relationship between clinical, laboratory, and sleep study data and frequency of painful crisis was investigated. Both univariate and multiple regression modeling showed that low nocturnal oxygen saturation was highly significantly associated with a higher rate of painful crisis in childhood (P <.0001). Screening and treatment for hypoxemia may reduce the frequency of this and other complications of the disease.

Adolescent↗

PubMed2002

D-chiro-inositol is more effective than myo-inositol in preventing folate-resistant mouse neural tube defects.

BACKGROUND: Among mouse genetic mutants that develop neural tube defects (NTDs), some respond to folic acid administration during early pregnancy, whereas NTDs in other mutants are not prevented. This parallels human NTDs, in which up to 30% of cases may be resistant to folic acid. Most spina bifida cases in the folic acid-resistant 'curly tail' mouse can be prevented by treatment with inositol early in embryonic development. Here, the effectiveness and safety during pregnancy of two isomers, myo- and D-chiro-inositol, in preventing mouse NTDs was compared. METHODS AND RESULTS: Inositol was administered either directly to embryos in vitro, or to pregnant females by s.c. or oral routes. Although D-chiro- and myo-inositol both reduced the frequency of spina bifida in curly tail mice by all routes of administration, D-chiro-inositol consistently exhibited the more potent effect, reducing spina bifida by 73-86% in utero compared with a 53-56% reduction with myo-inositol. Pathological analysis revealed no association of either myo- or D-chiro-inositol with reduced litter size or fetal malformation. CONCLUSIONS: D-chiro-inositol offers a safe and effective method for preventing folic acid-resistant NTDs in the curly tail mouse. This raises the possibility of using inositol as an adjunct therapy to folic acid for prevention of NTDs in humans.

Administration, Oral↗

PubMedDate not supplied

Effect of a participatory intervention with women's groups on birth outcomes in Nepal: cluster-randomised controlled trial.

BACKGROUND: Neonatal deaths in developing countries make the largest contribution to global mortality in children younger than 5 years. 90% of deliveries in the poorest quintile of households happen at home. We postulated that a community-based participatory intervention could significantly reduce neonatal mortality rates. METHODS: We pair-matched 42 geopolitical clusters in Makwanpur district, Nepal, selected 12 pairs randomly, and randomly assigned one of each pair to intervention or control. In each intervention cluster (average population 7000), a female facilitator convened nine women's group meetings every month. The facilitator supported groups through an action-learning cycle in which they identified local perinatal problems and formulated strategies to address them. We monitored birth outcomes in a cohort of 28?931 women, of whom 8% joined the groups. The primary outcome was neonatal mortality rate. Other outcomes included stillbirths and maternal deaths, uptake of antenatal and delivery services, home care practices, infant morbidity, and health-care seeking. Analysis was by intention to treat. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN31137309. FINDINGS: From 2001 to 2003, the neonatal mortality rate was 26.2 per 1000 (76 deaths per 2899 livebirths) in intervention clusters compared with 36.9 per 1000 (119 deaths per 3226 livebirths) in controls (adjusted odds ratio 0.70 [95% CI 0.53-0.94]). Stillbirth rates were similar in both groups. The maternal mortality ratio was 69 per 100000 (two deaths per 2899 livebirths) in intervention clusters compared with 341 per 100000 (11 deaths per 3226 livebirths) in control clusters (0.22 [0.05-0.90]). Women in intervention clusters were more likely to have antenatal care, institutional delivery, trained birth attendance, and hygienic care than were controls. INTERPRETATION: Birth outcomes in a poor rural population improved greatly through a low cost, potentially sustainable and scalable, participatory intervention with women's groups.

Adolescent↗