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    ABSTRACT: For the last decade, stringent monitoring of waiting time performance targets provided English hospitals with incentives to reduce official waiting times for elective surgery. It is less clear whether the total amount of time patients waited in secondary care, from first referral to outpatient clinic until treatment, has also fallen. We used Hospital Episode Statistics inpatient data for patients undergoing total joint replacement during a period of active monitoring of targets (between 2006/7 and 2008/9) and linked it to outpatient data to reconstruct patients' pathway in the 3 years before surgery and provide alternative measurements of waiting times. Our findings suggest that although official waiting times decreased drastically in our study period, total waiting time in secondary care has not declined. Patients with shorter official waits spent a longer time in a 'work-up' period prior to inclusion in the official waiting list, and socio-economic inequities persisted in waiting times for joint replacement. We found no evidence that target policies achieved efficiency gains during our study period. Copyright © 2013 John Wiley & Sons, Ltd.
    Health Economics 07/2014; 23(7). DOI:10.1002/hec.2954
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    ABSTRACT: Objective To determine whether maternal mental health mediates the relationship between eczema or asthma symptoms and mental well-being in children. Study design Analysis of 7250 children from the Avon Longitudinal Study of Parents and Children. Child mental well-being at 8 years was measured by the Strengths and Difficulties Questionnaire. Binary outcomes were high 'internalizing' (anxious/depressive) and 'externalizing' (oppositional/hyperactive) problems (high was >90th percentile). Child rash and wheeze categories were 'none'; 'early onset transient' (infancy/preschool only); 'persistent' (infancy/preschool and at school age); and 'late onset' (school age only). Maternal anxiety and depression were reported during pregnancy and when child was 8 years old. Results Persistent wheezing symptoms were associated with high externalizing (OR 1.74, 95% CI, 1.41-2.15) and internalizing (1.67, 1.35-2.06) problems compared with never wheeze. Maternal anxiety and depression, and disrupted child sleep, attenuated these associations. Persistent rash (externalizing: 1.74, 1.40-2.15; internalizing: 1.42, 1.16-1.74) and late onset rash (externalizing: 1.62, 1.17-2.25; internalizing: 1.46, 1.07-1.99) symptoms were associated with poorer mental well-being compared with no rash at any age. Maternal anxiety and depression, particularly when child was aged 8 years rather than during pregnancy, accounted for the association with internalizing symptoms and partly for externalizing symptoms. Sleep disruption did not mediate the association. Conclusions Maternal anxiety and depression may mediate the association between child rash and wheeze and child mental well-being.
    Journal of Pediatrics 06/2014; 165(3). DOI:10.1016/j.jpeds.2014.05.023
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    ABSTRACT: In a prospective birth cohort study of 5295 girls from the UK-based Avon Longitudinal Study of Parents and Children (ALSPAC), we examined the association between biological father absence in childhood and age at menarche whilst adjusting for antenatal indicators of socioeconomic disadvantage and maternal characteristics. We also examined whether exposure to maternal depression and financial problems during middle childhood mediate the association between father absence and age at menarche. There was stronger evidence for an association between father absence during the first 5 years of life and early timing of menarche compared with father absence between 5 and 10 years. There was evidence that maternal depression and major financial problems explained some of the association between early childhood father absence and age at menarche. Although father absence cannot be a direct target of prevention, family-based programs to address family processes influenced by maternal depression and socioeconomic disadvantage may be effective.
    Journal of Adolescence 04/2014; 37(3):291–301. DOI:10.1016/j.adolescence.2014.02.003
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    ABSTRACT: We hypothesised that bone resorption acts to increase bone strength through stimulation of periosteal expansion. Hence, we examined whether bone resorption, as reflected by serum β-C-telopeptides of type I collagen (CTX), is positively associated with periosteal circumference (PC), in contrast to inverse associations with parameters related to bone remodelling such as cortical bone mineral density (BMDC ). CTX and mid-tibial pQCT scans were available in 1130 adolescents (mean age 15.5 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass and height. CTX was positively related to PC [β= 0.19 (0.13, 0.24)] (coefficient = SD change per SD increase in CTX, 95% CI)], but inversely associated with BMDC [β= -0.46 (-0.52,-0.40)] and cortical thickness [β= -0.11 (-0.18, -0.03)]. CTX was positively related to bone strength as reflected by the strength-strain index (SSI) [β= 0.09 (0.03, 0.14)]. To examine the causal nature of this relationship, we then analysed whether SNPs within key osteoclast regulatory genes, known to reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants within or proximal to genes encoding RANK, RANKL and OPG were identified by literature search. Six of the 15 alleles that were inversely related to BMD were positively related to CTX (P < 0.05 cut-off) (n = 2379). Subsequently, we performed a meta-analysis of associations between these SNPs and PC in ALSPAC (n = 3382), Gothenburg Osteoporosis and Obesity Determinants (GOOD) (n = 938) and the Young Finns Study (YFS) (n = 1558). Five of the 15 alleles that were inversely related to BMD were positively related to PC (P < 0.05 cut-off). We conclude that despite having lower BMD, individuals with a genetic predisposition to higher bone resorption have greater bone size, suggesting that higher bone resorption is permissive for greater periosteal expansion.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 04/2014; 29(4). DOI:10.1002/jbmr.2093
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    ABSTRACT: Objectives A new method is presented for both synthesizing treatment effects on multiple outcomes subject to measurement error and estimating coherent mapping coefficients between all outcomes. It can be applied to sets of trials reporting different combinations of patient- or clinician-reported outcomes, including both disease-specific measures and generic health-related quality-of-life measures. It is underpinned by a structural equation model that includes measurement error and latent common treatment effect factor. Treatment effects can be expressed on any of the test instruments that have been used. Methods This is illustrated in a synthesis of eight placebo-controlled trials of TNF-α inhibitors in ankylosing spondylitis, each reporting treatment effects on between two and five of a total six test instruments. Results The method has advantages over other methods for synthesis of multiple outcome data, including standardization and multivariate normal synthesis. Unlike standardization, it allows synthesis of treatment effect information from test instruments sensitive to different underlying constructs. It represents a special case of previously proposed multivariate normal models for evidence synthesis, but unlike the former, it also estimates mappings. Combining synthesis and mapping as a single operation makes more efficient use of available data than do current mapping methods and generates treatment effects that are consistent with the mappings. A limitation, however, is that it can only generate mappings to and from those instruments on which some trial data exist. Conclusions The method should be assessed in a wide range of data sets on different clinical conditions, before it can be used routinely in health technology assessment.
    Value in Health 03/2014; 17(2):280–287. DOI:10.1016/j.jval.2013.12.006
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    ABSTRACT: Although the relationship between maternal bonding and risk of offspring depression has been demonstrated, it is unclear whether this risk exists for subsequent generations. This study examines the association between maternal reports of her own mother's parenting and later risk of depression in offspring at age 18. This study is based on data from the Avon Longitudinal Study of Parents and Children. Mothers enrolled in the study, completed the Parental Bonding Instrument to provide an assessment of how they were parented by their own mothers up to the age of 16. Offspring depression was assessed at age of 18 using the Clinical Interview Schedule-Revised. The sample comprised 10,405 respondents who had completed the Parental Bonding Instrument during the antenatal period. Results were adjusted for grandmother's history of depression, maternal depression, and a range of socioeconomic variables. A one standard deviation increase in mothers' perceived lack of care in their own childhood was associated with a 16% increase in the odds of offspring depression at age 18 (odds ratios = 1.16, 95% confidence intervals = [1.04, 1.30]). This effect remained following adjustment for potential confounders (odds ratios = 1.14, 95% confidence intervals = [1.02, 1.27]). There was no evidence for an association between overprotection and offspring depression. This study is consistent with the hypothesis that sensitive caregiving is important to future risk of depression across generations. Preventative interventions could be aimed at promoting positive parenting practices, which may help to reduce the risk of depression in subsequent generations.
    Depression and Anxiety 01/2014; 31(1). DOI:10.1002/da.22174
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    ABSTRACT: Mycoplasma genitalium is a sexually transmitted infection that causes significant morbidity in men and women and is a co-factor in HIV transmission. However, commercial diagnostic tests are not generally available for M. genitalium and sub-optimal treatment is often given. We review the literature on the burden of infection, how it may present in clinical practice and the effectiveness of current treatment regimens. In-vivo and in-vitro data strongly suggest that M. genitalium is an important cause of urethritis, cervicitis, pelvic inflammatory disease and potentially asymptomatic proctitis. Studies now consistently demonstrate suboptimal eradication rates with the current treatment regimens recommended first line for the treatment of nongonococcal urethritis. Concurrently, there has been a rapid emergence of antibiotic resistance in M. genitalium, with macrolide resistance now appearing to be endemic in some centres, and quinolone resistance is beginning to emerge. In the absence of specific M. genitalium diagnostic and antimicrobial resistance testing, azithromycin 1 g should not be used for the management of patients with symptomatic disease potentially caused by M. genitalium. This review offers an alternative evidence-based approach to managing such patients that should, theoretically, reduce the risk of the development of antimicrobial resistance.
    Current Opinion in Infectious Diseases 12/2013; DOI:10.1097/QCO.0000000000000030
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    ABSTRACT: Some studies have found an association between elevated cortisol and subsequent depression, but findings are inconsistent. The cortisol awakening response may be a more stable measure of hypothalamic-pituitary-adrenal function and potentially of stress reactivity. To investigate whether salivary cortisol, particularly the cortisol awakening response, is associated with subsequent depression in a large population cohort. Young people (aged 15 years, n = 841) from the Avon Longitudinal Study of Parents and Children (ALSPAC) collected salivary cortisol at four time points for 3 school days. Logistic regression was used to calculate odds ratios for developing depression meeting ICD-10 criteria at 18 years. We found no evidence for an association between salivary cortisol and subsequent depression. Odds ratios for the cortisol awakening response were 1.24 per standard deviation (95% CI 0.93-1.66, P = 0.14) before and 1.12 (95% CI 0.73-1.72, P = 0.61) after adjustment for confounding factors. There was no evidence that the other cortisol measures, including cortisol at each time point, diurnal drop and area under the curve, were associated with subsequent depression. Our findings do not support the hypothesis that elevated salivary cortisol increases the short-term risk of subsequent depressive illness. The results suggest that if an association does exist, it is small and unlikely to be of clinical significance.
    The British journal of psychiatry: the journal of mental science 12/2013; 204(2). DOI:10.1192/bjp.bp.113.126250
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    ABSTRACT: The duration and exclusivity of breastfeeding in infancy have been inversely associated with future cardiometabolic risk. We investigated the effects of an experimental intervention to promote increased duration of exclusive breastfeeding on cardiometabolic risk factors in childhood. We followed-up children in the Promotion of Breastfeeding Intervention Trial, a cluster-randomized trial of a breastfeeding promotion intervention based on the World Health Organization/United Nations Children's Fund Baby-Friendly Hospital Initiative. 17,046 breastfeeding mother-infant pairs were enrolled in 1996/7 from 31 Belarussian maternity hospitals and affiliated polyclinics (16 intervention vs 15 control sites); 13,879 (81.4%) children were followed-up at 11.5 years, with 13,616 (79.9%) fasted and without diabetes. The outcomes were blood pressure; fasting insulin, adiponectin, glucose and apolipoprotein A1; and presence of metabolic syndrome. Analysis was by intention to treat, accounting for clustering within hospitals/clinics. The intervention substantially increased breastfeeding duration and exclusivity compared with the control arm (43% vs. 6% and 7.9% vs. 0.6% exclusively breastfed at 3 and 6 months, respectively). Cluster-adjusted mean differences at 11.5 years between experimental vs control groups were: 1.0mmHg (95% CI: -1.1, 3.1) for systolic and 0.8mmHg (-0.6, 2.3) for diastolic blood pressure; -0.1mmol/l (-0.2, 0.1) for glucose; 8% (-3%, 34%) for insulin; -0.3μg/ml (-1.5, 0.9) for adiponectin; and 0.0g/l (-0.1, 0.1) for ApoA1. The cluster-adjusted odds ratio for metabolic syndrome, comparing experimental vs control groups, was 1.21 (0.85, 1.72). An intervention to improve breastfeeding duration and exclusivity among healthy term infants did not influence cardiometabolic risk factors in childhood. Current Controlled Trials: ISRCTN37687716 (http://www.controlled-trials.com/ISRCTN37687716); Clinicaltrials.gov. Identifier: NCT01561612.
    Circulation 12/2013; 129(3). DOI:10.1161/CIRCULATIONAHA.113.005160
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    ABSTRACT: Depression and anxiety co-occur with substance use and abuse at a high rate. Ascertaining whether substance use plays a causal role in depression and anxiety is difficult or impossible with conventional observational epidemiology. Mendelian randomisation uses genetic variants as a proxy for environmental exposures, such as substance use, which can address problems of reverse causation and residual confounding, providing stronger evidence about causality. Genetic variants can be used instead of directly measuring exposure levels, in order to gain an unbiased estimate of the effect of various exposures on depression and anxiety. The suitability of the genetic variant as a proxy can be ascertained by confirming that there is no relationship between variant and outcome in those who do not use the substance. At present, there are suitable instruments for tobacco use, so we use that as a case study. Proof-of-principle Mendelian randomisation studies using these variants have found evidence for a causal effect of smoking on body mass index. Two studies have investigated tobacco and depression using this method, but neither found strong evidence that smoking causes depression or anxiety; evidence is more consistent with a self-medication hypothesis. Mendelian randomisation represents a technique that can aid understanding of exposures that may or may not be causally related to depression and anxiety. As more suitable instruments emerge (including the use of allelic risk scores rather than individual single nucleotide polymorphisms), the effect of other substances can be investigated. Linkage disequilibrium, pleiotropy, and population stratification, which can distort Mendelian randomisation studies, are also discussed.
    Depression and Anxiety 12/2013; 30(12). DOI:10.1002/da.22150
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