[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
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.
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.
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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: To estimate the costs and benefits of clinical pathways incorporating a point of care (POC) nucleic acid amplification test (NAAT) for chlamydia and gonorrhoea in genitourinary medicine (GUM) clinics compared with standard off-site laboratory testing.
We simulated 1.2 million GUM clinic attendees in England. A simulation in Microsoft Excel was developed to compare existing standard pathways of management for chlamydia and gonorrhoea with a POC NAAT. We conducted scenario analyses to evaluate the robustness of the model findings. The primary outcome was the incremental cost-effectiveness ratio. Secondary outcomes included the number of inappropriate treatments, complications and transmissions averted.
The baseline cost of using the point of POC NAAT was £103.9 million compared with £115.6 million for standard care. The POC NAAT was also associated with a small increase of 46 quality adjusted life years, making the new test both more effective and cheaper. Over 95 000 inappropriate treatments might be avoided by using a POC NAAT. Patients receive diagnosis and treatment on the same day as testing, which may also prevent 189 cases of pelvic inflammatory disease and 17 561 onward transmissions annually.
Replacing standard laboratory tests for chlamydia and gonorrhoea with a POC test could be cost saving and patients would benefit from more accurate diagnosis and less unnecessary treatment. Overtreatment currently accounts for about a tenth of the reported treatments for chlamydia and gonorrhoea and POC NAATs would effectively eliminate the need for presumptive treatment.
[Show abstract][Hide abstract] ABSTRACT: Tourette syndrome and chronic tic disorder are heritable but aetiologically complex. Although environment plays a role in their development, existing studies of non-genetic risk factors are inconsistent.
To examine the association between pre- and perinatal exposures and Tourette syndrome/chronic tic disorder in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective longitudinal pre-birth cohort.
Relationships between exposures and Tourette syndrome/chronic tic disorder were examined in 6090 children using logistic regression.
Maternal alcohol and cannabis use, inadequate maternal weight gain and parity were associated with Tourette syndrome or Tourette syndrome/chronic tic disorder. Other previously reported exposures, including birth weight and prenatal maternal smoking, were not associated with Tourette syndrome/chronic tic disorder.
This study supports previously reported relationships between Tourette syndrome/chronic tic disorder and prenatal alcohol exposure, and identifies additional previously unexplored potential prenatal risk factors.
The British journal of psychiatry: the journal of mental science 11/2013;
[Show abstract][Hide abstract] ABSTRACT: Randomised controlled trials (RCTs) in surgery are complex to design and conduct and face unique challenges compared to trials in other specialties. The appropriate selection, measurement and reporting of outcomes are one aspect that requires attention. Outcomes in surgical RCTs are often ill-defined, inconsistent and at high risk of bias in their assessment and historically, there has been an undue focus on short-term outcomes and adverse events meaning the value of trial results for clinical practice and decision-making is limited.
This review addresses three key problems with surgical trial outcomes-choosing the right outcomes for the trial design and purpose, selecting relevant outcomes to measure from the range of possible outcomes, and measuring outcomes with minimal risk of bias. Each obstacle is discussed in turn, highlighting some suggested solutions and current initiatives working towards improvements in these areas. Some examples of good practice in this field are also discussed.
Many of the historical problems with surgical trial outcomes may be overcome with an increased understanding of the trial design and purpose and recognition that pragmatic trials require assessments of outcomes that are patient-centred in addition to measurement of short-term outcomes. The use of core outcome sets developed for specific surgical interventions and the application of novel methods to blind outcome assessors will also improve outcome measurement and reporting. It is recommended that surgeons work together with trial methodologists to integrate these approaches into RCTs in surgery. This will facilitate the appropriate evaluation of surgical interventions with informative outcomes so that results from trials can be useful for clinical practice.
[Show abstract][Hide abstract] ABSTRACT: -Blood pressure (BP) tends to increase across childhood and adolescence, but the genetic influences on rates of BP change are not known. Potentially important genetic influences could include genetic variants identified in genome wide association studies of adults as being associated with BP, height and body mass index (BMI). Understanding the contribution of these genetic variants to changes in BP across childhood and adolescence could yield understanding into the life course development of cardiovascular risk.
-Pooling data from two cohorts, (the Avon Longitudinal Study of Parents and Children, N=7,013 and the Western Australian Pregnancy Cohort, N=1,459), we examined the associations of allelic scores of 29 single nucleotide polymorphisms (SNPs) for adult BP, 180 height SNPs and 32 BMI SNPs, with trajectories of systolic BP (SBP) from age 6-17 years, using linear spline multilevel models. The allelic scores of BP and BMI SNPs was associated with SBP at age 6 (per allele effect sizes 0.097mmHg (SE=0.039) and 0.107mmHg (SE=0.037)); associations with age-related changes in SBP between 6-17 years were of small magnitude and imprecisely estimated. The allelic score of height SNPs was only weakly associated with SBP changes. No sex or cohort differences in genetic effects were observed.
-Allelic scores of BP and BMI SNPs demonstrated associations with SBP at age 6, with a similar magnitude, but were not strongly associated with changes in SBP with age between 6-17 years. Further work is required to identify variants associated with changes with age in BP.
Circulation Cardiovascular Genetics 11/2013;
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