Pharmacokinetic profile of a new matrix-type transdermal delivery system: Diclofenac diethyl ammonium patch

A transdermal delivery system containing the anti-inflammatory analgesic diclofenac diethyl ammonium in an ethyl hexyl acrylate and vinyl acetate pressure-sensitive adhesive system was developed for percutaneous absorption. These patches were subjected to in vitro permeation and permeation enhancement studies through rat skin using a specially designed diffusion cell. Further, the work deals with peucutaneous absorption studies carried out on both animals and human volunteers. The pharmacokinetic parameters calculated from the blood levels of the drug reveal a profile typical of a sustained-release formulation, with the ability to maintain adequate plasma levels for 24 hr (i.e., up to the next application). (Area under the curve [AUC]: 4.356 +/- 1.3 mcg/ml.hr in animals and 0.442 +/- 0.053 mcg/ml.hr in humans; T-max was 8 hr in both the cases, whereas C-max was 0.288 +/- 0.088 mcg/ml in animals and 0.034 +/- .008 mcg/ml in human volunteers.) The amount of the drug bioavailable for targeting the sites of action is lower than via the oral route, but the absorbed dose appears to be adequate for therapeutic use, particularly because of the absence of side effects

Adverse Childhood Experiences and their impact on health-harming behaviours in the Welsh adult population

This report is one in a series of reports examining the prevalence of Adverse Childhood Experiences (ACEs) in the Welsh adult population and their impact on health and well-being across the life course. Substantial proportions of the Welsh population reported suffering abuse, neglect and other ACEs during their childhood with 47% reporting having experienced at least one ACE and 14% experiencing four or more ACEs. This report focuses on: alcohol use, drug use, violence, sexual behaviour, incarceration, smoking and poor diet

Identifying Prenatal and Postnatal Determinants of Infant Growth: A Structural Equation Modelling Based Cohort Analysis

The growth and maturation of infants reflect their overall health and nutritional status. The purpose of this study is to examine the associations of prenatal and early postnatal factors with infant growth (IG). A data-driven model was constructed by structural equation modelling to examine the relationships between pre- and early postnatal environmental factors and IG at age 12 months. The IG was a latent variable created from infant weight and waist circumference. Data were obtained on 274 mother-child pairs during pregnancy and the postnatal periods. Maternal pre-pregnancy BMI emerged as an important predictor of IG with both direct and indirect (mediated through infant birth weight) effects. Infants who gained more weight from birth to 6 months and consumed starchy foods daily at age 12 months, were more likely to be larger by age 12 months. Infant physical activity (PA) levels also emerged as a determinant. The constructed model provided a reasonable fit ( (11) = 21.5, < 0.05; RMSEA = 0.07; CFI = 0.94; SRMR = 0.05) to the data with significant pathways for all examined variables. Promoting healthy weight amongst women of child bearing age is important in preventing childhood obesity, and increasing daily infant PA is as important as a healthy infant diet

Adverse childhood experiences during childhood and academic attainment at age 7 and 11 years: an electronic birth cohort study

Objectives Adverse childhood experiences (ACEs) have a negative impact on childhood health, but their impact on education outcomes is less well known. We investigated whether or not ACEs were associated with reduced educational attainment at age 7 and 11 years. Study design The study design used in the study is a population-based electronic cohort study. Methods We analysed data from a total population electronic child cohort in Wales, UK. ACEs (exposures) were living with an adult household member with any of (i) serious mental illness, (ii) common mental disorder (CMD), (iii) an alcohol problem; (iv) child victimisation, (v) death of a household member and (vi) low family income. We used multilevel logistic regression to model exposure to these ACEs and not attaining the expected level at statutory education assessments, Key Stage (KS) 1 and KS2 separately, adjusted for known confounders including perinatal, socio-economic and school factors. Results There were 107,479 and 43,648 children included in the analysis, with follow-up to 6–7 years (KS1) and 10–11 years (KS2), respectively. An increased risk of not attaining the expected level at KS1 was associated with living with adult household members with CMD (adjusted odds ratio [aOR]: 1.13 [95% confidence interval [CI]: 1.09–1.17]) or an alcohol problem (adjusted odds ratio [aOR]: 1.16 [95% confidence interval [CI]: 1.10–1.22]), childhood victimisation (adjusted odds ratio [aOR]: 1.58 [95% confidence interval [CI]: 1.37–1.82]), death of a household member (adjusted odds ratio [aOR]: 1.14 [95% confidence interval [CI]: 1.04–1.25]) and low family income (adjusted odds ratio [aOR]: 1.92 [95% confidence interval [CI]: 1.84–2.01]). Similar results were observed for KS2. Children with multiple adversities had substantially increased odds of not attaining the expected level at each educational assessment. Conclusion The educational potential of many children may not be achieved due to exposure to adversity in childhood. Affected children who come in to contact with services should have relevant information shared between health and care services, and schools to initiate and facilitate a coordinated approach towards providing additional support and help for them to fulfil their educational potential, and subsequent economic and social participation

The role of maternal stress in early pregnancy in the aetiology of gastroschisis : An incident case control study

We wish to thank all the women who took the time to take part in this study, the research nurses who undertook interviews and data collection: Sandra Edwards-Fenton, Anne Chamberlain, Marit Bodley, Sharon Brown, Isobel Clegg, Catherine Collins and the British Isles Network of Congenital Anomaly Registers (BINOCAR) for their support in facilitating this study.Peer reviewedPublisher PD

Pregnancy rates and outcomes amongst women with cystic fibrosis in the UK : comparisons with the general population before and after the introduction of disease modifying treatment, 2003-17

Acknowledgements We thank the UK CF Registry team and the UK CF centres and clinics for submitting data to the Registry. Special thanks to the people with cystic fibrosis and their families who have agreed for their UK CF Registry data to be used for research. Funding The study was funded by a Welsh Government Research for Patient and Public Benefit grant. The funder was not involved in the study design, data collection, data analysis, data interpretation or the writing of the report. DT-R is funded by the MRC on a Clinician Scientist Fellowship (MR/P008577/1).Peer reviewedPublisher PD

Mediators of socioeconomic inequalities in preterm birth: a systematic review.

BackgroundRates of preterm birth are substantial with significant inequalities. Understanding the role of risk factors on the pathway from maternal socioeconomic status (SES) to preterm birth can help inform interventions and policy. This study therefore aimed to identify mediators of the relationship between maternal SES and preterm birth, assess the strength of evidence, and evaluate the quality of methods used to assess mediation.MethodsUsing Scopus, Medline OVID, "Medline In Process & Other Non-Indexed Citation", PsycINFO, and Social Science Citation Index (via Web of Science), search terms combined variations on mediation, socioeconomic status, and preterm birth. Citation and advanced Google searches supplemented this. Inclusion criteria guided screening and selection of observational studies Jan-2000 to July-2020. The metric extracted was the proportion of socioeconomic inequality in preterm birth explained by each mediator (e.g. 'proportion eliminated'). Included studies were narratively synthesised.ResultsOf 22 studies included, over one-half used cohort design. Most studies had potential measurement bias for mediators, and only two studies fully adjusted for key confounders. Eighteen studies found significant socioeconomic inequalities in preterm birth. Studies assessed six groups of potential mediators: maternal smoking; maternal mental health; maternal physical health (including body mass index (BMI)); maternal lifestyle (including alcohol consumption); healthcare; and working and environmental conditions. There was high confidence of smoking during pregnancy (most frequently examined mediator) and maternal physical health mediating inequalities in preterm birth. Significant residual inequalities frequently remained. Difference-of-coefficients between models was the most common mediation analysis approach, only six studies assessed exposure-mediator interaction, and only two considered causal assumptions.ConclusionsThe substantial socioeconomic inequalities in preterm birth are only partly explained by six groups of mediators that have been studied, particularly maternal smoking in pregnancy. There is, however, a large residual direct effect of SES evident in most studies. Despite the mediation analysis approaches used limiting our ability to make causal inference, these findings highlight potential ways of intervening to reduce such inequalities. A focus on modifiable socioeconomic determinants, such as reducing poverty and educational inequality, is probably necessary to address inequalities in preterm birth, alongside action on mediating pathways