Network Meta-Analysis Techniques for Synthesizing Prevention Science Evidence.

Network meta-analysis is a popular statistical technique for synthesizing evidence from studies comparing multiple interventions. Benefits of network meta-analysis, over more traditional pairwise meta-analysis approaches, include evaluating efficacy/safety of interventions within a single framework, increased precision, comparing pairs of interventions that have never been directly compared in a trial, and providing a hierarchy of interventions in terms of their effectiveness. Network meta-analysis is relatively underutilized in prevention science. This paper therefore presents a primer of network meta-analysis for prevention scientists who wish to apply this method or to critically appraise evidence from publications using the method. We introduce the key concepts and assumptions of network meta-analysis, namely, transitivity and consistency, and demonstrate their applicability to the field of prevention science. We then illustrate the method using a network meta-analysis examining the comparative effectiveness of brief alcohol interventions for preventing hazardous drinking among college students. We provide data and code for all examples. Finally, we discuss considerations that are particularly relevant in network meta-analyses in the field of prevention, such as including non-randomized evidence.

Diversity and stability of cultured vaginal lactobacilli in pregnant women from a multi-ethnic urban UK population.

AIM: To determine the diversity and stability of cultured vaginal lactobacilli in a multi-ethnic population of pregnant women. METHODS AND RESULTS: A single-centre, prospective, cohort study was performed in a tertiary perinatal centre in East London, UK. Self-collected vaginal swabs at 13 and 20 weeks gestation were obtained from women attending for routine antenatal care and cultured for lactobacilli. In women who provided both swabs, 37 of 203 (18%) had no lactobacilli cultured at either time. Only 53 (26%) had the same species at both times. Black women were less likely to have lactobacilli cultured at 13 weeks (P = 0·014), and Black and Asian women were less likely to have lactobacilli cultured at 20 weeks (P = 0·002) compared with those in the White and Other groups. CONCLUSIONS: Significant differences exist between ethnic groups in the carriage and stability of vaginal lactobacilli. SIGNIFICANCE AND IMPACT OF THE STUDY: These differences have implications for the design of interventions aimed at normalizing the vaginal microbiota in pregnant women.

Is breastfeeding in infancy predictive of child mental well-being and protective against obesity at 9 years of age?

BACKGROUND: Preventing child mental health problems and child obesity have been recognized as public health priorities. The aim of the present study was to examine whether being breastfed (at all or exclusively) in infancy was a predictor of mental well-being and protective against risk of obesity at age 9. METHODS: Cross-sectional data from a large, nationally representative cohort study in the Republic of Ireland was used (n = 8357). Data on breastfeeding were retrospectively recalled. Child mental well-being was assessed using a parent-completed Strengths and Difficulties Questionnaire (SDQ). Child's height and weight were measured using scientifically calibrated instruments. RESULTS: Logistic regression analyses indicated that, after controlling for a wide range of potential confounding variables, being breastfed in infancy was associated with a 26% (P < 0.05) reduction in the risk of an abnormal SDQ score at 9 years. Being breastfed remained a significant predictor of child mental well-being when child obesity was controlled for, indicating that being breastfed, independent of child obesity, is a predictor of child mental well-being. The results of a second logistic regression indicated that, after controlling for a wide range of potential confounding variables, being breastfed for between 11 and 25 weeks was associated with a 36% (P < 0.05) reduction in the risk of obesity at 9 years, while being breastfed for 26 weeks or longer was associated with a 48% (P < 0.01) reduction in the risk of obesity at 9 years. CONCLUSIONS: Breastfeeding in infancy may protect against both poor mental well-being and obesity in childhood.

A systems biology analysis of the Drosophila phagosome.

Phagocytes have a critical function in remodelling tissues during embryogenesis and thereafter are central effectors of immune defence. During phagocytosis, particles are internalized into 'phagosomes', organelles from which immune processes such as microbial destruction and antigen presentation are initiated. Certain pathogens have evolved mechanisms to evade the immune system and persist undetected within phagocytes, and it is therefore evident that a detailed knowledge of this process is essential to an understanding of many aspects of innate and adaptive immunity. However, despite the crucial role of phagosomes in immunity, their components and organization are not fully defined. Here we present a systems biology analysis of phagosomes isolated from cells derived from the genetically tractable model organism Drosophila melanogaster and address the complex dynamic interactions between proteins within this organelle and their involvement in particle engulfment. Proteomic analysis identified 617 proteins potentially associated with Drosophila phagosomes; these were organized by protein-protein interactions to generate the 'phagosome interactome', a detailed protein-protein interaction network of this subcellular compartment. These networks predicted both the architecture of the phagosome and putative biomodules. The contribution of each protein and complex to bacterial internalization was tested by RNA-mediated interference and identified known components of the phagocytic machinery. In addition, the prediction and validation of regulators of phagocytosis such as the 'exocyst', a macromolecular complex required for exocytosis but not previously implicated in phagocytosis, validates this strategy. In generating this 'systems-based model', we show the power of applying this approach to the study of complex cellular processes and organelles and expect that this detailed model of the phagosome will provide a new framework for studying host-pathogen interactions and innate immunity.

An investigation into the reporting and management of late terminations of pregnancy (between 22 +0 and 26 +6 weeks of gestation) within NHS Hospitals in England in 2006: the EPICure preterm cohort study.

OBJECTIVE: To review all late terminations of pregnancy, between 22(+0) and 26(+6) weeks of gestation, collected as part of the EPICure2 study. DESIGN: Prospective cohort study. SETTING: All National Health Service (NHS) hospitals providing perinatal services for extremely preterm infants. POPULATION: All births between 22(+0) and 26(+6) weeks of gestation in England during 2006. METHODS: Data were collected for the defined cohort of births, including terminations of pregnancy, by designated unit staff using a standardised questionnaire. Rigorous validation processes were established to ensure comprehensive data collection. Gestational age was validated using a hierarchical classification of scan dates, certain date of last menstrual period and working gestation. Data for terminations of pregnancy (TOPs) were categorised into two groups, terminations for fetal abnormality and for maternal or fetal compromise, and were analysed in terms of their reporting, management and outcomes. MAIN OUTCOME MEASURES: Classification, rate of feticide and outcome following TOP. RESULTS: Of 3782 births between 22(+0) and 26(+6) weeks of gestation, 647 (17.1%) were TOPs; of these 584 (90.3%) were for fetal abnormality and 63 (9.7%) for maternal or fetal compromise. Feticide was carried out in 489 of 584 (83.7%) TOPs for fetal abnormality, and in 38 of 63 (60.3%) of the TOPs for maternal or fetal compromise. Live births resulted following 2.2% TOPs for fetal abnormality and 4.8% TOPs for maternal or fetal compromise. CONCLUSION: Terminations of pregnancy represent a relatively large proportion of very preterm births. Fetal abnormalities are the main cause for these terminations, and most include feticide. Better screening strategies are required to avoid the need for late terminations of pregnancy for fetal abnormalities.

Psychometric evaluation of the Multi-Dimensional Scale of Perceived Social Support in young adults with chronic health conditions.

INTRODUCTION: The Multi-Dimensional Scale of Perceived Social Support (MSPSS) is one of the most widely employed tools for measuring perceived social support from three sources: family, friends and a significant other. This study aimed to establish the factor structure of the MSPSS in young adults living with chronic health conditions (CHCs). It also aimed to examine the reliability and convergent validity of the tool. METHODS: A cross-sectional quantitative design was applied. Participants (n = 123, 90 females) were students aged 18-25 years recruited from Colleges of Further Education in Ireland (mean age of 20.1 years, s.d. = 2.43). Participants completed the MSPSS and two subscales of the Medical Outcomes Study 36-item Short Form Health Survey that assessed social functioning and emotional well-being. RESULTS: Exploratory factor analysis yielded a three-factor solution of the MSPSS in young adults living with CHCs. The three factors together explained 83% of the variance in MSPSS scores. All the items had high loadings on the factors (0.72-0.94). The MSPSS showed satisfactory reliability and convergent validity. CONCLUSIONS: These findings suggest that the MSPSS is a valid and reliable tool for measuring perceived social support from three sources in young adults living with CHCs. Social support has been associated with positive outcomes in young adults living with CHCs, thus it is imperative for researchers and clinicians to have access to psychometrically sound instruments to evaluate the construct.

Nature and severity of lung function abnormalities in extremely pre-term children at 11 years of age.

Advances in neonatal care have resulted in increased survival of children born extremely pre-term (EP). Nevertheless the incidence of bronchopulmonary dysplasia and long-term respiratory morbidity remains high. We investigated the nature of pathophysiological changes at 11 yrs of age to ascertain whether respiratory morbidity in EP children primarily reflects alterations in the lung periphery or more centralised airway function in this population. Spirometry, plethysmography, diffusing capacity, exhaled nitric oxide, multiple-breath washout, skin tests and methacholine challenge were used during laboratory-based assessments in a subgroup of the 1995 EPICure cohort and in controls. Results were obtained in 49 EP and 52 control children. Lung function abnormalities were found in 78% of EP children, with evidence of airway obstruction, ventilation inhomogeneity, gas trapping and airway hyperresponsiveness. Levels of atopy and exhaled nitric oxide were similar between the groups. Prior wheeze was associated with significant reductions in forced flows and volumes. By contrast, abnormalities of the lung periphery appear to be mediated primarily through EP birth per se. The prevalence of lung function abnormalities, which is largely obstructive in nature and likely to have long-term implications, remains high among 11-yr-old children born EP. Spirometry proved an effective means of detecting these persistent abnormalities.

Development of the Children's Attributions about Psychological Problems in their Peers Scale.

BACKGROUND: Research has shown that children's beliefs about the causes of psychological problems are related to their attitudes and reactions towards affected peers. This study describes the development of the Children's Attributions about Psychological Problems in their Peers (CAPPP) Scale, which assesses children's beliefs about the causes of an internalizing and an externalizing condition. METHODS: The 16 items comprising the CAPPP are derived from previous qualitative research findings. Five hundred and ninety-five young people, drawn from five different age groups spanning early childhood to late adolescence, completed a CAPPP Scale for each of two vignettes describing the behaviour of hypothetical peers with attention deficit hyperactivity disorder (ADHD) and depression. RESULTS: Modifications following consideration of psychometric properties and conceptual fit resulted in a 12-item scale. For both the ADHD and depression conditions, the components that emerged were 'Volition', 'Recent Life Stress', 'Family Factors' and 'School Factors'. CONCLUSIONS: The present study represents the first field trial of the CAPPP. Results suggest that children's and adolescents' beliefs about the causes of psychological problems are multidimensional and incorporate both individual and environmental factors.

Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT).

Bone marrow-derived mesenchymal stem cells (MSCs) are known to specifically migrate to and engraft at tumour sites. Understanding interactions between cancer cells and MSCs has become fundamental to determining whether MSC-tumour interactions should be harnessed for delivery of therapeutic agents or considered a target for intervention. Breast Cancer Cell lines (MDA-MB-231, T47D & SK-Br3) were cultured alone or on a monolayer of MSCs, and retrieved using epithelial specific magnetic beads. Alterations in expression of 90 genes associated with breast tumourigenicity were analysed using low-density array. Expression of markers of epithelial-mesenchymal transition (EMT) and array results were validated using RQ-PCR. Co-cultured cells were analysed for changes in protein expression, growth pattern and morphology. Gene expression and proliferation assays were also performed on indirect co-cultures. Following direct co-culture with MSCs, breast cancer cells expressed elevated levels of oncogenes (NCOA4, FOS), proto-oncogenes (FYN, JUN), genes associated with invasion (MMP11), angiogenesis (VEGF) and anti-apoptosis (IGF1R, BCL2). However, universal downregulation of genes associated with proliferation was observed (Ki67, MYBL2), and reflected in reduced ATP production in response to MSC-secreted factors. Significant upregulation of EMT specific markers (N-cadherin, Vimentin, Twist and Snail) was also observed following co-culture with MSCs, with a reciprocal downregulation in E-cadherin protein expression. These changes were predominantly cell contact mediated and appeared to be MSC specific. Breast cancer cell morphology and growth pattern also altered in response to MSCs. MSCs may promote breast cancer metastasis through facilitation of EMT.

Prospective matched-pair comparison of outcome after treatment for lobular and ductal breast carcinoma.

BACKGROUND: Whether the prognosis of invasive lobular carcinoma is different from that of other invasive breast cancers is controversial. The aim of this study was to compare the outcome in age- and stage-matched patients with lobular carcinoma and those with invasive breast cancer, and in particular to compare predictors of outcome. METHODS: Data were obtained from a prospectively maintained database that included patients who had breast surgery for invasive cancer. Patients were matched for International Union Against Cancer stage and age at diagnosis within 5 years. Two patients with invasive ductal carcinoma were matched to each patient with invasive lobular carcinoma. RESULTS: There was no significant difference between invasive ductal and lobular carcinomas in terms of overall survival. Oestrogen receptor (ER)-positive invasive ductal carcinoma had a better prognosis than ER-positive invasive lobular carcinoma (P = 0.011). Similarly, ER-negative invasive ductal carcinoma was associated with worse survival than ER-negative invasive lobular carcinoma (P = 0.054). CONCLUSION: These results suggested that the differences in outcome between invasive ductal and lobular carcinomas may be determined by ER status.

Molecular diagnosis of vascular access device-associated infection in children being treated for cancer or leukaemia.

Blood samples were collected for quantitative 16S rDNA analysis from the vascular access device (VAD) of patients presenting with fever at participating centres of the UK Children's Cancer and Leukaemia Group. In total, 260 of 301 episodes of fever were evaluable and were classified as probable, possible, unlikely or unclassifiable VAD-associated infection. The sensitivity of the 16S rDNA assay declined concomitantly with delays from time of presentation to sampling. The sensitivity with >0.125 pg of bacterial DNA/microL of whole blood was 80% for the 20 probable VAD-associated infections diagnosed with samples collected on the day of or day following presentation. The specificity rose with increasing amounts of bacterial DNA, from 93% with >0.125 pg, to 98% with 0.25-0.5 pg, and to 100% with >0.5 pg/microL blood. The positive predictive value (for probable or possible) was 88% (95% CI 70-98%) with 0.25 pg/microL, and 100% (95% CI 83-100%) with >0.5 pg/microL. All 18 (6.8%) episodes with >0.5 pg of bacterial DNA/microL blood were associated with positive blood cultures. Identifications derived from the DNA sequence were consistent with the blood culture identifications for 15 of the 17 episodes with a DNA sequence identification. The VAD was removed because of suspected infection in six (2.8%) of 216 episodes with <0.125 pg of bacterial DNA/microL, in one (5%) of 20 episodes with 0.125-0.25 pg/microL, in one (16.7%) of six episodes with 0.25-0.5 pg/microL, and in nine (50%) of 18 episodes with >0.5 pg/microL. A bacterial DNA concentration of >0.5 pg/microL in blood drawn through a central venous catheter at the time of fever presentation had a high positive predictive value for VAD-associated infection and predicted an increased risk of VAD removal because of suspected infection.

Relevance of basal serum FSH to IVF outcome varies with patient age.

Live birth rate (LBR), age and basal serum FSH values were analysed in 1589 women undergoing their first cycle of IVF. Four age groups (<30, 30-34, 35-38, 39-45 years) and three FSH groups (<5, 5-9.9, > or =10 IU/l) were established. Logistic regression analysis was used to determine the effect of age and FSH on live birth. A model to predict the probability of a live birth suggests that an additional 10 years of age reduces the odds for live birth (OR = 0.66, 95% CI 0.48-0.91); an increase of FSH by 5 IU/l reduces the probability of live birth (OR = 0.75, 95% CI 0.61-0.92); women > or =39 years have an additional reduction in probability of live birth (OR = 0.58, 95% CI 0.61-0.92). Analysis by age and FSH categories showed that pregnancy rate (PR) did not change significantly with rising FSH for women <35 years old. In cycles started with serum FSH <5 IU/l, increasing age did not effect PR and LBR. Cycles started with serum FSH > or =10 IU/l had a PR and LBR of 23.6 and 16.9% respectively. The clinical relevance of elevated FSH varies according to age; younger women with elevated FSH and older women with low FSH still have an acceptable LBR.

Topical or oral ibuprofen for chronic knee pain in older people. The TOIB study.

OBJECTIVES: To determine whether GPs should advise their older patients with chronic knee pain to use topical or oral non-steroidal anti-inflammatory drugs (NSAIDs). DESIGN: An equivalence study was designed to compare the effect of advice to use preferentially oral or topical ibuprofen (an NSAID) on knee pain and disability, NSAID-related adverse effects and NHS/societal costs, using a randomised controlled trial (RCT) and a patient preference study (PPS). Reasons for patient preferences for topical or oral preparations, and attitudes to adverse effects, were explored in a qualitative study. SETTING: Twenty-six general practices in the UK. PARTICIPANTS: Participants comprised 585 people with knee pain, aged 50 years or over; 44% were male, mean age 64 years. The RCT had 282 participants: 144 in the oral group and 138 in the topical group. The PPS had 303 participants: 79 in the oral group and 224 in the topical group. INTERVENTIONS: Advice to use preferentially oral or topical NSAIDs for knee pain. OUTCOME MEASURES: The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures were the Short Form with 36 Items (SF-36), perceived troublesomeness of knee pain, satisfaction with health status, major adverse effects (unplanned hospital admissions and deaths) and minor adverse events over 12 months. The health economic analysis measured the comparative cost per quality-adjusted life-year (QALY) from both an NHS and a societal perspective over 1 and 2 years. RESULTS: Changes in the global WOMAC score at 12-months were equivalent in both studies: topical - oral, RCT difference=2 [95% confidence interval (CI) -2 to 6], PPS difference=1 (95% CI -4 to 6). There were no differences in the secondary outcomes, except for a suggestion, in the RCT, that those in the topical group were more likely to have more severe overall pain and disability as measured by the chronic pain grade, and more likely to report changing treatment because of inadequate pain relief. There were no differences in the rate of major adverse effects but some differences in the number of minor ones. In the RCT, 17% and 10% in the oral and the topical group, respectively, had a defined respiratory adverse effect (95% CI of difference -17% to -2.0%); after 12 months, the change in serum creatinine was 3.7 mmol/l (95% CI 0.9 to 6.5) less favourable in the oral than in the topical group, and 11% of those in the oral group reported changing treatment because of adverse effects compared with 1% in the topical group (p=0.02). None of these differences were seen in the PPS. Oral NSAIDs cost the NHS 191 pounds and 72 pounds more per participant over 1 year in the RCT and PPS respectively. In the RCT the cost per QALY in the oral group, from an NHS perspective, was in the range 9000-12,000 pounds. In the PPS it was 2564 pounds over 1 year, but over 2 years the oral route was more cost-effective. Patient preference for medication type was affected by previous experience of medication (including adverse reactions), other illness, pain elsewhere, anecdotes, convenience, severity of pain and perceived degree of degeneration. Lack of understanding about knee pain and the action of medication led to increased tolerance of symptoms. Potentially important symptoms may inadvertently have been disregarded, increasing participants' risk of suffering a major adverse effect. CONCLUSIONS: Advice to use either oral or topical preparations has an equivalent effect on knee pain, but oral NSAIDs appear to produce more minor adverse effects than topical NSAIDs. Generally, these results support advising older people with knee pain to use topical rather than oral NSAIDS. However, for patients who prefer oral NSAID preparations rather than a topical NSAID, particularly those with more widespread or severe pain, the oral route is a reasonable treatment option, provided that patients are aware of the risks of potentially serious adverse effects from oral medication. Further research is needed into strategies to change prescribing behaviour and ensure that older patients are aware of the potential risks and benefits of using NSAIDs. Observational studies are needed to estimate rates of different predefined minor adverse effects associated with the use of oral NSAIDs in older people as are long-term studies of topical NSAIDs in those for whom oral NSAIDs are not appropriate.

Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells.

PURPOSE: Major barriers to effective adenovirus-based gene therapy include induction of an immune response and tumor-specific targeting of vectors. The use of mesenchymal stem cells (MSC) as systemic delivery vehicles for therapeutic genes has been proposed as a result of their combined ability to home in on the tumor site and evade the host immune response. This study is aimed at investigating factors mediating homing of human MSCs to breast cancer primary cultures and cell lines in vitro and in vivo. EXPERIMENTAL DESIGN: Fluorescently labeled MSCs were given to mice bearing breast cancer xenografts, and tumor tissue was harvested to detect MSC engraftment. MSC migration in response to primary breast tumors in vitro was quantified, and chemokines secreted by tumor cells were identified. The role of monocyte chemotactic protein-1 (MCP-1) in cell migration was investigated using antibodies and standards of the chemokine. Serum MCP-1 was measured in 125 breast cancer patients and 86 healthy controls. RESULTS: Engrafted MSCs were detected in metastatic breast tumors in mice after systemic administration. There was a significant increase in MSC migration in response to primary breast tumor cells in vitro (6-fold to 11-fold increase). Tumor explants secreted a variety of chemokines including GROalpha, MCP-1, and stromal cell-derived factor-1alpha. An MCP-1 antibody caused a significant decrease (37-42%) in MSC migration to tumors. Serum MCP-1 levels were significantly higher in postmenopausal breast cancer patients than age-matched controls (P < 0.05). CONCLUSIONS: These results highlight a role for tumor-secreted MCP-1 in stimulating MSC migration and support the potential of these cells as tumor-targeted delivery vehicles for therapeutic agents.

Children's understanding of psychological problems displayed by their peers: a review of the literature.

BACKGROUND: There is a widespread consensus in the literature that children who have psychological problems are more likely than other children to be excluded or rejected by their peers. The existence of this phenomenon has been established, primarily with the use of research on their sociometric status within groups of peers. Much less research has been performed on the way in which children develop attitudes and behavioural intentions towards peers with problems. AIMS: The primary aim of this article is to introduce readers to research on children's understanding of the nature of common childhood psychological problems, with a view to exploring the factors that might contribute to the development of negative attitudes and behaviour. METHOD: Relevant publications were identified through searches of electronic databases and articles in print. RESULTS: From the early years of primary school, children are able to identify peers whose behaviour deviates from the norm and to suggest causes for the behaviour of peers with psychological problems. Furthermore, their beliefs about peers' personal responsibility for these problems appear to be a significant determinant of attitudes and behavioural intentions. The article identifies the need for more research on the role of factors such as gender and personal contact in determining children's understanding of, and attitudes towards, peers with psychological problems. In addition, the article calls for more research on mental health education programmes and the extension of these programmes to younger children, given the fact that even young primary school children appear to have beliefs about the causes of psychological problems and negative attitudes to peers who display such problems. CONCLUSIONS: Research on children's understanding of mental health can make an important contribution to our understanding of why children with problems are so much more likely to be excluded from their peer group.

The EPICure study: associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth.

AIMS: To describe perinatal factors associated with later morbidity among extremely preterm children at 30 months of age corrected for prematurity. POPULATION: Of 308 surviving children born at

Randomized trial of folic acid supplementation and serum homocysteine levels.

BACKGROUND: Lowering serum homocysteine levels with folic acid is expected to reduce mortality from ischemic heart disease. Homocysteine reduction is known to be maximal at a folic acid dosage of 1 mg/d, but the effect of lower doses (relevant to food fortification) is unclear. METHODS: We randomized 151 patients with ischemic heart disease to 1 of 5 dosages of folic acid (0.2, 0.4, 0.6, 0.8, and 1.0 mg/d) or placebo. Fasting blood samples for serum homocysteine and serum folate analysis were taken initially, after 3 months of supplementation, and 3 months after folic acid use was discontinued. RESULTS: Median serum homocysteine level decreased with increasing folic acid dosage, to a maximum at 0.8 mg of folic acid per day, when the homocysteine reduction (placebo adjusted) was 2.7 micromol/L (23%), similar to the known effect of folic acid dosages of 1 mg/d and above. The higher a person's initial serum homocysteine level, the greater was the response to folic acid, but there were statistically significant reductions regardless of the initial level. Serum folate level increased approximately linearly (5.5 nmol/L for every 0.1 mg of folic acid). Within-person fluctuations over time in serum homocysteine levels, measured in the placebo group, were large compared with the effect of folic acid, indicating that monitoring of the reduction in an individual is impractical. CONCLUSIONS: A dosage of folic acid of 0.8 mg/d appears necessary to achieve the maximum reduction in serum homocysteine level across the range of homocysteine levels in the population. Current US food fortification levels will achieve only a small proportion of the achievable homocysteine reduction.

Changing patterns of sedation use for routine out-patient diagnostic gastroscopy between 1989 and 1998.

BACKGROUND: Knowledge of sedation trends for upper gastrointestinal endoscopy is important for health service planning, particularly in view of rapidly increasing demands on endoscopy services. However, no data are available on sedation trends in Britain over the past 10 years. AIM: To determine sedation use for routine gastroscopy in a single endoscopy unit between 1989 and 1998. METHODS: This was a retrospective study of 9795 consecutive adults (mean age 56 years, range 18-100 years; 4512 females) who had undergone a gastroscopy between 1989 and 1998. Clinical, pharmacological and endoscopic data were retrieved from a computerized database. RESULTS: Over the 10-year study period, the sedation rate remained constant for patients undergoing therapeutic endoscopy (P=0.99) and those undergoing in-patient diagnostic examinations (P=0.63). In contrast, the sedation rate for out-patient diagnostic endoscopy decreased by 54%, from a high of 70% in 1990 to 32% in 1998 (P < 0.0001). Logistic regression analysis showed that the decline in sedation use was greater in females (P < 0.0001) than males and in procedures performed by non-consultant compared to consultant staff (P=0.01). CONCLUSIONS: If our results form part of a national trend, they will have important implications for cardiopulmonary monitoring strategies, recovery room practices and for complication rates due to the use of sedation for upper gastrointestinal endoscopy.

The effects of own fetal growth on reported hypertension in parous women aged 33.

BACKGROUND: Data from the study of the British 1958 birth cohort, National Child Development Study (NCDS), has allowed wider investigation of the relationship between retarded fetal growth and risk of adult hypertension. METHODS: A history of self-reported hypertension was related to fetal growth in 3308 parous cohort members. Fetal growth, the measure used, is the difference in actual birthweight from that expected for the gestational age and subsequent adult height. The relationships were investigated both linearly and non-linearly adjusting for potential confounders. RESULTS: After adjustment for confounding factors, including adult weight for height, retarded fetal growth was associated with reported hypertension particularly when not confined to pregnancy. The latter was also associated with accelerated fetal growth, moderate or severe hypertension in the mother when pregnant with the cohort member, being relatively taller than your mother, and lack of educational qualifications. Hypertension confined to pregnancy was more likely among women who were themselves firstborn or older at childbirth. Neither maternal smoking during cohort's gestation nor cohort member's gestational age had a significant effect. The results are consistent with previous reports that fetal growth effects are less marked if gestation is short. CONCLUSIONS: The relationships between fetal growth and subsequent hypertension are extremely complex and variable, and need to be studied allowing for deviations from growth potential. Adult weight for height remains the strongest predictor of hypertension. The results suggest that losing weight is likely to have the same proportional benefit in women with and without a history of retarded fetal growth.