Evidence for avoiding the biopsy of typical fibroadenomas in women aged 25-29 years.

AIM: To determine if any malignancies would have been missed in women aged 25-29 years in the absence of needle biopsy of sonographically typical fibroadenomas, and to present a non-biopsy protocol for fibroadenomas in this age group using strict criteria. MATERIALS AND METHODS: Women aged 25-29 years undergoing needle biopsies in three centres over a collective 16-year period were identified. Imaging, clinical information, needle biopsy, and surgical histopathology results were obtained from hospital medical records at each centre. RESULTS: Between January 2001 and December 2016, 885 women aged 25-29 years underwent core biopsy. Of 595 sonographically typical fibroadenomas, 549 were histologically confirmed fibroadenomas, 46 were other benign entities, none were cancers. All cancers were scored as indeterminate or suspicious on ultrasound. With a non-biopsy protocol in clinical practice in Centre A, between 2009 and 2018, 259 sonographically typical fibroadenomas met criteria for non-biopsy, and to date, no cancers have been missed. CONCLUSION: This study provides evidence for safe non-biopsy of typical fibroadenomas in women aged 25-29 years when the clinical and sonographic presentations meet strict criteria. A protocol for non-biopsy to include this age group is suggested on incorporation of these results into existing guidance for managing younger women.

Barriers and facilitators to young children's physical activity and sedentary behaviour: a systematic review and synthesis of qualitative literature.

Positive activity behaviours (i.e. higher physical activity [PA]/lower sedentary behaviour [SB]) are beneficial from infancy, yet evidence suggests that young children (0- to 6-year-olds) are relatively inactive. To better understand the perceived influences on these behaviours and to aid intervention development, this paper systematically synthesizes the extensive qualitative literature regarding perceived barriers and facilitators to PA and SB in young children (0-6 years old). A search of eight electronic databases (July 2016) identified 43 papers for inclusion. Data extraction and evidence synthesis were conducted using thematic content analysis, underpinned by the socio-ecological model (i.e. individual, interpersonal, community, organizational and policy levels). Parents, childcare providers and children perceived seven broad themes to be important for PA and SB, including the child; the home; out-of-home childcare; parent-childcare provider interactions; environmental factors; safety; and weather. Each theme mapped onto between one and five levels of the socio-ecological model; barriers and facilitators at the interpersonal level (e.g. parents, care providers and family) were most frequently cited, reflecting the important (perceived) role adults/peers play in shaping young children's behaviours. We provide an overarching framework to explain PA and SB in early childhood. We also highlight where gaps in the current literature exist (e.g. from male carers; in developing countries; and barriers and facilitators in the environmental and policy domains) and where future quantitative work may focus to provide novel insights about children's activity behaviours (e.g. safety and weather).

Premenopausal abnormal uterine bleeding and risk of endometrial cancer.

BACKGROUND: Endometrial biopsies are undertaken in premenopausal women with abnormal uterine bleeding but the risk of endometrial cancer or atypical hyperplasia is unclear. OBJECTIVES: To conduct a systematic literature review to establish the risk of endometrial cancer and atypical hyperplasia in premenopausal women with abnormal uterine bleeding. SEARCH STRATEGY: Search of PubMed, Embase and the Cochrane Library from database inception to August 2015. SELECTION CRITERIA: Studies reporting rates of endometrial cancer and/or atypical hyperplasia in women with premenopausal abnormal uterine bleeding. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers and cross-checked. For each outcome, the risk and a 95% CI were estimated using logistic regression with robust standard errors to account for clustering by study. MAIN RESULTS: Sixty-five articles contributed to the analysis. Risk of endometrial cancer was 0.33% (95% CI 0.23-0.48%, n = 29 059; 97 cases) and risk of endometrial cancer or atypical hyperplasia was 1.31% (95% CI 0.96-1.80, n = 15 772; 207 cases). Risk of endometrial cancer was lower in women with heavy menstrual bleeding (HMB) (0.11%, 95% CI 0.04-0.32%, n = 8352; 9 cases) compared with inter-menstrual bleeding (IMB) (0.52%, 95% CI 0.23-1.16%, n = 3109; 14 cases). Of five studies reporting the rate of atypical hyperplasia in women with HMB, none identified any cases. CONCLUSIONS: The risk of endometrial cancer or atypical hyperplasia in premenopausal women with abnormal uterine bleeding is low. Premenopausal women with abnormal uterine bleeding should first undergo conventional medical management. Where this fails, the presence of IMB and older age may be indicators for further investigation. Further research into the risks associated with age and the cumulative risk of co-morbidities is needed. TWEETABLE ABSTRACT: Contrary to practice, premenopausal women with heavy periods or inter-menstrual bleeding rarely require biopsy.

Determinants of sugar-sweetened beverage consumption in young children: a systematic review.

Sugar-sweetened beverage (SSB) consumption is associated with adverse health outcomes. Improved understanding of the determinants will inform effective interventions to reduce SSB consumption. A total of 46,876 papers were identified through searching eight electronic databases. Evidence from intervention (n = 13), prospective (n = 6) and cross-sectional (n = 25) studies on correlates/determinants of SSB consumption was quality assessed and synthesized. Twelve correlates/determinants were associated with higher SSB consumption (child's preference for SSBs, TV viewing/screen time and snack consumption; parents' lower socioeconomic status, lower age, SSB consumption, formula milk feeding, early introduction of solids, using food as rewards, parental-perceived barriers, attending out-of-home care and living near a fast food/convenience store). Five correlates/determinants were associated with lower SSB consumption (parental positive modelling, parents' married/co-habiting, school nutrition policy, staff skills and supermarket nearby). There was equivocal evidence for child's age and knowledge, parental knowledge, skills, rules/restrictions and home SSB availability. Eight intervention studies targeted multi-level (child, parents, childcare/preschool setting) determinants; four were effective. Four intervention studies targeted parental determinants; two were effective. One (effective) intervention targeted the preschool environment. There is consistent evidence to support potentially modifiable correlates/determinants of SSB consumption in young children acting at parental (modelling), child (TV viewing) and environmental (school policy) levels.

Developing a programme for healthy growth and nutrition during infancy: understanding user perspectives.

BACKGROUND: Avoiding excess energy intake and rapid weight gain during infancy may be effective in preventing childhood obesity. We developed a programme for healthy growth and nutrition in formula milk-fed babies. The aim of this study was to understand users' perspectives about the programme and planned trial. METHODS: We conducted three focus group discussions (10 mothers) and nine individual interviews (seven health visitors, one midwife and one mother) discussing the programme materials and trial protocol. All sessions were transcribed verbatim and a thematic analysis was performed using the framework approach. RESULTS: Mothers reported receiving conflicting messages about infant feeding and were keen for consistent advice. They welcomed the support that the programme would offer to mothers who gave their babies formula milk, but some were sceptical about the feasibility of limiting formula milk quantities. They suggested that recommended quantities should be presented as general guidelines rather than rigid rules. Some mothers said that it was too early to intervene to prevent obesity, that babies could not be overfed and that the risks of formula milk feeding had been exaggerated. Because of the routine advice to feed on demand, babies were fed in response to crying, and crying was equated with 'hunger'. Some mothers said that growth was genetically determined so they ignored the growth charts. Health visitors used the growth charts to assess adequate weight gain rather than to identify excess weight gain. Health visitors said that mothers would need a lot of education and support to limit formula milk quantities. CONCLUSIONS: Efforts to prevent childhood obesity by avoiding excess weight gain during infancy have to address mothers' beliefs that babies cannot be overfed, that crying always signals hunger and that growth is determined by genes rather than nutrition. Mothers and healthcare providers have different motivations and understanding these are important in the development of any intervention.

Mothers' experiences of bottle-feeding: a systematic review of qualitative and quantitative studies.

OBJECTIVE: Most babies receive at least some formula milk. Variations in formula-feeding practices can have both short- and long-term health consequences. The literature on parents' experiences of bottle-feeding was systematically reviewed to understand how formula-feeding decisions are made. METHODS: Relevant English-language papers, identified by searching 12 electronic databases, reference lists and related articles and by contacting first authors of included papers, were systematically searched for and appraised. The included studies were analysed and synthesised using a combination of narrative and thematic approaches. Consensus on the final inclusion, interpretation and synthesis of studies was reached across the research team. RESULTS: Six qualitative studies and 17 quantitative studies (involving 13 263 participants) were included. Despite wide differences in study design, context, focus and quality, several consistent themes emerged. Mothers who bottle-fed their babies experienced negative emotions such as guilt, anger, worry, uncertainty and a sense of failure. Mothers reported receiving little information on bottle-feeding and did not feel empowered to make decisions. Mistakes in preparation of bottle-feeds were common. No studies examined how mothers made decisions about the frequency or quantity of bottle-feeds. CONCLUSIONS: Inadequate information and support for mothers who decide to bottle-feed may put the health of their babies at risk. While it is important to promote breastfeeding, it is also necessary to ensure that the needs of bottle-feeding mothers are met.

Association between age at menarche and risk of diabetes in adults: results from the EPIC-Norfolk cohort study.

AIMS/HYPOTHESIS: Earlier age at menarche is associated with increased BMI and obesity risk from early childhood through to adulthood. We hypothesised that earlier age at menarche would also predict subsequent diabetes risk. METHODS: This was a population-based prospective cohort study of 13,308 women, who were aged 40 to 75 years between 1993 and 1997 and participating in the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). We used data on age at menarche and ascertained diabetes incidence to 2005. RESULTS: There were 734 cases of diabetes (363 incident and 371 prevalent cases). Mean age at menarche was lower in women with diabetes than in non-diabetic women (12.8 vs 13.0 years, p = 0.008). Compared with the earliest quintile (menarche at 8-11 years), women in the oldest quintile (menarche at 15-18 years) had lower BMI (25.5 vs 27.4 kg/m2, p < 0.0001) and a reduced risk of diabetes (OR 0.66 [95% CI 0.51-0.86] adjusted for age, family history, physical activity, smoking, occupational social class, parity and use of hormonal preparations). The association between age at menarche and diabetes was linear (adjusted OR 0.91 [95% CI 0.87-0.96] per 1 year later menarche) and appeared to be completely mediated by adult BMI or waist circumference (OR 0.98 [95% CI 0.93-1.03], further adjusted for BMI at age 40-75 years). CONCLUSIONS/INTERPRETATION: Earlier age at menarche increases the risk of diabetes in women and this association appears to be mediated by increased adiposity. History of earlier menarche may help to identify women with increased subsequent risk of diabetes.

Implications of adopting the WHO 2006 Child Growth Standard in the UK: two prospective cohort studies.

BACKGROUND: The WHO 2006 Child Growth Standard is based on data from international optimally nourished breastfed infants from birth to age 5 years. OBJECTIVE: To assess the potential effect of its use on weight and growth monitoring of UK children. PARTICIPANTS: Full-term members of two population-based UK birth cohorts: the Children in Focus sub-cohort of the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 1335) and the Gateshead Millennium Baby Study (GMS; n = 923). DESIGN: Growth data from birth to 5 years were converted into z-scores relative to the WHO 2006 standard. RESULTS: Compared with the WHO standard, both UK cohorts had higher birth weights (mean z-scores: GMS, 0.17; ALSPAC, 0.34) and ALSPAC had higher birth lengths. After birth, length showed a good fit at all ages. By 2-4 months, both cohorts were similar in weight to the WHO median (mean WHO weight z-score at 4 months: GMS, 0.01; ALSPAC, -0.07), but thereafter the UK cohorts were heavier (mean WHO weight z-score at 12 months: GMS, 0.57; ALSPAC, 0.65). At age 12 months, the risk of being classified as underweight (weight <2nd centile) was considerably lower according to the WHO standard than by the UK 1990 Growth Reference (RR = 0.15, 95% CI = 0.07 to 0.32), and the risk of being classified as obese at 4-5 years (body mass index >98th centile) was slightly increased (RR = 1.35, 95% CI = 1.02 to 1.78). CONCLUSIONS: Adoption of the WHO 2006 Growth Charts would set a markedly lower standard of weight gain beyond the age of 4 months for UK infants and could support efforts to avoid future childhood obesity. However, the WHO standard is not representative of size at birth in the UK.

Complement, fetal antigen, and shaking rigors in parturients.

OBJECTIVES: To assess the relationship, if any, between complement, fetal antigen, and shaking rigors during labor and delivery. METHODS: We recruited 13 volunteers for serial blood sampling during labor and childbirth. RESULTS: Complement levels had a small but significant drop (11-15%) immediately following childbirth but had no association with fetal antigen levels or shaking rigors. Fetal antigen levels failed to show any consistent relationship with shaking rigors or the labor and delivery process. CONCLUSION: Shaking rigors do not appear to be associated with changes in either complement or fetal antigen levels. Complement levels remain stable during labor but drop immediately following birth.

Postmortem diagnosis of chronic granulomatous disease: how worthwhile is it?

A previously healthy 11 year old boy died unexpectedly after a rapid course of progressive pneumonia. Postmortem microbiology and histopathology suggested an underlying diagnosis of chronic granulomatous disease. This was confirmed by neutrophil oxidative burst and gene mutation analysis of other family members, one of whom benefited from early bone marrow transplantation.

Novel in vitro perfusion model to study the interaction between coagulation and blood-borne metastasis.

The association between cancer and hemostasis has long been studied in cell culture, animal models, and cancer patients developing thrombosis. The variety of biologic mechanisms involved in malignancy and metastasis makes the understanding of the relative importance of each mechanism difficult. We have developed a novel in vitro perfusion model that allows for the isolated study of the interactions between tumor cells and components of the hemostatic system under normal physiologic conditions. Segments of denuded umbilical cord or saphenous vein are cut longitudinally and mounted in a perfusion chamber under sterile conditions. Human breast cancer cells are perfused for 24 h under venous flow conditions with either whole blood (WB), platelet-rich plasma (PRP), platelet-poor plasma (PPP), or serum. Tissue samples are fixed and stained with hematoxylin and eosin as well as with pan-cytokeratin. Morphometric analysis is performed to quantify cancer cell adhesion. With PRP, this model maintains normal human physiologic conditions for the duration of the experiment. It differentiates between previously characterized high and low metastatic breast cancer cell lines. In addition, different vein tissue types do not alter tumor cell attachment. This model appears to be an accurate representation of the pathophysiology of in vivo metastasis. This model may serve as a useful bridge between cell culture studies and animal models. It may be a useful tool to elucidate the role of selected hemostatic systems in blood-borne metastasis and may potentially serve as a screening tool for the development of antimetastatic pharmaceutical agents.

Pneumococcal nasopharyngeal carriage in children following heptavalent pneumococcal conjugate vaccination in infancy.

AIMS: To ascertain whether the reduction in nasopharyngeal carriage of vaccine serotypes induced by pneumococcal conjugate vaccine (PnCV) administered to infants persists beyond the age of 2 years. METHODS: Non-randomised, unblinded controlled study of 2-5 year old children who had received three doses of heptavalent PnCV (7VPnCV) in infancy and 23-valent pneumococcal polysaccharide vaccine at 13 months, and unimmunised controls. Nasopharyngeal swabs were taken in summer (150 vaccinated subjects, 126 controls) and winter (143 vaccinated subjects, 188 controls). The swabs were cultured and serotyped for Streptococcus pneumoniae. RESULTS: Carriage rates (vaccinated subjects: 24.7% and 43.4%; controls: 27.0% and 41.0%, in summer and winter respectively) and carriage of vaccine serotypes (subjects: 10.0% and 30.0%; controls: 13.5% and 31.5%, in summer and winter respectively) were similar in the two groups. CONCLUSIONS: Effects of vaccination in infancy on rates of nasal carriage of pneumococcus and serotype replacement in children living in a largely unvaccinated population are no longer evident by 2-5 years of age.

Safety of a new conjugate meningococcal C vaccine in infants.

BACKGROUND: Group C conjugate meningococcal vaccines (Men C) were introduced into the UK primary immunisation schedule in November 1999. There has been extensive professional and public interest in their efficacy and safety. AIM: To determine the occurrence of at least one uncommon adverse event in infants related to the administration of the Chiron Men C vaccine. METHODS: A total of 2796 infants aged approximately 2 months were recruited into the study from areas in and around Sheffield and from Scotland. They were vaccinated with the Chiron Men C vaccine at 2, 3, and 4 months along with routine immunisations. Data on adverse events occurring one month after each dose were collected actively and prospectively and reviewed for possible relation to the vaccine. RESULTS: There were no deaths. There were no serious adverse events considered definitely or probably caused by the vaccine. Four infants developed serious adverse events (hypotonia, screaming syndrome, maculopapular rash, and agitation, respectively) that were considered possibly related to the vaccine. All recovered completely. Adverse events were seen in 1804 children but were considered possibly related to the vaccine in only 49 (1.8%). On subsequent immunisation there were no recurrences of adverse events considered to be possibly related to the vaccine.

Primary and booster mucosal immune responses to meningococcal group A and C conjugate and polysaccharide vaccines administered to university students in the United Kingdom.

Meningococcal group A+C capsular polysaccharide (PS) conjugate vaccines may prime for serum immunoglobulin G (IgG) memory responses to meningococcal capsular PS. It is not known whether these vaccines induce immunological memory at the mucosal level, which may be important in reducing nasopharyngeal carriage. Mucosal immune responses to meningococcal conjugate and PS vaccines in young adults were investigated. Healthy university students were randomized to receive either a groups A+C meningococcal conjugate vaccine (MACconj, n = 100) or a group A+C meningococcal PS vaccine (MACPS, n = 95). One year after the primary immunization, both groups were randomized again to receive a MACconj or a MACPS booster vaccination. Saliva samples were collected before and 1 month after the primary and booster vaccinations. Anti-meningococcal A (MenA) and C (MenC) PS IgA and IgG antibody levels were measured by a standard enzyme-linked immunosorbent assay. After the primary vaccination, salivary MenA and MenC IgG and MenA IgA concentrations were significantly increased after immunization with both MACconj and MACPS vaccines, but the salivary Men C IgA level was increased only after MACPS vaccine (P < 0.01). IgA responses to both serogroups were greater for MACPS than MACconj vaccine (P < 0.05), whereas no significant differences were seen for IgG responses. MenA IgG titers were higher after the MACPS booster in MACconj-primed subjects than after the MACPS primary vaccination, suggesting the presence of IgG memory. Antibody responses to a dose of either MACPS or MACconj were not significantly reduced in those previously given MACPS compared to the primary responses to those vaccines. Meningococcal A+C conjugate and PS vaccines induce significant mucosal responses in young adults. MACconj priming may induce IgG memory at the mucosal level, which is likely to be a reflection of an anamnestic serum IgG response. No evidence of mucosal hyporesponsiveness was observed after MACPS priming in this study.