Maternal bodies and medicines: a commentary on risk and decision-making of pregnant and breastfeeding women and health professionals

<p>Abstract</p> <p>Background</p> <p>The perceived risk/benefit balance of prescribed and over-the-counter (OTC) medicine, as well as complementary therapies, will significantly impact on an individual’s decision-making to use medicine. For women who are pregnant or breastfeeding, this weighing of risks and benefits becomes immensely more complex because they are considering the effect on two bodies rather than one. Indeed the balance may lie in opposite directions for the mother and baby/fetus. The aim of this paper is to generate a discussion that focuses on the complexity around risk, responsibility and decision-making of medicine use by pregnant and breastfeeding women. We will also consider the competing discourses that pregnant and breastfeeding women encounter when making decisions about medicine.</p> <p>Discussion</p> <p>Women rely not only on biomedical information and the expert knowledge of their health care professionals but on their own experiences and cultural understandings as well. When making decisions about medicines, pregnant and breastfeeding women are influenced by their families, partners and their cultural societal norms and expectations. Pregnant and breastfeeding women are influenced by a number of competing discourses. “Good” mothers should manage and avoid any risks, thereby protecting their babies from harm and put their children’s needs before their own – they should not allow toxins to enter the body. On the other hand, “responsible” women take and act on medical advice – they should take the medicine as directed by their health professional. This is the inherent conflict in medicine use for maternal bodies.</p> <p>Summary</p> <p>The increased complexity involved when one body’s actions impact the body of another – as in the pregnant and lactating body – has received little acknowledgment. We consider possibilities for future research and methodologies. We argue that considering the complexity of issues for maternal bodies can improve our understanding of risk and public health education.</p

A randomised trial of subcutaneous intermittent interleukin-2 without antiretroviral therapy in HIV-infected patients: the UK-Vanguard Study

Objective: The objective of the trial was to evaluate in a pilot setting the safety and efficacy of interleukin-2 (IL-2) therapy when used without concomitant antiretroviral therapy as a treatment for HIV infection. Design and Setting: This was a multicentre randomised three-arm trial conducted between September 1998 and March 2001 at three clinical centres in the United Kingdom. Participants: Participants were 36 antiretroviral treatment naive HIV-1-infected patients with baseline CD4 T lymphocyte counts of at least 350 cells/mm(3). Interventions: Participants were randomly assigned to receive IL-2 at 15 million international units (MIU) per day ( 12 participants) or 9 MIU/day ( 12 participants) or no treatment ( 12 participants). IL-2 was administered by twice-daily subcutaneous injections for five consecutive days every 8 wk. Outcome Measures: Primary outcome was the change from baseline CD4 T lymphocyte count at 24 wk. Safety and plasma HIV RNA levels were also monitored every 4 wk through 24 wk. The two IL-2 dose groups were combined for the primary analysis. Results: Area under curve (AUC) for change in the mean CD4 T lymphocyte count through 24 wk was 129 cells/mm(3) for those assigned IL-2 ( both dose groups combined) and 13 cells/mm(3) for control participants (95% CI for difference, 51.3 - 181.2 cells/mm(3); p = 0.0009). Compared to the control group, significant increases in CD4 cell count were observed for both IL-2 dose groups: 104.2/mm(3) ( p = 0.008) and 128.4 cells/mm(3) ( p = 0.002) for the 4.5 and 7.5 MIU dose groups, respectively. There were no significant differences between the IL-2 (0.13 log(10) copies/ ml) and control (0.09 log(10) copies/ml) groups for AUC of change in plasma HIV RNA over the 24-wk period of follow- up ( 95% CI for difference, - 0.17 to 0.26; p = 0.70). Grade 4 and dose-limiting side effects were in keeping with those previously reported for IL-2 therapy. Conclusions: In participants with HIV infection and baseline CD4 T lymphocyte counts of at least 350 cells/mm(3), intermittent subcutaneous IL-2 without concomitant antiretroviral therapy was well tolerated and produced significant increases in CD4 T lymphocyte counts and did not adversely affect plasma HIV RNA levels

Critical Role for the Host GTPase-Activating Protein ARAP2 in InlB-Mediated Entry of Listeria monocytogenes

The bacterial pathogen Listeria monocytogenes causes food-borne illnesses culminating in gastroenteritis, meningitis, or abortion. Listeria induces its internalization into some mammalian cells through binding of the bacterial surface protein InlB to the host receptor tyrosine kinase Met. Interaction of InlB with the Met receptor elicits host downstream signaling pathways that promote F-actin cytoskeletal changes responsible for pathogen engulfment. Here we show that the mammalian signaling protein ARAP2 plays a critical role in cytoskeletal remodeling and internalization of Listeria. Depletion of ARAP2 through RNA interference (RNAi) caused a marked inhibition of InlB-mediated F-actin rearrangements and bacterial entry. ARAP2 contains multiple functional domains, including a GTPase-activating protein (GAP) domain that antagonizes the GTPase Arf6 and a domain capable of binding the GTPase RhoA. Genetic data indicated roles for both the Arf GAP and RhoA binding domains in Listeria entry. Experiments involving Arf6 RNAi or a constitutively activated allele of Arf6 demonstrated that one of the ways in which ARAP2 promotes bacterial uptake is by restraining the activity of Arf6. Conversely, Rho activity was dispensable for Listeria internalization, suggesting that the RhoA binding domain in ARAP2 acts by engaging a host ligand other than Rho proteins. Collectively, our findings indicate that ARAP2 promotes InlB-mediated entry of Listeria, in part, by antagonizing the host GTPase Arf6

Ringing up about breastfeeding: a randomised controlled trial exploring early telephone peer support for breastfeeding (RUBY) - trial protocol

BACKGROUND: The risks of not breastfeeding for mother and infant are well established, yet in Australia, although most women initiate breastfeeding many discontinue breastfeeding altogether and few women exclusively breastfeed to six months as recommended by the World Health Organization and Australian health authorities. We aim to determine whether proactive telephone peer support during the postnatal period increases the proportion of infants who are breastfed at six months, replicating a trial previously found to be effective in Canada. DESIGN/METHODS: A two arm randomised controlled trial will be conducted, recruiting primiparous women who have recently given birth to a live baby, are proficient in English and are breastfeeding or intending to breastfeed. Women will be recruited in the postnatal wards of three hospitals in Melbourne, Australia and will be randomised to peer support or to 'usual' care. All women recruited to the trial will receive usual hospital postnatal care and infant feeding support. For the intervention group, peers will make two telephone calls within the first ten days postpartum, then weekly telephone calls until week twelve, with continued contact until six months postpartum. Primary aim: to determine whether postnatal telephone peer support increases the proportion of infants who are breastfed for at least six months. HYPOTHESIS: that telephone peer support in the postnatal period will increase the proportion of infants receiving any breast milk at six months by 10% compared with usual care (from 46% to 56%).Outcome data will be analysed by intention to treat. A supplementary multivariate analysis will be undertaken if there are any baseline differences in the characteristics of women in the two groups which might be associated with the primary outcomes. DISCUSSION: The costs and health burdens of not breastfeeding fall disproportionately and increasingly on disadvantaged groups. We have therefore deliberately chosen trial sites which have a high proportion of women from disadvantaged backgrounds. This will be the first Australian randomised controlled trial to test the effectiveness and cost effectiveness of proactive peer telephone support for breastfeeding. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12612001024831

Outcomes of a four-year specialist-taught physical education program on physical activity: a cluster randomized controlled trial, the LOOK study

BackgroundThe objective of this study was to investigate the effect of a 4-year specialist-taught Physical Education (PE) program on physical activity (PA) among primary school children.MethodsA 4-year cluster randomised controlled trial was conducted in children (initially aged 8 years) from 29 primary schools (13 Intervention, 16 Control). Intervention students (N&thinsp;=&thinsp;457) received 2&thinsp;&times;&thinsp;45 min PE lessons per week from specialist-trained PE teachers (68 lessons per year, 272 lessons over 4 years). Control group students (N&thinsp;=&thinsp;396) received usual practice PE from generalist classroom teachers. PA during PE lessons was examined using the System for Observing Fitness Instruction Time (SOFIT). Pedometers (steps/day) were worn for 7 days each year, and accelerometers were worn concurrently in the final two years to assess moderate to vigorous (MVPA) and sedentary activity. Linear and generalized mixed models were used to determine differences in Intervention and Control student PA and the proportion of students meeting PA guidelines.ResultsThe intervention increased SOFIT-observed student MVPA during PE lessons by 6.5 mins (16.7 v 10.2, p&thinsp;&lt;&thinsp;0.001). Within intervention schools, participants increased their whole-day step counts (boys&thinsp;=&thinsp;449 [CI,140 to 756]; girls&thinsp;=&thinsp;424 [CI,222 to 626]) and minutes of MVPA (boys&thinsp;=&thinsp;8.0 [CI,6.8 to 9.2]; girls&thinsp;=&thinsp;3.5 [CI,1.7 to 5.4]) on PE days. However, compared to the Control group the Intervention did not: increase habitual steps/day or MVPA when averaged over 7 days; elicit greater improvements in these measures over time; or increase the odds of meeting step/day or MVPA recommendations. At age 11 years Intervention group boys were 20 mins less sedentary per day (380 [CI,369 to 391] vs 360 [CI,350 to 369]) and this effect was sustained at age 12 years.ConclusionsWell-designed specialist-taught PE can improve student PA during PE lessons. However for PE to be a significant contributor to improving habitual PA in pre-adolescent children, daily classes are likely to be required, and even this would need to be supplemented with a wider multicomponent strategy. Our finding of a reduction in sedentary time among Intervention boys warrants further investigation into the potential role PE could play in influencing sedentary behaviour.<br /

Diabetes mellitus in centenarians

OBJECTIVES: Describe prevalence of diabetes mellitus among centenarians. DESIGN: Cross-sectional, population-based. SETTING: 44 counties in northern Georgia. PARTICIPANTS: 244 centenarians (aged 98-108, 15.8% men, 20.5% African-American, 38.0% community-dwelling) from the Georgia Centenarian Study (2001-2009). MEASUREMENTS: Nonfasting blood samples assessed HbA(1c) and relevant clinical parameters. Demographic, diagnosis, and diabetes complications covariates were assessed. RESULTS: 12.5% of centenarians were known to have diabetes. Diabetes was more prevalent among African-Americans (27.7%) than Whites (8.6%, p=.0002). There were no differences between men (16.7%) and women (11.7%, p=.414), centenarians living in the community (10.2%) or facilities (13.9%, p=.540). Diabetes was more prevalent among overweight/obese (23.1%) than non-overweight (7.1%, p=.002) centenarians. Anemia (78.6% versus 48.3%, p=.004) and hypertension (79.3% versus 58.6%, p=.041) were more prevalent among centenarians with diabetes than without and centenarians with diabetes took more nonhypoglycemic medications(8.6 versus 7.0, p=.023). No centenarians with hemoglobin A1c < 6.5% had random serum glucose levels above 200 mg/dl. Diabetes was not associated with 12 month all-cause mortality, visual impairment, amputations, cardiovascular disease or neuropathy. 37% of centenarians reported onset before age 80 (survivors), 47% between 80 and 97 years (delayers) and 15% age 98 or older (escapers). CONCLUSION: Diabetes is a risk factor for cardiovascular disease and mortality, but is seen in persons who live into very old age. Aside from higher rates of anemia and use of more medications, few clinical correlates of diabetes were observed in centenarians

A systematic review and meta-analysis of effects of early life non-cognitive skills on academic, psychosocial, cognitive and health outcomes

Success in school and the labour market relies on more than high intelligence. Associations between "non-cognitive" skills in childhood, such as attention, self-regulation, and perseverance, and later outcomes have been widely investigated. In a systematic review of this literature, we screened 9553 publications, reviewed 554 eligible publications, and interpreted results from 222 better quality publications. Better quality publications comprised randomised experimental and quasi-experimental studies (EQIs), and observational studies that made reasonable attempts to control confounding. For academic achievement outcomes there were 26 EQI publications but only 14 were available for meta-analysis with effects ranging from 0.16 to 0.37SD. However, within sub-domains effects were heterogeneous. The 95% prediction interval for literacy was consistent with negative, null and positive effects (-0.13 to 0.79). Similarly heterogeneous findings were observed for psychosocial, cognitive and language, and health outcomes. Funnel plots of EQIs and observational studies showed asymmetric distributions and potential for small study bias. There is some evidence that non-cognitive skills associate with improved outcomes. However, there is potential for small study and publication bias that may over-estimate true effects, and heterogeneity of effect estimates spanned negative, null and positive effects. The quality of evidence from EQIs under-pinning this field is lower than optimal and more than a third of observational studies made little or no attempt to control confounding. Interventions designed to develop children's non-cognitive skills could potentially improve outcomes. The inter-disciplinary researchers interested in these skills should take a more strategic and rigorous approach to determine which interventions are most effective.Lisa G. Smithers, Alyssa C.P. Sawyer, Catherine R. Chittleborough, Neil M. Davies, George Davey Smith and John W. Lync