Exhaled nitric oxide monitoring does not reduce exacerbation frequency or inhaled corticosteroid dose in paediatric asthma: a randomised controlled trial

Introduction: Inhaled corticosteroid therapy (ICS) for asthma is currently modified according to symptoms and lung function. Fractional exhaled nitric oxide (FENO) has been demonstrated to be a non-invasive marker of eosinophilic inflammation. Studies of FENO-driven asthma management show variable success. / Objectives: This study aimed to evaluate whether monitoring FENO can improve outpatient management of children with moderate to severe asthma using a pragmatic design. / Methods: Children aged 6–17 years with moderate to severe asthma were recruited. Their asthma was stabilised before randomisation to FENO-driven therapy or to a standard management group where therapy was driven by conventional markers of asthma control. ICS or long-acting bronchodilator therapies were altered according to FENO levels in combination with reported symptoms in the FENO group. Participants were assessed 2 monthly for 12 months. ICS dose and exacerbation frequency change were compared between groups in an intention to treat analysis. / Results: Ninety children were randomised. No difference was found between the two groups in either change in corticosteroid dose or exacerbation frequency. Results were similar in a planned secondary analysis of atopic asthmatics. / Conclusion: FENO-guided ICS titration does not appear to reduce corticosteroid usage or exacerbation frequency in paediatric outpatients with moderate to severe asthma. This may reflect limitations in FENO-driven management algorithms, as there are now concerns that FENO levels relate to atopy as much as they relate to asthma control

Task Shifting for Scale-up of HIV Care: Evaluation of Nurse-Centered Antiretroviral Treatment at Rural Health Centers in Rwanda

Fabienne Shumbusho and colleagues evaluate a task-shifting model of nurse-centered antiretroviral treatment prescribing in rural primary health centers in Rwanda and find that nurses can effectively and safely prescribe ART when given adequate training, mentoring, and support

Mental health policy process: a comparative study of Ghana, South Africa, Uganda and Zambia

<p>Abstract</p> <p>Background</p> <p>Mental illnesses are increasingly recognised as a leading cause of disability worldwide, yet many countries lack a mental health policy or have an outdated, inappropriate policy. This paper explores the development of appropriate mental health policies and their effective implementation. It reports comparative findings on the processes for developing and implementing mental health policies in Ghana, South Africa, Uganda and Zambia as part of the Mental Health and Poverty Project.</p> <p>Methods</p> <p>The study countries and respondents were purposively selected to represent different levels of mental health policy and system development to allow comparative analysis of the factors underlying the different forms of mental health policy development and implementation. Data were collected using semi-structured interviews and document analysis. Data analysis was guided by conceptual framework that was developed for this purpose. A framework approach to analysis was used, incorporating themes that emerged from the data and from the conceptual framework.</p> <p>Results</p> <p>Mental health policies in Ghana, South Africa, Uganda and Zambia are weak, in draft form or non-existent. Mental health remained low on the policy agenda due to stigma and a lack of information, as well as low prioritisation by donors, low political priority and grassroots demand. Progress with mental health policy development varied and respondents noted a lack of consultation and insufficient evidence to inform policy development. Furthermore, policies were poorly implemented, due to factors including insufficient dissemination and operationalisation of policies and a lack of resources.</p> <p>Conclusions</p> <p>Mental health policy processes in all four countries were inadequate, leading to either weak or non-existent policies, with an impact on mental health services. Recommendations are provided to strengthen mental health policy processes in these and other African countries.</p

Impact of lipid measurements in youth in addition to conventional clinic-based risk factors on predicting preclinical atherosclerosis in adulthood: The International Childhood Cardiovascular Cohort (i3C) Consortium

Background: Data suggest that the prediction of adult cardiovascular disease using a model comprised entirely of adult non-laboratory based risk factors is equivalent to an approach that additionally incorporates adult lipid measures. We assessed and compared the utility of a risk model based solely on non-laboratory risk factors in adolescence vs. a lipid model based on non-laboratory risk factors + lipids for predicting high-risk carotid intima-media thickness (cIMT) in adulthood. Methods: The study comprised 2,893 participants aged 12-18 years from four longitudinal cohort studies from the United States (Bogalusa Heart Study and the Insulin Study), Australia (Childhood Determinants of Adult Health Study) and Finland (The Cardiovascular Risk in Young Finns Study) and followed into adulthood when cIMT was measured (mean follow-up 23.4 years). Overweight status was defined according to the Cole classification. Hypertension was defined according to the Fourth Report on High Blood Pressure in Children and Adolescents from the National High Blood Pressure Education Program. High-risk plasma lipid levels were defined according to the National Cholesterol Education Program (NCEP) Expert Panel on Cholesterol Levels in Children. High cIMT was defined as a study-specific value ≥90th percentile. Age-and sex were included in each model. Results: In univariate models all risk factors except for borderline high-and high triglycerides in adolescence were associated with high cIMT in adulthood. In multivariable models (RR [95% CI]), male sex (2.7 [2.0-2.6]), pre-hypertension (1.4 [1.0-1.9]), hypertension (1.9 [1.3-2.9]), overweight (2.0 [1.4-2.9]), obesity (3.7 [2.0-7.0]), borderline high LDL-cholesterol (1.6 [1.2-2.2]), high LDL-cholesterol (1.6 [1.1-2.1]) and borderline low HDL-cholesterol (1.4 [1.0-1.8]) remained significant predictors of high cIMT (P always Conclusions: Non-laboratory-based risk factors and lipids measured in adolescence independently predicted preclinical atherosclerosis in young adulthood. The addition of lipid measurements to traditional clinic based risk factor assessment provided a statistically significant but clinically modest improvement on adolescent prediction of high cIMT in adulthood

Entropy of dynamical social networks

Human dynamical social networks encode information and are highly adaptive. To characterize the information encoded in the fast dynamics of social interactions, here we introduce the entropy of dynamical social networks. By analysing a large dataset of phone-call interactions we show evidence that the dynamical social network has an entropy that depends on the time of the day in a typical week-day. Moreover we show evidence for adaptability of human social behavior showing data on duration of phone-call interactions that significantly deviates from the statistics of duration of face-to-face interactions. This adaptability of behavior corresponds to a different information content of the dynamics of social human interactions. We quantify this information by the use of the entropy of dynamical networks on realistic models of social interactions

Staphylococcus aureus forms spreading dendrites that have characteristics of active motility

Staphylococcus aureus is historically regarded as a non-motile organism. More recently it has been shown that S. aureus can passively move across agar surfaces in a process called spreading. We re-analysed spreading motility using a modified assay and fo- cused on observing the formation of dendrites: branching structures that emerge from the central colony. We discovered that S. aureus can spread across the surface of media in struc- tures that we term ‘comets’, which advance outwards and precede the formation of dendrites. We observed comets in a diverse selection of S. aureus isolates and they exhibit the following behaviours: (1) They consist of phenotypically distinct cores of cells that move forward and seed other S. aureus cells behind them forming a comet ‘tail’; (2) they move when other cells in the comet tail have stopped moving; (3) the comet core is held together by a matrix of slime; and (4) the comets etch trails in the agar as they move forwards. Comets are not con- sistent with spreading motility or other forms of passive motility. Comet behaviour does share many similarities with a form of active motility known as gliding. Our observations therefore suggest that S. aureus is actively motile under certain conditions

Emergence of Minor Drug-Resistant HIV-1 Variants after Triple Antiretroviral Prophylaxis for Prevention of Vertical HIV-1 Transmission

Background: WHO-guidelines for prevention of mother-to-child transmission of HIV-1 in resource-limited settings recommend complex maternal antiretroviral prophylaxis comprising antenatal zidovudine (AZT), nevirapine single-dose (NVP-SD) at labor onset and AZT/lamivudine (3TC) during labor and one week postpartum. Data on resistance development selected by this regimen is not available. We therefore analyzed the emergence of minor drug-resistant HIV-1 variants in Tanzanian women following complex prophylaxis. Method: 1395 pregnant women were tested for HIV-1 at Kyela District Hospital, Tanzania. 87/202 HIV-positive women started complex prophylaxis. Blood samples were collected before start of prophylaxis, at birth and 1–2, 4–6 and 12–16 weeks postpartum. Allele-specific real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and applied on samples of mothers and their vertically infected infants to quantify key resistance mutations of AZT (K70R/T215Y/T215F), NVP (K103N/Y181C) and 3TC (M184V) at detection limits of,1%. Results: 50/87 HIV-infected women having started complex prophylaxis were eligible for the study. All women took AZT with a median duration of 53 days (IQR 39–64); all women ingested NVP-SD, 86 % took 3TC. HIV-1 resistance mutations were detected in 20/50 (40%) women, of which 70 % displayed minority species. Variants with AZT-resistance mutations were found in 11/50 (22%), NVP-resistant variants in 9/50 (18%) and 3TC-resistant variants in 4/50 women (8%). Three wome