To characterize the relationship between chlorhexidine gluconate (CHG) skin concentration and skin microbial colonization.

Serial cross-sectional study.

Adult patients in medical intensive care units (ICUs) from 7 hospitals; from 1 hospital, additional patients colonized with carbapenemase-producing Enterobacterales (CPE) from both ICU and non-ICU settings. All hospitals performed routine CHG bathing in the ICU.

Skin swab samples were collected from adjacent areas of the neck, axilla, and inguinal region for microbial culture and CHG skin concentration measurement using a semiquantitative colorimetric assay. We used linear mixed effects multilevel models to analyze the relationship between CHG concentration and microbial detection. We explored threshold effects using additional models.

We collected samples from 736 of 759 (97%) eligible ICU patients and 68 patients colonized with CPE. On skin, gram-positive bacteria were cultured most frequently (93% of patients), followed by Candida species (26%) and gram-negative bacteria (20%). The adjusted odds of microbial recovery for every twofold increase in CHG skin concentration were 0.84 (95% CI, 0.80–0.87; P < .001) for gram-positive bacteria, 0.93 (95% CI, 0.89–0.98; P = .008) for Candida species, 0.96 (95% CI, 0.91–1.02; P = .17) for gram-negative bacteria, and 0.94 (95% CI, 0.84–1.06; P = .33) for CPE. A threshold CHG skin concentration for reduced microbial detection was not observed.

On a cross-sectional basis, higher CHG skin concentrations were associated with less detection of gram-positive bacteria and Candida species on the skin, but not gram-negative bacteria, including CPE. For infection prevention, targeting higher CHG skin concentrations may improve control of certain pathogens.

To assess whether measurement and feedback of chlorhexidine gluconate (CHG) skin concentrations can improve CHG bathing practice across multiple intensive care units (ICUs).

A before-and-after quality improvement study measuring patient CHG skin concentrations during 6 point-prevalence surveys (3 surveys each during baseline and intervention periods).

The study was conducted across 7 geographically diverse ICUs with routine CHG bathing.

Adult patients in the medical ICU.

CHG skin concentrations were measured at the neck, axilla, and inguinal region using a semiquantitative colorimetric assay. Aggregate unit-level CHG skin concentration measurements from the baseline period and each intervention period survey were reported back to ICU leadership, which then used routine education and quality improvement activities to improve CHG bathing practice. We used multilevel linear models to assess the impact of intervention on CHG skin concentrations.

We enrolled 681 (93%) of 736 eligible patients; 92% received a CHG bath prior to survey. At baseline, CHG skin concentrations were lowest on the neck, compared to axillary or inguinal regions (P < .001). CHG was not detected on 33% of necks, 19% of axillae, and 18% of inguinal regions (P < .001 for differences in body sites). During the intervention period, ICUs that used CHG-impregnated cloths had a 3-fold increase in patient CHG skin concentrations as compared to baseline (P < .001).

Routine CHG bathing performance in the ICU varied across multiple hospitals. Measurement and feedback of CHG skin concentrations can be an important tool to improve CHG bathing practice.

To explore the formal and informal ways in which different actors involved in shaping trade agreements pursue their interests and understand the interactions with nutrition, in order to improve coherence between trade and nutrition policy goals.

The paper draws on empirical evidence from Australian key informant interviews that explore the underlying political dimensions of trade agreements that act as barriers or facilitators to getting nutrition objectives on trade agendas.

Countries experiencing greater availability and access to diets full of energy-dense and nutrient-poor foods through increased imports, greater foreign direct investment and increasing constraints on national health policy space as a result of trade agreements.

Interviews took place with Australian government officials, industry, public-interest non-government organizations and academics.

The analysis reveals the formal and informal mechanisms and structures that different policy actors use both inside and outside trade negotiations to pursue their interests. The analysis also identifies the discourses used by the different actors, as they attempt to influence trade agreements in ways that support or undermine nutrition-related goals.

Moving forward requires policy makers, researchers and health advocates to use various strategies including: reframing the role of trade agreements to include health outcomes; reforming the process to allow greater access and voice to health arguments and stakeholders; establishing cross-government partners through accountable committees; and building circles of consensus and coalitions of sympathetic public-interest actors.

Maximising synergies and minimising conflicts (i.e. building policy coherence) between trade and nutrition policy is an important objective. One understudied driver of policy coherence is the alignment in the frames, discourses and values of actors involved in the respective sectors. In the present analysis, we aim to understand how such actors interpret (i.e. ‘frame’) nutrition and the implications for building trade–nutrition policy coherence.

We adopted a qualitative single case study design, drawing on key informant interviews with those involved in trade policy.

We focused on the Australian trade policy sub-system, which has historically emphasised achieving market growth and export opportunities for Australian food producers.

Nineteen key informants involved in trade policy spanning the government, civil society, business and academic sectors.

Nutrition had low ‘salience’ in Australian trade policy for several reasons. First, it was not a domestic political priority in Australia nor among its trading partners; few advocacy groups were advocating for nutrition in trade policy. Second, a ‘productivist’ policy paradigm in the food and trade policy sectors strongly emphasised market growth, export opportunities and deregulation over nutrition and other social objectives. Third, few opportunities existed for health advocates to influence trade policy, largely because of limited consultation processes. Fourth, the complexity of nutrition and its inter-linkages with trade presented difficulties for developing a ‘broader discourse’ for engaging the public and political leaders on the topic.

Overcoming these ‘ideational challenges’ is likely to be important to building greater coherence between trade and nutrition policy going forward.

Effective treatments for patients with high levels of negative symptoms of schizophrenia are lacking. Brexpiprazole is a serotonin–dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors, all with subnanomolar potency. Long-term treatment with brexpiprazole demonstrated broad efficacy across all five Marder factor groupings, including positive, negative, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression. This post-hoc analysis of long-term effects of brexpiprazole in patients with clinically relevant levels of negative symptoms of schizophrenia is based on data from two similarly designed short-term, placebo-controlled studies (Vector; NCT01396421 or Beacon; NCT01393613) for the brexpiprazole-treated patients who continued into an open-label extension study (Zenith; NCT01397786).

In the short-term studies, patients with acute schizophrenia were randomly assigned to fixed once-daily doses of brexpiprazole 0.25mg (Vector), 1mg (Beacon), 2mg , 4mg or placebo for 6weeks. The long-term study was an open-label, 52-week (amended to 26weeks), safety extension study with flexible-dose (1–4mg/day) brexpiprazole. The post-hoc analyses were performed on brexpiprazole-treated patients from the short-term studies who continued into the long-term study, and who had clinically relevant negative symptoms, defined as PANSS Factor Score for Negative Symptoms (PANSS-FSNS; N1, N2, N3, N4, G7, G16) of ≥24, and score of ≥4 on at least two of three core negative symptom PANSS items at randomization in the parent study. The outcome of the analysis included change from baseline to up to 58weeks in PANSS-FSNS, PANSS Total, and PSP. Safety was also assessed.

A total of 187 patients with clinically relevant levels of negative symptoms in the parent study rolled-over into the open-label extension study and were available for analysis. Eighty-three of these patients remained in the studies for 58weeks. Due to the study amendment, not all patients had the opportunity of complete 52weeks of open-label treatment. Baseline PANSS Total score was 104.4, while baseline PANSS-FSNS was 27.6 and baseline PSP Total score was 41.3. Mean change (SD) from baseline in PANSS-FSNS was –10.9 (5.0), and –44.2 (17.5) for PANSS Total score at Week 58. Change from baseline (SD) to Week 58 for PSP Total score was 24.8 (12.9) with improvement in all domains (socially useful activities, personal and social relationship, self-care, and disturbing and aggressive behaviors). The TEAEs reported ≥5% were schizophrenia (18.9%), insomnia (8.6%), weight increased (5.9%) and akathisia (5.9%).

This post-hoc analysis suggests that brexpiprazole has long-term effectiveness on negative symptoms and functioning in patients with schizophrenia and clinically relevant levels of negative symptoms.

Funding Acknowledgements: The study was funded by Otsuka Pharmaceutical Development & Commercialization Inc. and H. Lundbeck A/S

To compare the tolerability and efficacy of different antipsychotic cross-titration schedules, using data from a brexpiprazole study (Equator; NCT01668797).

Patients with schizophrenia were cross-titrated from other antipsychotics to brexpiprazole monotherapy in a 1–4 week open-label conversion phase, then entered a single-blind brexpiprazole treatment phase. Patients were stratified into four “conversion groups,” according to the amount of time spent in the conversion phase. Discontinuation rates, treatment-emergent adverse events (TEAEs), and efficacy (Positive and Negative Syndrome Scale [PANSS]) were compared between conversion groups.

Of the 404 patients treated with brexpiprazole, the majority (72.0%) spent 22–33 days in the conversion phase. Discontinuation rates due to lack of efficacy or adverse events were low in all conversion groups. Of the 292 patients who successfully switched and completed 8 weeks of brexpiprazole treatment, most were converted to brexpiprazole over 22–33 days (80.1%), and fewer were converted over 1–7 days (2.4%), 8–14 days (6.5%), or 15–21 days (11.0%). The incidence of TEAEs over 8 weeks was lower among those converted over 22–33 days (44.4%) than in other conversion groups (62.5–84.2%), although low patient numbers with shorter conversion times limit the generalizability of this finding. Each conversion group showed comparable improvement in PANSS total score from baseline.

The majority of patients were cross-titrated to brexpiprazole over a period of 22–33 days, by investigators’ choice. Additional data on shorter conversions may help clinicians to choose a switching paradigm that best meets their patients’ needs.

Abnormalities in reward circuit function are considered a core feature of addiction. Yet, it is still largely unknown whether these abnormalities stem from chronic drug use, a genetic predisposition, or both.

In the present study, we investigated this issue using a large sample of adolescent children by applying structural equation modeling to examine the effects of several dopaminergic polymorphisms of the D1 and D2 receptor type on the reward function of the ventral striatum (VS) and orbital frontal cortex (OFC), and whether this relationship predicted the propensity to engage in early alcohol misuse behaviors at 14 years of age and again at 16 years of age.

The results demonstrated a regional specificity with which the functional polymorphism rs686 of the D1 dopamine receptor (DRD1) gene and Taq1A of the ANKK1 gene influenced medial and lateral OFC activation during reward anticipation, respectively. Importantly, our path model revealed a significant indirect relationship between the rs686 of the DRD1 gene and early onset of alcohol misuse through a medial OFC × VS interaction.

These findings highlight the role of D1 and D2 in adjusting reward-related activations within the mesocorticolimbic circuitry, as well as in the susceptibility to early onset of alcohol misuse.

The marketing of infant/child milk-based formulas (MF) contributes to suboptimal breast-feeding and adversely affects child and maternal health outcomes globally. However, little is known about recent changes in MF markets. The present study describes contemporary trends and patterns of MF sales at the global, regional and country levels.

Descriptive statistics of trends and patterns in MF sales volume per infant/child for the years 2008–2013 and projections to 2018, using industry-sourced data.

Eighty countries categorized by country income bracket, for developing countries by region, and in countries with the largest infant/child populations.

MF categories included total (for ages 0–36 months), infant (0–6 months), follow-up (7–12 months), toddler (13–36 months) and special (0–6 months).

In 2008–2013 world total MF sales grew by 40·8 % from 5·5 to 7·8 kg per infant/child/year, a figure predicted to increase to 10·8 kg by 2018. Growth was most rapid in East Asia particularly in China, Indonesia, Thailand and Vietnam and was led by the infant and follow-up formula categories. Sales volume per infant/child was positively associated with country income level although with wide variability between countries.

A global infant and young child feeding (IYCF) transition towards diets higher in MF is underway and is expected to continue apace. The observed increase in MF sales raises serious concern for global child and maternal health, particularly in East Asia, and calls into question the efficacy of current regulatory regimes designed to protect and promote optimal IYCF. The observed changes have not been captured by existing IYCF monitoring systems.

Nitrate and nitrite are probable human carcinogens when ingested under conditions that increase the formation of N-nitroso compounds. There have been limited efforts to develop US databases of dietary nitrate and nitrite for standard FFQ. Here we describe the development of a dietary nitrate and nitrite database and its calibration.

We analysed data from a calibration study of 1942 members of the NIH–AARP (NIH–AARP, National Institutes of Health–AARP) Diet and Health Study who reported all foods and beverages consumed on the preceding day in two non-consecutive 24 h dietary recalls (24HR) and completed an FFQ. Based on a literature review, we developed a database of nitrate and nitrite contents for foods reported on these 24HR and for food category line items on the FFQ. We calculated daily nitrate and nitrite intakes for both instruments, and used a measurement error model to compute correlation coefficients and attenuation factors for the FFQ-based intake estimates using 24HR-based values as reference data.

FFQ-based median nitrate intake was 68·9 and 74·1 mg/d, and nitrite intake was 1·3 and 1·0 mg/d, in men and women, respectively. These values were similar to 24HR-based intake estimates. Energy-adjusted correlation coefficients between FFQ- and 24HR-based values for men and women respectively were 0·59 and 0·57 for nitrate and 0·59 and 0·58 for nitrite; energy-adjusted attenuation factors were 0·59 and 0·57 for nitrate and 0·47 and 0·38 for nitrite.

The performance of the FFQ in assessing dietary nitrate and nitrite intakes is comparable to that for many other macro- and micronutrients.