Interventions targeting social determinants of mental disorders and the Sustainable Development Goals: a systematic review of reviews.

Globally, mental disorders account for almost 20% of disease burden and there is growing evidence that mental disorders are socially determined. Tackling the United Nations Sustainable Development Goals (UN SDGs), which address social determinants of mental disorders, may be an effective way to reduce the global burden of mental disorders. We conducted a systematic review of reviews to examine the evidence base for interventions that map onto the UN SDGs and seek to improve mental health through targeting known social determinants of mental disorders. We included 101 reviews in the final review, covering demographic, economic, environmental events, neighborhood, and sociocultural domains. This review presents interventions with the strongest evidence base for the prevention of mental disorders and highlights synergies where addressing the UN SDGs can be beneficial for mental health.

Targeted health and social care interventions for women and infants who are disproportionately impacted by health inequalities in high-income countries: a systematic review.

BACKGROUND: Disadvantaged populations (such as women from minority ethnic groups and those with social complexity) are at an increased risk of poor outcomes and experiences. Inequalities in health outcomes include preterm birth, maternal and perinatal morbidity and mortality, and poor-quality care. The impact of interventions is unclear for this population, in high-income countries (HIC). The review aimed to identify and evaluate the current evidence related to targeted health and social care service interventions in HICs which can improve health inequalities experienced by childbearing women and infants at disproportionate risk of poor outcomes and experiences. METHODS: Twelve databases searched for studies across all HICs, from any methodological design. The search concluded on 8/11/22. The inclusion criteria included interventions that targeted disadvantaged populations which provided a component of clinical care that differed from standard maternity care. RESULTS: Forty six index studies were included. Countries included Australia, Canada, Chile, Hong Kong, UK and USA. A narrative synthesis was undertaken, and results showed three intervention types: midwifery models of care, interdisciplinary care, and community-centred services. These intervention types have been delivered singularly but also in combination of each other demonstrating overlapping features. Overall, results show interventions had positive associations with primary (maternal, perinatal, and infant mortality) and secondary outcomes (experiences and satisfaction, antenatal care coverage, access to care, quality of care, mode of delivery, analgesia use in labour, preterm birth, low birth weight, breastfeeding, family planning, immunisations) however significance and impact vary. Midwifery models of care took an interpersonal and holistic approach as they focused on continuity of carer, home visiting, culturally and linguistically appropriate care and accessibility. Interdisciplinary care took a structural approach, to coordinate care for women requiring multi-agency health and social services. Community-centred services took a place-based approach with interventions that suited the need of its community and their norms. CONCLUSION: Targeted interventions exist in HICs, but these vary according to the context and infrastructure of standard maternity care. Multi-interventional approaches could enhance a targeted approach for at risk populations, in particular combining midwifery models of care with community-centred approaches, to enhance accessibility, earlier engagement, and increased attendance. TRIAL REGISTRATION: PROSPERO Registration number: CRD42020218357.

Longitudinal realist evaluation of the Dementia PersonAlised Care Team (D-PACT) intervention: protocol.

BACKGROUND: Different dementia support roles exist but evidence is lacking on which aspects are best, for whom, and in what circumstances, and on their associated costs and benefits. Phase 1 of the Dementia PersonAlised Care Team programme (D-PACT) developed a post-diagnostic primary care-based intervention for people with dementia and their carers and assessed the feasibility of a trial. AIM: Phase 2 of the programme aims to 1) refine the programme theory on how, when, and for whom the intervention works; and 2) evaluate its value and impact. DESIGN & SETTING: A realist longitudinal mixed-methods evaluation will be conducted in urban, rural, and coastal areas across South West and North West England where low-income or ethnic minority populations (for example, South Asian) are represented. Design was informed by patient, public, and professional stakeholder input and phase 1 findings. METHOD: High-volume qualitative and quantitative data will be collected longitudinally from people with dementia, carers, and practitioners. Analyses will comprise the following: 1) realist longitudinal case studies; 2) conversation analysis of recorded interactions; 3) statistical analyses of outcome and experience questionnaires; 4a) health economic analysis examining costs of delivery; and 4b) realist economic analysis of high-cost events and 'near misses'. All findings will be synthesised using a joint display table, evidence appraisal tool, triangulation, and stakeholder co-analysis. CONCLUSION: The realist evaluation will describe how, why, and for whom the intervention does or does not lead to change over time. It will also demonstrate how a non-randomised design can be more appropriate for complex interventions with similar questions or populations.

Project20: Maternity care mechanisms that improve (or exacerbate) health inequalities. A realist evaluation.

BACKGROUND: Women with low socioeconomic status and social risk factors are at a disproportionate risk of poor birth outcomes and experiences of maternity care. Specialist models of maternity care that offer continuity are known to improve outcomes but underlying mechanisms are not well understood. AIM: To evaluate two UK specialist models of care that provide continuity to women with social risk factors and identify specific mechanisms that reduce, or exacerbate, health inequalities. METHODS: Realist informed interviews were undertaken throughout pregnancy and the postnatal period with 20 women with social risk factors who experienced a specialist model of care. FINDINGS: Experiences of stigma, discrimination and paternalistic care were reported when women were not in the presence of a known midwife during care episodes. Practical and emotional support, and evidence-based information offered by a known midwife improved disclosure of social risk factors, eased perceptions of surveillance and enabled active participation. Continuity of care offered reduced women's anxiety, enabled the development of a supportive network and improved women's ability to seek timely help. Women described how specialist model midwives knew their medical and social history and how this improved safety. Care set in the community by a team of six known midwives appeared to enhance these benefits. CONCLUSION: The identification of specific maternity care mechanisms supports current policy initiatives to scale up continuity models and will be useful in future evaluation of services for marginalised groups. However, the specialist models of care cannot overcome all inequalities without improvements in the maternity system as a whole.

Addressing inequities in maternal health among women living in communities of social disadvantage and ethnic diversity.

The response to the coronavirus outbreak and how the disease and its societal consequences pose risks to already vulnerable groups such those who are socioeconomically disadvantaged and ethnic minority groups. Researchers and community groups analysed how the COVID-19 crisis has exacerbated persisting vulnerabilities, socio-economic and structural disadvantage and discrimination faced by many communities of social disadvantage and ethnic diversity, and discussed future strategies on how best to engage and involve local groups in research to improve outcomes for childbearing women experiencing mental illness and those living in areas of social disadvantage and ethnic diversity. Discussions centred around: access, engagement and quality of care; racism, discrimination and trust; the need for engagement with community stakeholders; and the impact of wider social and economic inequalities. Addressing biomedical factors alone is not sufficient, and integrative and holistic long-term public health strategies that address societal and structural racism and overall disadvantage in society are urgently needed to improve health disparities and can only be implemented in partnership with local communities.

Project 20: Midwives' insight into continuity of care models for women with social risk factors: what works, for whom, in what circumstances, and how.

INTRODUCTION: Continuity of care models are known to improve clinical outcomes for women and their babies, but it is not understood how. A realist synthesis of how women with social risk factors experience UK maternity care reported mechanisms thought to improve clinical outcomes and experiences. As part of a broader programme of work to test those theories and fill gaps in the literature base we conducted focus groups with midwives working within continuity of care models of care for women with social factors that put them at a higher chance of having poor birth outcomes. These risk factors can include poverty and social isolation, asylum or refugee status, domestic abuse, mental illness, learning difficulties, and substance abuse problems. OBJECTIVE: To explore the insights of midwives working in continuity models of care for women with social risk factors in order to understand the resources they provide, and how the model of care can improve women's outcomes. DESIGN: Realist methodology was used to gain a deeper understanding of how women react to specific resources that the models of care offer and how these resources are thought to lead to particular outcomes for women. Twelve midwives participated, six from a continuity of care model implemented in a community setting serving an area of deprivation in London, and six from a continuity of care model for women with social risk factors, based within a large teaching hospital in London. FINDINGS: Three main themes were identified: 'Perceptions of the model of care, 'Tailoring the service to meet women's needs', 'Going above and beyond'. Each theme is broken down into three subthemes to reveal specific resources or mechanisms which midwives felt might have an impact on women's outcomes, and how women with different social risk factors respond to these mechanisms. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Overall the midwives in both models of care felt the service was beneficial to women and had a positive impact on their outcomes. It was thought the trusting relationships they had built with women enabled midwives to guide women through a fragmented, unfamiliar system and respond to their individual physical, emotional, and social needs, whilst ensuring follow-up of appointments and test results. Midwives felt that for these women the impact of a trusting relationship affected how much information women disclosed, allowing for enhanced, needs led, holistic care. Interesting mechanisms were identified when discussing women who had social care involvement with midwives revealing techniques they used to advocate for women and help them to regain trust in the system and demonstrate their parenting abilities. Differences in how each team provided care and its impact on women's outcomes were considered with the midwives in the community-based model reporting how their location enabled them to help women integrate into their local community and make use of specialist services. The study demonstrates the complexity of these models of care, with midwives using innovative and compassionate ways of working to meet the multifaceted needs of this population.

Monitoring oral health of people in Early Intervention for Psychosis (EIP) teams: The extended Three Shires randomised trial.

BACKGROUND: The British Society for Disability and Oral Health guidelines made recommendations for oral health care for people with mental health problems, including providing oral health advice, support, promotion and education. The effectiveness of interventions based on these guidelines on oral health-related outcomes in mental health service users is untested. OBJECTIVE: To acquire basic data on the oral health of people with or at risk of serious mental illness. To determine the effects of an oral health checklist in routine clinical practice. DESIGN: Clinician and service user-designed cluster randomised trial. SETTINGS AND PARTICIPANTS: The trial compared a simple form for monitoring oral health care with standard care (no form) for outcomes relevant to service use and dental health behaviour for people with suspected psychosis in Mid and North England. Thirty-five teams were divided into two groups and recruited across 2012-3 with one year follow up. RESULTS: 18 intervention teams returned 882 baseline intervention forms and 274 outcome sheets one year later (31%). Control teams (n=17) returned 366 baseline forms. For the proportion for which data were available at one year we found no significant differences for any outcomes between those allocated to the initial monitoring checklist and people in the control group (Registered with dentist (p=0.44), routine check-up within last year (p=0.18), owning a toothbrush (p=0.99), cleaning teeth twice a day (p=0.68), requiring urgent dental treatment (p=0.11). CONCLUSION: This trial provides no clear evidence that Care Co-ordinators (largely nursing staff) using an oral health checklist improves oral health behaviour or oral health state in those thought to be at risk of psychosis or with early psychosis.

A multisite audit to assess how women with complex social factors access and engage with maternity services.

OBJECTIVE: to audit women with socially complex lives' documented access to and engagement with antenatal care provided by three inner city, UK maternity services in relation to birth and neonatal outcomes, and referral processes. BACKGROUND: women living socially complex lives, including young mothers, recently arrived immigrants, non-English speaking, and those experiencing domestic violence, poor mental health, drug and alcohol abuse, and poverty experience high rates of morbidity, mortality and poor birth outcomes. This is associated with late access to and poor engagement with antenatal care. METHOD: data was collected from three separate NHS trusts data management systems for a total of 182 women living socially complex lives, between January and December 2015. Data was presented by individual trust and compared to standards derived from NICE guidelines, local trust policy and national statistic using Excel and SPSS Version 22. Tests of correlation were carried out to minimise risks of confounding factors in characteristic differences. FINDINGS: non-English speaking women were much less likely to have accessed care within the recommended timeframes, with over 70% of the sample not booked for maternity care by 12 weeks gestation. On average 89% primiparous women across all samples had less than the recommended number of antenatal appointments. No sample met the audit criteria in terms of number of antenatal appointments attended. Data held on the perinatal data management systems for a number of outcomes and processes was largely incomplete and appeared unreliable. CONCLUSION: this data forms a baseline against which to assess the impact of future service developments aimed at improving access and engagement with services for women living with complex social factors. The audit identified issues with the completeness and reliability of data on the perinatal data management system.

Cholinergic Receptor Binding in Alzheimer Disease and Healthy Aging: Assessment In Vivo with Positron Emission Tomography Imaging.

OBJECTIVE: To compare regional nicotinic cholinergic receptor binding in older adults with Alzheimer disease (AD) and healthy older adults in vivo and to assess relationships between receptor binding and clinical symptoms. METHODS: Using cross-sectional positron emission tomography (PET) neuroimaging and structured clinical assessment, outpatients with mild to moderate AD (N = 24) and healthy older adults without cognitive complaints (C group; N = 22) were studied. PET imaging of α4ß2* nicotinic cholinergic receptor binding using 2-[18F]fluoro-3-(2(S)azetidinylmethoxy)pyridine (2FA) and clinical measures of global cognition, attention/processing speed, verbal memory, visuospatial memory, and neuropsychiatric symptoms were used. RESULTS: 2FA binding was lower in the AD group compared with the C group in the medial thalamus, medial temporal cortex, anterior cingulate, insula/opercula, inferior caudate, and brainstem (p < 0.05, corrected cluster), but binding was not associated with cognition. The C group had significant inverse correlations between 2FA binding in the thalamus (left: rs = -0.55, p = 0.008; right: rs = -0.50, p = 0.02; N = 22) and hippocampus (left: rs = -0.65, p = 0.001; right: rs = -0.55, p = 0.009; N = 22) and the Trails A score. The AD group had inverse correlation between 2FA binding in anterior cingulate (left: rs = -0.50, p = 0.01; right: rs = -0.50, p = 0.01; N = 24) and Neurobehavioral Rating Scale agitation/disinhibition factor score. CONCLUSION: Cholinergic receptor binding is reduced in specific brain regions in mild to moderate AD and is related to neuropsychiatric symptoms. Among healthy older adults, lower receptor binding may be associated with slower processing speed. Cholinergic receptor binding in vivo may reveal links to other key brain changes associated with aging and AD and may provide a potential molecular treatment target.

When stress gets into your head: Socioeconomic risk, executive functions, and maternal sensitivity across childrearing contexts.

Socioeconomic adversity has been targeted as a key upstream mechanism with robust pathogenic effects on maternal caregiving. Although research has demonstrated the negative repercussions of socioeconomic difficulties, little research has documented potential mechanisms underlying this association. Toward increasing understanding, the present study examined how maternal working memory capacity and inhibitory control may mediate associations between socioeconomic risk and change in maternal sensitivity across free-play and discipline caregiving contexts. This study used a longitudinal design, and utilized a socioeconomically diverse sample of 185 mothers and their 3.5-year-old toddlers. Multi-informants and methods were used to assess constructs. Findings revealed that maternal EF mediated associations between socioeconomic risk and parenting sensitivity with specific effects for working memory and baseline sensitivity and inhibitory control and change in sensitivity as childrearing demands increased. Results are interpreted within emerging conceptual frameworks regarding the role of parental neurocognitive functioning and caregiving. (PsycINFO Database Record

Utility of a human FcRn transgenic mouse model in drug discovery for early assessment and prediction of human pharmacokinetics of monoclonal antibodies.

Therapeutic antibodies continue to develop as an emerging drug class, with a need for preclinical tools to better predict in vivo characteristics. Transgenic mice expressing human neonatal Fc receptor (hFcRn) have potential as a preclinical pharmacokinetic (PK) model to project human PK of monoclonal antibodies (mAbs). Using a panel of 27 mAbs with a broad PK range, we sought to characterize and establish utility of this preclinical animal model and provide guidance for its application in drug development of mAbs. This set of mAbs was administered to both hemizygous and homozygous hFcRn transgenic mice (Tg32) at a single intravenous dose, and PK parameters were derived. Higher hFcRn protein tissue expression was confirmed by liquid chromatography-high resolution tandem mass spectrometry in Tg32 homozygous versus hemizygous mice. Clearance (CL) was calculated using non-compartmental analysis and correlations were assessed to historical data in wild-type mouse, non-human primate (NHP), and human. Results show that mAb CL in hFcRn Tg32 homozygous mouse correlate with human (r(2) = 0.83, r = 0.91, p < 0.01) better than NHP (r(2) = 0.67, r = 0.82, p < 0.01) for this dataset. Applying simple allometric scaling using an empirically derived best-fit exponent of 0.93 enabled the prediction of human CL from the Tg32 homozygous mouse within 2-fold error for 100% of mAbs tested. Implementing the Tg32 homozygous mouse model in discovery and preclinical drug development to predict human CL may result in an overall decreased usage of monkeys for PK studies, enhancement of the early selection of lead molecules, and ultimately a decrease in the time for a drug candidate to reach the clinic.

The Voices for Healthy Kids Campaign and US State Legislation to Prevent Childhood Obesity.

We documented childhood obesity legislative activity in all 50 US states that occurred in parallel to the first year of Voices for Healthy Kids (Voices), a campaign to mobilize evidence-based legislation addressing childhood obesity. We identified 217 bills in the year before Voices (November 2012 to October 2013) and 304 bills at follow-up (November 2013 to October 2014). In states with active Voices grantees, the bill enactment rate was 50% higher (increasing from 10% at baseline to 15% at follow-up).

Blastocyst genotyping for quality control of mouse mutant archives: an ethical and economical approach.

With the advent of modern developmental biology and molecular genetics, the scientific community has generated thousands of newly genetically altered strains of laboratory mice with the aim of elucidating gene function. To this end, a large group of Institutions which form the International Mouse Phenotyping Consortium is generating and phenotyping a knockout mouse strain for each of the ~20,000 protein-coding genes using the mutant ES cell resource produced by the International Knockout Mouse Consortium. These strains are made available to the research community via public repositories, mostly as cryopreserved sperm or embryos. To ensure the quality of this frozen resource there is a requirement that for each strain the frozen sperm/embryos are proven able to produce viable mutant progeny, before the live animal resource is removed from cages. Given the current requirement to generate live pups to demonstrate their mutant genotype, this quality control check necessitates the use and generation of many animals and requires considerable time, cage space, technical and economic resources. Here, we describe a simple and efficient method of genotyping pre-implantation stage blastocysts with significant ethical and economic advantages especially beneficial for current and future large-scale mouse mutagenesis projects.

An investigation of the relationship between the caseload model of midwifery for socially disadvantaged women and childbirth outcomes using routine data--a retrospective, observational study.

OBJECTIVE: the objective of this study was to describe and compare childbirth outcomes and processes for women with complex social factors who received caseload midwifery care, and standard maternity care in the UK. BACKGROUND: women with complex social factors experience high rates of morbidity, mortality and poor birth outcomes. A caseload team was established to support these women throughout pregnancy and childbirth by providing continuity and individualised care. METHODS: data was collected from computerised birth details of 194 women with complex social factors who presented for maternity care between May 2012 and June 2013; 96 received standard care and 98 caseload care. SPSS v21 was used to calculate descriptive and inferential statistics. Logistic regression modelling found no differences in demographics, therefore unadjusted statistics are presented. Comparative analysis between women receiving caseload care and those receiving standard care was accomplished using χ2 test, relative risk (RR) and 95% confidence intervals (CI). RESULTS: the relationship between type of care and outcome was not changed by the inclusion of confounding factors. Women receiving caseload care were more likely to experience; spontaneous vaginal childbirth (80% versus 55% RR 1.88, 95% CI 1.27-2.77, P=<0.001), use water for pain relief (32% versus 10%, RR 4.10 95% CI 1.95-8.64, p=<0.001), birth in the midwife led centre (26% versus 13% RR 1.48 95% CI 1.12-1.95, p=0.023), assessment by 10 weeks gestation (24% versus 8% RR 1.61 95% CI 1.24-2.10, p=0.008), shorter postnatal stay (1 day versus 3 days SD 1.2 versus 2.2, p=<0.001), and know their midwife (90% versus 8% RR 8.98 95% CI 4.97-16.2, p=<0.001). More women in the caseload group were referred to multidisciplinary support services; psychiatry (56% versus 19% RR 2.06 95% CI 1.59-2.65, p=<0.001), domestic violence advocacy (42% versus 18% RR 1.68 CI 1.31-2.15, p=<0.001) and other services (56% versus 31% RR 1.58 95% CI 1.15-2.16, p=0.03). They were less likely to have a caesarean section (11% versus 33% RR 0.26 95% CI 0.12-0.55, P=<0.001), an epidural/spinal for pain relief (35% versus 56%, RR 0.64 95% CI 0.46-0.86, p=0.004), give birth on the labour ward (70% versus 88% RR 0.63 95% CI 0.49-0.83, p=0.006), and had fewer antenatal admissions (0.9(SD 1.1) versus 1.3(SD1.5), p=0.036) and neonatal unit admissions (4% versus 18%, RR 0.35 95% CI 0.15-0.85, p=0.005). CONCLUSION: caseload midwifery care appeared to confer increased benefit and reduced harmful outcomes. Findings for individual outcomes differed from previous literature depending on outcome, suggesting caseload care may affect women in different ways depending on their individual needs.

An oral health intervention for people with serious mental illness (Three Shires Early Intervention Dental Trial): study protocol for a randomised controlled trial.

BACKGROUND: Oral health is an important part of general physical health and is essential for self-esteem, self-confidence and overall quality of life. There is a well-established link between mental illness and poor oral health. Oral health problems are not generally well recognized by mental health professionals and many patients experience barriers to treatment. METHODS/DESIGN: This is the protocol for a pragmatic cluster randomised trial that has been designed to fit within standard care. Dental awareness training for care co-ordinators plus a dental checklist for service users in addition to standard care will be compared with standard care alone for people with mental illness. The checklist consists of questions about service users' current oral health routine and condition. Ten Early Intervention in Psychosis (EIP) teams in Nottinghamshire, Derbyshire and Lincolnshire will be cluster randomised (five to intervention and five to standard care) in blocks accounting for location and size of caseload. The oral health of the service users will be monitored for one year after randomisation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN63382258.

How can informal caregivers in cancer and palliative care be supported? An updated systematic literature review of interventions and their effectiveness.

INTRODUCTION: Informal caregivers needs in cancer/advanced disease are largely unmet. The science of carer intervention evaluation is methodologically challenging, and the evidence historically weak. OBJECTIVE: This systematic review updates an earlier effectiveness review to determine both the effectiveness of subsequently published intervention studies, and the current state of science. METHOD: The evidence was identified and appraised using a comprehensive search strategy. Articles were searched from 2001 to 2010 using the following electronic databases: Medline, PsychINFO and CINAHL. Inclusion criteria were studies reporting intervention data for informal adult caregivers of a patient with a diagnosis of cancer or receiving palliative care. The design and evidence rigour were assessed using the Jadad Rating Scale, and the Quality Rating Scale. RESULTS: 33 studies met inclusion criteria. From the original review, an encouraging increase was identified in the number of evaluations (from 8 to 33), in carer-specific interventions (from 6 to 17) and in the robustness of the study design (an increase from 2 to 12 studies with before/after measures, comparison groups and prospective data). CONCLUSIONS: The evidence suggests a rapid increase in the number of robust intervention studies. However, the range of models remains narrow in relation to caregivers' needs and preferences.

PhRMA CPCDC initiative on predictive models of human pharmacokinetics, part 2: comparative assessment of prediction methods of human volume of distribution.

The objective of this study was to evaluate the performance of various empirical, semimechanistic and mechanistic methodologies with and without protein binding corrections for the prediction of human volume of distribution at steady state (Vss ). PhRMA member companies contributed a set of blinded data from preclinical and clinical studies, and 18 drugs with intravenous clinical pharmacokinetics (PK) data were available for the analysis. In vivo and in vitro preclinical data were used to predict Vss by 24 different methods. Various statistical and outlier techniques were employed to assess the predictability of each method. There was not simply one method that predicts Vss accurately for all compounds. Across methods, the maximum success rate in predicting human Vss was 100%, 94%, and 78% of the compounds with predictions falling within tenfold, threefold, and twofold error, respectively, of the observed Vss . Generally, the methods that made use of in vivo preclinical data were more predictive than those methods that relied solely on in vitro data. However, for many compounds, in vivo data from only two species (generally rat and dog) were available and/or the required in vitro data were missing, which meant some methods could not be properly evaluated. It is recommended to initially use the in vitro tissue composition-based equations to predict Vss in preclinical species and humans, putting the assumptions and compound properties into context. As in vivo data become available, these predictions should be reassessed and rationalized to indicate the level of confidence (uncertainty) in the human Vss prediction. The top three methods that perform strongly at integrating in vivo data in this way were the Øie-Tozer, the rat -dog-human proportionality equation, and the lumped-PBPK approach. Overall, the scientific benefit of this study was to obtain greater characterization of predictions of human Vss from several methods available in the literature.

Telemedicine can make healthcare greener.

The American healthcare industry is generally lacking environmentally sustainable practices. The environmental impact of healthcare practices in the country has been largely disregarded due to ambivalence, ignorance, and fears of additional costs and regulations. The current practices continue to pollute the environment by requiring large amounts of travel and paperwork by both the patient and the clinician. Telemedicine and health information technology help save time, energy, raw materials (such as paper and plastic), and fuel, thereby lowering the carbon footprint of the health industry. By implementing green practices, for instance, by engaging in carbon credit programs, the health industry could benefit financially as well as reduce its negative impact on the health of our planet. Companies that reduce their carbon emissions by implementing energy-saving practices can sell their carbon credits to companies that emit more carbon than permissible by their legally binding commitment. These carbon profits can then be used for healthcare research or to provide healthcare to the underserved. Alternatively, the savings could be used for green purchasing and to implement other carbon-reducing activities. This report reviews the numerous possible options for the American health industry to become greener and lower its carbon footprint while at the same time becoming more time- and cost efficient.

The mental wealth of nations.

Countries must learn how to capitalize on their citizens' cognitive resources if they are to prosper, both economically and socially. Early interventions will be key.

Maraviroc: in vitro assessment of drug-drug interaction potential.

AIMS: To characterize the cytochrome P450 enzyme(s) responsible for the N-dealkylation of maraviroc in vitro, and predict the extent of clinical drug-drug interactions (DDIs). METHODS: Human liver and recombinant CYP microsomes were used to identify the CYP enzyme responsible for maraviroc N-dealkylation. Studies comprised enzyme kinetics and evaluation of the effects of specific CYP inhibitors. In vitro data were then used as inputs for simulation of DDIs with ketoconazole, ritonavir, saquinavir and atazanvir, using the Simcyptrade mark population-based absorption, distribution, metabolism and elimination (ADME) simulator. Study designs for simulations mirrored those actually used in the clinic. RESULTS: Maraviroc was metabolized to its N-dealkylated product via a single CYP enzyme characterized by a K(m) of 21 microM and V(max) of 0.45 pmol pmol(-1) min(-1) in human liver microsomes and was inhibited by ketoconazole (CYP3A4 inhibitor). In a panel of recombinant CYP enzymes, CYP3A4 was identified as the major CYP responsible for maraviroc metabolism. Using recombinant CYP3A4, N-dealkylation was characterized by a K(m) of 13 microM and a V(max) of 3 pmol pmol(-1) CYP min(-1). Simulations therefore focused on the effect of CYP3A4 inhibitors on maraviroc pharmacokinetics. The simulated median AUC ratios were in good agreement with observed clinical changes (within twofold in all cases), although, in general, there was a trend for overprediction in the magnitude of the DDI. CONCLUSION: Maraviroc is a substrate for CYP3A4, and exposure will therefore be modulated by CYP3A4 inhibitors. Simcyptrade mark has successfully simulated the extent of clinical interactions with CYP3A4 inhibitors, further validating this software as a good predictor of CYP-based DDIs.