Incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease in patients with multiple sclerosis initiating disease-modifying therapies: Retrospective cohort study using a frequentist model averaging statistical framework.

Researchers are increasingly using insights derived from large-scale, electronic healthcare data to inform drug development and provide human validation of novel treatment pathways and aid in drug repurposing/repositioning. The objective of this study was to determine whether treatment of patients with multiple sclerosis with dimethyl fumarate, an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, results in a change in incidence of type 2 diabetes and its complications. This retrospective cohort study used administrative claims data to derive four cohorts of adults with multiple sclerosis initiating dimethyl fumarate, teriflunomide, glatiramer acetate or fingolimod between January 2013 and December 2018. A causal inference frequentist model averaging framework based on machine learning was used to compare the time to first occurrence of a composite endpoint of type 2 diabetes, cardiovascular disease or chronic kidney disease, as well as each individual outcome, across the four treatment cohorts. There was a statistically significantly lower risk of incidence for dimethyl fumarate versus teriflunomide for the composite endpoint (restricted hazard ratio [95% confidence interval] 0.70 [0.55, 0.90]) and type 2 diabetes (0.65 [0.49, 0.98]), myocardial infarction (0.59 [0.35, 0.97]) and chronic kidney disease (0.52 [0.28, 0.86]). No differences for other individual outcomes or for dimethyl fumarate versus the other two cohorts were observed. This study effectively demonstrated the use of an innovative statistical methodology to test a clinical hypothesis using real-world data to perform early target validation for drug discovery. Although there was a trend among patients treated with dimethyl fumarate towards a decreased incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease relative to other disease-modifying therapies-which was statistically significant for the comparison with teriflunomide-this study did not definitively support the hypothesis that Nrf2 activation provided additional metabolic disease benefit in patients with multiple sclerosis.

Prevalence and cardiometabolic correlates of ketohexokinase gene variants among UK Biobank participants.

Essential fructosuria (EF) is a benign, asymptomatic, autosomal recessive condition caused by loss-of-function variants in the ketohexokinase gene and characterized by intermittent appearance of fructose in the urine. Despite a basic understanding of the genetic and molecular basis of EF, relatively little is known about the long-term clinical consequences of ketohexokinase gene variants. We examined the frequency of ketohexokinase variants in the UK Biobank sample and compared the cardiometabolic profiles of groups of individuals with and without these variants alone or in combination. Study cohorts consisted of groups of participants defined based on the presence of one or more of the five ketohexokinase gene variants tested for in the Affymetrix assays used by the UK Biobank. The rs2304681:G>A (p.Val49Ile) variant was present on more than one-third (36.8%) of chromosomes; other variant alleles were rare (<1%). No participants with the compound heterozygous genotype present in subjects exhibiting the EF phenotype in the literature (Gly40Arg/Ala43Thr) were identified. The rs2304681:G>A (p.Val49Ile), rs41288797 (p.Val188Met), and rs114353144 (p.Val264Ile) variants were more common in white versus non-white participants. Otherwise, few statistically or clinically significant differences were observed after adjustment for multiple comparisons. These findings reinforce the current understanding of EF as a rare, benign, autosomal recessive condition.

Changing levels of local crime and mental health: a natural experiment using self-reported and service use data in Scotland.

BACKGROUND: This study contributes robust evidence on the association between mental health and local crime rates by showing how changing exposure to small area-level crime relates to self-reported and administrative data on mental health. METHODS: The study sample comprised 112 251 adults aged 16-60 years, drawn from the Scottish Longitudinal Study, a 5.3% representative sample of Scottish population followed across censuses. Outcomes were individual mental health indicators: self-reported mental illness from the 2011 Census and linked administrative data on antidepressants and antipsychotics prescribed through primary care providers in the National Health Service in 2010/2012. Crime rates at data zone level (500-1000 persons) were matched to the participants' main place of residence, as defined by general practitioner patient registration duration during 2004/2006, 2007/2009 and 2010/12. Average neighbourhood crime exposure and change in area crime were computed. Covariate-adjusted logistic regressions were conducted, stratified by moving status. RESULTS: In addition to average crime exposure during follow-up, recent increases in crime (2007/2009-2010/2012) were associated with a higher risk of self-reported mental illness, among 'stayers' aged 16-30 years (OR=1.11; 95% CI 1.00 to 1.22), and among 'movers' aged 31-45 years (OR=1.07; 95% CI 1.01 to 1.13). Prescribed medications reinforced these findings; worsening crime rates were linked with antidepressant prescriptions among young stayers (OR=1.09; 95% CI 1.04 to 1.14) and with antipsychotic prescriptions among younger middle-aged movers (OR=1.11; 95% CI 1.01 to 1.23). CONCLUSION: Changing neighbourhood crime exposure is related to individual mental health, but associations differ by psychiatric conditions, age and moving status. Crime reduction and prevention, especially in communities with rising crime rates, may benefit public mental health.

A qualitative study exploring the health-related quality of life and symptomatic experiences of adults and adolescents with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) often first presents during adolescence and early adulthood. Primary symptoms of UC are well known, yet similarities and differences of disease experience in adults and adolescents are not well characterized. METHODS: To understand the health-related quality of life (HRQoL) and symptomatic experience of UC, in-depth interviews were conducted in the US with 21 adults (20-70 years) and 14 adolescents (12-17 years). Eligibility and medical history were confirmed by clinician report. A previously conducted literature review and resultant conceptual model informed the discussion guide to explore symptoms and HRQoL. Age appropriate creative tasks ("animal" task and collage) were employed to facilitate discussion. Transcripts and collages were subjected to thematic analysis using ATLAS.ti software. RESULTS: Clinician-reported UC severity included 24% mild, 38% moderate, 38% severe among adults; and 64% mild, 29% moderate, 7% severe among adolescents. Among adults, 52% were female, 67% were white. Among adolescents, 50% were female, 71% were white. During analysis it was noted that all participants reported stomach/abdominal pain. Other key symptoms identified were frequent bowel movements, diarrhea, blood in stools, sudden need for bowel movement, stomach cramping, bloating, and feeling gassy/passing gas (≥75% of participants). Key impacts identified were embarrassment, dietary limitations, having to plan around UC, worry/fear, anger, low mood/depression, and relationship with others, (≥75% of participants). In creative tasks, animals were chosen to represent their UC and content included in the collages reflected the most commonly discussed themes from the interviews. Only adults discussed feeling dehydrated, while only adolescents discussed the impact of UC on school life. CONCLUSIONS: Open-ended interviews highlighted the HRQoL and symptomatic experiences of UC from the patient's perspective, which were similar between adult and adolescent UC patients.

Estimating the distribution of a novel clinical biomarker (FGF-23) in the US population using findings from a regional research registry.

Evidence of involvement of novel biomarkers in disease pathogenesis from research cohorts often precedes an understanding of their distributions in broader populations. This study aimed to estimate the distribution of fibroblast growth factor 23 (FGF-23), an endocrine hormone that helps to regulate serum phosphate levels, in the overall US population and in important subgroups. We used a predictive model generated using data from the Framingham Health Study to estimate FGF-23 values for adults in the US National Health and Nutrition Examination Survey and the size of patient subgroups with levels of FGF-23 above selected thresholds. To assess the face validity of our FGF-23 estimates, we examined the relationship between estimated FGF-23 and cardiovascular and all-cause mortality within NHANES using Kaplan-Meier estimates and Cox proportional-hazards regression models and compared it to that observed in Framingham. Estimated FGF-23 values from NHANES were lower (median [interquartile range] 47.4 [35.8, 64.0] vs. 67.0 [54.0, 85.0] RU/mL) than the observed FGF-23 values from the Framingham cohort. Age- and sex-adjusted 10-year all-cause mortality was significantly higher (hazard ratio 2.43 [95% confidence interval: 1.42, 4.16]) for subjects with estimated FGF-23 levels in the highest versus lowest quartile. Estimating the distribution of biomarker values in the general population by applying predictive equations from smaller research cohorts is feasible and can inform drug research decision making.

The experience of social determinants of health within a Southern European Maltese culture.

This study contributes to international research on geographies of health and wellbeing in Mediterranean cultures. The paper draws upon evidence from qualitative research in three localities in Malta, a country where previous research on this topic is quite limited. Through in-depth interviews with people from some of the most disadvantaged and socially marginalised groups in Maltese society, this research illustrates how psychosocial health and wellbeing of the inhabitants within this Mediterranean region are strongly influenced by wider social determinants, particularly the powerful dynamics of social norms involving roles of extended family, traditional attitudes towards marriage as an institution, family honour, gender roles and religious beliefs and practices. This research explores how these social determinants of health within a Maltese context are complex and contingent on personal and local socio-geographical conditions, so that while for some individuals they are beneficial for health and wellbeing, for others the effects are detrimental. The discussion considers how to interpret the 'Mediterranean model' of social determinants of health in light of the experiences of this group of inhabitants.

Medication adherence and improved outcomes among patients with type 2 diabetes.

OBJECTIVES: Examine the association between adherence to glucose-lowering agents (GLAs) and patient outcomes in an adult type 2 diabetes (T2D) population. STUDY DESIGN: Retrospective analysis. METHODS: Truven's Commercial Claims and Encounters database supplied data from July 1, 2009, to June 30, 2014. Patients 18 to 64 years with T2D were included if they received a GLA from July 1, 2010, through June 30, 2011. Multivariable analyses examined the relationships among 3-year patient outcomes and adherence, defined as proportion of days covered 80% or more. Outcomes included all-cause medical costs, acute care resource utilization, and acute complications. RESULTS: Although there was no statistically significant difference in total costs when comparing adherent and nonadherent patients ($38,633 vs $38,357; P = .0720), acute care costs ($12,153 vs $8233; P <.0001) and outpatient costs ($16,964 vs $15,457; P <.0001) were significantly lower for adherent patients. Adherence was also associated with a lower probability of hospitalization (22.71% vs 17.65%; P <.0001) and emergency department (ED) visits (45.61% vs 38.47%; P <.0001), fewer hospitalizations (0.40 vs 0.27; P <.0001) and ED visits (1.23 vs 0.83; P <.0001), and a shorter hospital length of stay (2.16 vs 1.25 days; P <.0001). Adherent patients were also less likely to be diagnosed with an acute complication in the 3-year post period (12.54% vs 9.64%; P <.0001). CONCLUSIONS: Compared with nonadherence, adherence to GLAs among patients with T2D was associated with a significant reduction in acute care costs and resource utilization, outcomes that may positively impact the welfare of patients.

Associations between adherence and outcomes among older, type 2 diabetes patients: evidence from a Medicare Supplemental database.

OBJECTIVE: To examine the association between adherence to glucose-lowering agents and patient outcomes, including costs, acute-care resource utilization, and complications, in an older, type 2 diabetic population. DATA AND METHODS: The study used Truven's Medicare Supplemental database from July 1, 2009 to June 30, 2014. Patients aged 65 years or older were included if they had at least two type 2 diabetes diagnoses and received a glucose-lowering agent from July 1, 2010 through June 30, 2011. Multivariable analyses examined the relationships among 3-year patient outcomes and levels of adherence, proxied by the proportion of days covered. Outcomes included all-cause medical costs, diabetes-related medical costs, acute-care resource utilization, and acute complications. RESULTS: In this study (N=123,235), higher adherence was linked to reduced costs and improved health outcomes. For example, comparing an individual with adherence of proportion of days covered <20% to one with proportion of days covered ≥80% illustrates an average saving of $28,824 in total 3-year costs. Furthermore, a 1% increase in adherence among 1,000 patients was associated with all-cause savings of $65,464 over 3 years. The probability of a hospitalization, an emergency room (ER) visit, or an acute complication decreased monotonically as adherence levels got higher, as did the number of hospitalizations, ER visits, and days hospitalized (P<0.005). CONCLUSION: Higher adherence was associated with substantially less need for acute care, as indicated by a lowered probability of hospitalization or ER use, a reduced risk of an acute complication, and a decreased number of hospitalizations, ER visits, and days hospitalized. Higher adherence was also generally associated with lower all-cause and diabetes-related total costs, despite higher drug costs. These lower total costs were driven by the diminished acute care and outpatient costs. Results suggest that higher glucose-lowering agent adherence is associated with significant benefits for payers and older patients with type 2 diabetes.

Preference for pharmaceutical formulation and treatment process attributes.

PURPOSE: Pharmaceutical formulation and treatment process attributes, such as dose frequency and route of administration, can have an impact on quality of life, treatment adherence, and disease outcomes. The aim of this literature review was to examine studies on preferences for pharmaceutical treatment process attributes, focusing on research in diabetes, oncology, osteoporosis, and autoimmune disorders. METHODS: The literature search focused on identifying studies reporting preferences for attributes of the pharmaceutical treatment process. Studies were required to use formal quantitative preference assessment methods, such as utility valuation, conjoint analysis, or contingent valuation. Searches were conducted using Medline, EMBASE, Cochrane Library, Health Economic Evaluation Database, and National Health Service Economic Evaluation Database (January 1993-October 2013). RESULTS: A total of 42 studies met inclusion criteria: 19 diabetes, nine oncology, five osteoporosis, and nine autoimmune. Across these conditions, treatments associated with shorter treatment duration, less frequent administration, greater flexibility, and less invasive routes of administration were preferred over more burdensome or complex treatments. While efficacy and safety often had greater relative importance than treatment process, treatment process also had a quantifiable impact on preference. In some instances, particularly in diabetes and autoimmune disorders, treatment process attributes had greater relative importance than some or all efficacy and safety attributes. Some studies suggested that relative importance of treatment process depends on disease (eg, acute vs chronic) and patient (eg, injection experience) characteristics. CONCLUSION: Despite heterogeneity in study methods and design, some general patterns of preference clearly emerged. Overall, the results of this review suggest that treatment process has a quantifiable impact on preference and willingness to pay for treatment, even in many situations where safety and efficacy were the primary concerns. Patient preferences for treatment process attributes can inform drug development decisions to better meet the needs of patients and deliver improved outcomes.

Physician perceptions of GLP-1 receptor agonists in the UK.

Objectives Glucagon-like peptide-1 (GLP-1) receptor agonists have been used to treat type 2 diabetes for almost a decade, and new treatments in this class have recently been introduced. The purpose of this study was to examine perceptions of GLP-1 receptor agonists among physicians who treat patients with type 2 diabetes in the UK. Methods A total of 670 physicians (226 diabetes specialists; 444 general practice [GP] physicians) completed a survey in 2014. Results Almost all physicians had prescribed GLP-1 receptor agonists (95.4% total sample; 99.1% specialists; 93.5% GP), most frequently to patients whose glucose levels are not adequately controlled with oral medications (85.9% of physicians) and obese/overweight patients (83.7%). Physicians' most common reasons for prescribing a GLP-1 receptor agonist were: associated with weight loss (65.8%), good efficacy (55.7%), less hypoglycemia risk than insulin (55.2%), not associated with weight gain (34.5%), and better efficacy than oral medications (32.7%). Factors that most commonly cause hesitation when prescribing this class were: not considered first line therapy according to guidelines (56.9%), injectable administration (44.6%), cost (36.7%), gastrointestinal side effects (33.4%), and risk of pancreatitis (26.7%). Almost all specialists (99.1%) believed they had sufficient knowledge to prescribe a GLP-1 receptor agonist, compared with 76.1% of GPs. Conclusions Results highlight the widespread use of GLP-1 receptor agonists for treatment of type 2 diabetes in the UK. However, almost a quarter of GPs reported that they do not have enough knowledge to prescribe GLP-1s, suggesting a need for increased dissemination of information to targeted groups of physicians. Study limitations were that the generalizability of the clinician sample is unknown; survey questions required clinicians to select answers from multiple response options rather than generating the responses themselves; and responses to this survey conducted in 2014 do not reflect perceptions of the most recently introduced GLP-1 receptor agonists.

Clustered randomised controlled trial of two education interventions designed to increase physical activity and well-being of secondary school students: the MOVE Project.

OBJECTIVE: To assess the effectiveness of 2 interventions in improving the physical activity and well-being of secondary school children. DESIGN: A clustered randomised controlled trial; classes, 1 per school, were assigned to 1 of 3 intervention arms or a control group based on a 2×2 factorial design. The interventions were peer-mentoring and participative learning. Year 7 children (aged 11-12) in the peer-mentoring intervention were paired with year 9 children for 6 weekly mentoring meetings. Year 7 children in the participative learning arm took part in 6 weekly geography lessons using personalised physical activity and Global Positioning System (GPS) data. Year 7 children in the combined intervention received both interventions, with the year 9 children only participating in the mentoring sessions. PARTICIPANTS: 1494 year 7 students from 60 schools in the North of England took part in the trial. Of these, 43 students opted out of taking part in the evaluation measurements, 2 moved teaching group and 58 changed school. Valid accelerometry outcome data were collected for 892 students from 53 schools; and well-being outcome data were available for 927 students from 52 schools. MAIN OUTCOME MEASURES: The primary outcomes were mean minutes of accelerometer-measured moderate-to-vigorous intensity physical activity per day, and well-being as evaluated by the KIDSCREEN-27 questionnaire. These data were collected 6 weeks after the intervention; a 12-month follow-up is planned. RESULTS: No significant effects (main or interaction) were observed for the outcomes. However, small positive differences were found for both outcomes for the participative learning intervention. CONCLUSIONS: These findings suggest that the 2 school-based interventions did not modify levels of physical activity or well-being within the period monitored. Change in physical activity may require more comprehensive individual behavioural intervention, and/or more system-based efforts to address wider environmental influences such as family, peers, physical environment, transport and educational policy. TRIAL REGISTRATION NUMBER: ISRCTN82956355.

Evaluating preferences for profiles of GLP-1 receptor agonists among injection-naïve type 2 diabetes patients in the UK.

OBJECTIVE: To use a discrete choice experiment (DCE) to evaluate preferences for the actual treatment features and overall profiles of two injectable glucagon-like peptide-1 receptor agonists (dulaglutide and liraglutide) among patients with type 2 diabetes mellitus (T2DM) in the UK. METHODS: In-person interviews were conducted in the UK to administer a DCE to patients with self-reported T2DM, naïve to treatment with injectable medications. The DCE examined six attributes of T2DM treatment each described by two levels: "dosing frequency," "hemoglobin A1c change," "weight change," "type of delivery system," "frequency of nausea," and "frequency of hypoglycemia." Part-worth utilities were estimated using random effects logit models and were used to calculate relative importance (RI) values for each attribute. A chi-square test was used to determine differences in preferences for dulaglutide versus liraglutide profiles. RESULTS: A total of 243 participants [mean age: 60.5 (standard deviation 10.9) years; 76.1% male; mean body mass index: 29.8 (standard deviation 5.4) kg/m(2)] completed the study. RI values for the attributes in rank order were: "dosing frequency" (41.6%), "type of delivery system" (35.5%), "frequency of nausea" (10.4%), "weight change" (5.9%), "hemoglobin A1c change" (3.6%), and "frequency of hypoglycemia" (3.0%). Significantly more participants preferred the dulaglutide profile (83.1%) compared with the liraglutide profile (16.9%; P<0.0001). CONCLUSION: This study elicited patients' preferences for attributes and levels representing the actual characteristics of two specific glucagon-like peptide-1 medications. In this context, dosing frequency and type of delivery system were most important, accounting for over 75% of the RI. While previous studies have identified efficacy as highly important in T2DM medication decisions, this study suggests that when differences in efficacy between medications are small, other treatment features (eg, dosing frequency and delivery system) are of much greater importance to patients.

'Therapeutic landscapes' and the importance of nostalgia, solastalgia, salvage and abandonment for psychiatric hospital design.

We examine emotional reactions to changes to medical spaces of care, linked with past experiences. In this paper we draw on findings from a qualitative study of the transfer of psychiatric inpatient care from an old to a newly built facility. We show how the meanings attributed to 'therapeutic landscapes' from one׳s past can evoke emotions and memories, manifesting in ideas about nostalgia, solastalgia, salvage and abandonment, which can impinge on one׳s present therapeutic experience. We reflect on how consideration of these ideas might contribute to better future design of psychiatric inpatient facilities and the wellbeing of those using them.

A model of mild hypoglycemia.

OBJECTIVE: To investigate the impact associated with mild hypoglycemia among patients with type 2 diabetes (T2DM) in the United States and to identify risk factors among different subpopulations. METHODS: We performed a literature search to gather available data allowing estimation of rates of mild hypoglycemia. Because risk factors are interdependent, risk factors included in the model were based on those reported within multivariate analyses or judged to be biologically plausible by the medical community. Based on literature search results, we built a mathematical model predicting the rates of mild hypoglycemia in individual patients as a function of the patient's antidiabetic medications, hemoglobin A1c levels, duration of diabetes, kidney function, and body mass index. RESULTS: We estimated an overall average rate of mild hypoglycemia among US patients with T2DM of 2.2 ± 0.8 events per person per year. Patients taking oral antidiabetic medications only had an average rate of 1.9 ± 0.8 events per person per year. The average rate for all patients taking insulin, including those combining it with other antidiabetic medications, was 4.9 ± 2.0 events per person per year. Mild hypoglycemia rates increased with age, with 80-year-old patients experiencing 1.5 times the risk of 40-year-old patients. Based on published values for direct and indirect medical costs for mild hypoglycemia events, we determined that the economic impact in the US of mild hypoglycemic events is approximately $900 million per year, roughly equal to that of severe hypoglycemic events. One of the key limitations to our model is that it applies to the US population under standard medical care and not to clinical trials and does not include certain known risk factors such as rigorous exercise. CONCLUSIONS: Understanding the benefit versus risk of glycemic control and hypoglycemia is fundamental to the successful management of patients with T2DM. Our validated hypoglycemia model is an important step in addressing this issue and may be helpful to researchers, clinicians, and payers to determine the patients who are at the highest risk for hypoglycemia, whether a patient is experiencing events at 'higher-than-expected' rates, and the corresponding economic burden.

Spaces for smoking in a psychiatric hospital: social capital, resistance to control, and significance for 'therapeutic landscapes'.

This paper reports on research framed by theories of therapeutic landscapes and the ways that the social, physical and symbolic dimensions of landscapes relate to wellbeing and healing. We focus especially on the question of how attributes of therapeutic landscapes are constructed in different ways according to the variable perspectives of individuals and groups. Through an ethnographic case study in a psychiatric hospital in the North of England we explore the perceived significance for wellbeing of 'smoking spaces' (where tobacco smoking is practiced in ways that may, or may not be officially sanctioned). We interpret our findings in light of literature on how smoking spaces are linked to the socio-geographical power relations that determine how smoking is organised within the hospital and how this is understood by different groups using the hospital building. We draw on qualitative research findings from discussion groups, observations, and interviews with patients, carers and staff. These focused on their views about the building design and setting of the new psychiatric hospital in relation to their wellbeing, and issues relating to smoking spaces emerged as important for many participants. Creating and managing smoking spaces as a public health measure in psychiatric hospitals is shown to be a controversial issue involving conflicting aims for health and wellbeing of patients and staff. Our findings indicate that although from a physical health perspective, smoking is detrimental, the spaces in which patients and staff smoke have social and psychological significance, providing a forum for the creation of social capital and resistance to institutional control. While the findings relate to one case study setting, the paper illustrates issues of wider relevance and contributes to an international literature concerning the tensions between perceived psychological and psychosocial benefits of smoking vs. physical harm that smoking is likely to cause. We consider the implications for hospital design and the model of care.

Neighbourhood deprivation and adolescent self-esteem: exploration of the 'socio-economic equalisation in youth' hypothesis in Britain and Canada.

Material deprivation is an important determinant of health inequalities in adults but there remains debate about the extent of its importance for adolescent wellbeing. Research has found limited evidence for an association between adolescent health and socio-economic status, leading authors to suggest that there is an 'equalisation' of health across socio-economic groups during the adolescent stage of the life-course. This paper explores this 'equalisation' hypothesis for adolescent psychological wellbeing from a geographical perspective by investigating associations between neighbourhood deprivation and self-esteem in Britain and Canada. Data from the British Youth Panel (BYP) and the National Longitudinal Survey of Children and Youth (NLSCY) on adolescents aged 11-15 for the time period 1994-2004 were used to estimate variations in low self-esteem between neighbourhoods using multilevel logistic regression. Models were extended to estimate associations between self-esteem and neighbourhood deprivation before and after adjustment for individual and family level covariates. Moderation by age, sex, urban/rural status, household income and family structure was investigated. There were no significant differences in self-esteem between the most deprived and most affluent neighbourhoods (Canada unadjusted OR = 1.00, 95% CI 0.76, 1.33; Britain unadjusted OR = 1.25, 95% CI 0.74, 2.13). The prevalence of low self-esteem was higher (in Canada) for boys in the least deprived neighbourhoods compared to other neighbourhoods. No other interactions were observed. The results presented here offer some (limited) support for the socio-economic equalisation in youth hypothesis from a geographical perspective: with specific reference to equalisation of the relationship between neighbourhood deprivation and self-esteem and psychological health in early adolescence. This contrasts with previous research in the United States but supports related work from Britain. The lack of interactions with key social and economic variables suggests that findings might apply across a range of family circumstances and different communities in Britain and Canada. Policy implications are discussed.

Creating 'therapeutic landscapes' for mental health carers in inpatient settings: a dynamic perspective on permeability and inclusivity.

Although there has been a shift toward treatment in the home and the community, in the UK, inpatient facilities are still important in modern mental health care. 'Informal carers', including family members, often play an essential role, not only in providing care in the community but also in care of patients during periods of hospitalisation. UK National Health Service policies increasingly consider the position of these carers as 'partners' in the care process, but relatively little attention has been paid to their position within the hospital settings where treatment is provided for inpatients. This paper contributes to geographical work on carers experiences, by reporting how this issue emerged through a study focused on perceptions of a newly built hospital, compared with the inpatient facilities it replaced. We draw on qualitative research findings from discussion groups and interviews with informal carers. The material considered here focused especially on carers' views of aspects of the hospital environment that were important for wellbeing of carers and the people they look after. The carers' views were supplemented by relevant material drawn from other interviews from our wider study, which included service users and members of hospital staff. These accounts revealed how informal carers experienced the hospital environment; we interpret our findings through a conceptual framework that emphasises carers' experiences of a 'journey' along a 'caring pathway' to and through the hospital space. This perspective allows us to make a connection between three bodies of literature. The first relates to phenomenological interpretations of one's environmental perception, formed as one moves through the world. The second derives from the literature concerning 'permeability' of hospital institutions. Bringing these ideas together provides an innovative, dynamic perspective on a third strand of literature from health geography that examines hospitals as 'therapeutic landscapes'. The analysis helps to explore the extent to which carers in this study were positioned as 'outsiders' in the hospital space.

Long-term local area employment rates as predictors of individual mortality and morbidity: a prospective study in England, spanning more than two decades.

BACKGROUND: Although long-term trends in local labour market conditions are likely to influence health, few studies have assessed whether this is so. This paper examines whether (1) trends in local employment rates have relevance for mortality and morbidity outcomes in England and (2) trends are stronger predictors of these outcomes than employment rates measured at one point in time. METHODS: Using latent class growth models, local areas were classified into eight groups following distinct trends in employment rates between 1981 and 2008. Areas were also categorised in 'octile' groups by rank of employment rates in 2001. These area groupings were linked to a sample of 207,959 individuals from the Office of National Statistics Longitudinal Study. Associations between area groupings and risk of all-cause mortality and of reporting a limiting long-term illness at the end of the period were measured using logistic regression. Models were adjusted for individuals' socio-demographic characteristics measured in 1981 and for their residential mobility between 1981 and 2001. RESULTS: Compared to areas with continuously high employment rates over the period, risk of mortality and morbidity was higher in areas with persistently low or declining employment rates. Findings suggest that long-term trends in local employment rates are useful as predictors of mortality and morbidity differences. These are not so clearly distinguished by only considering employment rates at one point in time. CONCLUSION: Poor health outcomes are associated with long-term economic disadvantage in some areas of England, reflected in employment rates, underlining the importance of efforts to improve health in areas with especially 'deep-seated' deprivation.

The geography of institutional psychiatric care in France 1800-2000: historical analysis of the spatial diffusion of specialised facilities for institutional care of mental illness.

As in other European countries, specialised psychiatric hospitals were established throughout France during the 19th Century. The construction of these hospitals can be considered as the concrete expression of a therapeutic innovation which recognized insanity as an illness that could be treated in such specialised institutions. The spatial diffusion of these innovative institutions through 19th and 20th century France is analysed and we explore how far this can be understood through theories of diffusion of innovations including geographical models of hierarchical and expansion diffusion (or whether other conceptual models are more appropriate). The research reported here particularly focuses on the period 1800-1961. It involved the construction of an original historical database of both psychiatric hospitals and information on the cities where these institutions were located. This was used to examine and interpret the different phases of development of psychiatric institutions and the parts of the country and types of geographical setting where they were concentrated. A multiple correspondence analysis was then performed to examine the connections between different aspects of the diffusion process. The study shows the limitations of classical models of spatial diffusion, which are found to be consistent with some, but not all aspects of the development of psychiatric institutions in France. An alternative political ecology approach seems more appropriate to conceptualise the various processes involved; national policies, social representations, medicalisation of care of mental illness, and urban and economic growth all seem to be associated with the emergence of a variable and complex pattern. This paper also opens a large field of research. Compared with other western countries, the geography of French psychiatric care is relatively under-researched, although there has been a strong spatial dimension to mental health policy in the country. This analysis provides a context for studies of more contemporary processes of French deinstitutionalisation, which is strongly structured by the past heritage of these large asylum facilities.