Limiting Behaviour of the Mean Residual Life

In survival or reliability studies, the mean residual life or life expectancy is an important characteristic of the model. Here, we study the limiting behaviour of the mean residual life, and derive an asymptotic expansion which can be used to obtain a good approximation for large values of the time variable. The asymptotic expansion is valid for a quite general class of failure rate distributions--perhaps the largest class that can be expected given that the terms depend only on the failure rate and its derivatives.Comment: 19 page

Treating hummingbirds as feathered bees : a case of ethological cross-pollination

Hummingbirds feed from hundreds of flowers every day. The properties of these flowers provide these birds with a wealth of information about colour, space and time to guide how they forage. To understand how hummingbirds might use this information, researchers have adapted established laboratory paradigms for use in the field. In recent years, however, experimental inspiration has come less from other birds, and more from looking at other nectar-feeders, particularly honeybees and bumblebees, which have been models for foraging behaviour and cognition for over a century. In a world in which the cognitive abilities of bees regularly make the news, research on the influence of ecology and sensory systems on bee behaviour is leading to novel insights in hummingbird cognition. As methods designed to study insects in the laboratory are being applied to hummingbirds in the field, converging methods can help us identify and understand convergence in cognition, behaviour and ecology.PostprintPeer reviewe

Housing prices and multiple employment nodes: is the relationship nonmonotonic?

Standard urban economic theory predicts that house prices will decline with distance from the central business district. Empirical results have been equivocal, however. Disjoints between theory and empirics may be due to a nonmonotonic relationship between house prices and access to employment arising from the negative externalities associated with proximity to multiple centres of employment. Based on data from Glasgow (Scotland), we use gravity-based measures of accessibility estimated using a flexible functional form that allows for nonmonotonicity. The results are thoroughly tested using recent advances in spatial econometrics. We find compelling evidence of a nonmonotonic effect in the accessibility measure and discuss the implications for planning and housing policy

Evidence supporting the best clinical management of patients with multimorbidity and polypharmacy: a systematic guideline review and expert consensus

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease-oriented guidelines often inadequate and complicates clinical decision making. To address this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow-up: strategies in care planning, self-management and medication-related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self-management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines.Journal of Internal MedicineKarolinska Institutet Strategic Research Area in Epidemiology (SfoEpi

Multimorbidity's research challenges and priorities from a clinical perspective: The case of 'Mr Curran'

This is the final version. Available on open access from Taylor & Francis via the DOI in this recordOlder patients, suffering from numerous diseases and taking multiple medications are the rule rather than the exception in primary care. A manifold of medical conditions are often associated with poor outcomes, and their multiple medications raise additional risks of polypharmacy. Such patients account for most healthcare expenditures. Effective approaches are needed to manage such complex patients in primary care. This paper describes the results of a scoping exercise, including a two-day workshop with 17 professionals from six countries, experienced in general practice and primary care research as well as epidemiology, clinical pharmacology, gerontology and methodology. This was followed by a consensus process investigating the challenges and core questions for multimorbidity research in primary care from a clinical perspective and presents examples of the best research practice. Current approaches in measuring and clustering multimorbidity inform policy-makers and researchers, but research is needed to provide support in clinical decision making. Multimorbidity presents a complexity of conditions leading to individual patient's needs and demanding complex processes in clinical decision making. The identification of patterns presupposes the development of strategies on how to manage multimorbidity and polypharmacy. Interventions have to be complex and multifaceted, and their evaluation poses numerous methodological challenges in study design, outcome measurement and analysis. Overall, it can be seen that complexity is a main underlying theme. Moreover, flexible study designs, outcome parameters and evaluation strategies are needed to account for this complexity. © 2014 Informa Healthcare

Pilot study to test the feasibility of a trial design and complex intervention on PRIoritising MUltimedication in Multimorbidity in general practices (PRIMUMpilot).

Published onlineJournal ArticleThis is the final version of the article. Available from BMJ Publishing Group via the DOI in this record.OBJECTIVE: To improve medication appropriateness and adherence in elderly patients with multimorbidity, we developed a complex intervention involving general practitioners (GPs) and their healthcare assistants (HCA). In accordance with the Medical Research Council guidance on developing and evaluating complex interventions, we prepared for the main study by testing the feasibility of the intervention and study design in a cluster randomised pilot study. SETTING: 20 general practices in Hesse, Germany. PARTICIPANTS: 100 cognitively intact patients ≥65 years with ≥3 chronic conditions, ≥5 chronic prescriptions and capable of participating in telephone interviews; 94 patients completed the study. INTERVENTION: The HCA conducted a checklist-based interview with patients on medication-related problems and reconciled their medications. Assisted by a computerised decision-support system (CDSS), the GPs discussed medication intake with patients and adjusted their medication regimens. The control group continued with usual care. OUTCOME MEASURES: Feasibility of the intervention and required time were assessed for GPs, HCAs and patients using mixed methods (questionnaires, interviews and case vignettes after completion of the study). The feasibility of the study was assessed concerning success of achieving recruitment targets, balancing cluster sizes and minimising drop-out rates. Exploratory outcomes included the medication appropriateness index (MAI), quality of life, functional status and adherence-related measures. MAI was evaluated blinded to group assignment, and intra-rater/inter-rater reliability was assessed for a subsample of prescriptions. RESULTS: 10 practices were randomised and analysed per group. GPs/HCAs were satisfied with the interventions despite the time required (35/45 min/patient). In case vignettes, GPs/HCAs needed help using the CDSS. The study made no patients feel uneasy. Intra-rater/inter-rater reliability for MAI was excellent. Inclusion criteria were challenging and potentially inadequate, and should therefore be adjusted. Outcome measures on pain, functionality and self-reported adherence were unfeasible due to frequent missing values, an incorrect manual or potentially invalid results. CONCLUSIONS: Intervention and trial design were feasible. The pilot study revealed important limitations that influenced the design and conduct of the main study, thus highlighting the value of piloting complex interventions. TRIAL REGISTRATION NUMBER: ISRCTN99691973; Results.Funding has been provided by the German Federal Ministry of Education and Research, BMBF, grant number 01GK0702

The Ethics of Corporate Governance

How should corporate directors determine what is the right decision? For at least the past 30 years the debate has raged as to whether shareholder value should take precedence over corporate social responsibility when crucial decisions arise. Directors face pressure, not least from ethical investors, to do the good thing when they seek to make the right choice. Corporate governance theory has tended to look to agency theory and the need of boards to curb excessive executive power to guide directors' decisions. While useful for those purposes, agency theory provides only limited guidance. Supplementing it with the alternatives - stakeholder theory and stewardship theory - tends to put directors in conflict with their legal obligations to work in the interests of shareholders. This paper seeks to reframe the discussion about corporate governance in terms of the ethical debate between consequential, teleological approaches to ethics and idealist, deontological ones, suggesting that directors are - for good reason - more inclined toward utilitarian judgments like those underpinning shareholder value. But the problems with shareholder value have become so great that a different framework is needed: strategic value, with an emphasis on long-term value creation judged from a decidedly utilitarian standpoint

Integrability breakdown in longitudinaly trapped, one-dimensional bosonic gases

A system of identical bosons with short-range (contact) interactions is studied. Their motion is confined to one dimension by a tight lateral trapping potential and, additionally, subject to a weak harmonic confinement in the longitudinal direction. Finite delay time associated with penetration of quantum particles through each other in the course of a pairwise one-dimensional collision in the presence of the longitudinal potential makes the system non-integrable and, hence, provides a mechanism for relaxation to thermal equilibrium. To analyse this effect quantitatively in the limit of a non-degenerate gas, we develop a system of kinetic equations and solve it for small-amplitude monopole oscillations of the gas. The obtained damping rate is long enough to be neglected in a realistic cold-atom experiment, and therefore longitudinal trapping does not hinder integrable dynamics of atomic gases in the 1D regime

Health-related preferences of older patients with multimorbidity: An evidence map

Objectives To systematically identify knowledge clusters and research gaps in the health-related preferences of older patients with multimorbidity by mapping current evidence.Design Evidence map (systematic review variant).Data sources MEDLINE, EMBASE, PsycINFO, PSYNDEX, CINAHL and Science Citation Index/Social Science Citation Index/-Expanded from inception to April 2018.Study selection Studies reporting primary research on health-related preferences of older patients (mean age ≥60 years) with multimorbidity (≥2 chronic/acute conditions).Data extraction Two independent reviewers assessed studies for eligibility, extracted data and clustered the studies using MAXQDA-18 content analysis software.Results The 152 included studies (62% from North America, 28% from Europe) comprised 57 093 patients overall (range 9–9105). All used an observational design except for one interventional study: 63 (41%) were qualitative (59 cross-sectional, 4 longitudinal), 85 (57%) quantitative (63 cross-sectional, 22 longitudinal) and 3 (2%) used mixed methods. The setting was specialised care in 85 (56%) and primary care in 54 (36%) studies. We identified seven clusters of studies on preferences: end-of-life care (n=51, 34%), self-management (n=34, 22%), treatment (n=32, 21%), involvement in shared decision making (n=25, 17%), health outcome prioritisation/goal setting (n=19, 13%), healthcare service (n=12, 8%) and screening/diagnostic testing (n=1, 1%). Terminology (eg, preferences, views and perspectives) and concepts (eg, trade-offs, decision regret, goal setting) used to describe health-related preferences varied substantially between studies.Conclusion Our study provides the first evidence map on the preferences of older patients with multimorbidity. Included studies were mostly conducted in developed countries and covered a broad range of issues. Evidence on patient preferences concerning decision-making on screening and diagnostic testing was scarce. Differences in employed terminology, decision-making components and concepts, as well as the sparsity of intervention studies, are challenges for future research into evidence-based decision support seeking to elicit the preferences of older patients with multimorbidity and help them construct preferences.Trial registration number Open Science Framework (OSF): DOI 10.17605/OSF.IO/MCRWQ

Rationale, design and conduct of a randomised controlled trial evaluating a primary care-based complex intervention to improve the quality of life of heart failure patients: HICMan (Heidelberg Integrated Case Management) : study protocol

Background: Chronic congestive heart failure (CHF) is a complex disease with rising prevalence, compromised quality of life (QoL), unplanned hospital admissions, high mortality and therefore high burden of illness. The delivery of care for these patients has been criticized and new strategies addressing crucial domains of care have been shown to be effective on patients' health outcomes, although these trials were conducted in secondary care or in highly organised Health Maintenance Organisations. It remains unclear whether a comprehensive primary care-based case management for the treating general practitioner (GP) can improve patients' QoL. Methods/Design: HICMan is a randomised controlled trial with patients as the unit of randomisation. Aim is to evaluate a structured, standardized and comprehensive complex intervention for patients with CHF in a 12-months follow-up trial. Patients from intervention group receive specific patient leaflets and documentation booklets as well as regular monitoring and screening by a prior trained practice nurse, who gives feedback to the GP upon urgency. Monitoring and screening address aspects of disease-specific selfmanagement, (non)pharmacological adherence and psychosomatic and geriatric comorbidity. GPs are invited to provide a tailored structured counselling 4 times during the trial and receive an additional feedback on pharmacotherapy relevant to prognosis (data of baseline documentation). Patients from control group receive usual care by their GPs, who were introduced to guidelineoriented management and a tailored health counselling concept. Main outcome measurement for patients' QoL is the scale physical functioning of the SF-36 health questionnaire in a 12-month follow-up. Secondary outcomes are the disease specific QoL measured by the Kansas City Cardiomyopathy questionnaire (KCCQ), depression and anxiety disorders (PHQ-9, GAD-7), adherence (EHFScBS and SANA), quality of care measured by an adapted version of the Patient Chronic Illness Assessment of Care questionnaire (PACIC) and NTproBNP. In addition, comprehensive clinical data are collected about health status, comorbidity, medication and health care utilisation. Discussion: As the targeted patient group is mostly cared for and treated by GPs, a comprehensive primary care-based guideline implementation including somatic, psychosomatic and organisational aspects of the delivery of care (HICMAn) is a promising intervention applying proven strategies for optimal care. Trial registration: Current Controlled Trials ISRCTN30822978