Triggered drug delivery from biomaterials

Importance of the field: Conventional dosing methods are frequently unable to deliver the clinical requirement of the patient. The ability to control the delivery of drugs from implanted materials is difficult to achieve, but offers promise in diverse areas such as infection-resistant medical devices and 10 responsive implants for diabetics. Areas covered in this review: This review gives a broad overview of recent progress in the use of triggers that can be used to achieve modulation of drug release rates from implantable biomaterials. In particular, these can be classified as being responsive to one or more of the following stimuli: a 15 chemical species, light, heat, magnetism, ultrasound and mechanical force. What the reader will gain: An overview of the potential for triggered drug delivery to give methods for tailoring the dose, location and time of release of a wide range of drugs where traditional dosing methods are not suitable. Particular emphasis is given to recently reported systems, and important 20 historical reports are included. Take home message: The use of externally or internally applied triggers of drug delivery to biomaterials has significant potential for improved delivery modalities and infection resistance.

Discovery and Development of a Potent and Highly Selective Small Molecule Muscarinic Acetylcholine Receptor Subtype I (mAChR 1 or M-1) Antagonist In Vitro and In Vivo Probe

This article describes the discovery and development of the first highly selective, small molecule antagonist of the muscarinic acetylcholine receptor subtype I (mAChR1 or M-1). An M-1 functional, cell-based, calcium-mobilization assay identified three distinct chemical series with initial selectivity for M-1 versus M-4. An iterative parallel synthesis approach was employed to optimize all three series in parallel, which led to the development of novel microwave-assisted chemistry and provided important take home lessons for probe development projects. Ultimately, this effort produced VU0255035, a potent (IC50 = 130 nM) and selective (>75-fold vs. M-2-M-5 and >10 mu M vs. a panel of 75 GPCRs, ion channels and transporters) small molecule M-1 antagonist. Further profiling demonstrated that VU0255035 was centrally penetrant (Brain(AUC)/Plasma(AUC) of 0.48) and active in vivo, rendering it acceptable as both an in vitro and in vivo MLSCN/MLPCN probe molecule for studying and dissecting M-1 function.

Risks to home care workers: Professional perspectives

Care at home is fundamental to community care policy, but the simultaneous growth of health and safety regulation has implications for home care services because of the duty of employers towards home care workers. This grounded theory study set in Northern Ireland used data from 19 focus groups and nine semi-structured interviews with a range of health and social services professionals and managers to explore perspectives on planning long term care for older people. Home care workers faced a wide range of hazards in the homes of clients, who themselves were faced with adapting their living habits due to their changing health and care needs and 'risks.' Creative approaches were used to ensure the health and safety of home care workers and simultaneously to meet the choices of clients. Staff experienced feelings of conflict when they judged it necessary to impose their way of providing home care and thus impose their values on clients to create a safe working environment. There was variation between and within organizations in terms of the staff focus on client needs or on their employer responsibility towards home care workers. The planning of home care services must take account of both the choices of clients and the hazards facing home care staff.

An Evaluation of the Impact of the Prospective Payment System on Antidepressant Use in Nursing Home Residents

Objectives: To determine the impact of the prospective payment system (PPS) for skilled nursing facilities on the pharmacologic treatment of depression.

Methods: We used a quasi-experimental study comparing the pharmacological treatment rates for depression in the pre-PPS period (1997) to the post-PPS period (2000) in 8149 residents with documented depression living in over 500 nursing facilities in Ohio. Logistic regression models adjusting for clustering effects of residents residing in homes using generalized estimating equations provided estimates of the PPS effect on use of any antidepressant and the use of selective serotonin reuptake inhibitors (SSRIs). We evaluated the extent to which the PPS effect was modified by organizational characteristics, including structural characteristics, resource characteristics, and staff resources available in the homes.

Results: Overall, there was no difference in the likelihood of any antidepressant [odds ratio (OR), 1.05; 95% confidence interval (CI), 0.93 to 1.18, resident-adjusted model] or an SSRI being used (OR, 0.98; 95% CI, 0.86 to 1.12, resident-adjusted model) after the introduction of PPS compared with 1997 when this reimbursement system was not in place (referent group). These trends did not appear to be modified substantially by organizational characteristics.

Conclusion: Although PPS did not appear to have influenced the treatment of depression in nursing homes, systems that provide checks and balances in relation to PPS are warranted.

Parent education and home-based behaviour analytic intervention: an examination of parents' perceptions of outcome

There is convincing evidence that applied behaviour analysis (ABA) offers a highly effective form of intervention for children with autistic spectrum disorder (ASD). There is less evidence, however, about how parents perceive and evaluate ABA programmes. In this paper an examination of parents’ perceptions of outcome is reported. Twenty-two questionnaires were completed by two groups of parents. The first group had just completed an introductory course in ABA and were in the early stages of implementing ABA programmes with their children. The second group had been involved in ABA education for more than 2 years. Overall, both groups of parents reported a positive impact of ABA on the lives of their children, their family life, and themselves. The long- term group reported that they had achieved complex goals with their children, whilst the short-term group reported an immediate positive impact on child and family functioning and parental self-esteem. Conclusions are drawn in the context of evidence-based practice.

A Home from Hospital service for older people.

Current policy and practice emphasises much more than ever before a need for purchasers and providers to reduce appropriately the length of hospital stay. Consequently, a number of early discharge “schemes” have been developed. This paper presents the findings from an evaluation of a “home from hospital” (HFH) scheme. The HFH service provides a maximum of six weeks intensive domiciliary care for older people on their discharge from hospital. The aim of the service is to facilitate early discharge from hospital and to assist patients to regain independence. The study reported here elicited the views and perceptions of clients and professionals involved in the HFH scheme about the quality, efficiency and effectiveness of the service. Seventy-five clients were discharged from hospital to the HFH scheme during a two month period and those who consented to participate in the study were interviewed after discharge from the HFH service (n = 40). Participants had attended hospital for various conditions but the largest group were fracture patients. Hospital staff and community based professionals completed a questionnaire about the service. Overall, clients and professionals perceived the HFH scheme as a beneficial service, though some minor problems existed at an individual level. Clients’ dependency levels generally decreased during their time on the scheme. Research using a controlled design is necessary in order to draw firm conclusions about the cost-effectiveness of a HFH service. Overall, home-from-hospital appears to be an effective model of an early discharge scheme worthy of further attention.

GP views about a home from hospital service

This paper reports the results of an investigation, by postal questionnaire, of the views of 30 General Practitioners about a model of out of hospital care – the home from hospital (HFH) service, which mainly provides social care and rehabilitation for patients in their own home. The GPs, who all worked within one of the Health and Social Services Board areas in Northern Ireland during the time of the study (March-April 1998), indicated that the introduction of the HFH service, unlike other models of out of hospital care, did not increase their workload. Therefore, it is suggested that the HFH model of care should be given more attention in terms of research evaluation and service development.