Novel methods of drug administration for the treatment and care of older patients

The number of older people globally is increasing, contributing to a growing burden of morbidity and mortality. With this shift in population demographic, comes a new challenge in terms of appropriate healthcare for the over 65 years age group. As medication is the principal therapeutic intervention, it is essential that it be fully optimised, to meet the needs of this heterogeneous population. The most common routes of drug administration are oral and injectable, which may display some limitations for older people, in cases of dysphagia or frailty for example. This review considers alternative methods of drug delivery to the norm, specifically discussing the nasal, pulmonary and transdermal routes, as well as novel orally disintegrating tablets. The changing physiology as ageing occurs must be considered in the development of novel drug delivery devices. This review considers the various aspects of ageing that will influence future drug formulation design and development.

Improving the quality of life for patients with angina pectoris: a team approach to disease management.

The evaluation of outcome of management of angina patients is now inextricably linked with an assessment of quality of life. Angina, as a manifestation of coronary heart disease, is a major cause of morbidity and mortality in many countries. Optimal management of patients with angina is of undeniable national and global significance.

This paper attempts to indicate the importance of a team approach and the implications for patients’ quality of life of involving professionals with a variety of different skills. It outlines current guidelines for the management of angina, including aspects of diagnosis, treatment and rehabilitation. Factors of relevance to the management of patients as individuals are discussed. The association of improved quality of life and reduced severity of symptoms with benefit for both the individual and society is considered.

Judicial Rehabilitation and the ‘Clean Bill of Health’ in Criminal Justice.

Drawing on an important survey of European and Australian policies toward ‘judicial rehabilitation,’ this article makes the following arguments. First, the rehabilitation movement should return to the origins of the word ‘rehabilitation’ and focus at least as much on efforts to remove and relieve ex-prisoner stigma as on treatment and reform efforts. There will be no ‘rehabilitation revolution’ without this. Second, these efforts should involve active, not passive redemption. Rehabilitation processes that require almost a decade or more of ‘crime-free’ behaviour before forgiving an individual for his or her crimes are just and fair, but they miss the point of rehabilitation. Policies should encourage, support and facilitate good behaviour and not just reward it in retrospect. Third, rehabilitation should not just be done, but be ‘seen to be done,’ ideally in a ritualised format. This sends an important message to the individual and wider society. Finally, I argue that it may be better to forgive than forget past crimes. That is, rather than burying past crimes as if they never happened, states should instead acknowledge and formally recognise that people can change, that good people can do bad things, and that all individuals should be able to move on from past convictions.

Triangular Objects and Systematic K-Theory

We investigate modules over “systematic” rings. Such rings are “almost graded” and have appeared under various names in the literature; they are special cases of the G-systems of Grzeszczuk. We analyse their K-theory in the presence of conditions on the support, and explain how this generalises and unifies calculations of graded and filtered K-theory scattered in the literature. Our treatment makes systematic use of the formalism of idempotent completion and a theory of triangular objects in additive categories, leading to elementary and transparent proofs throughout.

Restorative Justice as a Response to Sexual Offending – Addressing the Failings of Current Punitive Approaches

This article explores the use of restorative justice as a response to sexual crime. The management of high risk sex offenders, particularly in the community post-release, has been a key focus of contemporary popular and political debates on sexual offending. Many offenders fail to come to the attention of the criminal justice system. For those that do, there is the almost blanket application of recent control in the community measures such as sex offender registries and community notification which have failed to prevent reoffending. The response by the media and the public to the presence of sex offenders in the community may also impede offender rehabilitation. The use of punishment alone via formal criminal justice is, therefore, an inadequate deterrent for sexual crimes. Although controversial, this article advocates the use of restorative practices with sexual crime as a proactive, holistic response to the problem and ultimately as a more effective means of reducing the incidence of sexual offences and sex offender recidivism.

Tooth loss and implant outcomes in patients refractory to treatment in a periodontal practice

Aim: The aim of this study was to investigate the factors associated with continued significant tooth loss due to periodontal reasons during maintenance following periodontal therapy in a specialist periodontal practice in Norway.
Material and Methods: A case-control design was used. Refractory cases were patients who lost multiple teeth during a maintenance period of 13.4 (range 8-19) years following definitive periodontal treatment in a specialist practice. Controls were age- and gender-matched maintenance patients from the same practice. Characteristics and treatment outcomes were assessed, and all teeth classified as being lost due to periodontal disease during follow-up were identified. The use of implants in refractory cases and any complications relating to such a treatment were recorded.
Results: Only 27 (2.2%) patients who received periodontal treatment between 1986 and 1998 in a specialist practice met the criteria for inclusion in the refractory to treatment group. Each refractory subject lost 10.4 (range 4-16) teeth, which represented 50% of the teeth present at baseline. The rate of tooth loss in the refractory group was 0.78 teeth per year, which was 35 times greater than that in the control group. Multivariate analysis indicated that being in the refractory group was predicted by heavy smoking (p=0.026), being stressed (p=0.016) or having a family history of periodontitis (p=0.002). Implants were placed in 14 of the refractory patients and nine (64%) of these lost at least one implant. In total, 17 (25%) of the implants placed in the refractory group were lost during the study period.
Conclusions: A small number of periodontal maintenance patients are refractive to treatment and go on to experience significant tooth loss. These subjects also have a high level of implant complications and failure. Heavy smoking, stress and a family history of periodontal disease were identified as factors associated with a refractory outcome.

Entrepreneurial and Business Growth and the Quest for a “Comprehensive Theory”: Tilting at Windmills?

Even though there has been sustained interest in growth for almost 50 years, relatively little is known about this phenomenon and much confusion and misunderstanding surrounds it. Based on a literature review and the articles in this special issue we make three recommendations that we believe will allow theory to advance and be applicable in practice. First, that discourse between key stakeholders is encouraged in order to achieve greater understanding. Second, that focus is placed on " growth as a process," rather than as a " change in amount." Third, that knowledge production requires inclusivity and pluralism in research perspectives and approaches. © 2010 Baylor University.

Mapping NGO Competency to Reduce Human Vulnerability in Post-disaster Communities: Comparing Strategies in Sri Lanka and Bangladesh

Natural hazards trigger disasters, the scale of which is largely determined by vulnerability. Developing countries suffer the most from disasters due to various conditions of vulnerability which exist and there is an opportunity after disasters to take mitigative action. NGOs implementing post-disaster rehabilitation projects must be able to address the issues causing communities to live at risk of disaster and therefore must build dynamic capacity, capabilities and competencies, enabling them to operate in unstable environments. This research is built upon a theoretical framework of dynamic competency established by combining elements of disaster management, strategic management and project management theory. A number of NGOs which have implemented reconstruction and rehabilitation projects both in Sri Lanka following the Asian Tsunami and Bangladesh following Cyclone Sidr are being investigated in great depth using a causal mapping procedure. ‘Event’ specific maps have been developed for each organization in each disaster. This data will be analysed with a view to discovering the strategies which lead to vulnerability reduction in post-disaster communities and the competencies that NGOs must possess in order to achieve favourable outcomes. It is hypothesized that by building organizational capacity, capabilities and competencies to be dynamic in nature, while focusing on a more emergent strategic approach, with emphasis on adaptive capability and innovation, NGOs will be better equipped to contribute to sustainable community development through reconstruction. We believe that through this study it will be possible to glean a new understanding of social processes that emerge within community rehabilitation projects.

Fasciola hepatica: Histological changes in the reproductive structures of triclabendazole (TCBZ)-sensitive and TCBZ-resistant flukes after treatment in vivo with TCBZ and the related benzimidazole derivative, Compound Alpha

Twenty-four shed-reared lambs were each infected orally with 250 metacercariae of Fasciola hepatica, using either the triclabendazole (TCBZ)-sensitive Cullompton isolate or the TCBZ-resistant Sligo isolate. Twelve weeks after infection the lambs were treated with TCBZ (10 mg/kg) or with the experimental fasciolicide, Compound Alpha (Cpd alpha), a benzimidazole derivative of TCBZ (15 mg/kg). The lambs were euthanised 48,72 and 96 h after TCBZ treatment, or 24, 48 and 72 h after Cpd a treatment, and flukes were collected from the liver and/or gall bladder of each animal. Untreated animals harbouring 12-week infections were euthanised 24 h after administration of anthelmintic to the treatment groups, and the untreated flukes provided control material. A semi-quantitative assessment of the degree of histological change induced by the two drugs after different times of exposure was achieved by scoring the intensity of three well-defined lesions that developed in the testes and uteri of a representative sample of flukes from each lamb. In general, it was found that in those tissues where active meiosis and/or mitosis occurred (testis, ovary, and vitelline follicles), there was progressive loss of cell content due to apparent failure of cell division to keep pace with expulsion of the mature or effete products. Further, actively dividing cell types tended to become individualised, rounded and condensed, characteristic of apoptotic cell death. Protein synthetic activity was apparently inhibited in the Mehlis' secretory cells. In the uterus, where successful formation of shelled eggs represents the culmination of a complex sequence of cytokinetic, cytological and synthetic activity involving the vitelline follicles, the ovary and the Mehlis' gland, histological evidence indicating failure of ovigenesis was evident from 24 h post-treatment onwards. The development of these lesions may be related to the known antitubulin activity of the benzimidazole class of anthelmintics, to the induction of apoptosis in cells where mitosis or meiosis has aborted due to failure of spindle formation, and to drug-induced inhibition of protein synthesis. The semi-quantitative findings indicated that Cpd a is slightly less efficacious than TCBZ itself in causing histological damage to the reproductive structures of TCBZ-sensitive flukes, and that, like TCBZ, it caused no histological damage in flukes of the TCBZ-resistant isolate. This study illustrates the potential utility of histological techniques for conveniently screening representative samples of flukes in field trials designed to validate instances of drug resistance or to test the efficacy of new products against known drug-resistant and drug-susceptible fluke isolates. It also provides reference criteria for drug-induced histopathological changes in fluke reproductive structures which may aid interpretation of TEM findings. (C) 2009 Elsevier B.V. All rights reserved.

Studies on the persistence of estradiol benzoate and nortestosterone decanoate in hair of cattle following treatment with growth promoters, determined by ultra-high-performance liquid chromatography-tandem mass spectrometry

Measurement of steroid esters in bovine hair samples, using sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS), provides a powerful tool for identifying animals treated illicitly with growth promoters. The successful application of such testing requires appropriate sampling of hair from treated animals. This paper describes the results of hair analysis by LC-MS/MS for two animal studies in which animals were treated with estradiol-3-benzoate and nortestosterone decanoate. The results from the first animal study indicate that animals treated with these anabolic steroids may not always be identified from analysis of hair samples; positive test results occur sporadically and only for some of the treated animals. The results from the second animal study identify conditions attaching to positive hair samples, such as, that concentrations of steroid esters in hair are related to distance of sampling from point of injection and to time post-treatment, that concentrations of steroid esters in hair are related to dose given to the animal but that this relationship may vary over time post-treatment, and that steroid esters may be measured in regrowth hair taken some weeks after treatment. Steroid esters are determined along the length of the hair, confirming that accumulation of steroid esters into hair occurs from various sources, including blood, sweat and sebum. The reported research provides some useful insights into the mechanisms governing the persistence of steroid esters in bovine hair following illicit treatment with growth promoters. (C) 2009 Elsevier B.V. All rights reserved.

Use of culture and molecular analysis to determine the effect of antibiotic treatment on microbial community diversity and abundance during exacerbation in patients with cystic fibrosis

Background: Anaerobic bacteria are increasingly regarded as important in cystic fibrosis (CF) pulmonary infection. The aim of this study was to determine the effect of antibiotic treatment on aerobic and anaerobic microbial community diversity and abundance during exacerbations in patients with CF.

Methods: Sputum was collected at the start and completion of antibiotic treatment of exacerbations and when clinically stable. Bacteria were quantified and identified following culture, and community composition was also examined using culture-independent methods.

Results: Pseudomonas aeruginosa or Burkholderia cepacia complex were detected by culture in 24/26 samples at the start of treatment, 22/26 samples at completion of treatment and 11/13 stable samples. Anaerobic bacteria were detected in all start of treatment and stable samples and in 23/26 completion of treatment samples. Molecular analysis showed greater bacterial diversity within sputum samples than was detected by culture; there was reasonably good agreement between the methods for the presence or absence of aerobic bacteria such as P aeruginosa (kappa=0.74) and B cepacia complex (kappa=0.92), but agreement was poorer for anaerobes. Both methods showed that the composition of the bacterial community varied between patients but remained relatively stable in most individuals despite treatment. Bacterial abundance decreased transiently following treatment, with this effect more evident for aerobes (median decrease in total viable count 2.3 x 10(7) cfu/g, p=0.005) than for anaerobes (median decrease in total viable count 3 x 10(6) cfu/g, p=0.046).

Conclusion: Antibiotic treatment targeted against aerobes had a minimal effect on abundance of anaerobes and community composition, with both culture and molecular detection methods required for comprehensive characterisation of the microbial community in the CF lung. Further studies are required to determine the clinical significance of and optimal treatment for these newly identified bacteria.