Exploring motivation and confidence in taking prescribed medicines in coexisting diseases: a qualitative study

Aims and objectives: To explore the motivation and confidence of people with coexisting diabetes, chronic kidney disease (CKD) and hypertension to take their medicines as prescribed. Background: These comorbidities are major contributors to disease burden globally. Self-management of individuals with these coexisting diseases is much more complicated than that of those with single diseases and is critical for improved health outcomes. Design: Motivational interviewing telephone calls were made with participants with coexisting diabetes, CKD and hypertension. Methods: Patients aged ≥18 years with diabetes, CKD and systolic hypertension were recruited from outpatient clinics of an Australian metropolitan hospital between 2008-2009. An average of four motivational interviewing telephone calls was made with participants (n = 39) in the intervention arm of a randomised controlled trial. Data were thematically analysed using the modified Health Belief Model as a framework. Results: Participants' motivation and confidence in taking prescribed medicines was thwarted by complex medicine regimens and medical conditions. Participants wanted control over their health and developed various strategies to confront threats to health. The perceived barriers of taking recommended health action outweighed the benefits of taking medicines as prescribed and were primarily related to copious amounts of medicines. Conclusion: Taking multiple prescribed medicines in coexisting diabetes, CKD and hypertension is a perpetual vocation with major psychosocial effects. Participants were overwhelmed by the number of medicines that they were required to take. The quest for personal control of health, fear of the future and the role of stress and gender in chronic disease management have been highlighted. Participants require supportive emotional interventions to self-manage their multiple medicines on a daily basis. Relevance to clinical practice: Reducing the complexity of medicine regimens in coexisting diseases is paramount. Individualised psychosocial approaches that address the emotional needs of patients with regular follow-up and feedback are necessary for optimal chronic disease self-management. © 2013 John Wiley & Sons Ltd.

Identification of novel therapeutics for complex diseases from genome-wide association data

Human genome sequencing has enabled the association of phenotypes with genetic loci, but our ability to effectively translate this data to the clinic has not kept pace. Over the past 60 years, pharmaceutical companies have successfully demonstrated the safety and efficacy of over 1,200 novel therapeutic drugs via costly clinical studies. While this process must continue, better use can be made of the existing valuable data. In silico tools such as candidate gene prediction systems allow rapid identification of disease genes by identifying the most probable candidate genes linked to genetic markers of the disease or phenotype under investigation. Integration of drug-target data with candidate gene prediction systems can identify novel phenotypes which may benefit from current therapeutics. Such a drug repositioning tool can save valuable time and money spent on preclinical studies and phase I clinical trials.

CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria

To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections.

Urbanicity and lifestyle risk factors for cardiometabolic diseases in rural Uganda: a cross-sectional study

Urban living is associated with unhealthy lifestyles that can increase the risk of cardiometabolic diseases. In sub-Saharan Africa (SSA), where the majority of people live in rural areas, it is still unclear if there is a corresponding increase in unhealthy lifestyles as rural areas adopt urban characteristics. This study examines the distribution of urban characteristics across rural communities in Uganda and their associations with lifestyle risk factors for chronic diseases.

Interleukin-10 inhibits bone resorption: a potential therapeutic strategy in periodontitis and other bone loss diseases

Periodontitis and other bone loss diseases, decreasing bone volume and strength, have a significant impact on millions of people with the risk of tooth loss and bone fracture. The integrity and strength of bone are maintained through the balance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively, so the loss of bone results from the disruption of such balance due to increased resorption or/and decreased formation of bone. The goal of therapies for diseases of bone loss is to reduce bone loss, improve bone formation, and then keep healthy bone density. Current therapies have mostly relied on long-term medication, exercise, anti-inflammatory therapies, and changing of the life style. However there are some limitations for some patients in the effective treatments for bone loss diseases because of the complexity of bone loss. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and recent studies have indicated that IL-10 can contribute to the maintenance of bone mass through inhibition of osteoclastic bone resorption and regulation of osteoblastic bone formation. This paper will provide a brief overview of the role of IL-10 in bone loss diseases and discuss the possibility of IL-10 adoption in therapy of bone loss diseases therapy.

The neuro-immune pathophysiology of central and peripheral fatigue in systemic immune-inflammatory and neuro-immune diseases

Many patients with systemic immune-inflammatory and neuro-inflammatory disorders, including depression, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's disease, cancer, cardiovascular disorder, Parkinson's disease, multiple sclerosis, stroke, and chronic fatigue syndrome/myalgic encephalomyelitis, endure pathological levels of fatigue. The aim of this narrative review is to delineate the wide array of pathways that may underpin the incapacitating fatigue occurring in systemic and neuro-inflammatory disorders. A wide array of immune, inflammatory, oxidative and nitrosative stress (O&NS), bioenergetic, and neurophysiological abnormalities are involved in the etiopathology of these disease states and may underpin the incapacitating fatigue that accompanies these disorders. This range of abnormalities comprises: increased levels of pro-inflammatory cytokines, e.g., interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF) α and interferon (IFN) α; O&NS-induced muscle fatigue; activation of the Toll-Like Receptor Cycle through pathogen-associated (PAMPs) and damage-associated (DAMPs) molecular patterns, including heat shock proteins; altered glutaminergic and dopaminergic neurotransmission; mitochondrial dysfunctions; and O&NS-induced defects in the sodium-potassium pump. Fatigue is also associated with altered activities in specific brain regions and muscle pathology, such as reductions in maximum voluntary muscle force, downregulation of the mitochondrial biogenesis master gene peroxisome proliferator-activated receptor gamma coactivator 1-alpha, a shift to glycolysis and buildup of toxic metabolites within myocytes. As such, both mental and physical fatigue, which frequently accompany immune-inflammatory and neuro-inflammatory disorders, are the consequence of interactions between multiple systemic and central pathways.

Aptamer-targeted oligonucleotide theranostics: a smarter approach for brain delivery and the treatment of neurological diseases

Aptamers represent the novel class of oligonucleotides holding multiple applications in the area of biomedicine. The advancements introduced with the Systematic Evolution of Ligands by EXponential enrichment (SELEX) approach further eased the scope of producing modified aptamers within a short span yet retaining the properties of stability and applicability. In the recent times, aptamers were identified to have the potential for penetrating into the deep human crevices and thus can be utilized in addressing the issues of complex neurological disorders. Considering the specificity and stability enhancement by chemical modifications, aptamer-based nanotechnologies may have great potential for future therapeutics and diagnostics (theranostics). The research community has already witnessed success with the approval of macugen (an anti-vascular endothelial growth factor aptamer) for treating degenerating eye disease, and hopefully those that are in the clinical trials will soon be translated for human application. Herein, we have summarized the aptamer chemistry, aptamer-nanoconjugates and their applications against neurological diseases.

Individual prevention courses for occupational skin diseases: changes in and relationships between proximal and distal outcomes

BACKGROUND: To treat people with occupational contact dermatitis, the German Accident Prevention and Insurance Association in the Health and Welfare Services offers 2-day individual prevention (IP) seminars. OBJECTIVES: We investigated whether there are short-term and medium-term changes in proximal (e.g. behaviour) and distal (e.g. symptoms) outcomes after an IP seminar, whether changes in proximal outcomes are associated with changes in distal outcomes, and whether subgroups can be identified that benefit in particular. PATIENTS/MATERIALS/METHODS: In a prospective study, 502 participants of 85 IP courses completed the health education impact questionnaire (heiQ™) and skin symptom questionnaire (Skindex-29) at the start of the course, immediately thereafter, and after 6 months. Change was assessed according to standardized effect size. Regression techniques were used to analyse associations between proximal and distal outcomes. RESULTS: After 6 months, participants showed improved self-management skills and preventive behaviour, and less fear of job loss, disease-related symptoms, and emotional distress. Significant associations between proximal and distal outcomes were found. Participants who felt more limited by their skin disease showed greater effects. CONCLUSIONS: The results are consistent with the assumption that IP courses provide a range of benefits for people with occupational contact dermatitis. Changes in distal outcomes may be influenced by changes in proximal outcomes.

What doesn’t kill you makes you fitter: A systematic review of high-intensity interval exercise for patients with cardiovascular and metabolic diseases

High-intensity interval exercise (HIIE) has gained popularity in recent years for patients with cardiovascular and metabolic diseases. Despite potential benefits, concerns remain about the safety of the acute response (during and/or within 24 hours postexercise) to a single session of HIIE for these cohorts. Therefore, the aim of this study was to perform a systematic review to evaluate the safety of acute HIIE for people with cardiometabolic diseases. Electronic databases were searched for studies published prior to January 2015, which reported the acute responses of patients with cardiometabolic diseases to HIIE (≥80% peak power output or ≥85% peak aerobic power, VO2peak). Eleven studies met the inclusion criteria (n = 156; clinically stable, aged 27-66 years), with 13 adverse responses reported (∼8% of individuals). The rate of adverse responses is somewhat higher compared to the previously reported risk during moderate-intensity exercise. Caution must be taken when prescribing HIIE to patients with cardiometabolic disease. Patients who wish to perform HIIE should be clinically stable, have had recent exposure to at least regular moderate-intensity exercise, and have appropriate supervision and monitoring during and after the exercise session.

A framework for cloud-based healthcare services to monitor noncommunicable diseases patient

Monitoring patients who have noncommunicable diseases is a big challenge. These illnesses require a continuous monitoring that leads to high cost for patients' healthcare. Several solutions proposed reducing the impact of these diseases in terms of economic with respect to quality of services. One of the best solutions is mobile healthcare, where patients do not need to be hospitalized under supervision of caregivers. This paper presents a new hybrid framework based on mobile multimedia cloud that is scalable and efficient and provides cost-effective monitoring solution for noncommunicable disease patient. In order to validate the effectiveness of the framework, we also propose a novel evaluation model based on Analytical Hierarchy Process (AHP), which incorporates some criteria from multiple decision makers in the context of healthcare monitoring applications. Using the proposed evaluation model, we analyzed three possible frameworks (proposed hybrid framework, mobile, and multimedia frameworks) in terms of their applicability in the real healthcare environment.

Effects of stress on reproduction in non-rodent mammals : the role of glucocorticoids and sex differences

The means by which stress influences reproduction is not clearly understood, but may involve a number of endocrine, paracrine and neural systems. Stress impacts on the reproductive axis at the hypothalamus (to affect GnRH secretion) and the pituitary gland (to affect gonadotrophin secretion), with direct effects on the gonads being of less importance. Different stressors have different effects and there are differences in response to short- and long-term stress. Many short-term stresses fail to affect reproduction and there are reports of stimulatory effects of some 'stressors'. There are species differences in the way that specific stressors affect reproduction. Sex differences in the effects of a particular stressor have been delineated and these may relate to effects of stress at different levels of the hypothalamo-pituitary axis. The significance of stress-induced secretion of cortisol varies with species. In some instances, there appears to be little impact of short-term increases in cortisol concentrations and protracted increases in plasma concentration seem to be required before any deleterious effect on reproduction is apparent. Issues of sex, sex steroid status, type of stressor and duration of stress need to be considered to improve understanding of this issue.

Stress and reproduction: central mechanisms and sex differences in non-rodent species

Despite extensive research, the mechanisms by which stress affects reproduction are unknown. Activation of stress systems could potentially influence reproduction at any level of the hypothalamo-pituitary gonadal axis. Nonetheless, the predominant impact is on the secretion of gonadotrophin releasing hormone (GnRH) from the brain and the secretion of the gonadotrophins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), from the gonadotrophs of the anterior pituitary gland. When stress is prolonged, it is likely that secretion of the gonadotrophins will be suppressed but the effects of acute stress or repeated acute stress are not clear. Different stressors activate different pathways for varying durations, and the actions of stress vary with sex and are influenced by the predominance of particular sex steroids in the circulation. The mechanisms by which stress influences reproduction are likely to involve complex interactions between a number of central and peripheral pathways and may be different in males and females. To understand these mechanisms, it is important to determine the stress pathways that are activated by particular stressors and to establish how these pathways affect the secretion and actions of GnRH. Furthermore, there is a need to know how stress influences the feedback actions of gonadal steroids and inhibin.

Fire affects microhabitat selection, movement patterns, and body condition of an Australian rodent (Rattus fuscipes)

Resource selection by animals influences individual fitness, the abundance of local populations, and the distribution of species. Further, the degree to which individuals select particular resources can be altered by numerous factors including competition, predation, and both natural- and human-induced environmental change. Understanding the influence of such factors on the way animals use resources can guide species conservation and management in changing environments. In this study, we investigated the effects of a prescribed fire on small-scale (microhabitat) resource selection, abundance, body condition, and movement pathways of a native Australian rodent, the bush rat (Rattus fuscipes). Using a before-after, control-impact design, we gathered data from 60 individuals fitted with spool and line tracking devices. In unburnt forest, selection of resources by bush rats was positively related to rushes, logs and complex habitat, and negatively related to ferns and litter. Fire caused selection for spreading grass, rushes, and complex habitat to increase relative to an unburnt control location. At the burnt location after the fire, rats selected patches of unburnt vegetation, and no rats were caught at a trapping site where most of the understory had been burnt. The fire also reduced bush rat abundance and body condition and caused movement pathways to become more convoluted. After the fire, some individuals moved through burnt areas but the majority of movements occurred within unburnt patches. The effects of fire on bush rat resource selection, movement, body condition, and abundance were likely driven by several linked factors including limited access to shelter and food due to the loss of understory vegetation and heightened levels of perceived predation risk. Our findings suggest the influence of prescribed fire on small mammals will depend on the resulting mosaic of burnt and unburnt patches and how well this corresponds to the resource requirements of particular species.