Algorithm of medication review in frail older people: Focus on minimizing the use of high-risk medications

Aim Frail older people typically suffer several chronic diseases, receive multiple medications and are more likely to be institutionalized in residential aged care facilities. In such patients, optimizing prescribing and avoiding use of high-risk medications might prevent adverse events. The present study aimed to develop a pragmatic, easily applied algorithm for medication review to help clinicians identify and discontinue potentially inappropriate high-risk medications. Methods The literature was searched for robust evidence of the association of adverse effects related to potentially inappropriate medications in older patients to identify high-risk medications. Prior research into the cessation of potentially inappropriate medications in older patients in different settings was synthesized into a four-step algorithm for incorporation into clinical assessment protocols for patients, particularly those in residential aged care facilities. Results The algorithm comprises several steps leading to individualized prescribing recommendations: (i) identify a high-risk medication; (ii) ascertain the current indications for the medication and assess their validity; (iii) assess if the drug is providing ongoing symptomatic benefit; and (iv) consider withdrawing, altering or continuing medications. Decision support resources were developed to complement the algorithm in ensuring a systematic and patient-centered approach to medication discontinuation. These include a comprehensive list of high-risk medications and the reasons for inappropriateness, lists of alternative treatments, and suggested medication withdrawal protocols. Conclusions The algorithm captures a range of different clinical scenarios in relation to potentially inappropriate medications, and offers an evidence-based approach to identifying and, if appropriate, discontinuing such medications. Studies are required to evaluate algorithm effects on prescribing decisions and patient outcomes.

Geriatrician interventions on medication prescribing for frail older people in residential aged care facilities

Objective: In Australian residential aged care facilities (RACFs), the use of certain classes of high-risk medication such as antipsychotics, potent analgesics, and sedatives is high. Here, we examined the prescribed medications and subsequent changes recommended by geriatricians during comprehensive geriatric consultations provided to residents of RACFs via videoconference. Design: This is a prospective observational study. Setting: Four RACFs in Queensland, Australia, are included. Participants: A total of 153 residents referred by general practitioners for comprehensive assessment by geriatricians delivered by video-consultation. Results: Residents’ mean (standard deviation, SD) age was 83.0 (8.1) years and 64.1% were female. They had multiple comorbidities (mean 6), high levels of dependency, and were prescribed a mean (SD) of 9.6 (4.2) regular medications. Ninety-one percent of patients were taking five or more medications daily. Of total medications prescribed (n=1,469), geriatricians recommended withdrawal of 9.8% (n=145) and dose alteration of 3.5% (n=51). New medications were initiated in 47.7% (n=73) patients. Of the 10.3% (n=151) medications considered as high risk, 17.2% were stopped and dose altered in 2.6%. Conclusion: There was a moderate prevalence of potentially inappropriate high-risk medications. However, geriatricians made relatively few changes, suggesting either that, on balance, prescription of these medications was appropriate or, because of other factors, there was a reluctance to adjust medications. A structured medication review using an algorithm for withdrawing medications of high disutility might help optimize medications in frail patients. Further research, including a broader survey, is required to understand these dynamics.

On the functional ordering of biomembranes : Implications for drug binding

Cells are packed with membrane structures, defining the inside and outside, and the different subcellular compartments. These membranes consisting mainly of phospholipids have a variety of functions in addition to providing a permeability barrier for various compounds. These functions involve cellular signaling, where lipids can act as second messengers, or direct regulation of membrane associating proteins. The first part of this study focuses on relating some of the physicochemical properties of membrane lipids to the association of drug compounds to membranes. A fluorescence based method is described allowing for determination of the membrane association of drugs. This method was subsequently applied to a novel drug, siramesine, previously shown to have anti-cancer activity. Siramesine was found to associate with anionic lipids. Especially interesting is its strong affinity for a second messenger lipid phosphatidic acid. This is the first example of a small molecule drug compound specifically interacting with a cellular lipid. Phosphatidic acid in cells is required for the activation of many signaling pathways mediating growth and proliferation. This provides an intriguing possibility for a simple molecular mechanism of the observed anti-cancer activity of siramesine. In the second part the thermal behavior and self assembly of charged and uncharged membrane assemblies was studied. Strong inter-lamellar co-operativity was observed for multilamellar DPPC vesicles using fluorescence techniques together with calorimetry. The commonly used membrane models, large unilamellar vesicles (LUV) and multilamellar vesicles (MLV) were found to possess different biophysical properties as interlamellar interactions of MLVs drive segregation of a pyrene labeled lipid analogue into clusters. The effect of a counter-ion lattice on the self assembly of a cationic gemini surfactant was studied. The presence of NaCl strongly influenced the thermal phase behavior of M-1 vesicles, causing formation of giant vesicles upon exceeding a phase transition temperature, followed by a subsequent transition into a more homogenous dispersion. Understanding the underlying biophysical aspects of cellular membranes is of fundamental importance as the complex picture of the structure and function of cells is evolving. Many of the cellular reactions take place on membranes and membranes are known to regulate the activity of many peripheral and intergral membrane associating proteins. From the point of view of drug design and gene technology, membranes can provide an interesting target for future development of drugs, but also a vehicle sensitive for environmental changes allowing for encapsulating drugs and targeting them to the desired site of action.

There is 'hope for you yet': The female drug offender in sentencing discourse

Language and gender research has, in recent years, emphasised the importance of examining the context-specific ways in which people ‘do gender’ in different situations. In this paper, we explore how women involved in drug offences, specifically methamphetamine manufacture offences, are constructed within the language of the courts. Thirty-six sentencing transcripts from the New Zealand courts were examined to investigate how such offences, committed by women, are understood. In order to explore the representation of female offenders, a critical discourse analytic approach was adopted. Such an approach recognises that linguistic modes not only create and legitimise power inequalities but also embody a specific worldview. Three gendered discourses were identified in the sentencing texts: (i) the discourse of femininity, reinforcing the socially prescribed female role; (ii) the discourse of aberration, concerning women who breach traditional gender role expectations, and; (iii) the discourse of salvation, presenting aberrant women with an opportunity to become ‘good’ women once again. The findings illustrate the ways in which processes of gendering take place within a specific community of practice: the courtroom.

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of approximately 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications

BACKGROUND Given moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50% to 60% heritability) with high correlation of genetic influences, we have conducted a quantitative trait genome-wide association study (GWAS) for phenotypes related to alcohol use and dependence. METHODS Diagnostic interview and blood/buccal samples were obtained from sibships ascertained through the Australian Twin Registry. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed with 8754 individuals (2062 alcohol-dependent cases) selected for informativeness for alcohol use disorder and associated quantitative traits. Family-based association tests were performed for alcohol dependence, dependence factor score, and heaviness of drinking factor score, with confirmatory case-population control comparisons using an unassessed population control series of 3393 Australians with genome-wide SNP data. RESULTS No findings reached genome-wide significance (p = 8.4 x 10(-8) for this study), with lowest p value for primary phenotypes of 1.2 x 10(-7). Convergent findings for quantitative consumption and diagnostic and quantitative dependence measures suggest possible roles for a transmembrane protein gene (TMEM108) and for ANKS1A. The major finding, however, was small effect sizes estimated for individual SNPs, suggesting that hundreds of genetic variants make modest contributions (1/4% of variance or less) to alcohol dependence risk. CONCLUSIONS We conclude that: - 1) meta-analyses of consumption data may contribute usefully to gene discovery; - 2) translation of human alcoholism GWAS results to drug discovery or clinically useful prediction of risk will be challenging, and; - 3) through accumulation across studies, GWAS data may become valuable for improved genetic risk differentiation in research in biological psychiatry (e.g., prospective high-risk or resilience studies).

Age-related changes in hepatic function: An update on implications for drug therapy

The accumulation of deficits with increasing age results in a decline in the functional capacity of multiple organs and systems. These changes can have a significant influence on the pharmacokinetics and pharmacodynamics of prescribed drugs. Although alterations in body composition and worsening renal clearance are important considerations, for most drugs the liver has the greatest effect on metabolism. Age-related change in hepatic function thereby causes much of the variability in older people’s responses to medication. In this review, we propose that a decline in the ability of the liver to inactivate toxins may contribute to a proinflammatory state in which frailty can develop. Since inflammation also downregulates drug metabolism, medication prescribed to frail older people in accordance with disease-specific guidelines may undergo reduced systemic clearance, leading to adverse drug reactions, further functional decline and increasing polypharmacy, exacerbating rather than ameliorating frailty status. We also describe how increasing chronological age and frailty status impact liver size, blood flow and protein binding and enzymes of drug metabolism. This is used to contextualise our discussion of appropriate prescribing practices. For example, while the general axiom of ‘start low, go slow’ should underpin the initiation of medication (titrating to a defined therapeutic goal), it is important to consider whether drug clearance is flow or capacity-limited. By summarising the effect of age-related changes in hepatic function on medications commonly used in older people, we aim to provide a guide that will have high clinical utility for practising geriatricians.

Prescribing for older people discharged from the acute sector to residential aged-care facilities

For frail older people, admission to hospital is an opportunity to review the indications for specific medications. This research investigates prescribing for 206 older people discharged into residential aged care facilities from 11 acute care hospitals in Australia. Patients had multiple comorbidities (mean 6), high levels of dependency, and were prescribed a mean of 7.2 regular medications at admission to hospital and 8.1 medications on discharge, with hyper-polypharmacy (≥10 drugs) increasing from 24.3% to 32.5%. Many drugs were preventive medications whose time until benefit was likely to exceed the expected lifespan. In summary, frail patients continue to be exposed to extensive polypharmacy and medications with uncertain risk–benefit ratio.

Rural energy consumption patterns - A field study

This paper is a condensed version of the final report of a detailed field study of rural energy consumption patterns in six villages located west of Bangalore in the dry belt of Karnataka State in India. The study was carried out in two phases; first, a pilot study of four villages and second, the detailed study of six villages, the populations of which varied from around 350 to about 950. The pilot survey ended in late 1976, and most of the data was collected for the main project in 1977. Processing of the collected data was completed in 1980. The aim was to carry out a census survey, rather than a sample study. Hence, considerable effort was expended in production of both a suitable questionnaire, ensuring that all respondents were contacted, and devising methods which would accurately reflect the actual energy use in various energy-utilising activities. In the end, 560 households out of 578 (97%) were surveyed. The following ranking was found for the various energy sources in order of average percentage contribution to the annual total energy requirement: firewood, 81A·6%; human energy, 7A·7%; animal energy, 2A·7%; kerosene, 2A·1%; electricity, 0A·6% and all other sources (rice husks, agro-wastes, coal and diesel fuel), 5A·3%. In other words commercial fuels made only a small contribution to the overall energy use. It should be noted that dung cakes are not burned in this region. The average energy use pattern, sector by sector, again on a percentage basis, was as follows: domestic, 88A·3%; industry, 4A·7%; agriculture, 4A·3%; lighting, 2A·2% and transport, 0A·5%. The total annual per capita energy consumption was 12A·6 A± 1A·2 GJ, giving an average annual household consumption of around 78A·6 GJ.

Sweetpotato consumer research: insights to increasing consumption

This report provides an evaluation of the behaviours and purchasing drivers of key sweetpotato consumers defined by Nielsen consumer research as Established Couples (two or more adults with no children 17 and under, and head of house 35-59), Senior Couples (two or more adults with no children 17 or under, and head of house 60 or over), and Independent Singles (one person household 35 or over, no children 17 or under). Research was qualitative in nature. Methods used included focus groups, depth interviews and shop-a-longs. The report found that preferences for sweetpotato amongst these groups were varied. In general a smaller torpedo shaped vegetable was valued for ease of preparation and the convenience of being of sufficient size for a meal for two. Satisfaction with sweetpotato was high with negative comments on quality exceedingly rare within discussions. However, shop-a-longs revealed that some quality issues were apparent at retail such as withered product, pitting and occasionally damage. A display with stock resting in any amount of water was a barrier to purchase for consumers and this was apparent on two out 15 occasions. A high quality sweetpotato was of a deep orange/red colour, had a smooth skin and was extremely dense and hard. An inferior sweetpotato was wrinkly, spongy, pitted and damaged. Awareness of sweetpotato was a relatively recent phenomenon amongst the respondents of this study with most recalling eating the vegetable in the last five to 10 years. Life-time eating patterns emerged as a consequence of childhood food experiences such as growing up with a ‘meat and three’ veg philosophy and traditional Australian meals. However, this was dependent on cultural background and those with ties to diverse cultures were more likely to have always known of the vegetable. Sweetpotato trial and consumption coincided with a breaking away from these traditional patterns, or was integrated into conventional meals such as a baked vegetable to accompany roasts. Increased health consciousness also led to awareness of the vegetable. A primary catalyst for consumption within the Established and Senior Couples groups was the health benefits associated with sweetpotato. Consumers had very little knowledge of the specific health properties of the vegetable and were surprised at the number of benefits consumption provided. Sweetpotato was important for diabetics for its low Glycemic Index status. Top-of-the-mind awareness of the vegetable resulted from the onset of the disease. Increasing fibre was a key motive for this demographic and this provided a significant link between consumption and preventing bowel cancer. For those on a weight loss regime, sweetpotato was perceived as a tasty, satisfying food that was low in carbohydrates. Swapping behaviours where white potato was replaced by sweetpotato was often a response to these health concerns. Other health properties mentioned by participants through the course of the research included the precursor β-carotene and Vitamins A & C. The sweetpotato was appreciated for its hedonic and timesaving qualities. For consumers with a high involvement in food, the vegetable was valued for its versatility in meals. These consumers took pride in cooking and the flavour and texture of sweetpotato lent itself to a variety of meals such as soups, salads, roasts, curries, tagines and so on. Participants who had little time or desire to prepare and cook meals valued sweetpotato because it was an easy way to add colour and variety to the plate and because including an orange vegetable to meals is a shortcut to ensuring vitamin intake. Several recommendations are made to the sweetpotato industry. • Vigorously promote the distinct nutritional and health properties of sweetpotatoes, particularly if they can be favourably compared to other vegetables or foods • Promote the salient properties to specific targets such as diabetics, those that are at risk to bowel cancer, and those embarking on a weight-loss regime. Utilise specialist channels of communication such as diabetic magazines and websites • Promote styles of cooking of sweetpotato that would appeal to traditionalists such as roasts and BBQs • Promote the vegetable as a low maintenance vegetable, easy to store, easy to cook and particularly focusing on it as a simple way to boost the appearance and nutritional value of meals. • Promote the vegetable to high food involvement consumers through exotic recipes and linking it to feelings of accomplishment with cooking • Promote the versatility of the vegetable • Devise promotions that link images and tone of communications with enjoying life to the fullest, having time to enjoy family and grandchildren, and of partaking in social activities • Educate retailers on consumer perceptions of quality and ensuring moisture and mould is not present at displays Qualitative information while providing a wealth of detail cannot be extrapolated to the overall target population and this may be considered a limitation to the research. However, within research theory, effective quantitative design is believed to stem from the insights developed from qualitative studies. • Develop and implement a quantitative study on sweetpotato attitudes and behaviours based on the results of this study.

Structure and conformation of an anti-depressant drug, nitroxazepine hydrochloride monohydrate

CIsH20N3Oa+.C1-.H2 O, M r = 395, orthorhombic, Pn21a, a = 7.710 (4), b = 11.455 (3), c -- 21.199 (3)/k, Z = 4, V = 1872.4/k 3, D m = 1.38, D C = 1.403 g cm -3, F(000) = 832, g(Cu Kct) = 20.94 cm -l. Intensities for 1641 reflections were measured on a Nonius CAD-4 diffractometer; of these, 1470 were significant. The structure was solved by direct methods and refined to an R index of 0.045 using a blockdiagonal least-squares procedure. The angle between the least-squares planes through the benzene rings is 125.0 (5) ° and the side chain is folded similarly to one of the independent molecules of imipramine hydrochloride.

Debunking Weak Sustainable Consumption : Towards Strong Sustainable Consumption Governance

Achieving sustainable consumption patterns is a crucial step on the way towards sustainability. The scientific knowledge used to decide which priorities to set and how to enforce them has to converge with societal, political, and economic initiatives on various levels: from individual household decision-making to agreements and commitments in global policy processes. The aim of this thesis is to draw a comprehensive and systematic picture of sustainable consumption and to do this it develops the concept of Strong Sustainable Consumption Governance. In this concept, consumption is understood as resource consumption. This includes consumption by industries, public consumption, and household consumption. Next to the availability of resources (including the available sink capacity of the ecosystem) and their use and distribution among the Earth’s population, the thesis also considers their contribution to human well-being. This implies giving specific attention to the levels and patterns of consumption. Methods: The thesis introduces the terminology and various concepts of Sustainable Consumption and of Governance. It briefly elaborates on the methodology of Critical Realism and its potential for analysing Sustainable Consumption. It describes the various methods on which the research is based and sets out the political implications a governance approach towards Strong Sustainable Consumption may have. Two models are developed: one for the assessment of the environmental relevance of consumption activities, another to identify the influences of globalisation on the determinants of consumption opportunities. Results: One of the major challenges for Strong Sustainable Consumption is that it is not in line with the current political mainstream: that is, the belief that economic growth can cure all our problems. So, the proponents have to battle against a strong headwind. Their motivation however is the conviction that there is no alternative. Efforts have to be taken on multiple levels by multiple actors. And all of them are needed as they constitute the individual strings that together make up the rope. However, everyone must ensure that they are pulling in the same direction. It might be useful to apply a carrot and stick strategy to stimulate public debate. The stick in this case is to create a sense of urgency. The carrot would be to articulate better the message to the public that a shrinking of the economy is not as much of a disaster as mainstream economics tends to suggest. In parallel to this it is necessary to demand that governments take responsibility for governance. The dominant strategy is still information provision. But there is ample evidence that hard policies like regulatory instruments and economic instruments are most effective. As for Civil Society Organizations it is recommended that they overcome the habit of promoting Sustainable (in fact green) Consumption by using marketing strategies and instead foster public debate in values and well-being. This includes appreciating the potential of social innovation. A countless number of such initiatives are on the way but their potential is still insufficiently explored. Beyond the question of how to multiply such approaches, it is also necessary to establish political macro structures to foster them.

Biochemical effects of the porphyrinogenic drug allylisopropylacetamide. A comparative study with phenobarbital

Successive administrations of allylisopropylacetamide, a potent porphyrinogenic drug, increase liver weight, microsomal protein and phospholipid contents. There is an increase in the rate of microsomal protein synthesis in vivo and in vitro. The drug decreases microsomal ribonuclease activity and increases NADPH–cytochrome c reductase activity. Phenobarbital, which has been reported to exhibit all these changes mentioned, is a weaker inducer of δ-aminolaevulinate synthetase and increases the rate of haem synthesis only after a considerable time-lag in fed female rats, when compared with the effects observed with allylisopropylacetamide. Again, phenobarbital does not share the property of allylisopropylacetamide in causing an initial decrease in cytochrome P-450 content. Haematin does not counteract most of the biochemical effects caused by allylisopropylacetamide, although it is quite effective in the case of phenobarbital. Haematin does not inhibit the uptake of [2-14C]allylisopropylacetamide by any of the liver subcellular fractions.

Hospital in the Nursing Home program reduces emergency department presentations and hospital admissions from residential aged care facilities in Queensland, Australia: A quasi-experimental study

Background There has been considerable publicity regarding population ageing and hospital emergency department (ED) overcrowding. Our study aims to investigate impact of one intervention piloted in Queensland Australia, the Hospital in the Nursing Home (HiNH) program, on reducing ED and hospital attendances from residential aged care facilities (RACFs). Methods A quasi-experimental study was conducted at an intervention hospital undertaking the program and a control hospital with normal practice. Routine Queensland health information system data were extracted for analysis. Results Significant reductions in the number of ED presentations per 1000 RACF beds (rate ratio (95 % CI): 0.78 (0.67–0.92); p = 0.002), number of hospital admissions per 1000 RACF beds (0.62 (0.50–0.76); p < 0.0001), and number of hospital admissions per 100 ED presentations (0.61 (0.43–0.85); p = 0.004) were noticed in the experimental hospital after the intervention; while there were no significant differences between intervention and control hospitals before the intervention. Pre-test and post-test comparison in the intervention hospital also presented significant decreases in ED presentation rate (0.75 (0.65–0.86); p < 0.0001) and hospital admission rate per RACF bed (0.66 (0.54–0.79); p < 0.0001), and a non-significant reduction in hospital admission rate per ED presentation (0.82 (0.61–1.11); p = 0.196). Conclusions Hospital in the Nursing Home program could be effective in reducing ED presentations and hospital admissions from RACF residents. Implementation of the program across a variety of settings is preferred to fully assess the ongoing benefits for patients and any possible cost-savings.