Elucidation of the controlled-release behavior of metoprolol succinate from directly compressed xanthan gum-chitosan polymers: computational and experimental studies

The development and evaluation of a controlled-release (CR) pharmaceutical solid dosage form comprising xanthan gum (XG), low molecular weight chitosan (LCS) and metoprolol succinate (MS) is reported. The research is, partly, based upon the utilization of computational tools; in this case molecular dynamics simulations (MDs) and response surface method (RSM), in order to underpin the design/prediction and to minimize the experimental work required to achieve the desired pharmaceutical outcomes. The capability of the system to control the release of MS was studied as a function of LCS (% w/w) and total polymer (LCS and XG) to drug ratio (P:D) at different tablet tensile strengths. MDs trajectories, obtained by using different ratios of XG:LCS as well as XG and high molecular weight CS (HCS), showed that the driving force for the interaction between XG and LCS is electrostatic in nature, the most favourable complex is formed when LCS is used at 15 % (w/w) and, importantly, that the interaction between XG and LCS is more favourable than that between XG and HCS. RSM outputs revealed that the release of the drug from the LCS/XG matrix is highly dependent on both the % LCS and the P:D ratio and that the required CR effect can be achieved when using weight fractions of LCS ≤ 20% and P:D ratios ≥ 2.6:1. Results obtained from in-vitro drug release and swelling studies on the prepared tablets showed that using LCS at the weight fractions suggested by MDs and RSM data plays a major role in overcoming the high sensitivity of the controlled drug release effect of XG on ionic strength and pH changes of the dissolution media. In addition, it was found that polymer relaxation is the major contributor to the release of MS from LCS-XG tablets. Using Raman spectroscopy, MS was shown to be localized more in the core of the tablets at the initial stages of dissolution due to film formation between LCS and XG on the tablet surface which prevents excess water penetration into the matrix. In the later stages of the dissolution process, the film starts to dissolve/erode allowing full tablet hydration and a uniform drug distribution in the swollen tablet

Ongoing challenges in the management of malaria

This article gives an overview of some of the ongoing challenges that are faced in the prevention, diagnosis and treatment of malaria

"CAN Stop" - Implementation and evaluation of a secondary group prevention for adolescent and young adult cannabis users in various contexts - study protocol

<p>Abstract</p> <p>Background</p> <p>Current research shows that overall numbers for cannabis use among adolescents and young adults dropped in recent years. However, this trend is much less pronounced in continuous cannabis use. With regard to the heightened risk for detrimental health- and development-related outcomes, adolescents and young adults with continuous cannabis use need special attention. The health services structure for adolescents and young adults with substance related problems in Germany, is multifaceted, because different communal, medical and judicial agencies are involved. This results in a rather decentralized organizational structure of the help system. This and further system-inherent characteristics make the threshold for young cannabis users rather high. Because of this, there is a need to establish evidence-based low-threshold help options for young cannabis users, which can be easily disseminated. Therefore, a training programme for young cannabis users (age 14-21) was developed in the "CAN Stop" project. Within the project, we seek to implement and evaluate the training programme within different institutions of the help system. The evaluation is sensitive to the different help systems and their specific prerequisites. Moreover, within this study, we also test the practicability of a training provision through laypersons.</p> <p>Methods/Design</p> <p>The CAN Stop study is a four-armed randomized wait-list controlled trial. The four arms are needed for the different help system settings, in which the CAN Stop training programme is evaluated: (a) the drug addiction aid and youth welfare system, (b) the out-patient medical system, (c) the in-patient medical system and (d) prisons for juvenile offenders. Data are collected at three points, before and after the training or a treatment as usual, and six months after the end of either intervention.</p> <p>Discussion</p> <p>The CAN Stop study is expected to provide an evidence-based programme for young cannabis users seeking to reduce or quit their cannabis use. Moreover, we seek to gain knowledge about the programme's utility within different settings of the German help system for young cannabis users and information about the settings' specific clientele. The study protocol is discussed with regard to potential difficulties within the different settings.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN57036983">ISRCTN57036983</a></p

Exposure Assessment Approaches for Engineered Nanomaterials

Products based on nanotechnology are rapidly emerging in the marketplace, sometimes with little notice to consumers of their nanotechnology pedigree. This wide variety of nanotechnology products will result (in some cases) in unintentional human exposure to purposely engineered nanoscale materials via the dermal, inhalation, ingestion, and ocular pathways. Occupational, consumer, and environmental exposure to the nanomaterials should be characterized during the entire product lifecycle—manufacture, use, and disposal. Monitoring the fate and transport of engineered nanomaterials is complicated by the lack of detection techniques and the lack of a defined set of standardized metrics to be consistently measured. New exposure metrics may be required for engineered nanomaterials, but progress is possible by building on existing tools. An exposure metric matrix could organize existing data by relating likely exposure pathways (dermal, inhalation, ocular, ingestion) with existing measurements of important characteristics of nanoscale materials (particle number, mass, size distribution, charge). Nanomaterial characteristics not commonly measured, but shown to initiate a biological response during toxicity testing, signal a need for further research, such as the pressing need to develop monitoring devices capable of measuring those aspects of engineered nanomaterials that result in biological responses in humans. Modeling the behavior of nanoparticles may require new types of exposure models that individually track particles through the environment while keeping track of the particle shape, surface area, and other surface characteristics as the nanoparticles are transformed or become reactive. Lifecycle analysis could also be used to develop conceptual models of exposure from engineered nanomaterials.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79200/1/j.1539-6924.2010.01446.x.pd

The Pine River Statement: Human Health Consequences of DDT Use

Objectives: Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction: We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis: Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions: Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT.Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDThttp://dx.doi.org/10.1289/ehp.1174

Validating the Johns Hopkins ACG Case-Mix System of the elderly in Swedish primary health care

BACKGROUND: Individualbased measures for comorbidity are of increasing importance for planning and funding health care services. No measurement for individualbased healthcare costs exist in Sweden. The aim of this study was to validate the Johns Hopkins ACG Case-Mix System's predictive value of polypharmacy (regular use of 4 or more prescription medicines) used as a proxy for health care costs in an elderly population and to study if the prediction could be improved by adding variables from a population based study i.e. level of education, functional status indicators and health perception. METHODS: The Johns Hopkins ACG Case-Mix System was applied to primary health care diagnoses of 1402 participants (60–96 years) in a cross-sectional community based study in Karlskrona, Sweden (the Swedish National study on Ageing and Care) during a period of two years before they took part in the study. The predictive value of the Johns Hopkins ACG Case-Mix System was modeled against the regular use of 4 or more prescription medicines, also using age, sex, level of education, instrumental activity of daily living- and measures of health perception as covariates. RESULTS: In an exploratory biplot analysis the Johns Hopkins ACG Case-Mix System, was shown to explain a large part of the variance for regular use of 4 or more prescription medicines. The sensitivity of the prediction was 31.9%, whereas the specificity was 88.5%, when the Johns Hopkins ACG Case-Mix System was adjusted for age. By adding covariates to the model the sensitivity was increased to 46.3%, with a specificity of 90.1%. This increased the number of correctly classified by 5.6% and the area under the curve by 11.1%. CONCLUSION: The Johns Hopkins ACG Case-Mix System is an important factor in measuring comorbidity, however it does not reflect an individual's capability to function despite a disease burden, which has importance for prediction of comorbidity. In this study we have shown that information on such factors, which can be obtained from short questionnaires increases the probability to correctly predict an individual's use of resources, such as medications

Impact of geriatric comorbidity and polypharmacy on cholinesterase inhibitors prescribing in dementia

<p>Abstract</p> <p>Background</p> <p>Although most guidelines recommend the use of cholinesterase inhibitors (ChEIs) for mild to moderate Alzheimer's Disease, only a small proportion of affected patients receive these drugs. We aimed to study if geriatric comorbidity and polypharmacy influence the prescription of ChEIs in patients with dementia in Germany.</p> <p>Methods</p> <p>We used claims data of 1,848 incident patients with dementia aged 65 years and older. Inclusion criteria were first outpatient diagnoses for dementia in at least three of four consecutive quarters (incidence year). Our dependent variable was the prescription of at least one ChEI in the incidence year. Main independent variables were polypharmacy (defined as the number of prescribed medications categorized into quartiles) and measures of geriatric comorbidity (levels of care dependency and 14 symptom complexes characterizing geriatric patients). Data were analyzed by multivariate logistic regression.</p> <p>Results</p> <p>On average, patients were 78.7 years old (47.6% female) and received 9.7 different medications (interquartile range: 6-13). 44.4% were assigned to one of three care levels and virtually all patients (92.0%) had at least one symptom complex characterizing geriatric patients. 13.0% received at least one ChEI within the incidence year. Patients not assigned to the highest care level were more likely to receive a prescription (e.g., no level of care dependency vs. level 3: adjusted Odds Ratio [OR]: 5.35; 95% CI: 1.61-17.81). The chance decreased with increasing numbers of symptoms characterizing geriatric patients (e.g., 0 vs. 5+ geriatric complexes: OR: 4.23; 95% CI: 2.06-8.69). The overall number of prescribed medications had no influence on ChEI prescription and a significant effect of age could only be found in the univariate analysis. Living in a rural compared to an urban environment and contacts to neurologists or psychiatrists were associated with a significant increase in the likelihood of receiving ChEIs in the multivariate analysis.</p> <p>Conclusions</p> <p>It seems that not age as such but the overall clinical condition of a patient including care dependency and geriatric comorbidities influences the process of decision making on prescription of ChEIs.</p

Junkie love : romance and addiction on the big screen

This article investigates the filmic construction of two disparate but intertwining cultural practices: those engaging in the life-affirming rituals of romantic love and those performing the potentially self-destructive rituals of hard drug consumption. Discussing a number of key feature films from the (mini) genre “junkie love”, it aims to show what happens when elements of mainstream romantic drama merge with the horror conventions of the heroin addiction film. Drawing amongst others on Murray Smith’s theory of “levels of [spectator] engagement” and Greg Smith’s concept of the “emotion system”, the article concludes that junkie love films, using tropes of the romantic tragedy in the tradition of Romeo and Juliet, present a more complex and nuanced approach to drug addicts than the predominantly condemnatory media coverage—one that arguably invites the spectator’s understanding and compassion