Race against time: The export of essential medicines to Rwanda

This article considers the significance of the first export of essential medicines under the WTO General Council Decision 2003. In July 2007, Rwanda became the first country to provide a notification under the WTO General Council Decision 2003 of its intent to import a fixed-dose, triple combination HIV/AIDS drug manufactured by the Canadian generic pharmaceuticalmanufacturer Apotex, Inc. In September 2007, Apotex was granted the first compulsory licence application under Canada's Access to Medicines Regime. This article considers the convoluted and protracted negotiations between the Government of Rwanda, Apotex and three patent holders, GlaxoSmithKline, Boehringer Ingleheim Canada and Shire BioChemical, Inc. It questions the efficiency of this process. This article considers the review of the Jean Chretien Pledge to Africa Act 2004 (Canada). It is critical of the refusal of the Conservative Government of Canada to make any amendments to the legislation to improve the cost-effective delivery of essential medicines. This article queries the proposed Hong Kong Amendment to the TRIPS Agreement 1994, given the concerns of the Africa Group. It is submitted that it is undesirable to codify the WTO General Council Decision 2003, given its failure to provide a speedy, efficient and cost-effective delivery of essential medicines.

Irrational addicts and responsible pleasure seekers: Constructions of the drug user

Historically, drug use has been understood as a problem of epidemiology, psychiatry, physiology, and criminality requiring legal and medical governance. Consequently drug research tends to be underpinned by an imperative to better govern, and typically proposes policy interventions to prevent or solve drug problems. We argue that categories of ‘addictive’ and ‘recreational’ drug use are discursive forms of governance that are historically, politically and socially contingent. These constructions of the drug problem shape what drug users believe about themselves and how they enact these beliefs in their drug use practices. Based on qualitative interviews with young illicit drug users in Brisbane, Australia, this paper uses Michel Foucault’s concept of governmentality to provide insights into how the governance of illicit drugs intersects with self-governance to create a drug user self. We propose a reconceptualisation of illicit drug use that takes into account the contingencies and subjective factors that shape the drug experience. This allows for an understanding of the relationships between discourses, policies, and practices in constructions of illicit drug users.

Morphometric analysis of the thoracic intervertebral foramen osseous anatomy in adolescent idiopathic scoliosis using low dose computerized tomography

Introduction. The dimensions of the thoracic intervertebral foramen in adolescent idiopathic scoliosis (AIS) have not previously been quantified. During posterior approach scoliosis correction surgery pedicle screws may occasionally breach into the foramen. Better understanding of the dimensions of the foramen may be useful in surgical planning. This study describes a reproducible method for measurement of the thoracic foramen in AIS using computerized tomography (CT). Methods. In 23 pre-operative female patients with Lenke 1 type AIS with right side convexity major curves confined to the thoracic spine the foraminal height (FH), foraminal width (FW), pedicle to superior articular process distance (P-SAP) and cross sectional foraminal area (FA) were measured using multiplanar reconstructed CT. Measurements were made at entrance, midpoint and exit of the thoracic foramina from T1/T2 to T11/T12. Results were correlated with potential dependent variables of major curve Cobb Angle measured on X-ray and CT, Age, Weight, Lenke classification subtype, Risser Grade and number of spinal levels in the major curve. Results. The FH, FW, P-SAP and FA dimensions and ratios are all significantly larger on the convexity of the major curve and maximal at or close to the apex. Mean thoracic foraminal dimensions change in a predictable manner relative to position on the major thoracic curve. There was no significant correlation with the measured foraminal dimensions or ratios and the potential dependent variables. The average ratio of convexity to concavity dimensions at the apex foramina for entrance, midpoint and exit respectively are FH (1.50, 1.38, 1.25), FW (1.28, 1.30, 0.98), FA (2.06, 1.84, 1.32), P-SAP (1.61, 1.47, 1.30). Conclusion. Foraminal dimensions of the thoracic spine are significantly affected by AIS. Foraminal dimensions have a predictable convexity to concavity ratio relative to the proximity to the major curve apex. Surgeons should be aware of these anatomical differences during scoliosis correction surgery.

Using low dose computerized tomography to morphometrically analyse the thoracic intervertebral foramen osseous anatomy in adolescent idiopathic scoliosis

INTRODUCTION The dimensions of the thoracic intervertebral foramen in adolescent idiopathic scoliosis (AIS) have not previously been quantified. During posterior approach scoliosis correction surgery pedicle screws may occasionally breach into the foramen. Better understanding of the dimensions of the foramen may be useful in surgical planning. This study describes a reproducible method for measurement of the thoracic foramen in AIS using computerized tomography (CT). METHODS In 23 pre-operative female patients with Lenke 1 type AIS with right side convexity major curves confined to the thoracic spine the foraminal height (FH), foraminal width (FW), pedicle to superior articular process distance (P-SAP) and cross sectional foraminal area (FA) were measured using multiplanar reconstructed CT. Measurements were made at entrance, midpoint and exit of the thoracic foramina from T1/T2 to T11/T12. Results were correlated with potential dependent variables of major curve Cobb Angle measured on X-ray and CT, Age, Weight, Lenke classification subtype, Risser Grade and number of spinal levels in the major curve. RESULTS The FH, FW, P-SAP and FA dimensions and ratios are all significantly larger on the convexity of the major curve and maximal at or close to the apex. Mean thoracic foraminal dimensions change in a predictable manner relative to position on the major thoracic curve. There was no significant correlation with the measured foraminal dimensions or ratios and the potential dependent variables. The average ratio of convexity to concavity dimensions at the apex foramina for entrance, midpoint and exit respectively are FH (1.50, 1.38, 1.25), FW (1.28, 1.30, 0.98), FA (2.06, 1.84, 1.32), P-SAP (1.61, 1.47, 1.30). CONCLUSION Foraminal dimensions of the thoracic spine are significantly affected by AIS. Foraminal dimensions have a predictable convexity to concavity ratio relative to the proximity to the major curve apex. Surgeons should be aware of these anatomical differences during scoliosis correction surgery.

Targeting drug-resistant prostate cancer with dual PI3K/mTOR inhibition

The phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR pathway is one of the most frequently activated signaling pathways in prostate cancer cells, and loss of the tumor suppressor PTEN and amplification of PIK3CA are the two most commonly detected mechanisms for the activation of these pathways. Aberrant activation of PI3K/Akt/mTOR has been implicated not only in the survival and metastasis of prostate cancer cells but also in the development of drug resistance. As such, selective inactivation of this pathway may provide opportunities to attack prostate cancer from all fronts. However, while preclinical studies examining specific inhibitors of PI3K or mTOR have yielded promising results, the evidence from clinical trials is less convincing. Emerging evidence from the analyses of some solid tumors suggests that a class of dual PI3K/mTOR inhibitors, which bind to and inactivate both PI3K and mTOR, may achieve better anti-cancer outcomes. In this review, we will summarize the mechanisms of action of these inhibitors, their effectiveness when used alone or in combination with other chemotherapeutic compounds, and their potential to serve as the next generation therapies for prostate cancer patients, particularly those who are resistant to the frontline chemotherapeutic drugs.

Ultrasound attenuation computed tomography assessment of PAGAT gel dose

Ultrasound has been previously investigated as an alternative readout method for irradiated polymer gel dosimeters, with authors reporting varying dose responses. We extend previous work utilizing a new computed tomography ultrasound scanner comprising of two identical 5 MHz, 128-element linear-array ultrasound transducers, co-axially aligned and submerged in water as a coupling agent, with rotational of the gel dosimeter between the transducers facilitated by a robotic arm. We have investigated the dose-dependence of both ultrasound bulk attenuation and broadband ultrasound attenuation (BUA) for the PAGAT gel dosimeter. The ultrasound bulk attenuation dose sensitivity was found to be 1.46  ±  0.04 dB m −1 Gy −1, being in agreement with previously published results for PAG and MAGIC gels. BUA was also found to be dose dependent and was measured to be 0.024  ±  0.003 dB MHz −1 Gy −1; the advantage of BUA being its insensitivity to frequency-independent attenuation mechanisms including reflection and refraction, thereby minimizing image reconstruction artefacts.

Low-dose curcumin stimulates proliferation, migration and phagocytic activity of olfactory ensheathing cells

One of the promising strategies for neural repair therapies is the transplantation of olfactory ensheathing cells (OECs) which are the glial cells of the olfactory system. We evaluated the effects of curcumin on the behaviour of mouse OECs to determine if it could be of use to further enhance the therapeutic potential of OECs. Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinases. In contrast, we found that low-dose curcumin (0.5 µM) applied to OECs strikingly modulated the dynamic morphology, increased the rate of migration by up to 4-fold, and promoted significant proliferation of the OECs. Most dramatically, low-dose curcumin stimulated a 10-fold increase in the phagocytic activity of OECs. All of these potently stimulated behavioural characteristics of OECs are favourable for neural repair therapies. Importantly, low-dose curcumin gave a transient activation of p38 kinases, which is in contrast to the high dose curcumin effects on cancer cells in which these MAP kinases tend to undergo prolonged activation. Low-dose curcumin mediated effects on OECs demonstrate cell-type specific stimulation of p38 and ERK kinases. These results constitute the first evidence that low-dose curcumin can modulate the behaviour of olfactory glia into a phenotype potentially more favourable for neural repair and thereby improve the therapeutic use of OECs for neural repair therapies

The dependence of computed tomography number to relative electron density conversion on phantom geometry and its impact on planned dose

A computed tomography number to relative electron density (CT-RED) calibration is performed when commissioning a radiotherapy CT scanner by imaging a calibration phantom with inserts of specified RED and recording the CT number displayed. In this work, CT-RED calibrations were generated using several commercially available phantoms to observe the effect of phantom geometry on conversion to electron density and, ultimately, the dose calculation in a treatment planning system. Using an anthropomorphic phantom as a gold standard, the CT number of a material was found to depend strongly on the amount and type of scattering material surrounding the volume of interest, with the largest variation observed for the highest density material tested, cortical bone. Cortical bone gave a maximum CT number difference of 1,110 when a cylindrical insert of diameter 28 mm scanned free in air was compared to that in the form of a 30 × 30 cm2 slab. The effect of using each CT-RED calibration on planned dose to a patient was quantified using a commercially available treatment planning system. When all calibrations were compared to the anthropomorphic calibration, the largest percentage dose difference was 4.2 % which occurred when the CT-RED calibration curve was acquired with heterogeneity inserts removed from the phantom and scanned free in air. The maximum dose difference observed between two dedicated CT-RED phantoms was ±2.1 %. A phantom that is to be used for CT-RED calibrations must have sufficient water equivalent scattering material surrounding the heterogeneous objects that are to be used for calibration.

Characteristics of microbial drug resistance and its correlates in chronic diabetic foot ulcer infections

While virulence factors and the biofilm-forming capabilities of microbes are the key regulators of the wound healing process, the host immune response may also contribute in the events following wound closure or exacerbation of non-closure. We examined samples from diabetic and non-diabetic foot ulcers/wounds for microbial association and tested the microbes for their antibiotic susceptibility and ability to produce biofilms. A total of 1074 bacterial strains were obtained with staphylococci, Pseudomonas, Citrobacter and enterococci as major colonizers in diabetic samples. Though non-diabetic samples had a similar assemblage, the frequency of occurrence of different groups of bacteria was different. Gram-negative bacteria were found to be more prevalent in the diabetic wound environment while Gram-positive bacteria were predominant in non-diabetic ulcers. A higher frequency of monomicrobial infection was observed in samples from non-diabetic individuals when compared to samples from diabetic patients. The prevalence of different groups of bacteria varied when the samples were stratified according to age and sex of the individuals. Several multidrug-resistant strains were observed among the samples tested and most of these strains produced moderate to high levels of biofilms. The weakened immune response in diabetic individuals and synergism among pathogenic micro-organisms may be the critical factors that determine the delicate balance of the wound healing process.

We know this: How to apply what you already know to treat alcohol and other drug problems

Background Implementing effective AOD supports and treatments into our daily practice can occur via a range of strategies. While specialist treatments exclusively targeting pathways toward substance reduction are an option, it is often not within the scope of many psychologists working in generalist or tertiary mental health settings. Regardless of the perceived barriers for integrating AOD practice into our work, there are key principles and approaches that can be adopted to improve the outcomes for many clients. Aim Irrespective of the client’s perceived need to address AOD issues, significant substance use will impact on the development, prognosis and treatment of most mental health conditions. Embedding AOD practice across our clinical work requires an openness to consider evidence-based approaches for all levels of substance use. Method This presentation will outline a series of approaches that all practitioners can adopt, based on the principles of harm reduction and empowerment of client’s choice. An emphasis will be made toward outlining approaches that are consistent with best practice, easily accessible and do not require extensive resources to embed. Conclusion Applying effective AOD treatments as a standard treatment component is achievable for all practitioners and is essential for achieving better outcomes for a high proportion of the community accessing treatment from psychologists.

An analysis of ethical issues in using wastewater analysis to monitor illicit drug use

Aims To discuss ethical issues that may arise in using WWA to monitor illicit drug use in the general population and in entertainment precincts, prisons, schools and work-places. Method Review current applications of WWA and identify ethical and social issues that may be raised with current and projected future uses of this method. Results Wastewater analysis (WWA) of drug residues is a promising method of monitoring illicit drug use that may overcome some limitations of other monitoring methods. When used for monitoring purposes in large populations, WWA does not raise major ethical concerns because individuals are not identified and the prospects of harming residents of catchment areas are remote. When WWA is used in smaller catchment areas (entertainment venues, prisons, schools or work-places) their results could, possibly, indirectly affect the occupants adversely. Researchers will need to take care in reporting their results to reduce media misreporting. Fears about possible use of WWA for mass individual surveillance by drug law enforcement officials are unlikely to be realized, but will need to be addressed because they may affect public support adversely for this type of research. Conclusions Using wastewater analysis to monitor illicit drug use in large populations does not raise major ethical concerns, but researchers need to minimize possible adverse consequences in studying smaller populations, such as workers, prisoners and students.

Profiles of illicit drug use during annual key holiday and control periods in Australia: Wastewater analysis in an urban, a semi-rural and a vacation area

AIMS: To examine changes in illicit drug consumption between peak holiday season (23 December-3 January) in Australia and a control period two months later in a coastal urban area, an inland semi-rural area and an island populated predominantly by vacationers during holidays. DESIGN: Analysis of representative daily composite wastewater samples collected from the inlet of the major wastewater treatment plant in each area. SETTING: Three wastewater treatment plants. PARTICIPANTS: Wastewater treatment plants serviced approximately 350, 000 persons in the urban area, 120,000 in the semi-rural area and 1100-2400 on the island. MEASUREMENTS: Drug residues were analysed using liquid chromatography coupled to a tandem mass spectrometer. Per capita drug consumption was estimated. Changes in drug use were quantified using Hedges' g. FINDINGS: During the holidays, cannabis consumption in the semi-rural area declined (g = -2.8) as did methamphetamine (-0.8), whereas cocaine (+1.5) and ecstasy (+1.6) use increased. In the urban area, consumption of all drugs increased during holidays (cannabis +1.6, cocaine +1.2, ecstasy +0.8 and methamphetamine +0.3). In the vacation area, methamphetamine (+0.7), ecstasy (+0.7) and cocaine (+1.1) use increased, but cannabis (-0.5) use decreased during holiday periods. CONCLUSIONS: While the peak holiday season in Australia is perceived as a period of increased drug use, this is not uniform across all drugs and areas. Substantial declines in drug use in the semi-rural area contrasted with substantial increases in urban and vacation areas. Per capita drug consumption in the vacation area was equivalent to that in the urban area, implying that these locations merit particular attention for drug use monitoring and harm minimisation measures.

Monitoring illicit drug use through wastewater analysis in south east Queensland, Australia

Introduction and Aims: Wastewater analysis has become a useful technique for monitoring illicit drug use in communities. Findings have been reported from different countries in Europe and North America. We applied this technique to gauge the illicit drug consumption in an urban catchment from South East Queensland, Australia. Design and Methods: The sampling campaigns were conducted in 2009 (21st November – 2nd December) and 2010 (19th – 25th November). We collected daily composite wastewater samples from the inlet of the sewage treatment plant using continuous flow-proportional sampling. Ten illicit drug residues (parent compounds and key metabolites) in the samples were measured using liquid chromatography coupled to tandem mass spectrometer. Results: Seven compounds were quantified in all the samples. Our data indicated higher drug consumption on weekends. Cannabis was the highest used drug in both sampling periods. Compared to the first sampling campaign which indicated that cocaine and methamphetamine use exceeded ecstasy usage, the second sampling campaign suggested the use of methamphetamine exceeded that of ecstasy which in turn exceeded cocaine use. Discussion and Conclusions: The observed weekly trend of drug use in our study is in agreement with findings in other studies. The variation between two sampling periods in the prevalence of drug use may relate to the availability and prices of the drugs on markets. The cocaine use we estimated in 2009 was much greater than estimations obtained through the national household survey [1], implying under- reporting of cocaine use in surveys. Future work is underway to tackle methodological challenges for more accurate estimation.

Illicit drug use between an annual key holiday and a control period: Wastewater analysis in a semi-rural, an urban and a vacation area

Introduction and Aims: Holiday periods are potentially a time for increased substance use as social events and private parties are more common. Data on community illicit drug consumption during holiday periods are limited. Besides existing methods for determining drug use, such as population surveys, one emerging method is to measure illicit drugs and/or their metabolites in wastewater samples. This study examined the change in consumption of cannabis, methamphetamine, cocaine and 3,4- methylenedioxymethamphetamine in three different types of areas (an inland semi-rural area, a coastal urban area and a vacation island) with respect to holiday times. Design and Methods: Samples were collected at the inlet of the major wastewater treatment plant in each area during a key annual holiday (i.e. the summer holiday including Christmas and New Year) and control period. Illicit drug residues in the daily composited samples were measured by liquid chromatography coupled with tandem mass spectrometry. Results: Drug use varied substantially among the three areas within each monitoring period as well as between the holiday and control period within each area. Use consistently increased and peaked over New Year particularly for cocaine and 3,4-methylenedioxymethamphetamine whereas cannabis and methamphetamine were relatively less subjected to holiday times in all the areas. Discussion and Conclusions: Wastewater sampling and analysis provides higher spatio-temporal resolution than national surveys and supplements drug epidemiology studies originating primary in metropolitan locations. Such data is essential for policy makers to plan potential intervention strategies associated with these illicit substances in regional areas and other settings besides urban areas in the future.

Challenges and opportunities in using wastewater analysis to measure drug use in a small prison facility

Introduction and Aims Wastewater analysis (WWA) is intended to be a direct and objective method of measuring substance use in large urban populations. It has also been used to measure prison substance use in two previous studies. The application of WWA in this context has raised questions as to how best it might be used to measure illicit drug use in prisons, and whether it can also be used to measure prescription misuse. We applied WWA to a small regional prison to measure the use of 12 licit and illicit substances. We attempted to measure the non-medical use of methadone and buprenorphine and to compare our findings with the results of the prison's mandatory drug testing (MDT). Design and Methods Representative daily composite samples were collected for two periods of 12 consecutive days in May to July 2013 and analysed for 18 drug metabolites. Prescription data and MDT results were obtained from the prison and compared with the substance use estimates calculated from WWA data. Results Daily use of methamphetamine, methadone, buprenorphine and codeine was detected, while sporadic detection of ketamine and methylone was also observed. Overall buprenorphine misuse appeared to be greater than methadone misuse. Discussion and Conclusions Compared with MDT, WWA provides a more comprehensive picture of prison substance use. WWA also has the potential to measure the misuse of medically prescribed substances. However, a great deal of care must be exercised in quantifying the usage of any substance in small populations, such as in prisons.