A survey of regular ecstasy users' knowledge and practices around determining pill content and purity: Implications for policy and practice.

Objective: To examine the methods used by a sample of regular ecstasy users to determine the content and purity of ecstasy pills, their knowledge of the limitations of available pill testing methods, and how pill test results would influence their drug use behaviour. Method: Data were collected from regular ecstasy users (n = 810) recruited from all eight capital cities of Australia. Data were analysed using multiple logistic regression and chi-square (chi(2)) tests of association. Open-ended responses were coded for themes. Results: The majority of the sample(84%) reported attempting to find out the content and purity of ecstasy at least some of the time, most commonly asking friends or dealers. Less than one quarter (22%) reported personal use of testing kits. There was a moderate level of awareness of the limitations of testing kits among those who reported having used them. Over half (57%) of those reporting personal use of testing kits reported that they would not take a pill if test results indicated that it contained ketamine and over three quarters (76%) reported that they would not take an "unknown" pill (producing no reaction in a reagent test). Finally, a considerable majority (63%) expressed interest in pill testing should it be more widely available. Conclusions: The majority of regular ecstasy users sampled in this Australian study report previous attempts to determine the content and purity of pills sold as ecstasy. Although only a small proportion have used testing kits, many report that they would do so if they were more widely available. The results of pill tests may influence drug use if they indicate that pills contain substances which ecstasy users do not want to ingest or are of unknown content. More detailed research examining ways in which pill testing may influence drug use is required to inform evidence-based policy. (c) 2006 Elsevier B.V. All rights reserved.

The influence of gender on perceived treatment need among a community sample of substance users

Purpose: Most individuals do not perceive a need for substance use treatment despite meeting diagnostic criteria for substance use disorders and they are least likely to pursue treatment voluntarily. There are also those who perceive a need for treatment and yet do not pursue it. This study aimed to understand which factors increase the likelihood of perceiving a need for treatment for individuals who meet diagnostic criteria for substance use disorders in the hopes to better assist with more targeted efforts for gender-specific treatment recruitment and retention. Using Andersen and Newman's (1973/2005) model of individual determinants of healthcare utilization, the central hypothesis of the study was that gender moderates the relationship between substance use problem severity and perceived treatment need, so that women with increasing problems due to their use of substances are more likely than men to perceive a need for treatment. Additional predisposing and enabling factors from Andersen and Newman's (1973/2005) model were included in the study to understand their impact on perceived need. Method: The study was a secondary data analysis of the 2010 National Survey on Drug Use and Health (NSDUH) using logistic regression. The weighted sample consisted of a total 20,077,235 American household residents (The unweighted sample was 5,484 participants). Results of the logistic regression were verified using Relogit software for rare events logistic regression due to the rare event of perceived treatment need (King & Zeng, 2001a; 2001b). Results: The moderating effect of female gender was not found. Conversely, men were significantly more likely than women to perceive a need for treatment as substance use problem severity increased. The study also found that a number of factors such as race, ethnicity, socioeconomic status, age, marital status, education, co-occurring mental health disorders, and prior treatment history differently impacted the likelihood of perceiving a need for treatment among men and women. Conclusion: Perceived treatment need among individuals who meet criteria for substance use disorders is rare, but identifying factors associated with an increased likelihood of perceiving need for treatment can help the development of gender-appropriate outreach and recruitment for social work treatment, and public health messages.

Exploring the Life-Saving Potential of Naloxone : A Systematic Review and Descriptive Meta-Analysis of Take Home Naloxone (THN) Programmes for Opioid Users

Date of Acceptance: 21/09/2015 This study was funded by NHS Health Scotland. The opinions expressed in this paper as those of the authors alone and are not necessarily those of NHS Health Scotland. The funders had no role in the conduct of the research.

Exploring the Life-Saving Potential of Naloxone : A Systematic Review and Descriptive Meta-Analysis of Take Home Naloxone (THN) Programmes for Opioid Users

Date of Acceptance: 21/09/2015 This study was funded by NHS Health Scotland. The opinions expressed in this paper as those of the authors alone and are not necessarily those of NHS Health Scotland. The funders had no role in the conduct of the research.

BAP Guidelines on the Management of Weight Gain, Metabolic Disturbances and Cardiovascular Risk Associated With Psychosis and Antipsychotic Drug Treatment

Excess deaths from cardiovascular disease are a major contributor to the significant reduction in life expectancy experienced by people with schizophrenia. Important risk factors in this are smoking, alcohol misuse, excessive weight gain and diabetes. Weight gain also reinforces service users’ negative views of themselves and is a factor in poor adherence with treatment. Monitoring of relevant physical health risk factors is frequently inadequate, as is provision of interventions to modify these. These guidelines review issues surrounding monitoring of physical health risk factors and make recommendations about an appropriate approach. Overweight and obesity, partly driven by antipsychotic drug treatment, are important factors contributing to the development of diabetes and cardiovascular disease in people with schizophrenia. There have been clinical trials of many interventions for people experiencing weight gain when taking antipsychotic medications but there is a lack of clear consensus regarding which may be appropriate in usual clinical practice. These guidelines review these trials and make recommendations regarding appropriate interventions. Interventions for smoking and alcohol misuse are reviewed, but more briefly as these are similar to those recommended for the general population. The management of impaired fasting glycaemia and impaired glucose tolerance (‘pre-diabetes’), diabetes and other cardiovascular risks, such as dyslipidaemia, are also reviewed with respect to other currently available guidelines. These guidelines were compiled following a consensus meeting of experts involved in various aspects of these problems. They reviewed key areas of evidence and their clinical implications. Wider issues relating to primary care/secondary care interfaces are discussed but cannot be resolved within guidelines such as these.

Studies of antihypertensive drug persistence and adherence in the Glasgow Blood Pressure Clinic

Hypertension (HTN) is a major risk factor for cardiovascular diseases including stroke, coronary heart disease (CHD), chronic renal failure, peripheral vascular disease, myocardial infarction, congestive heart failure and premature death. The prevalence of HTN in Scotland is very high and although a high proportion of the patients receive antihypertensive medications, blood pressure (BP) control is very low. Recommendations for starting a specific antihypertensive class have been debated between various guidelines over the years. Some guidelines and HTN studies have preferred to start with a combination of an antihypertensive class instead of using a single therapy, and they have found greater BP reductions with combination therapies than with monotherapy. However, it has been shown in several clinical trials that 20% to 35% of hypertensive patients could not achieve the target BP, even though they received more than three antihypertensive medications. Several factors were found to affect BP control. Adherence and persistence were considered as the factors contributing the most to uncontrolled hypertension. Other factors such as age, sex, body mass index (BMI), alcohol intake, baseline systolic BP (SBP), and the communication between physicians and patients have been shown to be associated with uncontrolled BP and resistant hypertension. Persistence, adherence and compliance are interchangeable terms and have been used in the literature to describe a patient’s behaviour with their antihypertensive drugs and prescriptions. The methods used to determine persistence and adherence, as well as the inclusion and exclusion criteria, vary between persistence and adherence studies. The prevalence of persistence and adherence have varied between these studies, and were determined to be high in some studies and low in others. The initiation of a specific antihypertensive class has frequently been associated with an increase or decrease in adherence and persistence. The tolerability and efficacy of the initial antihypertensive class have been the most common methods of explaining this association. There are also many factors that suggest a relationship with adherence and persistence. Some factors in previous studies, such as age, were frequently associated with adherence and persistence. On the other hand, relationships with certain factors have varied between the studies. The associations of age, sex, alcohol use, smoking, baseline systolic blood pressure (SBP) and diastolic BP (DBP), the presence of comorbidities, an increase in the number of pills and the relationship between patients and physicians with adherence and persistence have been the most commonly investigated factors. Most studies have defined persistence in terms of a patient still taking medication after a period of time. A medication possession ratio (MPR) ≥ 80 has been used to define compliance. Either of these terminologies, or both, have been used to estimate adherence. In this study, I used the same definition for persistence to identify patients who have continued with their initial treatment, and used persistence and MPR to define patients who adhered to their initial treatment. The aim of this study was to estimate the prevalence of persistence and adherence in Scotland. Also, factors that could have had an effect on persistence and adherence were studied. The number of antihypertensive drugs taken by patients during the study and factors that led to an increase in patients being on a combination therapy were also evaluated. The prevalence of resistance and BP control were determined by taking the BP after the last drug had been taken by persistent patients during five follow-up studies. The relationship of factors such as age, sex, BMI, alcohol use, smoking, estimated glomerular filtration rate (eGFR), and albumin levels with BP reductions for each antihypertensive class were determined. Information Services Division (ISD) data, which includes all antihypertensive drugs, were collected from pharmacies in Scotland and linked to the Glasgow Blood Pressure Clinic (GBPC) database. This database also includes demographic characteristics, BP readings and clinical results for all patients attending the GBPC. The case notes for patients who attended the GBPC were reviewed and all new antihypertensive drugs that were prescribed between visits, BP before and after taking drugs, and any changes in the hypertensive drugs were recorded. A total of 4,232 hypertensive patients were included in the first study. The first study showed that angiotensin converting enzyme inhibitor (ACEI) and beta-blockers (BB) were the most prescribed antihypertensive classes between 2004 and 2013. Calcium channel blockers (CCB), thiazide diuretics and angiotensin receptor blockers (ARB) followed ACEI and BB as the most prescribed drugs during the same period. The prescription trend of the antihypertensive class has changed over the years with an increase in prescriptions for ACEI and ARB and a decrease in prescriptions for BB and diuretics. I observed a difference in antihypertensive class prescriptions by age, sex, SBP and BMI. For example, CCB, thiazide diuretics and alpha-blockers were more likely to be prescribed to older patients, while ACEI, ARB or BB were more commonly prescribed for younger patients. In a second study, 4,232 and 3,149 hypertensive patients were included to investigate the prevalence of persistence in the Scottish population in 1- and 5-year studies, respectively. The prevalence of persistence in the 1-year study was 72.9%, while it was only 62.8% in the 5-year study. Those patients taking ARB and ACEI showed high rates of persistence and those taking diuretics and alpha blockers had low rates of persistence. The association of persistence with clinical characteristics was also investigated. Younger patients were more likely to totally stop their treatment before restarting their treatment with other antihypertensive drugs. Furthermore, patients who had high SBP tended to be non-persistent. In a third study, 3,085 and 1,979 patients who persisted with their treatment were included. In the first part of the study, MPR was calculated, and patients with an MPR ≥ 80 were considered as adherent. Adherence rates were 29.9% and 23.4% in the 1- and 5-year studies, respectively. Patients who initiated the study with ACEI were more likely to adhere to their treatments. However, patients who initiated the study with thiazide diuretics were less likely to adhere to their treatments. Sex, age and BMI were different between the adherence and non-adherence groups. Age was an independent factor affecting adherence rates during both the 1- and 5-year studies with older patients being more likely to be adherent. In the second part of the study, pharmacy databases were checked with patients' case notes to compare antihypertensive drugs that were collected from the pharmacy with the antihypertensive prescription given during the patient’s clinical visit. While 78.6% of the antihypertensive drugs were collected between clinical visits, 21.4% were not collected. Patients who had more days to see the doctor in the subsequent visit were more likely to not collect their prescriptions. In a fourth study, 3,085 and 1,979 persistent patients were included to calculate the number of antihypertensive classes that were added to the initial drug during the 1-year and 5-year studies, respectively. Patients who continued with treatment as a monotherapy and who needed a combination therapy were investigated during the 1- and 5-year studies. In all, 55.8% used antihypertensive drugs as a monotherapy and 44.2% used them as a combination therapy during the 1-year study. While 28.2% of patients continued with treatment without the required additional therapy, 71.8% of the patients needed additional therapy. In all, 20.8% and 46.5% of patients required three different antihypertensive classes or more during the 1-year and 5-year studies, respectively. Patients who started with ACEI, ARB and BB were more likely to continue as monotherapy and less likely to need two more antihypertensive drugs compared with those who started with alpha-blockers, non-thiazide diuretics and CCB. Older ages, high BMI levels, high SBP and high alcohol intake were independent factors that led to an increase in the probability of patients taking combination therapies. In the first part of the final study, BPs were recorded after the last drug had been taken during the 5 year study. There were 815 persistent patients who were assigned for this purpose. Of these, 39% had taken one, two or three antihypertensive classes and had controlled BP (controlled hypertension [HTN]), 29% of them took one or two antihypertensive classes and had uncontrolled BP (uncontrolled HTN), and 32% of the patients took three antihypertensive classes or more and had uncontrolled BP (resistant HTN). The initiation of an antihypertensive drug and the factors affecting BP pressure were compared between the resistant and controlled HTN groups. Patients who initiated the study with ACEI were less likely to be resistant compared with those who started with alpha blockers and non-thiazide diuretics. Older patients, and high BMI tended to result in resistant HTN. In the second part of study, BP responses for patients who initiated the study with ACEI, ARB, BB, CCB and thiazide diuretics were compared. After adjusting for risk factors, patients who initiated the study with ACEI and ARB were more respondent than those who took CCB and thiazide diuretics. In the last part of this study, the association between BP reductions and factors affecting BP were tested for each antihypertensive drug. Older patients responded better to alpha blockers. Younger patients responded better to ACEI and ARB. An increase in BMI led to a decreased reduction in patients on ACEI and diuretics (thiazide and non-thiazide). An increase in albumin levels and a decrease in eGFR led to decreases in BP reductions in patients on thiazide diuretics. An increase in eGFR decreased the BP response with ACEI. In conclusion, although a high percentage of hypertensive patients in Scotland persisted with their initial drug prescription, low adherence rates were found with these patients. Approximately half of these patients required three different antihypertensive classes during the 5 years, and 32% of them had resistant HTN. Although this study was observational in nature, the large sample size in this study represented a real HTN population, and the large pharmacy data represented a real antihypertensive population, which were collected through the support of prescription data from the GBPC database. My findings suggest that ACEI, ARB and BB are less likely to require additional therapy. However, ACEI and ARB were better tolerated than BB in that they were more likely to be persistent than BB. In addition, users of ACEI, and ARB have good BP response and low resistant HTN. Linkage patients who participated in these studies with their morbidity and mortality will provide valuable information concerning the effect of adherence on morbidity and mortality and the potential benefits of using ACEI or ARB over other drugs.

The Influence of Gender on Perceived Treatment Need among a Community Sample of Substance Users

Purpose: Most individuals do not perceive a need for substance use treatment despite meeting diagnostic criteria for substance use disorders and they are least likely to pursue treatment voluntarily. There are also those who perceive a need for treatment and yet do not pursue it. This study aimed to understand which factors increase the likelihood of perceiving a need for treatment for individuals who meet diagnostic criteria for substance use disorders in the hopes to better assist with more targeted efforts for gender-specific treatment recruitment and retention. Using Andersen and Newman’s (1973/2005) model of individual determinants of healthcare utilization, the central hypothesis of the study was that gender moderates the relationship between substance use problem severity and perceived treatment need, so that women with increasing problems due to their use of substances are more likely than men to perceive a need for treatment. Additional predisposing and enabling factors from Andersen and Newman’s (1973/2005) model were included in the study to understand their impact on perceived need. Method: The study was a secondary data analysis of the 2010 National Survey on Drug Use and Health (NSDUH) using logistic regression. The weighted sample consisted of a total 20,077,235 American household residents (The unweighted sample was 5,484 participants). Results of the logistic regression were verified using Relogit software for rare events logistic regression due to the rare event of perceived treatment need (King & Zeng, 2001a; 2001b). Results: The moderating effect of female gender was not found. Conversely, men were significantly more likely than women to perceive a need for treatment as substance use problem severity increased. The study also found that a number of factors such as race, ethnicity, socioeconomic status, age, marital status, education, co-occurring mental health disorders, and prior treatment history differently impacted the likelihood of perceiving a need for treatment among men and women. Conclusion: Perceived treatment need among individuals who meet criteria for substance use disorders is rare, but identifying factors associated with an increased likelihood of perceiving need for treatment can help the development of gender-appropriate outreach and recruitment for social work treatment, and public health messages.

3D bioprinted organ models for drug screening

In recent years, 3D bioprinting has emerged as an innovative and versatile technology able to produce in vitro models that resemble the native spatial organization of organ tissues, by employing or more bioinks composed of various types of cells suspended in hydrogels. Natural and semi-synthetic hydrogels are extensively used for 3D bioprinting models since they can mimic the natural composition of the tissues, they are biocompatible and bioactive with customizable mechanical properties, allowing to support cell growth. The possibility to tailor hydrogels mechanical properties by modifying the chemical structures to obtain photo-crosslinkable materials, while maintaining their biocompatibility and biomimicry, make their use versatile and suitable to simulate a broad spectrum of physiological features. In this PhD Thesis, 3D bioprinted in vitro models with tailored mechanical properties and physiologically-like features were fabricated. AlgMa-based bioinks were employed to produce a living platform with gradient stiffness, with the aim to create an easy to handle and accessible biological tool to evaluate mechanobiology. In addition, GelMa, collagen and IPN of GelMa and collagen were used as bioinks to fabricate a proof-of-concept of 3D intestinal barrier, which include multiple cell components and multi-layered structure. A useful rheological guide to drive users to the selection of the suitable bioinks for 3D bioprinting and to correlate the model’s mechanical stability after crosslinking is proposed. In conclusion, a platform capable to reproduce models with physiological gradient stiffness was developed and the fabrication of 3D bioprinted intestinal models displaying a good hierarchical structure and cells composition was fully reported and successfully achieved. The good biological results obtained demonstrated that 3D bioprinting can be used for the fabrications of 3D models and that the mechanical properties of the external environment plays a key role on the cell pathways, viability and morphology.

Exploratory Study Of The Effect Of Lifestyle Counselling On Bone Mineral Density And Body Composition In Users Of The Contraceptive Depot-medroxyprogesterone Acetate.

To compare variations in bone mineral density (BMD) and body composition (BC) in depot-medroxyprogesterone acetate (DMPA) users and nonusers after providing counselling on healthy lifestyle habits. An exploratory study in which women aged 18 to 40 years participated: 29 new DMPA users and 25 new non-hormonal contraceptive users. All participants were advised on healthy lifestyle habits: sun exposure, walking and calcium intake. BMD and BC were assessed at baseline and 12 months later. Statistical analysis included the Mann-Whitney test or Student's t-test followed by multiple linear regression analysis. Compared to the controls, DMPA users had lower BMD at vertebrae L1 and L4 after 12 months of use. They also had a mean increase of 2 kg in total fat mass and an increase of 2.2% in body fat compared to the non-hormonal contraceptive users. BMD loss at L1 was less pronounced in DMPA users with a calcium intake ≥ 1 g/day compared to DMPA users with a lower calcium intake. DMPA use was apparently associated with lower BMD and an increase in fat mass at 12 months of use. Calcium intake ≥ 1 g/day attenuates BMD loss in DMPA users. Counselling on healthy lifestyle habits failed to achieve its aims.

Iis--integrated Interactome System: A Web-based Platform For The Annotation, Analysis And Visualization Of Protein-metabolite-gene-drug Interactions By Integrating A Variety Of Data Sources And Tools.

High-throughput screening of physical, genetic and chemical-genetic interactions brings important perspectives in the Systems Biology field, as the analysis of these interactions provides new insights into protein/gene function, cellular metabolic variations and the validation of therapeutic targets and drug design. However, such analysis depends on a pipeline connecting different tools that can automatically integrate data from diverse sources and result in a more comprehensive dataset that can be properly interpreted. We describe here the Integrated Interactome System (IIS), an integrative platform with a web-based interface for the annotation, analysis and visualization of the interaction profiles of proteins/genes, metabolites and drugs of interest. IIS works in four connected modules: (i) Submission module, which receives raw data derived from Sanger sequencing (e.g. two-hybrid system); (ii) Search module, which enables the user to search for the processed reads to be assembled into contigs/singlets, or for lists of proteins/genes, metabolites and drugs of interest, and add them to the project; (iii) Annotation module, which assigns annotations from several databases for the contigs/singlets or lists of proteins/genes, generating tables with automatic annotation that can be manually curated; and (iv) Interactome module, which maps the contigs/singlets or the uploaded lists to entries in our integrated database, building networks that gather novel identified interactions, protein and metabolite expression/concentration levels, subcellular localization and computed topological metrics, GO biological processes and KEGG pathways enrichment. This module generates a XGMML file that can be imported into Cytoscape or be visualized directly on the web. We have developed IIS by the integration of diverse databases following the need of appropriate tools for a systematic analysis of physical, genetic and chemical-genetic interactions. IIS was validated with yeast two-hybrid, proteomics and metabolomics datasets, but it is also extendable to other datasets. IIS is freely available online at: http://www.lge.ibi.unicamp.br/lnbio/IIS/.

Study Of The Homogeneity Of Drug Loaded In Polymeric Films Using Near-infrared Chemical Imaging And Split-plot Design.

Split-plot design (SPD) and near-infrared chemical imaging were used to study the homogeneity of the drug paracetamol loaded in films and prepared from mixtures of the biocompatible polymers hydroxypropyl methylcellulose, polyvinylpyrrolidone, and polyethyleneglycol. The study was split into two parts: a partial least-squares (PLS) model was developed for a pixel-to-pixel quantification of the drug loaded into films. Afterwards, a SPD was developed to study the influence of the polymeric composition of films and the two process conditions related to their preparation (percentage of the drug in the formulations and curing temperature) on the homogeneity of the drug dispersed in the polymeric matrix. Chemical images of each formulation of the SPD were obtained by pixel-to-pixel predictions of the drug using the PLS model of the first part, and macropixel analyses were performed for each image to obtain the y-responses (homogeneity parameter). The design was modeled using PLS regression, allowing only the most relevant factors to remain in the final model. The interpretation of the SPD was enhanced by utilizing the orthogonal PLS algorithm, where the y-orthogonal variations in the design were separated from the y-correlated variation.

[adherence To Statin Treatment And Associated Factors In Female Users From The Unified Health System (sus)].

To identify the adherence rate of a statin treatment and possible related factors in female users from the Unified Health System. Seventy-one women were evaluated (64.2 ± 11.0 years) regarding the socio-economic level, comorbidities, current medications, level of physical activity, self-report of muscular pain, adherence to the medical prescription, body composition and biochemical profile. The data were analyzed as frequencies, Chi-Squared test, and Mann Whitney test (p<0.05). 15.5% of women did not adhere to the medical prescription for the statin treatment, whose had less comorbidities (p=0.01), consumed less quantities of medications (p=0.00), and tended to be younger (p=0.06). Those patients also presented higher values of lipid profile (CT: p=0.01; LDL-c: p=0.02). Musculoskeletal complains were not associated to the adherence rate to the medication. The associated factors to adherence of dyslipidemic women to statin medical prescription were age, quantity of comorbidities and quantity of current medication.

Impact Of Pharmacist Interventions On Drug-related Problems And Laboratory Markers In Outpatients With Human Immunodeficiency Virus Infection.

Substantial complexity has been introduced into treatment regimens for patients with human immunodeficiency virus (HIV) infection. Many drug-related problems (DRPs) are detected in these patients, such as low adherence, therapeutic inefficacy, and safety issues. We evaluated the impact of pharmacist interventions on CD4+ T-lymphocyte count, HIV viral load, and DRPs in patients with HIV infection. In this 18-month prospective controlled study, 90 outpatients were selected by convenience sampling from the Hospital Dia-University of Campinas Teaching Hospital (Brazil). Forty-five patients comprised the pharmacist intervention group and 45 the control group; all patients had HIV infection with or without acquired immunodeficiency syndrome. Pharmaceutical appointments were conducted based on the Pharmacotherapy Workup method, although DRPs and pharmacist intervention classifications were modified for applicability to institutional service limitations and research requirements. Pharmacist interventions were performed immediately after detection of DRPs. The main outcome measures were DRPs, CD4+ T-lymphocyte count, and HIV viral load. After pharmacist intervention, DRPs decreased from 5.2 (95% confidence interval [CI] =4.1-6.2) to 4.2 (95% CI =3.3-5.1) per patient (P=0.043). A total of 122 pharmacist interventions were proposed, with an average of 2.7 interventions per patient. All the pharmacist interventions were accepted by physicians, and among patients, the interventions were well accepted during the appointments, but compliance with the interventions was not measured. A statistically significant increase in CD4+ T-lymphocyte count in the intervention group was found (260.7 cells/mm(3) [95% CI =175.8-345.6] to 312.0 cells/mm(3) [95% CI =23.5-40.6], P=0.015), which was not observed in the control group. There was no statistical difference between the groups regarding HIV viral load. This study suggests that pharmacist interventions in patients with HIV infection can cause an increase in CD4+ T-lymphocyte counts and a decrease in DRPs, demonstrating the importance of an optimal pharmaceutical care plan.

Cheaper Faster Drug Development Validated By The Repositioning Of Drugs Against Neglected Tropical Diseases.

There is an urgent need to make drug discovery cheaper and faster. This will enable the development of treatments for diseases currently neglected for economic reasons, such as tropical and orphan diseases, and generally increase the supply of new drugs. Here, we report the Robot Scientist 'Eve' designed to make drug discovery more economical. A Robot Scientist is a laboratory automation system that uses artificial intelligence (AI) techniques to discover scientific knowledge through cycles of experimentation. Eve integrates and automates library-screening, hit-confirmation, and lead generation through cycles of quantitative structure activity relationship learning and testing. Using econometric modelling we demonstrate that the use of AI to select compounds economically outperforms standard drug screening. For further efficiency Eve uses a standardized form of assay to compute Boolean functions of compound properties. These assays can be quickly and cheaply engineered using synthetic biology, enabling more targets to be assayed for a given budget. Eve has repositioned several drugs against specific targets in parasites that cause tropical diseases. One validated discovery is that the anti-cancer compound TNP-470 is a potent inhibitor of dihydrofolate reductase from the malaria-causing parasite Plasmodium vivax.

Weight Variation In Users Of Depot-medroxyprogesterone Acetate, The Levonorgestrel-releasing Intrauterine System And A Copper Intrauterine Device For Up To Ten Years Of Use.

Data on record regarding weight variation in depot-medroxyprogesterone acetate (DMPA) and levonorgestrel-releasing intrauterine system (LNG-IUS) users are controversial. To date, no studies have yet evaluated weight variation in DMPA and LNG-IUS users in up to ten years of use compared to non-hormonal contraceptive users. A retrospective study analysed weight variations in 2138 women using uninterruptedly DMPA (150 mg intramuscularly, three-monthly; n = 714), the LNG-IUS (n = 701) or a copper-intrauterine device (Cu-IUD; n = 723). At the end of the first year of use, there was a mean weight increase of 1.3 kg, 0.7 kg and 0.2 kg among the DMPA-, LNG-IUS- and Cu-IUD users, respectively, compared to weight at baseline (p < 0.0001). After ten years of use, the mean weight had risen by 6.6 kg, 4.0 and 4.9 kg among the DMPA-, LNG-IUS- and Cu-IUD users, respectively. DMPA-users had gained more weight than LNG-IUS- (p = 0.0197) and than Cu-IUD users (p = 0.0294), with the latter two groups not differing significantly from each other in this respect (p = 0.5532). Users of hormonal and non-hormonal contraceptive methods gained a significant amount of weight over the years. DMPA users gained more weight over the treatment period of up to ten years than women fitted with either a LNG-IUS or a Cu-IUD.