Psychosis with coexisting substance misuse: assessment and management in adults and young people.

This guideline offers best practice advice on the assessment and management of people with psychosis and coexisting substance misuse. Psychosis is a condition that affects a person’s mental state, including their thoughts, mood and behaviour. The symptoms of psychosis are:• hallucinations – hearing voices and sometimes seeing things that are not really there• delusions – having fixed beliefs that are false but which the person believes in completely. Substance misuse is a broad term encompassing, in this guideline, the harmful use of any psychotropic substance, including alcohol and either legal or illicit drugs. Use of such substances is harmful when it has a negative effect on a person’s life, including their physical and mental health, relationships, work, education and finances or leads to offending behaviour.This resource was contributed by The National Documentation Centre on Drug Use.

Local and regional drugs task forces: handbook.

This handbook has been developed within the context of the institutional structures recommended under the National Drugs Strategy 2009-2016 and within the overall framework of the National Social Inclusion Plan 2007-2016. It sets out the role of the Drugs Task Forces within the national and local framework required to address the existing and emerging problems associated with drug use for individuals, families and communities in the context of the long term development of the work of the Drugs Task Forces.This resource was contributed by The National Documentation Centre on Drug Use.

Mental health and growing up factsheet. Drugs and alcohol - what parents need to know.

Information about drugs and alcohol - what parents need to know: information for parents, carers and anyone who works with young people. About this leaflet This is one in a series of leaflets for parents, teachers and young people entitled Mental Health and Growing Up. These leaflets aim to provide practical, up-to-date information about mental health problems (emotional, behavioural and psychiatric disorders) that can affect children and young people. This leaflet offers practical advice for parents, teachers and carers who are worried that a young person is misusing drugs or alcohol. Why do I need to know about a young person using drugs or alcohol? Many young people smoke, drink alcohol and may try drugs. It is important you are aware of this and do not ignore it as a time when they are just having fun or experimenting. It doesnââ,‰"¢t take much for the young people to soon lose control and to need help to recover from this problem. How common is it? By the age of 16, up to half of young people have tried an illegal drug. Young people are trying drugs earlier and more are drinking alcohol. What are the different types of drugs which cause problems? The most commonly used, readily available and strongly addictive drugs are tobacco and alcohol. There are numerous others that can be addictive. Alcohol and cannabis are sometimes seen as ââ,¬Ëogatewayââ,‰"¢ drugs that lead to the world of other drugs like cocaine and heroin. Drugs are also classed as ââ,¬Ëolegalââ,‰"¢ andââ,¬Ëoillegalââ,‰"¢. The obviously illegal drugs include cannabis (hash), speed (amphetamines), ecstasy (E), cocaine and heroin. Using ââ,¬Ëolegalââ,‰"¢ drugs (like cigarettes, alcohol, petrol, glue) does not mean they are safe or allowed to be misused. It just means they may be bought or sold for specific purposes and are limited to use by specific age groups. There are clear laws regarding alcohol and young people. For more detailed information on various drugs, their side-effects and the law, see ââ,¬ËoFurther Informationââ,‰"¢ at the end of the factsheet. Why do young people use drugs or alcohol? Young people may try or use drugs or alcohol for various reasons. They may do it for fun, because they are curious, or to be like their friends. Some are experimenting with the feeling of intoxication. Sometimes they use it to cope with difficult situations or feelings of worry and low mood. A young person is more likely to try or use drugs or alcohol if they hang out or stay with friends or family who use them. What can be the problems related to using drugs or alcohol? Drugs and alcohol can have different effects on different people. In young people especially the effects can be unpredictable and potentially dangerous. Even medications for sleep or painkillers can be addictive and harmful if not used the way they are prescribed by a doctor. Drugs and alcohol can damage health. Sharing needles or equipment can cause serious infections, such as HIV and hepatitis. Accidents, arguments and fights are more likely after drinking and drug use. Young people are more likely to engage in unprotected sex when using drugs. Using drugs can lead to serious mental illnesses, such as psychosis and depression. When does it become addiction or problem? It is very difficult to know when exactly using drugs or alcohol is more than just ââ,¬Ëocasualââ,‰"¢. Addiction becomes more obvious when the young person spends most of their time thinking about, looking for or using drugs. Drugs or alcohol then become the focus of the young personââ,‰"¢s life. They ignore their usual work, such as not doing their schoolwork, or stop doing their usual hobbies/sports such as dancing or football. How do I know if there is a problem or addiction? Occasional use can be very difficult to detect. If the young person is using on a regular basis, their behaviour often changes. Look for signs such as: ïâ?s§ unexplained moodiness ïâ?s§ behaviour that is ââ,¬Ëoout of character' ïâ?s§ loss of interest in school or friends ïâ?s§ unexplained loss of clothes or money ïâ?s§ unusual smells and items like silver foil, needle covers. Remember, the above changes can also mean other problems, such as depression, rather than using drugs. What do I do if I am worried? If you suspect young person is using drugs, remember some general rules. ïâ?s§ Pay attention to what the child is doing, including schoolwork, friends and leisure time. ïâ?s§ Learn about the effects of alcohol and drugs (see websites listed below). ïâ?s§ Listen to what the child says about alcohol and drugs, and talk about it with them. ïâ?s§ Encourage the young person to be informed and responsible about drugs and alcohol. ïâ?s§ Talk to other parents, friends or teachers about drugs - the facts and your fears and seek help. If someone in the family or close friend is using drugs or alcohol, it is important that they seek help too. It may be hard to expect the young person to give up, especially if a parent or carer is using it too. My child is abusing drugs. What do I do? ïâ?s§ If your child is using drugs or alcohol, seek help. ïâ?s§ Do stay calm and make sure of facts. ïâ?s§ Don't give up on them, get into long debates or arguments when they are drunk, stoned or high. ïâ?s§ Donââ,‰"¢t be angry or blame themââ,‰?othey need your help and trust to make journey of recovery. Where can I get help? You can talk in confidence to a professional like your GP or practice nurse, a local drug project or your local child and adolescent mental health. They can refer your child to relevant services and they will be able to offer you advice and support. You may also be able to seek help through a school nurse, teacher or social worker. You can find this information from your local area telephone book or council website, or ask for the address from your health centre. [For the full factsheet, click on the link above]This resource was contributed by The National Documentation Centre on Drug Use.

Benznidazole vs benznidazole in multilamellar liposomes: how different they interact with blood components?

In spite of its widespread use, benznidazole's (BNZ) toxicity and low efficacy remains as major drawbacks that impair successful treatments against Chagas disease. Previously, attempting to increase the selectivity and reduce its toxicity on infected tissues, multilamellar liposomes (MLV) composed of hydrogenated soybean phosphatidylcholine (HSPC): distearoyl-phosphatidylglycerol (DSPG): cholesterol (CHOL) 2:1:2 mol:mol loaded with BNZ (MLV-BNZ) were designed. In this work we compared different properties of MLV-BNZ with those of BNZ. Opposite to other hydrophobic drugs, the results indicated that slight changes of BNZ×s association degree to proteins and lipoproteins should not modify the percentage of unbound drug available to exert pharmacological action. On the other hand, when loaded in MLV, BNZ reduced its association to plasma proteins in 45% and became refractory to the sinking effect of blood, dropping 4.5 folds. Additionally, when loaded in MLV, BNZ had higher volume distribution (160 ± 20 vs 102 ± 15 ml/kg) and total clearance (35.23 ± 2.3 vs 21.9 ± 1.4 ml/h.kg), and lower concentration-time curve (7.23 ± 0.2 vs 9.16 ± 0.5 µg.h/ml) than BNZ. Hence, these studies showed that for MLV-BNZ, the amount of BNZ can be substantially increased, from 25 to 70%, being this formulation more rapidly cleared from circulation than free drug; also due to the lower interaction with blood components, lower side effects can be expected.

More is not always better-comparison of three instruments measuring volume of drinking in a sample of young men and their association with consequences

OBJECTIVE: In general population survey instruments that measure volume of drinking, additional questions and shorter reference periods yield higher volumes. Comparison studies have focused on volume but not on associations between volume and consequences. METHOD: From a cohort study on substance use risk factors (Cohort Study on Substance Use Risk Factors [C-SURF]), baseline data were analyzed for 5,074 young (approximately 20-year-old) men who were drinkers in the past 12 months. Volume of drinking was measured by a generic quantity-frequency (QF) instrument, an extended QF (separately for weekends and weekdays) instrument with 12-months recall, and a retrospective past-week diary. Associations of consequences with and without attribution of alcohol as a cause, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for dependence, and DSM-5 alcohol use disorder in the past 12 months were analyzed. RESULTS: The generic QF measure resulted in lower volume compared with either the extended QF measure (more questions) or the retrospective diary (the most questions and the shortest recall period). For outcomes, however, the extended QF assessment performed the best and the diary the worst. CONCLUSIONS: Higher volume yields are not always better regarding associations with outcomes. The extended QF instrument better captures the variability of drinking. The retrospective diary performs poorly for associations because of the mismatch with the recall period for past-12-months consequences and the potential for misclassification of past-week abstainers and heavy drinkers because of an uncommon past week. Diaries are not recommended for research investigating individual associations between exposure and outcomes in young populations if consequences are measured with a sufficiently long interval to capture rare consequences. (J. Stud. Alcohol Drugs, 75, 880-888, 2014).

Concurrent versus simultaneous use of alcohol and non-medical use of prescription drugs: is simultaneous use worse for mental, social, and health issues?

Abstract This study investigated the difference between concurrent and simultaneous use of alcohol and non-medical use of prescription drugs (NMUPD) in relation to mental, social, and health issues. The 544 study participants of the Swiss ongoing Cohort Study on Substance Use Risk Factors (C-SURF) had a combined use of alcohol with NMUPD during the previous 12 months. Alcohol-related problems (i.e., dependence and consequences), as well as mental, social, and health concerns (i.e., depression, general mental/physical health, and social/health consequences), were assessed. The simultaneous use of alcohol and NMUPD proved to be a greater risk factor for mental, social, and health issues than concurrent use. This study adds information regarding simultaneous polydrug use, which results in distinct effects compared to concurrent use, including important social, psychosocial, and health-related consequences.

Selective PDE4 inhibitors as potent anti-inflammatory drugs for the treatment of airway diseases

Phosphodiesterases (PDEs) are responsible for the breakdown of intracellular cyclic nucleotides, from which PDE4 are the major cyclic AMP metabolizing isoenzymes found in inflammatory and immune cells. This generated greatest interest on PDE4 as a potential target to treat lung inflammatory diseases. For example, cigarette smoke-induced neutrophilia in BAL was dose and time dependently reduced by cilomilast. Beside the undesired side effects associated with the first generation of PDE4 inhibitors, the second generation of selective inhibitors such as cilomilast and roflumilast showed clinical efficacy in asthma and chronic obstrutive pulmonary diseases trials, thus re-enhancing the interest on these classes of compounds. However, the ability of PDE4 inhibitors to prevent or modulate the airway remodelling remains relatively unexplored. We demonstrated that selective PDE4 inhibitor RP 73-401 reduced matrix metalloproteinase (MMP)-9 activity and TGF-beta1 release during LPS-induced lung injury in mice and that CI-1044 inhibited the production of MMP-1 and MMP-2 from human lung fibroblasts stimulated by pro-inflammatory cytokines. Since inflammatory diseases of the bronchial airways are associated with destruction of normal tissue structure, our data suggest a therapeutic benefit for PDE4 inhibitors in tissue remodelling associated with chronic lung diseases.

Polypharmacy is Associated with an Increased Risk of Bleeding in Elderly Patients with Venous Thromboembolism.

BACKGROUND: Polypharmacy, defined as the concomitant use of multiple medications, is very common in the elderly and may trigger drug-drug interactions and increase the risk of falls in patients receiving vitamin K antagonists. OBJECTIVE: To examine whether polypharmacy increases the risk of bleeding in elderly patients who receive vitamin K antagonists for acute venous thromboembolism (VTE). DESIGN: We used a prospective cohort study. PARTICIPANTS: In a multicenter Swiss cohort, we studied 830 patients aged ≥ 65 years with VTE. MAIN MEASURES: We defined polypharmacy as the prescription of more than four different drugs. We assessed the association between polypharmacy and the time to a first major and clinically relevant non-major bleeding, accounting for the competing risk of death. We adjusted for known bleeding risk factors (age, gender, pulmonary embolism, active cancer, arterial hypertension, cardiac disease, cerebrovascular disease, chronic liver and renal disease, diabetes mellitus, history of major bleeding, recent surgery, anemia, thrombocytopenia) and periods of vitamin K antagonist treatment as a time-varying covariate. KEY RESULTS: Overall, 413 (49.8 %) patients had polypharmacy. The mean follow-up duration was 17.8 months. Patients with polypharmacy had a significantly higher incidence of major (9.0 vs. 4.1 events/100 patient-years; incidence rate ratio [IRR] 2.18, 95 % confidence interval [CI] 1.32-3.68) and clinically relevant non-major bleeding (14.8 vs. 8.0 events/100 patient-years; IRR 1.85, 95 % CI 1.27-2.71) than patients without polypharmacy. After adjustment, polypharmacy was significantly associated with major (sub-hazard ratio [SHR] 1.83, 95 % CI 1.03-3.25) and clinically relevant non-major bleeding (SHR 1.60, 95 % CI 1.06-2.42). CONCLUSIONS: Polypharmacy is associated with an increased risk of both major and clinically relevant non-major bleeding in elderly patients receiving vitamin K antagonists for VTE.

Antibacterial and cytotoxic activity of Brazilian plant extracts - Clusiaceae

Twelve extracts obtained from nine plants belonging to six different genera of Clusiaceae were analyzed against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and Enterococcus faecalis) bacteria using the microdilution broth assay. Tovomita aff. longifolia, T. brasiliensis, Clusia columnaris, Garcinia madruno, Haploclathra paniculata, and Caraipa grandifolia extracts showed significant results against the bacteria. The organic extract obtained from the leaves of T. aff. longifolia showed minimal inhibitory concentration (MIC) = 70 µg/ml and minimal bactericidal concentration (MBC) = 90 µg/ml against E. faecalis and the organic extract made with the stem of C. columnaris showed MIC = 180 µg/ml and MBC = 270 µg/ml against P. aeruginosa. None of the antibacterial extracts showed lethal activity against brine shrimp nauplii. On the other hand, both aqueous and organic extracts obtained from the aerial organs of Vismia guianensis that were cytotoxic to brine shrimp nauplii did not show a significant antibacterial activity in the assay.

BDAWG Scoping Report: Drugs and alcohol services in Belfast

Mary Black, Assistant Director for Health and Social Wellbeing Improvement in the Public Health Agency, established the Belfast Drug and Alcohol Working Group in early 2010 to undertake a scoping exercise of drugs and alcohol services in Belfast, and to produce a report outlining their findings and making some recommendations as to how services could be better promoted, targeted, co-ordinated and ultimately improved.� This report is the culmination of a series of meetings and workshops (from June to November 2010) where members considered all of the available information in the context of what they, and the organisations they represent, consider to be the gaps and areas which could be improved upon for PHA to consider when taking forward alcohol and drug work and services over the next 5-year period (i.e. 2011-2016).� The report takes a systematic approach to scoping and compiling evidence on: funding of drug and alcohol services; information and awareness-raising; education and prevention; treatment and support; services for vulnerable groups; workforce development; skilling up and supporting of communities; reducing availability; tackling substance related crime; and coordination and information sharing. Each section of the report ends with an analysis of the gaps and recommendations for action, with all of the recommendations presented in a tabular format in Section 13.

Stimulant drugs : Professional guidance

This guidance is aimed at professionals who come into contact with stimulant drug users through their work. This may include those in the community and voluntary sectors or in health and social care.

The effects of drugs, ions, and poly-l-lysine on the excretory system of Schistosoma mansoni

We have been able to label the excretory system of cercariae and all forms of schistosomula, immature and adult worms with the highly fluorescent dye resorufin. We have shown that the accumulation of the resorufin into the excretory tubules and collecting ducts of the male adult worm depends on the presence of extracellular calcium and phosphate ions. In the adult male worms, praziquantel (PZQ) prevents this accumulation in RPMI medium and disperses resorufin from tubules which have been prelabelled. Female worms and all other developmental stages are much less affected either by the presence of calcium and phosphate ions, or the disruption caused by PZQ. The male can inhibit the excretory system in paired female. Fluorescent PZQ localises in the posterior gut (intestine) region of the male adult worm, but not in the excretory system, except for the anionic carboxy fluorescein derivative of PZQ, which may be excreted by this route. All stages of the parasite can recover from damage by PZQ treatment in vitro. The excretory system is highly sensitive to damage to the surface membrane and may be involved in vesicle movement and damage repair processes. In vivo the adult parasite does not recover from PZQ treatment, but what is inhibiting recovery is unknown, but likely to be related to immune effector molecules.

New imidazolidinic bioisosters: potential candidates for antischistosomal drugs

The emergence of strains of Schistosoma resistant to praziquantel has drawn attention to the search for new schistosomacide drugs. Imidazolidinic derivatives have performed outstandingly against adult S. mansoni worms when evaluated in vitro. The molecular modification of imidazolidine by way of bioisosteric replacement gives rise to variations in its biological response. This study verifies the potential of substituent groups in the derivatives (Z)3-benzyl-5-(2-fluoro-benzylidene)-imidazolidine-2,4-dione NE4, 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin -2-ona PT5, 3-benzyl-5-(3-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-one JT53; 3-benzyl-1-methyl-5-(4-methyl-benzylidene)-2-thioxo-imidazolidin-4-one JT63; 3-benzyl-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo -imidazolidin-4-one JT68; 3-(4-chloro-benzyl)-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo-imidazolidin-4-one JT69; 3-(4-phenyl-benzyl)-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo-imidazolidin-4-one JT72 by determining the viability in vitro of adult S. mansoni worms in the presence of these derivatives. The susceptibility of the worms obtained from mice and kept in culture in the presence of different concentrations was determined by way of schistosomacide kinetic, observed every 24 h over a period of eight days. The results show that the worms were more sensitive to the PT5 derivative at a concentration of 58 µM which killed 100% of the worms after 24 h of contact, also giving rise to alterations in the tegument surface of the worms with the formation of bubbles and peeling. These observations suggest a strong electronic contribution of the arylazo grouping in the biological response.

Antimalarial drugs disrupt ion homeostasis in malarial parasites

Plasmodium chabaudi malaria parasite organelles are major elements for ion homeostasis and cellular signaling and also target for antimalarial drugs. By using confocal imaging of intraerythrocytic parasites we demonstrated that the dye acridine orange (AO) is accumulated into P. chabaudi subcellular compartments. The AO could be released from the parasite organelles by collapsing the pH gradient with the K+/H+ ionophore nigericin (20 µM), or by inhibiting the H+-pump with bafilomycin (4 µM). Similarly, in isolated parasites loaded with calcium indicator Fluo 3-AM, bafilomycin caused calcium mobilization of the acidic calcium pool that could also be release with nigericin. Interestingly after complete release of the acidic compartments, addition of thapsigargin at 10 µM was still effective in releasing parasite intracellular calcium stores in parasites at trophozoite stage. The addition of antimalarial drugs chloroquine and artemisinin resulted in AO release from acidic compartments and also affected maintenance of calcium in ER store by using different drug concentrations.

Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM), a highly invasive and vascular cancer, responds poorly to conventional cytotoxic therapy. Integrins, widely expressed in GBM and tumor vasculature, mediate cell survival, migration and angiogenesis. Cilengitide is a potent alphavbeta3 and alphavbeta5 integrin inhibitor. OBJECTIVE: To summarize the preclinical and clinical experience with cilengitide for GBM. METHODS: Preclinical studies and clinical trials evaluating cilengitide for GBM were reviewed. RESULTS/CONCLUSIONS: Cilengitide is active and synergizes with external beam radiotherapy in preclinical GBM models. In clinical trials for recurrent GBM, single-agent cilengitide has antitumor benefits and minimal toxicity. Among newly diagnosed GBM patients, single-arm studies incorporating cilengitide into standard external beam radiotherapy/temozolomide have shown encouraging activity with no increased toxicity and have led to a planned randomized Phase III trial.