HIV behavioural surveillance in Switzerland: trends in drug consumption, injection and syringe distribution, 1993-2011

Background: As part of the second generation surveillance system for HIV/Aids in Switzerland, repeated cross-sectional surveys were conducted in 1993, 1994, 1996, 2000, 2006 and 2011 among attenders of all low threshold facilities (LTFs) with needle exchange programmes and/or supervised drug consumption rooms for injection or inhalation. The number of syringes distributed to the injectors has also been measured annually since 2000. Distribution in other settings, such as pharmacies, is also monitored nationally. Methods: Periodic surveys of LTFs have been conducted using an interviewer/self-administered questionnaire structured along four themes: socio-demographic characteristics, drug consumption, risk/preventive behaviour and health. Analysis is restricted to attenders who had injected drugs during their lifetime (IDU´s). Pearson's chi-square test and trend analysis were conducted on annual aggregated data. Trend significance was assessed using Stata's non parametric test nptrend. Results: Median age of IDU´s increased from 26 years in 1993 to 40 in 2011; most are men (78%). Total yearly number of syringes distributed by LTFs has decreased by 44% in 10 years. Use of cocaine has increased (Table 1). Injection, regular use of heroin and borrowing of syringes/needles have decreased, while sharing of other material remains stable. There are fewer new injectors; more IDU´s report substitution treatment. Most attenders had ever been tested for HIV (90% in 1993, 94% in 2011). Reported prevalence of HIV remained stable around 10%; that of HCV decreased from 62% in 2000 to 42% in 2011. Conclusions: Overall, findings indicate a decrease in injection as a means of drug consumption in that population. This interpretation is supported by data from other sources, such as a national decrease in distribution from other delivery points. Switzerland's behavioural surveillance system is sustainable and allows the HIV epidemic to be monitored among this hard-to-reach population, providing information for planning and evaluation.

Impact of a computerized physician order entry system on compliance with prescription accuracy requirements.

OBJECTIVE: To assess the change in non-compliant items in prescription orders following the implementation of a computerized physician order entry (CPOE) system named PreDiMed. SETTING: The department of internal medicine (39 and 38 beds) in two regional hospitals in Canton Vaud, Switzerland. METHOD: The prescription lines in 100 pre- and 100 post-implementation patients' files were classified according to three modes of administration (medicines for oral or other non-parenteral uses; medicines administered parenterally or via nasogastric tube; pro re nata (PRN), as needed) and analyzed for a number of relevant variables constitutive of medical prescriptions. MAIN OUTCOME MEASURE: The monitored variables depended on the pharmaceutical category and included mainly name of medicine, pharmaceutical form, posology and route of administration, diluting solution, flow rate and identification of prescriber. RESULTS: In 2,099 prescription lines, the total number of non-compliant items was 2,265 before CPOE implementation, or 1.079 non-compliant items per line. Two-thirds of these were due to missing information, and the remaining third to incomplete information. In 2,074 prescription lines post-CPOE implementation, the number of non-compliant items had decreased to 221, or 0.107 non-compliant item per line, a dramatic 10-fold decrease (chi(2) = 4615; P < 10(-6)). Limitations of the computerized system were the risk for erroneous items in some non-prefilled fields and ambiguity due to a field with doses shown on commercial products. CONCLUSION: The deployment of PreDiMed in two departments of internal medicine has led to a major improvement in formal aspects of physicians' prescriptions. Some limitations of the first version of PreDiMed were unveiled and are being corrected.

Differentiated normalization and drug transitions among rural youth in Ireland.

Prevalence surveys in Ireland indicate an increased trend of youth drug use with rural areas reporting comparable drug availability and prevalence of use in urban settings (Currie, C., Nic Gabhainn, S., Godeau, E., Roberts, C., Smith, R., & Currie, D. (Eds.). (2008). Inequalities in young people's health: HBSC international report from the 2005/2006 survey. Copenhagen: WHO Regional Office for Europe). Few studies have explored the contexts and meaning of drug use on rural youth transitions in terms of increased drug prevalence, recent influx of rural drug activity, normative tolerance of recreational drug consumption and fragmentation of traditional rural communities. Qualitative interviews were conducted with 220 young people (15–17 years), and 78 service providers in a rural area of Ireland, in order to yield contextualized narratives of their experiences of drug use and achieve a wider exploration of processes, drug transitions and realities of rural youth. The thematic analysis of the research described varied pathways, attitudes and typologies of rural youth drug use, ranging from abstinent, recreational and moderated to maturing out. The research suggests support for a ‘differentiated’ normalization theory (Shildrick, T. (2002). Young people, illicit drug use and the question of normalisation theory. Journal of Youth Studies, 5, 35–48) in terms of consumerist and normative rural youth drug use transitions in their negotiation of risk within integrating rural and urban dichotomies. In conclusion, it is recommended that drug education programmes need to situate localized rural drug taking behaviours within a wider understanding of rural community life.This resource was contributed by The National Documentation Centre on Drug Use.

Health at a glance: Europe 2012.

This second edition of Health at a Glance: Europe presents a set of key indicators of health and health systems in 35 European countries, including the 27 European Union member states, 5 candidate countries and 3 EFTA countries. The selection of indicators is based largely on the European Community Health Indicators (ECHI) shortlist, a list of indicators that has been developed by the European Commission to guide the development and reporting of health statistics. It is complemented by additional indicators on health expenditure and quality of care, building on the OECD expertise in these areas. Contents: Introduction 12 Chapter 1. Health status 15 1.1. Life expectancy and healthy life expectancy at birth 1.2. Life expectancy and healthy life expectancy at age 65 1.3. Mortality from all causes 1.4. Mortality from heart disease and stroke 1.5. Mortality from cancer 1.6. Mortality from transport accidents 1.7. Suicide 1.8. Infant mortality 1.9. Infant health: Low birth weight 1.10. Self-reported health and disability 1.11. Incidence of selected communicable diseases 1.12. HIV/AIDS 1.13. Cancer incidence 1.14. Diabetes prevalence and incidence 1.15. Dementia prevalence 1.16. Asthma and COPD prevalence Chapter 2. Determinants of health 49 2.1. Smoking and alcohol consumption among children 2.2. Overweight and obesity among children 2.3. Fruit and vegetable consumption among children 2.4. Physical activity among children 2.5. Smoking among adults 2.6. Alcohol consumption among adults 2.7. Overweight and obesity among adults 2.8. Fruit and vegetable consumption among adults Chapter 3. Health care resources and activities 67 3.1. Medical doctors 3.2. Consultations with doctors 3.3. Nurses 3.4. Medical technologies: CT scanners and MRI units 3.5. Hospital beds 3.6. Hospital discharges 3.7. Average length of stay in hospitals 3.8. Cardiac procedures (coronary angioplasty) 3.9. Cataract surgeries 3.10. Hip and knee replacement 3.11. Pharmaceutical consumption 3.12. Unmet health care needs Chapter 4. Quality of care 93 Care for chronic conditions 4.1. Avoidable admissions: Respiratory diseases 4.2. Avoidable admissions: Uncontrolled diabetes Acute care 4.3. In-hospital mortality following acute myocardial infarction 4.4. In-hospital mortality following stroke Patient safety 4.5. Procedural or postoperative complications 4.6. Obstetric trauma Cancer care 4.7. Screening, survival and mortality for cervical cancer 4.8. Screening, survival and mortality for breast cancer 4.9. Screening, survival and mortality for colorectal cancer Care for communicable diseases 4.10. Childhood vaccination programmes 4.11. Influenza vaccination for older people Chapter 5. Health expenditure and financing 117 5.1. Coverage for health care 5.2. Health expenditure per capita 5.3. Health expenditure in relation to GDP 5.4. Health expenditure by function. 5.5. Pharmaceutical expenditure 5.6. Financing of health care 5.7. Trade in health services Bibliography 133 Annex A. Additional information on demographic and economic context 143 Most European countries have reduced tobacco consumption via public awareness campaigns, advertising bans and increased taxation. The percentage of adults who smoke daily is below 15% in Sweden and Iceland, from over 30% in 1980. At the other end of the scale, over 30% of adults in Greece smoke daily. Smoking rates continue to be high in Bulgaria, Ireland and Latvia (Figure 2.5.1). Alcohol consumption has also fallen in many European countries. Curbs on advertising, sales restrictions and taxation have all proven to be effective measures. Traditional wine-producing countries, such as France, Italy and Spain, have seen consumption per capita fall substantially since 1980. Alcohol consumption per adult rose significantly in a number of countries, including Cyprus, Finland and Ireland (Figure 2.6.1).This resource was contributed by The National Documentation Centre on Drug Use.

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Human immunodeficiency virus type 1 (HIV-1) genotyping in Rio de Janeiro, Brazil: assessing subtype and drug-resistance associated mutations in HIV-1 infected individuals failing highly active antiretroviral therapy

In order to assess the human immunodeficiency virus type 1 (HIV-1) drug resistance mutation profiles and evaluate the distribution of the genetic subtypes in the state of Rio de Janeiro, Brazil, blood samples from 547 HIV-1 infected patients failing antiretroviral (ARV) therapy, were collected during the years 2002 and 2003 to perform the viral resistance genotyping at the Renageno Laboratory from Rio de Janeiro (Oswaldo Cruz Foundation). Viral resistance genotyping was performed using ViroSeqTM Genotyping System (Celera Diagnostic-Abbott, US). The HIV-1 subtyping based on polymerase (pol) gene sequences (protease and reverse transcriptase-RT regions) was as follows: subtype B (91.2%), subtype F (4.9%), and B/F viral recombinant forms (3.3%). The subtype C was identified in two patients (0.4%) and the recombinant CRF_02/AG virus was found infecting one patient (0.2%). The HIV-1 genotyping profile associated to the reverse transcriptase inhibitors has shown a high frequency of the M184V mutation followed by the timidine-associated mutations. The K103N mutation was the most prevalent to the non-nucleoside RT inhibitor and the resistance associated to protease inhibitor showed the minor mutations L63P, L10F/R, and A71V as the more prevalent. A large proportion of subtype B was observed in HIV-1 treated patients from Rio de Janeiro. In addition, we have identified the circulation of drug-resistant HIV-1 subtype C and are presenting the first report of the occurrence of an African recombinant CRF_02/AG virus in Rio de Janeiro, Brazil. A clear association between HIV-1 subtypes and protease resistance mutations was observed in this study. The maintenance of resistance genotyping programs for HIV-1 failing patients is important to the management of ARV therapies and to attempt and monitor the HIV-1 subtype prevalence in Brazil.

Interest of qualitative and quantitative profiling of endocannabinoids for evaluation of their implication in drug addiction process

Introduction: In the middle of the 90's, the discovery of endogenous ligands for cannabinoid receptors opened a new era in this research field. Amides and esters of arachidonic acid have been identified as these endogenous ligands. Arachidonoylethanolamide (anandamide or AEA) and 2-Arachidonoylglycerol (2-AG) seem to be the most important of these lipid messengers. In addition, virodhamine (VA), noladin ether (2-AGE), and N-arachidonoyl dopamine (NADA) have been shown to bind to CB receptors with varying affinities. During recent years, it has become more evident that the EC system is part of fundamental regulatory mechanisms in many physiological processes such as stress and anxiety responses, depression, anorexia and bulimia, schizophrenia disorders, neuroprotection, Parkinson disease, anti-proliferative effects on cancer cells, drug addiction, and atherosclerosis. Aims: This work presents the problematic of EC analysis and the input of Information Dependant Acquisition based on hybrid triple quadrupole linear ion trap (QqQLIT) system for the profiling of these lipid mediators. Methods: The method was developed on a LC Ultimate 3000 series (Dionex, Sunnyvale, CA, USA) coupled to a QTrap 4000 system (Applied biosystems, Concord, ON, Canada). The ECs were separated on an XTerra C18 MS column (50 × 3.0 mm i.d., 3.5 μm) with a 5 min gradient elution. For confirmatory analysis, an information-dependant acquisition experiment was performed with selected reaction monitoring (SRM) as survey scan and enhanced produced ion (EPI) as dependant scan. Results: The assay was found to be linear in the concentration range of 0.1-5 ng/mL for AEA, 0.3-5 ng/mL for VA, 2-AGE, and NADA and 1-20 ng/mL for 2-AG using 0.5 mL of plasma. Repeatability and intermediate precision were found less than 15% over the tested concentration ranges. Under non-pathophysiological conditions, only AEA and 2-AG were actually detected in plasma with concentration ranges going from 104 to 537 pg/mL and from 2160 to 3990 pg/mL respectively. We have particularly focused our scopes on the evaluation of EC level changes in biological matrices through drug addiction and atherosclerosis processes. We will present preliminary data obtained during pilot study after administration of cannabis on human patients. Conclusion: ECs have been shown to play a key role in regulation of many pathophysiological processes. Medical research in these different fields continues to growth in order to understand and to highlight the predominant role of EC in the CNS and peripheral tissues signalisation. The profiling of these lipids needs to develop rapid, highly sensitive and selective analytical methods.

Les combinaisons fixes de medicaments antihypertenseurs. [Fixed antihypertensive drug combinations]

Arterial hypertension is a highly heterogeneous condition. It is therefore not surprising that blood pressure lowering agents acting via a given mechanism allow a normalization of blood pressure in a fraction of hypertensive subjects only. The combination of drugs with different mechanisms of action on the cardiovascular system results in a considerably higher antihypertensive efficacy, not only with regard to the absolute blood pressure reduction but also in the number of responders. This effect is not achieved at the expenses of tolerance, because usually lower doses of the combined agents are sufficient to achieve the target blood pressure. The administration of antihypertensive agents in fixed combination has the advantage of its simplicity for both the physician as well as the patient. This aspect also explains the increasing popularity of fixed combinations as a valuable option in the initial treatment of the hypertensive patient.

Species differences in the response of liver drug-metabolizing enzymes to (S)-4-O-tolylsulfanyl-2-(4-trifluormethyl-phenoxy)-butyric acid (EMD 392949) in vivo and in vitro.

Induction of drug-metabolizing enzymes (DMEs) is highly species-specific and can lead to drug-drug interaction and toxicities. In this series of studies we tested the species specificity of the antidiabetic drug development candidate and mixed peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist (S)-4-O-tolylsulfanyl-2-(4-trifluormethyl-phenoxy)-butyric acid (EMD 392949, EMD) with regard to the induction of gene expression and activities of DMEs, their regulators, and typical PPAR target genes. EMD clearly induced PPARalpha target genes in rats in vivo and in rat hepatocytes but lacked significant induction of DMEs, except for cytochrome P450 (P450) 4A. CYP2C and CYP3A were consistently induced in livers of EMD-treated monkeys. Interestingly, classic rodent peroxisomal proliferation markers were induced in monkeys after 17 weeks but not after a 4-week treatment, a fact also observed in human hepatocytes after 72 h but not 24 h of EMD treatment. In human hepatocyte cultures, EMD showed similar gene expression profiles and induction of P450 activities as in monkeys, indicating that the monkey is predictive for human P450 induction by EMD. In addition, EMD induced a similar gene expression pattern as the PPARalpha agonist fenofibrate in primary rat and human hepatocyte cultures. In conclusion, these data showed an excellent correlation of in vivo data on DME gene expression and activity levels with results generated in hepatocyte monolayer cultures, enabling a solid estimation of human P450 induction. This study also clearly highlighted major differences between primates and rodents in the regulation of major inducible P450s, with evidence of CYP3A and CYP2C inducibility by PPARalpha agonists in monkeys and humans.

The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53-Independent Manner in Colon and Breast Cancer Cells

The chemotherapeutic drug 5-FU is widely used in the treatment of a range of cancers, but resistance to the drug remains a major clinical problem. Since defects in the mediators of apoptosis may account for chemo-resistance, the identification of new targets involved in 5-FU-induced apoptosis is of main clinical interest. We have identified the ds-RNA-dependent protein kinase (PKR)as a key molecular target of 5-FU involved in apoptosis induction in human colon and breast cancer cell lines. PKR distribution and activation, apoptosis induction and cytotoxic effects were analyzed during 5-FU and 5-FU/IFNalpha treatment in several colon and breast cancer cell lines with different p53 status. PKR protein was activated by 5-FU treatment in a p53-independent manner,inducing phosphorylation of the protein synthesis translation initiation factor eIF-2alpha and cell death by apoptosis. Furthermore, PKR interference promoted a decreased response to 5-FU treatment and those cells were not affected by the synergistic antitumor activity of 5-FU/IFNalpha combination. These results, taken together, provide evidence that PKR is a key molecular target of 5-FU with potential relevance in the clinical use of this drug.

Randomized trial of pacemaker and lead system for safe scanning at 1.5 Tesla.

BACKGROUND: Magnetic resonance imaging (MRI) of pacemakers is a relative contraindication because of the risks to the patient from potentially hazardous interactions between the MRI and the pacemaker system. Chest scans (ie, cardiac magnetic resonance scans) are of particular importance and higher risk. The previously Food and Drug Administration-approved magnetic resonance conditional system includes positioning restrictions, limiting the powerful utility of MRI. OBJECTIVE: To confirm the safety and effectiveness of a pacemaker system designed for safe whole body MRI without MRI scan positioning restrictions. METHODS: Primary eligibility criteria included standard dual-chamber pacing indications. Patients (n = 263) were randomized in a 2:1 ratio to undergo 16 chest and head scans at 1.5 T between 9 and 12 weeks postimplant (n = 177) or to not undergo MRI (n = 86) post-implant. Evaluation of the pacemaker system occurred immediately before, during (monitoring), and after MRI, 1-week post-MRI, and 1-month post-MRI, and similarly for controls. Primary end points measured the MRI-related complication-free rate for safety and compared pacing capture threshold between MRI and control subjects for effectiveness. RESULTS: There were no MRI-related complications during or after MRI in subjects undergoing MRI (n = 148). Differences in pacing capture threshold values from pre-MRI to 1-month post-MRI were minimal and similar between the MRI and control groups. CONCLUSIONS: This randomized trial demonstrates that the Advisa MRI pulse generator and CapSureFix MRI 5086MRI lead system is safe and effective in the 1.5 T MRI environment without positioning restrictions for MRI scans or limitations of body parts scanned.

Improvement in secondary hyperparathyroidism due to drug adherence monitoring in dialysis patients.

BACKGROUND: Poor medication adherence is a frequent cause of treatment failure but is difficult to diagnose. In this study we have evaluated the impact of measuring adherence to cinacalcet-HCl and phosphate binders in dialysis patients with uncontrolled secondary hyperparathyroidism. METHODS: 7 chronic dialysis patients with iPTH-levels >= 300 pg/ml despite treatment with >= 60 mg cinacalcet-HCl were included. Medication adherence was measured using the "Medication Events Monitoring System" during 3 months, followed by another 3-month period without monitoring. The adherence results were monthly discussed with the patients, as well as strategies to improve them. RESULTS: During monitoring, the percentage of prescribed doses taken was higher for cinacalcet-HCl (87.4%) and sevelamer (86.3%) than for calcium acetate (76.1%), as was the taking adherence (81.9% vs. 57.3% vs. 49.1%) but not the percentage of drug holidays (12.3% vs. 4.5% vs. 3.6%). Mean PO4 levels (from 2.24 +/- 0.6 mmol/l to 1.73 +/- 0.41 mmol/l; p = 0.14) and Ca++ x PO4 product (4.73 +/- 1.43 to 3.41 +/- 1.04 mmol2/l2; p = 0.12) improved and iPTH-level improved significantly from 916 +/- 618 pg/ml to 442 +/- 326 pg/ml (p = 0.04), without any change in medication. However, as drug monitoring was interrupted, all laboratory parameters worsened again. CONCLUSIONS: Assessment of drug adherence helped to document episodes of non-compliance and helped to avoid seemingly necessary dose increases.

A new rating scale to evaluate the potential benefit of therapeutic drug monitoring

Aims: Therapeutic Drug Monitoring (TDM) is an established tool to optimize thepharmacotherapy with immunosupressants, antibiotics, antiretroviral agents, anticonvulsantsand psychotropic drugs. The TDM expert group of the Association ofNeuropsychopharmacolgy and Pharmacopsychiatry recommended clinical guidelinesfor TDM of psychotropic drugs in 2004 and in 2011. They allocate 4 levelsof recommendation based on studies reporting plasma concentrations and clinicaloutcomes. To evaluate the additional benefit for drugs without direct evidence forTDM and to verify the recommendation levels of the expert group the authorsbuilt a new rating scale. Methods: This rating scale included 28 items and wasdivided in 5 categories: Efficacy, toxicity, pharmacokinetics, patient characteristicsand cost effectiveness. A literature search was performed for 10 antidepressants,10 antipsychotics, 8 drugs used in the treatment of substance related disordersand lithium, thereafter, a comparison with the assessment of the TDMexpert group was carried out. Results: The antidepressants as well as the antipsychoticsshowed a high and significant correlation with the recommendations inthe consensus guidelines. However, meanderings could be detected for the drugsused in the therapy of substance related disorders, for which TDM is mostly notestablished yet. The result of the antidepressants and antipsychotics permits aclassification of the reachable points; upper 13 - TDM strongly recommended10 to 13 - TDM recommended, 8 to 10 - TDM useful and below 8 - TDMpotentially useful. Conclusion: These results suggest this rating scale is sensitiveto detect the appropriateness of TDM for drug treatment. For those drugs TDM isnot established a more objective estimation is possible, thus the scoring helps tofocus on the most likely drugs to require TDM.

Drugs Associated with Hepatotoxicity and their Reporting Frequency of Liver Adverse Events in VigiBase (TM) Unified List Based on International Collaborative Work

BACKGROUND Challenges exist in the clinical diagnosis of drug-induced liver injury (DILI) and in obtaining information on hepatotoxicity in humans. OBJECTIVE (i) To develop a unified list that combines drugs incriminated in well vetted or adjudicated DILI cases from many recognized sources and drugs that have been subjected to serious regulatory actions due to hepatotoxicity; and (ii) to supplement the drug list with data on reporting frequencies of liver events in the WHO individual case safety report database (VigiBase). DATA SOURCES AND EXTRACTION (i) Drugs identified as causes of DILI at three major DILI registries; (ii) drugs identified as causes of drug-induced acute liver failure (ALF) in six different data sources, including major ALF registries and previously published ALF studies; and (iii) drugs identified as being subjected to serious governmental regulatory actions due to their hepatotoxicity in Europe or the US were collected. The reporting frequency of adverse events was determined using VigiBase, computed as Empirical Bayes Geometric Mean (EBGM) with 90% confidence interval for two customized terms, 'overall liver injury' and 'ALF'. EBGM of >or=2 was considered a disproportional increase in reporting frequency. The identified drugs were then characterized in terms of regional divergence, published case reports, serious regulatory actions, and reporting frequency of 'overall liver injury' and 'ALF' calculated from VigiBase. DATA SYNTHESIS After excluding herbs, supplements and alternative medicines, a total of 385 individual drugs were identified; 319 drugs were identified in the three DILI registries, 107 from the six ALF registries (or studies) and 47 drugs that were subjected to suspension or withdrawal in the US or Europe due to their hepatotoxicity. The identified drugs varied significantly between Spain, the US and Sweden. Of the 319 drugs identified in the DILI registries of adjudicated cases, 93.4% were found in published case reports, 1.9% were suspended or withdrawn due to hepatotoxicity and 25.7% were also identified in the ALF registries/studies. In VigiBase, 30.4% of the 319 drugs were associated with disproportionally higher reporting frequency of 'overall liver injury' and 83.1% were associated with at least one reported case of ALF. CONCLUSIONS This newly developed list of drugs associated with hepatotoxicity and the multifaceted analysis on hepatotoxicity will aid in causality assessment and clinical diagnosis of DILI and will provide a basis for further characterization of hepatotoxicity.