Marica Ferri

Hepatitis C Virus Infection Epidemiology among People Who Inject Drugs in Europe: A Systematic Review of Data for Scaling Up Treatment and Prevention

Background People who inject drugs (PWID) are a key population affected by hepatitis C virus (HCV). Treatment options are improving and may enhance prevention; however access for PWID may be poor. The availability in the literature of information on seven main topic areas (incidence, chronicity, genotypes, HIV co-infection, diagnosis and treatment uptake, and burden of disease) to guide HCV treatment and prevention scale-up for PWID in the 27 countries of the European Union is systematically reviewed. Methods and Findings We searched MEDLINE, EMBASE and Cochrane Library for publications between 1 January 2000 and 31 December 2012, with a search strategy of general keywords regarding viral hepatitis, substance abuse and geographic scope, as well as topic-specific keywords. Additional articles were found through structured email consultations with a large European expert network. Data availability was highly variable and important limitations existed in comparability and representativeness. Nine of 27 countries had data on HCV incidence among PWID, which was often high (2.7-66/100 person-years, median 13, Interquartile range (IQR) 8.7–28). Most common HCV genotypes were G1 and G3; however, G4 may be increasing, while the proportion of traditionally ‘difficult to treat’ genotypes (G1+G4) showed large variation (median 53, IQR 43–62). Twelve countries reported on HCV chronicity (median 72, IQR 64–81) and 22 on HIV prevalence in HCV-infected PWID (median 3.9%, IQR 0.2–28). Undiagnosed infection, assessed in five countries, was high (median 49%, IQR 38–64), while of those diagnosed, the proportion entering treatment was low (median 9.5%, IQR 3.5–15). Burden of disease, where assessed, was high and will rise in the next decade. Conclusion Key data on HCV epidemiology, care and disease burden among PWID in Europe are sparse but suggest many undiagnosed infections and poor treatment uptake. Stronger efforts are needed to improve data availability to guide an increase in HCV treatment among PWID.

Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies

Objective To compare the risk for all cause and overdose mortality in people with opioid dependence during and after substitution treatment with methadone or buprenorphine and to characterise trends in risk of mortality after initiation and cessation of treatment. Design Systematic review and meta-analysis. Data sources Medline, Embase, PsycINFO, and LILACS to September 2016. Study selection Prospective or retrospective cohort studies in people with opioid dependence that reported deaths from all causes or overdose during follow-up periods in and out of opioid substitution treatment with methadone or buprenorphine. Data extraction and synthesis Two independent reviewers performed data extraction and assessed study quality. Mortality rates in and out of treatment were jointly combined across methadone or buprenorphine cohorts by using multivariate random effects meta-analysis. Results There were 19 eligible cohorts, following 122 885 people treated with methadone over 1.3-13.9 years and 15 831 people treated with buprenorphine over 1.1-4.5 years. Pooled all cause mortality rates were 11.3 and 36.1 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% confidence interval 2.65 to 3.86) and reduced to 4.3 and 9.5 in and out of buprenorphine treatment (2.20, 1.34 to 3.61). In pooled trend analysis, all cause mortality dropped sharply over the first four weeks of methadone treatment and decreased gradually two weeks after leaving treatment. All cause mortality remained stable during induction and remaining time on buprenorphine treatment. Overdose mortality evolved similarly, with pooled overdose mortality rates of 2.6 and 12.7 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) and 1.4 and 4.6 in and out of buprenorphine treatment. Conclusions Retention in methadone and buprenorphine treatment is associated with substantial reductions in the risk for all cause and overdose mortality in people dependent on opioids. The induction phase onto methadone treatment and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies to mitigate such risk. These findings are potentially important, but further research must be conducted to properly account for potential confounding and selection bias in comparisons of mortality risk between opioid substitution treatments, as well as throughout periods in and out of each treatment.

An emergency clinical pathway for stroke patients – results of a cluster randomised trial (isrctn41456865)

BackgroundEmergency Clinical Pathways (ECP) for stroke have never been tested in randomized controlled trials (RCTs).ObjectiveTo evaluate the effectiveness of an ECP for stroke patients in Latium (Italy) emergency system.Methodscluster-RCT designed to compare stroke patient referrals by Emergency Medical Service (EMS) and Emergency Room (ER) health professionals trained in the ECP, with those of non-trained EMS and ER controls. Primary outcome measure was the proportion of eligible (aged ≤ 80 and symptom onset ≤ 6 hours) stroke patients referred to a stroke unit (SU). Intention to treat (ITT) and per-protocol (PP) analyses were performed, and risk ratios (RR) adjusted by age, gender and area, were calculated.Results2656 patients in the intervention arm and 2239 in the control arm required assistance; 78.3% of the former and 80.6% of the latter were admitted to hospitals, and respectively 74.8% and 78.3% were confirmed strokes. Of the eligible confirmed strokes, 106/434 (24.4%) in the intervention arm and 43/328 (13.1%) in the control arm were referred to the SU in the ITT analysis (RR = 2.01; 95% CI: 0.79–4.00), and respectively 105/243 (43.2%) and 43/311 (13.8%) in the PP analysis (RR = 3.21; 95%CI: 1.62–4.98). Of patients suitable for i.v. thrombolysis, 15/175 (8.6%) in the intervention arm and 2/115 (1.7%) in the control arm received thrombolysis (p = 0.02) in the ITT analysis, and respectively 15/99 (15.1%) and 2/107 (1.9%)(p = 0.001) in the PP analysis.ConclusionOur data suggest potenti efficiency and feasibility of an ECP. The integration of EMS and ERs with SU networks for organised acute stroke care is feasible and may ameliorate the quality of care for stroke patients.Trial registrationCurrent Controlled Trials (ISRCTN41456865).

Visual servoing with exploitation of redundancy: An experimental study

Within the standard IBVS framework for control of generic robotic systems, a suitable exploitation of redundancy w.r.t. the given visual task can significantly improve the overall task execution. Indeed, redundancy can be used to avoid occlusions, joint limits, or to realize tasks that would be ill-conditioned if addressed altogether. In this respect, we propose an experimental evaluation of the performance of two redundancy resolution schemes, namely Task Priority and Task Sequencing, when adopted to realize IBVS tasks on a mobile robot equipped with a pan-tilt camera onboard.

New psychoactive substances: Current health-related practices and challenges in responding to use and harms in Europe

BACKGROUND The availability of new psychoactive substances (NPS) in Europe has rapidly increased over the last decade. Although prevalence levels of NPS use remain low in the general European population, there are serious concerns associated with more problematic forms of use and harms in particular populations and settings. It has thus become a priority to formulate and implement effective public health responses. However, considerable knowledge gaps remain on current practices as well as on the challenges and needs of European health professionals who are responding to use and harms caused by these substances. The aim of this study was to explore current health responses to NPS, and highlight key issues in order to inform planning and implementation of adequate responses. METHODS This scoping study was based on a targeted multi-source data collection exercise focusing on the provision of health and drug interventions associated with NPS use and harms, in selected intervention settings across Europe. RESULTS Findings revealed that in the absence of specific evidence, health professionals across most intervention settings rely primarily on acquired expertise with traditional drugs when addressing NPS-related harms. This study also identified a gap in the availability and access to timely and reliable information on NPS to users and health professionals. Health professionals in sexual health settings and custodial settings in contact with certain risk groups reported particular challenges in responding to NPS-related harms. CONCLUSION Immediate investments are required in expanding substance identification capabilities, competence building among professionals and dissemination of risk information among relevant stakeholders. The risks of neglecting under-served risk populations and failure to address the information needs of health professionals and users on NPS harms in a context of rapid changing drug markets in Europe may have unforeseeable consequences at societal level.

Are mass-media campaigns effective in preventing drug use? A Cochrane systematic review and meta-analysis

Objective To determine whether there is evidence that mass-media campaigns can be effective in reducing illicit drug consumption and the intent to consume. Design Systematic review of randomised and non-randomised studies. Methods We searched four electronic databases (MEDLINE, EMBASE, ProQuest Dissertations & Theses A&I and CENTRAL) and further explored seven additional resources to obtain both published and unpublished materials. We appraised the quality of included studies using standardised tools. We carried out meta-analyses of randomised controlled trials and a pooled analysis of interrupted time-series and controlled before-and-after studies. Results We identified 19 studies comprising 184 811 participants. Pooled analyses and narrative synthesis provided mixed evidence of effectiveness. Eight interventions evaluated with randomised controlled trials leaned towards no evidence of an effect, both on drug use (standardised mean difference (SMD) −0.02; 95% CI −0.15 to 0.12) and the intention to use drugs (SMD −0.07; 95% CI −0.19 to 0.04). Four campaigns provided some evidence of beneficial effects in preventing drug use and two interventions provided evidence of iatrogenic effects. Conclusions Studies were considerably heterogeneous in type of mass-media intervention, outcome measures, underlying theory, comparison groups and design. Such factors can contribute to explaining the observed variability in results. Owing to the risk of adverse effects, caution is needed in disseminating mass-media campaigns tackling drug use. Large studies conducted with appropriate methodology are warranted to consolidate the evidence base.

Roundtable discussion: how lessons learned from HIV can inform the global response to viral hepatitis

IntroductionBy Jeffrey V Lazarus.In the last few years, as viral hepatitis has become amore prominent issue on national and internationalhealth agendas, talk of“learning from HIV” has becomequite common. It is understandable for researchers, pol-icy-makers and activists to make this link, given the nota-ble commonalities between HIV, hepatitis B and hepatitisC. All are life-threatening blood-borne viruses that affecthundreds of millions of people worldwide. All can remainasymptomatic for many years, making it difficult to pro-mote awareness of their danger. Ignorance about all ofthe major forms of viral hepatitis, particularly B and C,understandably reminds many people who are workingto confront this issue of the early years of the AIDS epi-demic, when a combination of misinformation andunwillingness to candidly address stigmatised behavioursand social inequalities led to a widespread failure to for-mulate a cohesive public health response.Other parallels might be elucidated, and there is cer-tainly good reason to think of the global HIV, hepatitisB and hepatitis C epidemics as having similar trajectoriesin some regards. Nonetheless, the differences betweenHIV and viral hepatitis– in terms of how these varieddiseases manifest both biologically and socially– shouldmake us wary of oversimplifying the connection.As discussions about hepatitis policies and strategiesgain momentum at the national and global level, it isbecoming increasingly important to articulate the“lessons learned” from the HIV field. Pertinent issuesinclude disease preventionmeasures, testing and earlydiagnosis, the scale-up of treatment, and barriers to ser-vice uptake and retention in care. Key social and politicalfactors associated with viral hepatitis call to mind otherpossible lessons relating to the value of civil societyengagement, leadership and governance issues, resourcemobilization including innovative financing, the causesand consequences of stigma, and the role of socialscience in addressing health threats.This is clearly a rich and important realm of inquiry–and it is time to move beyond the general calls to learnfrom HIV and begin to systematically formulate specificlessons. As a preliminary step, the following roundtablepresents the insights of a range of experts who were invitedto reflect on how experiences from the global response toHIV might inform the global response to viral hepatitis.Kicking off the discussion is Jens Lundgren, a renownedHIV researcher, head of the new WHO CollaboratingCentre on HIV and Viral Hepatitis and co-founder of theHIV in Europe Initiative. His perspective is much broaderthan that of a medical doctor gazing at his own disease. Inthe next two pieces, Jordi Casabona of the EpidemiologicalCenter for HIV/AIDS/STI of Catalonia and Lucas Wies-sing of the European Monitoring Centre for Drugs andDrug Addiction (and colleagues) consider surveillance andmonitoring issues. Sounding a cautionary note about the“discourse of hope and expectation” associated with hepa-titis C treatment, Magdalena Harris, a qualitativeresearcher at the London School of Hygiene and TropicalMedicine, critically reflects on treatment as prevention.

Does a pre-hospital emergency pathway improve early diagnosis and referral in suspected stroke patients? – Study protocol of a cluster randomised trial [ISRCTN41456865]

BackgroundEarly interventions proved to be able to improve prognosis in acute stroke patients. Prompt identification of symptoms, organised timely and efficient transportation towards appropriate facilities, become essential part of effective treatment. The implementation of an evidence based pre-hospital stroke care pathway may be a method for achieving the organizational standards required to grant appropriate care. We performed a systematic search for studies evaluating the effect of pre-hospital and emergency interventions for suspected stroke patients and we found that there seems to be only a few studies on the emergency field and none about implementation of clinical pathways.We will test the hypothesis that the adoption of emergency clinical pathway improves early diagnosis and referral in suspected stroke patients. We designed a cluster randomised controlled trial (C-RCT), the most powerful study design to assess the impact of complex interventions. The study was registered in the Current Controlled Trials Register: ISRCTN41456865 – Implementation of pre-hospital emergency pathway for stroke – a cluster randomised trial.Methods/designTwo-arm cluster-randomised trial (C-RCT). 16 emergency services and 14 emergency rooms were randomised either to arm 1 (comprising a training module and administration of the guideline), or to arm 2 (no intervention, current practice). Arm 1 participants (152 physicians, 280 nurses, 50 drivers) attended an interactive two sessions course with continuous medical education CME credits on the contents of the clinical pathway. We estimated that around 750 patients will be met by the services in the 6 months of observation. This duration allows recruiting a sample of patients sufficient to observe a 30% improvement in the proportion of appropriate diagnoses.Data collection will be performed using current information systems. Process outcomes will be measured at the cluster level six months after the intervention. We will assess the guideline recommendations for emergency and pre-hospital stroke management relative to: 1) promptness of interventions for hyperacute ischaemic stroke; 2) promptness of interventions for hyperacute haemorrhagic stroke 3) appropriate diagnosis. Outcomes will be expressed as proportions of patients with a positive CT for ischaemic stroke and symptoms onset <= 6 hour admitted to the stroke unit.DiscussionThe fields in which this trial will play are usually neglected by Randomised Controlled Trial (RCT). We have chosen the Cluster-randomised Controlled Trial (C-RCT) to address the issues of contamination, adherence to real practice, and community dimension of the intervention, with a complex definition of clusters and an extensive use of routine data to collect the outcomes.

El portal de promoción de buenas prácticas en Europa del OEDT. Un instrumento de diseminación vía Internet

Best practice is the best application of available evidence to current activities in the drugs field. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) created a web-based tool aimed at bridging together scientific evidence and current practices in the drug addiction field. Beyond dissemination of evidence, the scope is to share best practice among the European countries. The synthesis of the evidence is based on the methods of the Cochrane collaboration (the Drugs and Alcohol Group) and the Grade working group. As of February 2013 the portal encompasses four modules on the effectiveness of demand reduction interventions, a collection of European projects on prevention, treatment, harm reduction and social reintegration and an inventory of European Guidelines and Standards including a bank of instruments to evaluate interventions (http://www.emcdda.europa.eu/bestpractice). The summaries of evidence are presented in a plain language format and include brief explanation of the measures of effect supporting the evidence, but do not provide specific recommendations. The main future challenge of EMCDDAs best practice promotion is to become a service for those willing to implement best practice. The Best Practice Portal should become a platform where to find all is needed for successful implementation (handbooks, training materials, guidelines for evaluation and contacts for mentoring).

What is needed in future drug treatment research? A systematic approach to identify gaps on effectiveness of drug treatment from the EMCDDA.

Abstract There is a perceived global need to bridge the existing gap between researchers and other stakeholders to make research more helpful and to realign “the mismatch between what clinical researchers do and what patients need”. The EMCDDA carried out a pilot analysis to explore the gaps in research on treatment for drug dependence as indicated by systematic reviewers of studies on effectiveness of interventions together with a stakeholder’s consultation to ensure a broader participation in the definition of research needs. The rough comparisons of the gaps identified by the researchers in the reviews and those suggested by the stakeholders reflect their different perception of research. The reviewers focus on the quality of studies and on how this may impair reaching conclusive evidence, while the stakeholders are more concerned by the management of effective interventions and by the needs of specific patients. With this exercise, the EMCDDA wants to contribute to the broader debate on how to translate evidence into action and it offers a possible way to support decision makers to set the health research agenda.