The combined effect of surgeon and hospital volume on health outcomes: a systematic review.

OBJECTIVES: To explore the interaction between surgeon volumes (SVs) and hospital volumes (HVs) on health outcomes. MATERIALS AND METHODS: We searched MEDLINE, Embase, CINAHL, Web of Science as of May 2017. We included studies investigating the interaction between high or low SVs operating in high or low HVs. Review process follows the PRISMA guidelines. We assessed the methodological quality of the included studies using validated critical appraisal checklists. RESULTS: Sixteen studies were included. Due to the heterogeneity of studies, it was not possible to perform a quantitative analysis. Heath outcome are worse when high SV operating in low HV vs high HV, for the majority of the conditions (colorectal cancer, cystectomy, liver resection, mitral valve surgery, pancreatico-duodenectomy). Results for low SV are better when operating in high HV vs low HV for patients undergoing pancreatic-duodenectomy for mortality, 30 days complications and length of stay. Results for low SV are worse vs high SV when operating in high HV for most considered conditions. Results were in favour of higher SV vs low SV when operating in low HV for digital replantation success after injuries, 30 days mortality and complications after pancreatic-duodenectomy. CONCLUSIONS: The available evidence is limited. It is necessary to increase the monitoring of the association between surgeons volumes and hospitals volumes in which they operate, to ensure fairness and accuracy of care for better health outcomes.

miR-194-5p/BCLAF1 deregulation in AML tumorigenesis.

This corrects the article DOI: 10.1038/leu.2017.64.

Imaging of underground cavities with cosmic-ray muons from observations at Mt. Echia (Naples).

Muography is an imaging technique based on the measurement of absorption profiles for muons as they pass through rocks and earth. Muons are produced in the interactions of high-energy cosmic rays in the Earth's atmosphere. The technique is conceptually similar to usual X-ray radiography, but with extended capabilities of investigating over much larger thicknesses of matter thanks to the penetrating power of high-energy muons. Over the centuries a complex system of cavities has been excavated in the yellow tuff of Mt. Echia, the site of the earliest settlement of the city of Naples in the 8th century BC. A new generation muon detector designed by us, was installed under a total rock overburden of about 40 metres. A 26 days pilot run provided about 14 millions of muon events. A comparison of the measured and expected muon fluxes improved the knowledge of the average rock density. The observation of known cavities proved the validity of the muographic technique. Hints on the existence of a so far unknown cavity was obtained. The success of the investigation reported here demonstrates the substantial progress of muography in underground imaging and is likely to open new avenues for its widespread utilisation.

miR-194-5p/BCLAF1 deregulation in AML tumorigenesis.

Deregulation of epigenetic mechanisms, including microRNA, contributes to leukemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal hematopoietic progenitors. In acute myeloid leukemias this balance is perturbed, locking cells into an immature, potentially 'immortal' state. Enhanced expression of miR-194-5p by treatment with the histone deacetylase inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol. miR-194-5p/BCLAF1 balance was found commonly deregulated in 60 primary acute myeloid leukemia patients and was largely restored by ex vivo SAHA treatment. Our findings link treatment responsiveness to re-instatement of miR-194-5p/BCLAF1 balance.

Factors Predicting Patient's Allocation to Short- and Long-Term Therapeutic Community Treatments in the Italian VOECT Cohort Study.

The Evaluation of Therapeutic Community Treatments and Outcomes (VOECT) study was conducted in 131 Italian Therapeutic Communities (TCs) in 2008/2009. All of the patients entering residential treatment for drug or alcohol dependence were invited to participate. Data regarding patient socio-demographic characteristics, drug and alcohol consumption, health and psychopathological status, prior treatments and outcomes, and their motivation score were collected upon enrolment onto the study. The aim of this work was to identify the factors associated with allocation to short- versus long-term programmes in drug or alcohol dependent patients entering TCs in Italy. Of the 2470 patients included in the analysis, 30.8% were allocated to short-term treatment and 69.2% to long-term treatment. Several factors were significantly associated with the allocation to short- and long-term treatments: unstable living conditions; entering the TC when not detoxified; a high Symptom Checklist-90 somatization score; prior cessation episodes; previous in-patient detoxification treatments; psychosocial treatments; entering the TC by oneself; and a low motivation score.

Modernizing methodology for the WHO assessment of substances for the international drug control conventions.

BACKGROUND: The WHO Executive Board revised the guidance that governs the procedures for the WHO review of psychoactive substances for international drug control in 2010. To meet the standards defined in these guidelines, the current evaluation methodology at WHO must be an evidence-based assessment. METHODS: We describe the history of substance evaluation from 1912 to the present and the development of the evaluation methods over time including a description of the current assessment system, using reports from WHO and its predecessor, the League of Nations. Furthermore, we describe the current review system. RESULTS: We found that some substances under international control were never reviewed; other substances were reviewed decades ago. CONCLUSIONS: We argue that assessments do not have unlimited validity, and therefore, substances need to be re-assessed periodically, as already recommended by the Expert Committee on Drug Dependence in 1982. We propose that the evaluation time be shortened; that the influence of the route of administration and/or dosage form of the preparation is considered in the evaluation; and we recommend studying national and regional assessment systems and adopting their best practices. With this article, we make a case for the inclusion of systematic review and other methods of comprehensive analysis of substance evaluation to arrive at a process of equal rigour and quality as already applied by WHO for the development of treatment guidelines.

Natalizumab is effective in multiple sclerosis patients switching from other disease modifying therapies in clinical practice.

Natalizumab is one option for multiple sclerosis patients responding poorly to classical immunomodulators, but pilot studies did not point to its effectiveness as a second-line therapy. Aim of this study was to assess the efficacy of natalizumab as second-line therapy in patients switching from disease modifying therapies (DMTs) in a clinical setting. We retrospectively selected patients who had been treated with natalizumab for at least 12 months after switching from one or more DMTs. We collected clinical and neuroradiological data and we analysed the reduction in annualised relapse rate (ARR), the change of Expanded Disability Status Scale (EDSS) and the reduction of contrast-enhancing lesions (CELs) at magnetic resonance imaging (MRI) of the brain at 12 months of natalizumab and of previous DMT therapy. Fifty patients were included in the analysis (11 males, 39 females).We observed a reduction of ARR on natalizumab (p = 0.000) and a statistically significant different trend of relapse event between the two treatments (p = 0.0149). EDSS was stable during natalizumab therapy whilst it showed an increase on DMTs (p = 0.0244). The number of CELs decreased significantly (p = 0.006) during the 12 months of treatment with natalizumab, whilst it was stable on DMTs. Natalizumab showed to decrease ARR, stabilize EDSS, increase the percentage of CELs free patients and decrease the number of CELs in a group of 50 poor responders to classical DMT, after the first 12 months of therapy.

Measurement of scaling laws for shock waves in thermal nonlocal media.

We are able to detect the details of spatial optical collisionless wave breaking through the high aperture imaging of a beam suffering shock in a fluorescent nonlinear nonlocal thermal medium. This allows us to directly measure how nonlocality and nonlinearity affect the point of shock formation and compare results with numerical simulations.

Role of cytosolic calcium-dependent phospholipase A2 in Alzheimer's disease pathogenesis.

Phospholipases (PLA2s) are a superfamily of enzymes characterized by the ability to specifically hydrolyze the sn-2 ester bond of phospholipids generating arachidonic acid, utilized in inflammatory responses, and lysophospholipids involved in the control of cell membrane remodeling and fluidity. PLA2s have been so far considered a crucial element in the etiopathogenesis of several neurological diseases such as cerebral ischemia, multiple sclerosis, Parkinson's disease, and Alzheimer's disease (AD). In AD, the role of beta-amyloid (Aß) fragments is well established although still more elusive are the molecular events of the cascade that from the Aß accumulation leads to neurodegeneration with its clinical manifestations. However, it is well known that inflammation and alteration of lipid metabolism are common features of AD brains. Findings obtained from in vitro studies, animal models, and human brain imaging analysis point towards cPLA2 as a key molecule in the onset and maintenance of the neurodegenerative mechanism(s) of AD. In this review, we have focused on the molecular and biological evidence of the involvement of cPLA2s in the pathogenesis of AD. An insight into the molecular mechanism(s) underlying the action and the regulation of cPLA2 is of tremendous interest in the pharmaceutical and biotechnology industry in developing selective and potent inhibitors able to modulate the onset and/or the outcome of AD.

Do Cochrane reviews provide useful information to guide policy and practice? The experience of the Cochrane drugs and alcohol group.

This contribution reviewed the experience of the Cochrane Drugs and Alcohol Group (CDAG) in terms of production of evidence to guide policy and practice. By December 2010, the group had published 55 reviews, with 299 authors involved and 744 primary studies included out of 2114 studies considered for inclusion. 90% of the studies included were randomized controlled trials (RCTs). Considering the 'Implication for practice' section of each review, 31% interventions were classified as to do, 11% as do not do it, 52% to do only in research and for 6% a final judgment was impossible because the reviews included no studies or only one study. These proportions varied according to the type of substance of abuse studied; interventions judged as to do were 42% for alcohol, 32% for opioids, 12% for psychostimulants, 33% for poly drugs, and for prevention. The reviews produced by the CDAG provide evidence on effectiveness of several interventions, and identify areas of uncertainty, where more primary research is needed.

Recombination dynamics of deep defect states in zinc oxide nanowires.

The recombination dynamics of defect states in zinc oxide nanowires has been studied by developing a general expression for time-resolved photoluminescence intensity based on a second-order approximation for the radiative and non-radiative recombination rates. The model allows us to determine the parameters that characterize the recombination from deep defect states (defect concentration, unimolecular lifetime and bimolecular coefficient) through multi-fitting analysis of time-resolved photoluminescence measurements. Analyses conducted on zinc oxide nanowires gave deep state concentrations of the order of 10(18) cm(-3) and unimolecular lifetimes and bimolecular recombination coefficient comparable to those typical of interband recombination in direct gap semiconductors. The consistency of a 'two-channel decay' model (double exponential decay) has been tested by means of a similar analysis procedure. The results suggest that double exponential fitting of time-resolved photoluminescence data of zinc oxide nanowires may be just a mere phenomenological tool which does not reflect the real recombination dynamics of the visible emission band.

Maintenance agonist treatments for opiate dependent pregnant women.

BACKGROUND: The prevalence of opiate use among pregnant women ranges from 1% to 2% to as much as 21%. Heroin crosses the placenta and pregnant opiate dependent women experience a six fold increase in maternal obstetric complications such as low birth weight, toxaemia, 3rd trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neurobehavioral problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome. OBJECTIVES: To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions on child health status, neonatal mortality, retaining pregnant women in treatment, and reducing use of substances SEARCH STRATEGY: We searched Cochrane Drugs and Alcohol Group' Register of Trials (June 2007), PubMed (1966 - June 2007), CINAHL (1982- June 2007), reference lists of relevant papers, sources of ongoing trials, conference proceedings, National focal points for drug research. Authors of included studies and experts in the field were contacted. SELECTION CRITERIA: Randomised controlled trials enrolling opiate dependent pregnant women DATA COLLECTION AND ANALYSIS: The authors assessed independently the studies for inclusion and methodological quality. Doubts were solved by discussion. MAIN RESULTS: We found three trials with 96 pregnant women. Two compared methadone with buprenorphine and one methadone with oral slow morphine. For the women there was no difference in drop out rate RR 1.00 (95% CI 0.41 to 2.44) and use of primary substance RR 2.50 (95% CI 0.11 to 54.87) between methadone and buprenorphine, whereas oral slow morphine seemed superior to methadone in abstaining women from the use of heroin RR 2.40 (95% CI 1.00 to 5.77)For the newborns in one trial buprenorphine performed better than methadone for birth weight WMD -530 gr (95% CI -662 to -397), this result is not confirmed in the other trial. For the APGAR score both studies didn't find significant difference . No differences for NAS measures used. Comparing methadone with oral slow morphine no differences for birth weight and mean duration of NAS. The APGAR score wasn't considered. AUTHORS' CONCLUSIONS: We didn't find any significant difference between the drugs compared both for mother and for child outcomes; the trials retrieved were too few and the sample size too small to make firm conclusion about the superiority of one treatment over another. There is an urgent need of big randomized controlled trials.

Anticonvulsants for cocaine dependence.

BACKGROUND: Cocaine dependence is a major public health problem that is characterized by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence none exists currently for cocaine dependence despite two decades of clinical trials primarily involving antidepressant, anti convulsivant and dopaminergic medications. There has been extensive consideration of optimal pharmacological approaches to the treatment of cocaine dependence with consideration of both dopamine antagonists and agonists. Anticonvulsants have been candidates for the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction. OBJECTIVES: To evaluate the efficacy and the acceptability of anticonvulsants for cocaine dependence SEARCH STRATEGY: We searched the Cochrane Drugs and Alcohol Groups specialised register (issue 4, 2007), MEDLINE (1966 - march 2007), EMBASE (1988 - march 2007), CINAHL (1982- to march 2007) SELECTION CRITERIA: All randomised controlled trials and controlled clinical trials which focus on the use of anticonvulsants medication for cocaine dependence DATA COLLECTION AND ANALYSIS: Two authors independently evaluated the papers, extracted data, rated methodological quality MAIN RESULTS: Fifteen studies (1066 participants) met the inclusion criteria for this review: the anticonvulsants drugs studied were carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate, valproate. No significant differences were found for any of the efficacy measures comparing any anticonvulsants with placebo. Placebo was found to be superior to gabapentin in diminishing the number of dropouts, two studies, 81 participants, Relative Risk (RR) 3.56 (95% CI 1.07 to 11.82) and superior to phenythoin for side effects, two studies, 56 participants RR 2.12 (95% CI 1.08 to 4.17). All the other single comparisons are not statistically significant. AUTHORS' CONCLUSIONS: Although caution is needed when assessing results from a limited number of small clinical trials at present there is no current evidence supporting the clinical use of anticonvulsants medications in the treatment of cocaine dependence. Aiming to answer the urgent demand of clinicians, patients, families, and the community as a whole for an adequate treatment for cocaine dependence, we need to improve the primary research in the field of addictions in order to make the best possible use out of a single study and to investigate the efficacy of other pharmacological agent.

Prognosis of isolated acute post-traumatic subdural haematoma.

AIM: Acute subdural haematoma (ASDH) is seldom an isolated lesion and it is difficult to understand the mechanisms which determine the poor prognosis associated to this occurrence. Aim of this study was estimating the outcome of patients with ASDH without any companion lesions by analysing the haematoma volume, its thickness and midline shift. METHODS: Twenty-eight severely head injured patients (Glasgow Coma Scale, GCS =/<8) with isolated unilateral ASDH admitted in intensive care unit (ICU) were retrospectively studied. The haematoma thickness, the midline shift, the ASDH volume were obtained from the first emergency computerized tomography (CT) scan and analysed by a computer assisted programme (Osiris). Patients' outcome was scored according to the Glasgow Outcome Scale (GOS) 6 months after the event. According to their GOS the patients were further divided in 2 groups (favourable outcome: GOS 4-5, poor outcome: GOS 1-2-3). RESULTS: Midline shift ranged from 0 to 19.2 mm; we found a larger midline shift in those patients who died and in patients with severe disability or vegetative state 6 months after the trauma. CONCLUSION: The presence and size of midline shift was a more important determinant of outcome than ASDH volume or its thickness.

Antipsychotic medications for cocaine dependence.

BACKGROUND: Cocaine dependence is a public health problem characterized by recidivism and a host of medical and psychosocial complications. Cocaine dependence remains a disorder for which no pharmacological treatment of proven efficacy exists, although considerable advances in the neurobiology of this addiction could guide future medication development OBJECTIVES: To evaluate the efficacy and the acceptability of antipsychotic medications for cocaine dependence SEARCH STRATEGY: We searched the following sources: MEDLINE (1966 to October 2006), EMBASE (1980 to October 2006), CINAHL (1982 to October 2006), Cochrane Drug and Alcohol Group Specialised Register (October 2006). We also searched the reference lists of trials, the main electronic sources of ongoing trials (National Research Register, meta-Register of Controlled Trials; Clinical Trials.gov) and conference proceedings likely to contain trials relevant to the review. All searches included also non-English language literature. SELECTION CRITERIA: All randomised controlled trials and controlled clinical trials with focus on the use of any antipsychotic medication for cocaine dependence DATA COLLECTION AND ANALYSIS: Two authors independently evaluated the papers, extracted data, rated methodological quality MAIN RESULTS: Seven small studies were included (293 participants): the antipsychotic drugs studied were risperidone, olanzapine and haloperidol. No significant differences were found for any of the efficacy measures comparing any antipsychotic with placebo. Risperidone was found to be superior to placebo in diminishing the number of dropouts, four studies, 178 participants, Relative Risk (RR) 0.77 (95% CI 0.77 to 0.98). Most of the included studies did not report useful results on important outcomes such as side effects, use of cocaine during treatment and craving. The results on olanzapine and haloperidol come from studies too small to give conclusive results. AUTHORS' CONCLUSIONS: Although caution is needed when assessing results from a limited number of small clinical trials there is no current evidence, at the present , supporting the clinical use of antipsychotic medications in the treatment of cocaine dependence. Furthermore, most of the included studies did not report useful results on important outcomes such as side effects, use of cocaine during the treatment and craving. Aiming to answer the urgent demand of clinicians, patients, families, and the community as a whole for an adequate treatment for cocaine dependence, larger randomised investigations should be designed investigating relevant outcomes and reporting data to allow comparison of results between studies. Moreover some efforts should be done also to investigate the efficacy of other type medications, like anticonvulsant, currently used in clinical practice.

The end of the central dogma of neurobiology: stem cells and neurogenesis in adult CNS.

Until the 1990s, neurologists were practising their profession under the doctrine established in the late 19th to early 20th century by the prominent histologist Ramon y Cajal: "Once the development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. In the adult centers, the nerve paths are something fixed, ended, and immutable. Everything may die, nothing may be regenerated. It is for the science of the future to change, if possible, this harsh decree." Similarly, Giulio Bizzozero, the most prominent Italian histologist and mentor of Camillo Golgi, classified the tissues of the human body into "labile, stable and perennial". Among the latter were the nerve cells, believed to be unable to proliferate in the postnatal brain. This classification was taught until a few years ago to generations of medical students and biologists all over the world. We have investigated the historical, methodological and technical reasons why this "central dogma of neurology", so influential in clinical and experimental neurology, has lasted so long. We examined how this dogma was broken and who contributed, and the difficulties encountered by the "heretical" researchers who contributed to this goal, especially between the 1960s and the early 1990s, when at last neurogenesis in the adult brain could no longer be denied. Finally, we propose that the understanding of the mechanisms underlying various neurological diseases and the interpretations of clinical syndromes, as well as the design of new therapies, are being revolutionised by the breaking of this dogma and the discovery of the presence of neural stem cells in the adult brain.

The effects of hydroxyethyl starch solution in critically ill patients.

AIM: In the treatment of the critically ill patients an adequate fluid therapy appears to be essential to optimize hemodynamics and to get a suitable tissue perfusion. In this study we have evaluated the effects of volume replacement, carried out with 2 different solutions: hydroxyethyl starch 6% (HAES) and albumin 20% (HA). METHODS: Twenty patients suffering from sepsis were recruited and randomized into 2 groups. The first group was treated with hydroxyethyl starch 6% ( HAES treated group), and the second with albumin 20% (HA treated group). The volume of colloids was given to maintain pulmonary capillary wedge pressure (PCWP) between 15 and 18 mmHg. Daily, both hemodynamic parameters and blood gas analyses were monitored. RESULTS: Groups were homogeneous for age, sex and pathology. During the treatment we observed that cardiac index (CI), right ventricular ejection fraction (RVEF), oxygen consumption index (VO(2)I), oxygen delivery index (DO(2)I), and rate between arterial oxygen pressure and fraction of inspired oxygen (PaO(2)/FiO(2)) were increased significantly only in HAES treated group (P<0.05). APACHE II score decreased significantly only in HAES treated group (P<0.05), contrarily to the HA treated group, in which we observed a non significant increase. CONCLUSIONS: Since hydroxyethyl starch induced a hemodynamic and clinical improvement, these effects translated into an improvement of sensorium and a reduction of APACHE II score, without causing pulmonary edema, we can conclude that hydroxyethyl starch 6% ws 130,000 dalton ms 0.4 (Voluven) is an effective fluid for resuscitation of hypovolemic patients and represent an attractive alternative to albumin.

Alcoholics Anonymous and other 12-step programmes for alcohol dependence.

BACKGROUND: Alcoholics Anonymous (AA) is an international organization of recovering alcoholics that offers emotional support through self-help groups and a model of abstinence for people recovering from alcohol dependence, using a 12-step approach. Although it is the most common, AA is not the only 12-step intervention available there are other 12-step approaches (labelled Twelve Step Facilitation (TSF)). OBJECTIVES: To assess the effectiveness of AA or TSF programmes compared to other psychosocial interventions in reducing alcohol intake, achieving abstinence, maintaining abstinence, improving the quality of life of affected people and their families, and reducing alcohol associated accidents and health problems. SEARCH STRATEGY: We searched the Specialized Register of Trials of the Cochrane Group on Drugs and Alcohol, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE from 1966, EMBASE from 1980, CINAHL from 1982, PsychINFO from 1967. Searches were updated in February 2005. We also inspected lists of references for relevant studies. SELECTION CRITERIA: Studies involving adults (<18) of both genders with alcohol dependence attending on a voluntary or coerced basis AA or TSF programmes comparing no treatment, other psychological interventions, 12-step variants. DATA COLLECTION AND ANALYSIS: One reviewer (MF) assessed studies for inclusion and extracted data using a pre-defined data extraction form. Studies were evaluated for methodological quality and discussed by all reviewers. MAIN RESULTS: Eight trials involving 3417 people were included. AA may help patients to accept treatment and keep patients in treatment more than alternative treatments, though the evidence for this is from one small study that combined AA with other interventions and should not be regarded as conclusive. Other studies reported similar retention rates regardless of treatment group. Three studies compared AA combined with other interventions against other treatments and found few differences in the amount of drinks and percentage of drinking days. Severity of addiction and drinking consequence did not seem to be differentially influenced by TSF versus comparison treatment interventions, and no conclusive differences in treatment drop out rates were reported. Included studies did not allow a conclusive assessment of the effect of TSF in promoting complete abstinence. AUTHORS' CONCLUSIONS: No experimental studies unequivocally demonstrated the effectiveness of AA or TSF approaches for reducing alcohol dependence or problems. One large study focused on the prognostic factors associated with interventions that were assumed to be successful rather than on the effectiveness of interventions themselves, so more efficacy studies are needed.

Oral naltrexone maintenance treatment for opioid dependence.

BACKGROUND: Research on the clinical application of oral naltrexone agrees on several things. From a pharmacological perspective, naltrexone works. From an applied perspective, however, this medication is not used since the medication compliance and the retention rates are very poor. OBJECTIVES: To evaluate the effects of naltrexone maintenance treatment versus placebo or other treatments in preventing relapse in opioid addicts after detoxification. SEARCH STRATEGY: We searched the Cochrane Drugs and Alcohol Group Register of Trials (January 2005), Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library Issue 1, 2005), MEDLINE (1973-first year of naltrexone use in humans- January 2005), EMBASE (1974- January 2005), PsycINFO (OVID-January 1985 to January 2004). We inspected reference lists of relevant articles and we contacted pharmaceutical producers of naltrexone, authors and other Cochrane review groups. SELECTION CRITERIA: All randomised and controlled clinical trials which focus on the use of naltrexone maintenance treatment versus placebo, or other treatments to reach sustained abstinence from opiate drugs DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed studies for inclusion and extracted data. One reviewer carried out the qualitative assessments of the methodology of eligible studies using validated checklists. MAIN RESULTS: Ten studies, 696 participants, met the criteria for inclusion in this review. Only two studies described an adequate allocation concealment. The results show that naltrexone maintenance therapy alone or associated with psychosocial therapy is more efficacious that placebo alone or associated with psychosocial therapy in limiting the use of heroin during the treatment (RR 0,72 95% confidence interval 0.58 to 0.90). If we consider only the studies comparing naltrexone with placebo, the difference do not reach the statistical significancy, RR 0.79 (95%CI 0.59 to 1.06). With respect to the number of participants re incarcerated during the study period, the naltrexone associated with psychosocial therapy is more effective than the psychosocial treatment alone; RR 0.50 (95%CI 0.27 to 0.91). No statistically significant benefit was shown in terms of retention in treatment, side effects or relapse results at follow-up for any of the considered comparisons. AUTHORS' CONCLUSIONS: Unfortunately the studies did not provide an objective evaluation of naltrexone treatment in the field of opioid dependence. The conclusions are also limited due to the heterogeneity of the trials both in the interventions and in the assessment of outcomes.