Disulfiram for the treatment of cocaine dependence.

BACKGROUND: Cocaine is a psychostimulant used by approximately 0.4% of the general population worldwide. Cocaine dependence is a chronic mental disorder characterised by the inability to control cocaine use and a host of severe medical and psychosocial complications. There is current no approved pharmacological treatment for cocaine dependence. Some researchers have proposed disulfiram, a medication approved to treat alcohol use disorder. This is an update of a Cochrane review first published in 2010. OBJECTIVES: To evaluate the efficacy and safety of disulfiram for the treatment of cocaine dependence. SEARCH METHODS: We updated our searches of the following databases to August 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO. We also searched for ongoing and unpublished studies via two trials registries. We handsearched the references of topic-related systematic reviews and included studies. The searches had no language restrictions. SELECTION CRITERIA: We included randomised controlled trials that evaluated disulfiram alone or associated with psychosocial interventions versus placebo, no intervention, other pharmacological interventions, or any psychosocial intervention for the treatment of cocaine dependence. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Thirteen studies (1191 participants) met our inclusion criteria. Disulfiram versus placebo or no treatment Disulfiram compared to placebo may increase the number of people who are abstinent at the end of treatment (point abstinence; risk ratio (RR) 1.58, 95% confidence interval (CI) 1.05 to 2.36; 3 datasets, 142 participants; low-certainty evidence). However, compared to placebo or no pharmacological treatment, disulfiram may have little or no effect on frequency of cocaine use (standardised mean difference (SMD) -0.11 standard deviations (SDs), 95% CI -0.39 to 0.17; 13 datasets, 818 participants), amount of cocaine use (SMD -0.00 SDs, 95% CI -0.30 to 0.30; 7 datasets, 376 participants), continuous abstinence (RR 1.23, 95% CI 0.80 to 1.91; 6 datasets, 386 participants), and dropout for any reason (RR 1.20, 95% CI 0.92 to 1.55; 14 datasets, 841 participants). The certainty of the evidence was low for all these outcomes. We are unsure about the effects of disulfiram versus placebo on dropout due to adverse events (RR 12.97, 95% CI 0.77 to 218.37; 1 study, 67 participants) and on the occurrence of adverse events (RR 3.00, 95% CI 0.35 to 25.98), because the certainty of the evidence was very low for these outcomes. Disulfiram versus naltrexone Disulfiram compared with naltrexone may reduce the frequency of cocaine use (mean difference (MD) -1.90 days, 95% CI -3.37 to -0.43; 2 datasets, 123 participants; low-certainty evidence) and may have little or no effect on amount of cocaine use (SMD 0.12 SDs, 95% CI -0.27 to 0.51, 2 datasets, 123 participants; low-certainty evidence). We are unsure about the effect of disulfiram versus naltrexone on dropout for any reason (RR 0.86, 95% CI 0.56 to 1.32, 3 datasets, 131 participants) and dropout due to adverse events (RR 0.50, 95% CI 0.07 to 3.55; 1 dataset, 8 participants), because the certainty of the evidence was very low for these outcomes. AUTHORS' CONCLUSIONS: Our results show that disulfiram compared to placebo may increase point abstinence. However, disulfiram compared to placebo or no pharmacological treatment may have little or no effect on frequency of cocaine use, amount of cocaine use, continued abstinence, and dropout for any reason. We are unsure if disulfiram has any adverse effects in this population. Caution is required when transferring our results to clinical practice.

Pre- and post-treatment in flexor tendon tenolysis: An observational study.

BACKGROUND: Glide deficit of the distal flexors' tendons following primary repair in zone 1-3 are very common. Adhesions of tendons have multi factorial origins and are closely related to the healing of the affected tissues. The surgical practice used to resolve these complications is tenolysis. PURPOSE: The purpose of this study was to identify and compare the Visual Analog Scale (VAS) relate to pain and Total Active Motion (TAM) of adult patients of both sexes undergoing tenolysis surgery. The results will then be compared to existing research to confirm their significance. STUDY DESIGN: Case-series. METHODS: Retrospective data for TAM and pain VAS were extracted from the medical records for 63 patients (73 fingers) who underwent flexor tenolysis between 2017 and 2019. Data were compared pre-operatively and 3 months after surgery. All patients underwent pre- and post-surgery therapy by hand therapists. RESULTS: The sample presented very encouraging improvements, except in the VAS and active range of motion (AROM) of thumb where some patients maintained the same assessment. The fingers reported statistically significant results, whereas the thumb group did not meet significant criteria. Overall, TAM improved from 134.6° to 196.7 and VAS decreased from 2.7 to 1.2. DISCUSSION: According to the results and the data change between pre- and post-treatment, the sample demonstrated improvements in all areas examined, reporting statistically significant results for the fingers with an improvement of TAM of 62.1° with a percentage value (%TAM) of 75.6%. CONCLUSIONS: A specific treatment for this type of surgery is required for the patients so they can return to their daily and working activities. This article can be used as a starting point for further studies.

[SENTIERI Project: a systematic review on the association between sources of environmental exposure in contaminated sites and health outcomes]. / Progetto SENTIERI: revisione della letteratura scientifica sull'associazione tra fonti di esposizione ambientale in siti contaminati ed esiti di salute.

BACKGROUND: the epidemiological surveillance programme carried out in the Italian Contaminated Sites (SENTIERI Project) is based on an a priori evaluation of the epidemiological evidence of a causal association between environmental exposures and health outcomes. OBJECTIVES: to produce an updated review of the epidemiological evidence (January 2009-May 2020) on the association between environmental exposures and health outcomes predefined and published by the SENTIERI working group. METHODS: a systematic review was conducted on MEDLINE, EMBASE, and Web of Science. Additional searches were conducted on the websites of relevant organizations. The sources of environmental exposure considered were the ones included in SENTIERI Projects (chemicals, petrochemicals and refineries, steel plants, power plants, port area, waste, mines and source of asbestos). RESULTS: a total of 16,817 records were identified and, after the screening process, 14 systematic reviews were identified: two IARC Monograph, two WHO Reports, one WHO/UNEP Report, and 15 observational studies. Living in proximity of contaminated sites was associated with specific diseases (mortality or incidence), with a high heterogeneity across environmental sources. For some exposures, data suggests a gender differential effect for some causes of disease. CONCLUSIONS: compared to a previous evidence evaluation, this systematic review shows a higher number of diseases associated with residential exposure to some contaminated sites (petrochemical facilities, waste, mines, and sources of asbestos). According to the results of this review, the a priori evidence evaluation was updated and used to interpret the epidemiological data of the Sixth SENTIERI Project Report.

[SENTIERI - Epidemiological Study of Residents in National Priority Contaminated Sites. Sixth Report]. / SENTIERI - Studio epidemiologico nazionale dei territori e degli insediamenti esposti a rischio da inquinamento. Sesto Rapporto.

INTRODUCTION ADN OBJECTIVES: The Sixth Report presents the results of the "SENTIERI Project: implementation of the permanent epidemiological surveillance system of populations residing in Italian Sites of Remediation Interest", promoted and financed by the Italian Ministry of Health (Centre for Disease Control and Prevention - CCM Project 2018). The aim of this study is to update the mortality and hospitalization analyses concerning the 6,227,531 inhabitants (10.4% of the Italian population) residing in 46 contaminated sites (39 of national interest and 7 of regional interest). The sites include 316 municipalities distributed as follows: 15 in the North-East (20.3% of the investigated population); 104 in the North-West (12% of the investigated population), 32 in the Centre (12.6% of the investigated population), 165 in the South and Islands (55.5% of the investigated population). Analyses were carried out on the paediatric-adolescent (1,128,396 residents) and youth (665,284 residents) population, and a study on congenital anomalies (CA) was carried out at sites covered by congenital malformation registers. Accompanying the epidemiological assessments, site-specific socioeconomic conditions were examined and an overall estimate of excess risk for populations residing at contaminated sites was drawn up. By means of a systematic review of the scientific literature, the epidemiological evidence on causal links between sources of environmental exposure and health effects was updated to identify pathologies of a priori interest. METHODOLOGY: In the 46 sites included in the SENTIERI Project, mortality (time window: 2013-2017) and hospital admissions (time window: 2014-2018) of the general population of all ages, divided by gender, and of the paediatric-adolescent (0-1 year, 0-14 years, 0-19 years), youth (20-29 years), and overall (0-29 years) age groups, divided by gender, were analysed. In 21 sites, CA diagnosed within the first year of life were studied. Standardised mortality ratios (SMR) and hospitalization ratios (SHR) were calculated with reference to the rates in the regions to which the sites belong. The reference population was calculated net of residents in the sites. CA were studied by calculating the prevalence per 10,000 births and the ratio, multiplied by 100, between the cases observed at the site and those expected on the basis of the prevalences observed in the reference area (region or sub-regional area of belonging, according to the geographical coverage of the registry). The socioeconomic condition studied in the 46 sites is based on the convergence of three deprivation indicators with respect to the reference region: deprivation index at municipal level, deprivation index at census section level, premature mortality indicator (age range 30-69 years) for chronic non-communicable diseases. For the estimation of excess risk for the entire study population, meta-analysis of the mortality and hospitalization risk estimates for each site was carried out and the number of excess deaths estimated for the sites as a whole. The epidemiological evidence was updated through a systematic literature review (January 2009-May 2020), following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was carried out on the search engines MEDLINE, EMBASE and Web of Science; the quality of the studies included in the review was assessed using the AMSTAR 2 checklist for systematic reviews and the NewCastle-Ottawa Scale for observational studies in the case of cohort and case-control studies and a modified version thereof for ecological and cross-sectional studies. The update was based on the selection of 14 systematic reviews, 15 primary studies, 6 monographs/reports from international scientific organisations on health effects due to the presence of environmental exposure sources. RESULTS: Mortality. The a priori causes of interest that occur most frequently in excess are, in descending order: malignant lung cancer, malignant mesothelioma of the pleura, malignant bladder cancer, respiratory diseases, non-Hodgkin lymphomas, malignant liver cancer, all malignant tumours, malignant colorectal cancer, malignant stomach cancer, total mesotheliomas, malignant breast cancer, and asbestosis. Hospitalization. The a priori causes of interest that occur most frequently in excess are represented in descending order by: respiratory diseases, malignant lung cancer, malignant tumours of the pleura, malignant bladder cancer, malignant breast cancer, malignant liver cancer, asthma, malignant colorectal cancer, all malignant tumours, malignant stomach cancer, non-Hodgkin's lymphomas, acute respiratory diseases, leukaemias. The differences observed between mortality and hospitalization can be attributed to the intrinsic characteristics of the diseases (higher or lower lethality, gender differences in incidence), lifestyles, and occupational phenomena. Age classes. Excesses of general mortality were observed in the first year of life at the Manfredonia, Basso Bacino Fiume Chienti, Litorale Domizio Flegreo and Agro Aversano sites; in the 0-1 year and 0-19 year age groups at Casale Monferrato; in the paediatric age group at Serravalle Scrivia and at the Trento Nord site; in the 0-19 year age group at Sassuolo Scandiano; in the young age group (0-29 years) at the two municipalities of Cerchiara and Cassano (Crotone-Cassano-Cerchiara site). With regard to hospitalization due to natural causes, risk excesses in both genders are found in the first year of life in 35% of the sites (Porto Torres industrial areas, Bari-Fibronit, Basso bacino fiume Chienti, Bolzano, Crotone-Cassano-Cerchiara, Cerro al Lambro, Bologna ETR large repair workshop, Gela, Manfredonia, Massa Carrara, Pioltello Rodano, Pitelli, Priolo, Sesto San Giovanni, Trento Nord, and Trieste). These same sites, with the addition of Casale Monferrato, Cengio e Saliceto, Serravalle Scrivia, and Sulcis-Iglesiente-Guspinese (total: 43% of sites), show excesses for all natural causes, in both genders, even in the paediatric-adolescent age group (0-19 years). Among young adults (20-29 years), the analyses show excesses of hospitalization for all natural causes in both genders in the Bolzano, Crotone-Cassano-Cerchiara, Gela, Manfredonia, Pitelli, Priolo, and Sulcis-Iglesiente-Guspinese sites. Among young women only, excesses for all natural causes are also found in Brescia Caffaro, Brindisi, Broni, Casale Monferrato, Crotone-Cassano-Cerchiara, Falconara Marittima, Fidenza, and Massa Carrara. Congenital anomalies. In the 21 sites investigated for CA, 10,126 cases of CA, validated by participating registers, were analysed out of 304,620 resident births. Genital CA is the subgroup for which the greatest number of excesses was observed (in 6 out of 21 sites). The available evidence does not allow a causal link to be established between the excesses observed for specific subgroups of ACs and exposure to industrial sources, but the results suggest further action. The interpretation of the results appears, in fact, particularly complex as the scientific literature on the association between exposure to industrial sources and AC is very limited. Socioeconomic status. The sites in which the indicators converge to show the presence of fragility are: Litorale Vesuviano area, Val Basento industrial areas, Basso Bacino fiume Chienti, Biancavilla, Crotone-Cassano-Cerchiara, Litorale Domizio Flegreo and Agro Aversano, Livorno, Massa Carrara, Trieste. Global impact. Over the period 2013-2017, an estimated 8,342 excess deaths (CI90% 1,875-14,809) or approximately 1,668 excess cases/year, 4,353 excess deaths among males (CI90% 334-8,372) and 3,989 among females (CI90% -1,122;9,101). The pooled excess risk of general mortality is 2% in both genders (pooled SMR 1.02; CI90% 1.00-1.04). The proportion of excess deaths to total observed deaths is almost constant over time, rising from 2.5% in 1995-2002 to 2.6% in 2013-2017. The number of deaths in absolute value is also very similar between the periods analysed. Deaths from all malignant tumours contribute the most by accounting for 56% of the observed excesses, the excess risk of mortality from malignant tumours across all sites, compared to the reference populations, is 4% in the male population (pooled SMR 1.04; CI90% 1.01-1.06) and 3% among the female population (pooled SMR 1.03; CI90% 1.01-1.05). Hospitalization (2014-2018) in the 46 sites as a whole was in excess of 3% for all causes, in both genders, for all major disease groups (males: SHR pooled 1.03; CI90% 1.01-1.04 - females: SHR pooled 1.03; CI90% 1.01-1.05). The results for the pooled estimates at the 46 sites on the general population, both with regard to mortality and hospitalization, are consistent in indicating excess risk in both genders for all the diseases considered and, in particular, for all malignancies. A total of 1,409 paediatric-adolescent deaths and 999 young adult deaths were observed, and the pooled analysis of mortality across the 46 sites showed no critical issues, with pooled estimates for all causes, perinatal morbid conditions and all malignancies falling short of expectations. The analysis of hospitalizations, on the other hand, showed an excess risk of 8% (males: SHR pooled 1.08; CI90% 1.03-1.13 - females: SHR pooled 1.08; CI90% 1.03-1.14) for all causes in the first year of life, and in paediatric-adolescent and juvenile age of 3-4% among males (age 0-19 years: SHR pooled 1.04; CI90% 1.02-1.06 - age 20-29 years: SHR pooled 1.03; CI90% 1.00-1.05) and 5% among females (in both age groups; SHR pooled 1.05; CI90% 1.02-1.08). The pooled analysis of mortality for the a priori identified diseases reported excesses for specific diseases in the group of sites with sources of exposure associated with them. Mortality from total mesotheliomas is three times higher at sites with asbestos present (males:pooled SMR 3.02; CI90% 2.18-3.87 - females: pooled SMR 3.61; CI90% 2.33-4.88) and that from pleural mesotheliomas more than two times higher at the group of sites with asbestos and port areas (males: pooled SMR 2.47; CI90% 1.94-3.00 - females: pooled SMR 2.43; CI90% 1.67-3.19). Lung cancer was in excess by 6% among males (pooled SMR 1.06; CI90% 1.03-1.10) and 7% among females (pooled SMR 1.07; CI90% 1.00-1.13). In addition, there are excess mortalities for colorectal cancer at sites with chemical plants, by 4 % among males (SMR pooled 1.04; CI90% 1.01-1.08) and 3 % among females (SMR pooled 1.03; CI90% 1.00-1.07) and for bladder cancer among the male population of sites with landfills (+6 %: SMR pooled 1.06; CI90% 1.02-1.11). Among the diseases of a priori interest, stomach and soft tissue cancers are at fault as a cause of death among all the sites considered. LITERATURE REVIEW: The update of the epidemiological evidence underlying the Sixth SENTIERI Report has highlighted in the general population a possible association, previously undiscovered, between certain diseases and residence near petrochemical and steel plants, landfills, coal mines and asbestos sources. CONCLUSIONS AND PERSPECTIVES: Despite the fact that this is an ecological study, and the excesses of pathologies with multifactorial aetiology can never be mechanically attributed solely to the environmental pressure factors that exist or existed in the areas studied, the ability to identify the excesses found in the contaminated sites investigated by the SENTIERI Project confirms the validity of this method of assessing the site-specific health profile, based on the use of epidemiological evidence to identify pathologies of interest a priori. In interpreting the data and lending robustness to what has been observed, comparison with the results obtained in previous Reports is essential. The global estimates give an overall picture that shows excess mortality and hospitalization in these populations compared to the rest of the population, and show how, for specific pathologies, comparable effects are produced at sites with similar contamination characteristics. The themes developed in the in-depth chapters broaden the vision and understanding of the complex interactions between environment and health, describe the possibilities offered by new ways of communicating the results, and confirm the modernity of a Project that began way back in 2006, and that could be grafted onto the objectives of the National Recovery and Resilience Plan within the framework of the Operational Programme Health, Environment, Biodiversity and Climate.

Italian guidelines on management of persons with multimorbidity and polypharmacy.

Multimorbidity and polypharmacy are emerging health priorities and the care of persons with these conditions is complex and challenging. The aim of the present guidelines is to develop recommendations for the clinical management of persons with multimorbidity and/or polypharmacy and to provide evidence-based guidance to improve their quality of care. The recommendations have been produced in keeping with the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Overall, 14 recommendations were issued, focusing on 4 thematic areas: (1.) General Principles; (2.) target population for an individualized approach to care; (3.) individualized care of patients with multimorbidity and/or polypharmacy; (4.) models of care. These recommendations support the provision of individualized care to persons with multimorbidity and/or polypharmacy as well as the prioritization of care through the identification of persons at increased risk of negative health outcomes. Given the limited available evidence, recommendations could not be issued for all the questions defined and, therefore, some aspects related to the complex care of patients with multimorbidity and/or polypharmacy could not be covered in these guidelines. This points to the need for more research in this field and evidence to improve the care of this population.

Atrial thrombosis: Not only left, think also about right!

Atrial fibrillation (AF) is the most common arrhythmia in the general population. Systemic thromboembolism from left atrial appendage (LAA) thrombosis is a well-known complication of AF, whereas thromboembolic complications from a right atrial (RA) thrombus are infrequent. Nevertheless, the prevalence of RA thrombosis is debated; despite having a low prevalence in echocardiographic studies, the higher prevalence found in autoptic studies rises the hypothesis of an under detection of RA clots, possibly related to the limited evaluation of right atrial appendage (RAA) with non-invasive imaging. Here we present a review of the current literature about RA thrombosis, regarding its diagnosis, differentials, and best treatment options.

Industrial odour pollution and human health: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review to evaluate the association between residential or occupational short- and long-term exposure to odour pollution from industrial sources and the health status of the exposed population. METHODS: The searches were conducted in Medline, EMBASE and Scopus in April 2021. Exposure to an environmental odour from industrial sources in population resident near the source or in workers was considered. We considered outcomes for which there was a biological plausibility, such as wheezing and asthma, cough, headache, nausea and vomiting (primary outcomes). We also included stress-related symptoms and novel outcomes (e.g. mood states). Risk of bias was evaluated using the OHAT tool. For primary outcomes, when at least 3 studies provided effect estimates by comparing exposed subjects versus not exposed, we pooled the study-specific estimates of odour-related effect using random effects models. Heterogeneity was evaluated with Higgins I2. RESULTS: Thirty studies were eligible for this review, mainly cross-sectional (n = 23). Only one study involved school-age children and two studies involved workers. Only five studies reported odour effects on objective laboratory or clinical outcomes. Animal Feeding Operations and waste were the most common industrial sources. The overall odds ratios in exposed versus not exposed population were 1.15 (95% CI 1.01 to 1.29) for headache (7 studies), 1.09 (95% CI 0.88 to 1.30) for nausea/vomiting (7 studies), and 1.27 (95% CI 1.10 to 1.44) for cough/phlegm (5 studies). Heterogeneity was a moderate concern. Overall, the body of evidence was affected by a definitely high risk of bias in exposure and outcome assessment since most studies used self-reported information. CONCLUSIONS: Findings underline the public health importance of odour pollution for population living nearby industrial odour sources. The limited evidence for most outcomes supports the need for high quality epidemiological studies on the association between odour pollution and its effects on human health.

Anti-hypertensive drugs deprescribing: an updated systematic review of clinical trials.

BACKGROUND: Polypharmacy is defined as the prescription of at least 5 different medicines for therapeutic or prophylactic effect and is a serious issue among elderly patients, who are frequently affected by multi-morbidity. Deprescribing is one of the proposed approaches to reduce the number of administered drugs, by eliminating those that are inappropriately prescribed. The aim of this systematic review is to provide an updated and systematic assessment of the benefit-risk profile of deprescribing of anti-hypertensive drugs, which are among the most commonly used drugs. METHODS: MEDLINE, EMBASE and The Cochrane Library were searched for studies assessing the efficacy and safety of anti-hypertensive drugs deprescribing in the period between January, 12,016 and December, 312,019. The quality of randomized clinical trials (RCTs) was assessed using the GRADE approach for the evaluation of the main outcomes. The risk of bias assessment was carried out using the Cochrane risk-of-bias tool. RESULTS: Overall, two RCTs were identified. Despite summarized evidence was in favor of anti-hypertensive deprescribing, the overall risk of bias was rated as high for each RCT included. According to the GRADE approach, the overall quality of the RCTs included was moderate regarding the following outcomes: systolic blood pressure < 150 mmHg after 12 weeks of follow-up, quality of life, frailty and cardiovascular risk. CONCLUSIONS: This updated systematic review of the efficacy and safety of anti-hypertensive treatment deprescribing found two recently published RCTs, in addition to the previous guideline of the National Institute for Health and Care Excellence (NICE). Evidence points towards non-inferiority of anti-hypertensive deprescribing as compared to treatment continuation, despite the quality of published studies is not high. High quality experimental studies are urgently needed to further assess the effect of deprescribing for this drug class in specific categories of patients.

A systematic review of economic evaluations of neonatal and maternal healthcare in immigrant and ethnic minority women.

BACKGROUND: less access to appropriate care during pregnancy for immigrant/ethnic minority women can lead to worse health outcomes and higher costs for health services. OBJECTIVES: to conduct a systematic review of studies on the economic evaluation of maternal and child healthcare among immigrants and racial/ethnic minority groups in advanced economy countries. METHODS: the main biomedical/economic bibliographic databases and institutional sources were searched. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: encouraging breastfeeding and reducing inappropriate hospital use/length of hospital stay proved potentially able to reduce costs. Most studies showed a cost reduction if immigrant and ethnic minority women were included both in national and targeted programmes, such as nutritional programmes or case management. Screening campaigns targeting immigrants and ethnic minority groups were more cost-effective than broader, universal or non-screening strategies. Screenings were cost-effective when extended to newborns/relatives of pregnant women (Chagas disease) and were cost-effective for unvaccinated women in low-vaccination rates regions (rubella), immigrant women reporting no/uncertain vaccination history (varicella), and first-generation immigrants (HCV). DISCUSSION: promoting inclusion in pregnancy healthcare programmes or in targeted screening campaigns could be effective in cost saving for health services.

Neonatal Marfan Syndrome.

OBJECTIVE: The Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue resulting from pathogenic variants of the fibrillin-1 gene (FBN1) with skeletal, cardiac, and ocular involvement. STUDY DESIGN: We report on a full-term male neonate, who showed at birth characteristics and dysmorphisms suggestive of nMFS, combined with the detection of severe cardiovascular disease. A multidisciplinary team made up of neonatologists and pediatricians, cardiologists, geneticists, ophtalmologists, physiatrists and physioterapists was formed to manage this patient. RESULTS AND CONCLUSION: Early diagnosis of this rare condition is critical for adequate treatment and specific follow-up, and impacts significantly on prognosis.

Quality improvement strategies at primary care level to reduce inequalities in diabetes care: an equity-oriented systematic review.

BACKGROUND: There is evidence that disparities exist in diabetes prevalence, access to diabetes care, diabetes-related complications, and the quality of diabetes care. A wide range of interventions has been implemented and evaluated to improve diabetes care. We aimed to review trials of quality improvement (QI) interventions aimed to reduce health inequities among people with diabetes in primary care and to explore the extent to which experimental studies addressed and reported equity issues. METHODS: Pubmed, EMBASE, CINAHL, and the Cochrane Library were searched to identify randomized controlled studies published between January 2005 and May 2016. We adopted the PROGRESS Plus framework, as a tool to explore differential effects of QI interventions across sociodemographic and economic factors. RESULTS: From 1903 references fifty-eight randomized trials met the inclusion criteria (with 17.786 participants), mostly carried out in USA. The methodological quality was good for all studies. Almost all studies reported the age, gender/sex and race distribution of study participants. The majority of trials additionally used at least one further PROGRESS-Plus factor at baseline, with education being the most commonly used, followed by income (55%). Large variation was observed between these studies for type of interventions, target populations, and outcomes evaluated. Few studies examined differential intervention effects by PROGRESS-plus factors. Existing evidence suggests that some QI intervention delivered in primary care can improve diabetes-related health outcomes in social disadvantaged population subgroups such as ethnic minorities. However, we found very few studies comparing health outcomes between population subgroups and reporting differential effect estimates of QI interventions. CONCLUSIONS: This review provides evidence that QI interventions for people with diabetes is feasible to implement and highly acceptable. However, more research is needed to understand their effective components as well as the adoption of an equity-oriented approach in conducting primary studies. Moreover, a wider variety of socio-economic characteristics such as social capital, place of residence, occupation, education, and religion should be addressed.

A scoping review of the epidemiological methods used to investigate the health effects of industrially contaminated sites.

BACKGROUND: this paper is based upon work from COST Action ICSHNet. Industrial contaminated sites (ICSs) are of high concern since industrial plants have produced widespread contamination potentially affecting the health of local population OBJECTIVES: to assess the types of epidemiological designs applied in studies of health effects related to ICSs according to time periods, type of ICS, and geography. METHODS: a literature search was conducted in Medline (OVID) through June 30th, 2018, using MeSH and customized terms, and no restrictions on publication year or language. We included all studies throughout the world where a potential contamination of industrial origin occurred, an epidemiological approach (including biomonitoring, HBM) was applied, and health outcomes or exposure biomarkers among residents were investigated. Data on publication year, geographical localization and ICS characterization, study design (systematic reviews, cohort, case-control, temporal changes, cross-sectional, ecological, descriptive - area-level, case-series, narrative reviews, and HBM), and health outcomes were extracted from the abstracts. To check the sensitivity of the main search strategy, a case-study on Italy was conducted applying an ad-hoc search. RESULTS: from a literature search capturing 5,485 studies, 655 studies on resident populations were identified. The review includes more than 376 different ICSs, 86% from Europe, North America, and Asia combined, mostly dealing with nuclear sites and mining industries, waste and petrochemical activities. Most of the studies were descriptive (32.5%), cross-sectional (16.3%), or narrative review (14.8%), while analytical studies - case-control and cohort studies (9.6% and 8.4%, respectively) - were rarer; HBM were only 6.9%. A total of 235 studies, conducted mostly in Asia (34.5%), Europe (25.5%), and North America (22.3%), included children. The most frequently studied outcome was cancer (33.7%), followed by respiratory diseases (11.4%), and reproductive health (11.4%). The ad-hoc strategy greatly increased the number of detected papers (+122%). CONCLUSIONS: future research should adopt the most valid and suitable study design, according to the area-specific social and environmental context, also in areas of the world which are less studied, but with very high environmental worries of the resident population suffering the industrial contamination. Involvement of local experts on ICSs and local inventories are recommended to improve the coverage of the present inventory.

Supervised dosing with a long-acting opioid medication in the management of opioid dependence.

BACKGROUND: Opioid dependence (OD) is an increasing clinical and public health problem worldwide. International guidelines recommend opioid substitution treatment (OST), such as methadone and buprenorphine, as first-line medication treatment for OD. A negative aspect of OST is that the medication used can be diverted both through sale on the black market, and the unsanctioned use of medications. Daily supervised administration of medications used in OST has the advantage of reducing the risk of diversion, and may promote therapeutic engagement, potentially enhancing the psychosocial aspect of OST, but costs more and is more restrictive on the client than dispensing for off-site consumption. OBJECTIVES: The objective of this systematic review is to compare the effectiveness of OST with supervised dosing relative to dispensing of medication for off-site consumption. SEARCH METHODS: We searched in Cochrane Drugs and Alcohol Group Specialised Register and Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, Web of Science from inception up to April 2016. Ongoing and unpublished studies were searched via ClinicalTrials.gov (www.clinicaltrials.gov) and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (http://www.who.int/ictrp/en/).All searches included non-English language literature. We handsearched references on topic-related systematic reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs), controlled clinical trials (CCTs), and prospective controlled cohort studies, involving people who are receiving OST (methadone, buprenorphine) and comparing supervised dosing with dispensing of medication to be consumed away from the dispensing point, usually without supervision. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: Six studies (four RCTs and two prospective observational cohort studies), involving 7999 participants comparing supervised OST treatment with unsupervised treatment, met the inclusion criteria. The risk of bias was generally moderate across trials, but the results reported on outcomes that we planned to consider were limited. Overall, we judged the quality of the evidence from very low to low for all the outcomes.We found no difference in retention at any duration with supervised compared to unsupervised dosing (RR 0.99, 95% CI 0.88 to 1.12, 716 participants, four trials, low-quality evidence) or in retention in the shortest follow-up period, three months (RR 0.94; 95% CI 0.84 to 1.05; 472 participants, three trials, low-quality evidence). Additional data at 12 months from one observational study found no difference in retention between groups (RR 0.94, 95% CI 0.77 to 1.14; n = 300).There was no difference in abstinence at the end of treatment (self-reported drug use) (67% versus 60%, P = 0.33, 293 participants, one trial, very low-quality evidence); and in diversion of medication (5% versus 2%, 293 participants, one trial, very low-quality evidence).Regarding our secondary outcomes, we did not found a difference in the incidence of adverse effects in the supervised compared to unsupervised control group (RR 0.63; 96% CI 0.10 to 3.86; 363 participants, two trials, very low-quality evidence). Data on severity of dependence were very limited (244 participants, one trial) and showed no difference between the two approaches. Data on deaths were reported in two studies. One trial reported two deaths in the supervised group (low-quality evidence), while in the cohort study all-cause mortality was found lower in regular supervision group (crude mortality rate 0.60 versus 0.81 per 100 person-years), although after adjustment insufficient evidence existed to suggest that regular supervision was protective (mortality rate ratio = 1.23, 95% CI = 0.67 to 2.27).No studies reported pain symptoms, drug craving, aberrant opioid-related behaviours, days of unsanctioned opioid use and overdose. AUTHORS' CONCLUSIONS: Take-home medication strategies are attractive to treatment services due to lower costs, and place less restrictions on clients, but it is unknown whether they may be associated with increased risk of diversion and unsanctioned use of medication. There is uncertainty about the effects of supervised dosing compared with unsupervised medication due to the low and very low quality of the evidence for the primary outcomes of interest for this review. Data on defined secondary outcomes were similarly limited. More research comparing supervised and take-home medication strategies is needed to support decisions on the relative effectiveness of these strategies. The trials should be designed and conducted with high quality and over a longer follow-up period to support comparison of strategies at different stages of treatment. In particular, there is a need for studies assessing in more detail the risk of diversion and safety outcomes of using supervised OST to manage opioid dependence.

[Systematic review of safeness and therapeutic efficacy of cannabis in patients with multiple sclerosis, neuropathic pain, and in oncological patients treated with chemotherapy]. / Revisione sistematica sull'efficacia terapeutica e la sicurezza della cannabis per i pazienti affetti da sclerosi multipla, dolore neuropatico cronico e pazienti oncologici che assumono chemioterapie.

BACKGROUND: medical cannabis refers to the use of cannabis or cannabinoids as medical therapy to treat disease or alleviate symptoms. In the United States, 23 states and Washington DC (May 2015) have introduced laws to permit the medical use of cannabis. Within the European Union, medicinal cannabis laws and praxis vary wildly between Countries. OBJECTIVES: to provide evidence for benefits and harms of cannabis (including extracts and tinctures) treatment for adults in the following indications: control of spasticity and pain in patients with multiple sclerosis; control of pain in patients with chronic neuropathic pain; control of nausea and vomiting in adults with cancer receiving chemotherapy. METHODS: we searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE from inception to September 2016. We also searched for on-going studies via ClinicalTrials.gov and the World Health Organization and International Clinical Trials Registry Platform (ICTRP) search portal. All searches included also non-English language literature. All relevant randomized controlled trials (RCTs) evaluating the safety and efficacy of cannabis (including extracts and tinctures) compared with placebo or other pharmacological agents were included. Three authors independently evaluated the titles and abstracts of studies identified in the literature searches for their eligibility. For studies considered eligible, we retrieved full texts. Three investigators independently extracted data. For the assessment of the quality of evidence, we used the standard methodological procedures recommended by Cochrane and GRADE working Group. RESULTS: 41 trials (4,550 participants) were included; 15 studies considered efficacy and safety of cannabis for patients with multiple sclerosis, 12 for patients with chronic pain, and 14 for patients with cancer receiving chemotherapy. The included studies were published between 1975 and 2015, and the majority of them were conducted in Europe. We judged almost 50% of these studies to be at low risk of bias. The large majority (80%) of the comparisons were with placebo; only 8 studies included patients with cancer receiving chemotherapy comparing cannabis with other antiemetic drugs. Concerning the efficacy of cannabis (compared with placebo) in patients with multiple sclerosis, confidence in the estimate was high in favour of cannabis for spasticity (numerical rating scale and visual analogue scale, but not the Ashworth scale) and pain. For chronic and neuropathic pain (compared with placebo), there was evidence of a small effect; however, confidence in the estimate is low and these results could not be considered conclusive. There is uncertainty whether cannabis, including extracts and tinctures, compared with placebo or other antiemetic drugs reduces nausea and vomiting in patients with cancer requiring chemotherapy, although the confidence in the estimate of the effect was low or very low. In the included studies, many adverse events were reported and none of the studies assessed the development of abuse or dependence. CONCLUSIONS: there is incomplete evidence of the efficacy and safety of medical use of cannabis in the clinical contexts considered in this review. Furthermore, for many of the outcomes considered, the confidence in the estimate of the effect was again low or very low. To give conclusive answers to the efficacy and safety of cannabis used for medical purposes in the clinical contexts considered, further studies are needed, with higher quality, larger sample sizes, and possibly using the same diagnostic tools for evaluating outcomes of interest.

[Implementation of DNA-HPV primary screening in Italian cervical cancer screening programmes. Results of the MIDDIR Project]. / L'implementazione del DNA-HPV come test primario nei programmi italiani di screening del cervicocarcinoma. Risultati del Progetto MIDDIR.

OBJECTIVES: to obtain data on conversion paths to HPV testing as part of screening programmes and to harmonize the introduction of HPV testing in primary cervical cancer screening protocols of Italian programmes. DESIGN: survey by questionnaire on strategies adopted by screening programmes for transition to primary HPV testing; systematic review of the literature; discussion among experts. SETTING AND PARTICIPANT S: managers of Italian Regions' cervical cancer screening programmes. MAIN OUTCOME MEASURES: transition planning; activity volumes; modalities of centralization; criteria for dismissal; staff training; communication initiatives. RESULTS: nine cervical screening programmes responded to the survey. Most of them chose to schedule a transition of a few years to allow for adjustment of the volume of activity in the passage from the three-year screening interval to the five-year one. To select women to be given precedence, 7 programmes use the age, starting from the oldest. The liquid base is the choice by far preferred both for HPV test and for Pap test. The reading of HPV test "born" already centralized, but a centralization process is in place also for cytology. CONCLUSIONS: the survey on conversion strategies to primary HPV testing showed the opportunity to schedule a transition phase. For HPV test, cost, organization, and quality benefits of centralization are clear, thus the central organization should be preferred and managed immediately. Moreover, the need for a centralization of cytology is evident. The tariff scheme should be based on the whole process rather than on single performances. Dismissal strategies have to be tailored on peculiarities of single services, but some typologies can be outlined.

Volume and health outcomes: evidence from systematic reviews and from evaluation of Italian hospital data. / Volumi di attività ed esiti delle cure: prove scientifiche in letteratura ed evidenze empiriche in Italia.

BACKGROUND Improving quality and effectiveness of healthcare is one of the priorities of health policies. Hospital or physician volume represents a measurable variable with an impact on effectiveness of healthcare. An Italian law calls for the definition of «qualitative, structural, technological, and quantitative standards of hospital care¼. There is a need for an evaluation of the available scientific evidence in order to identify qualitative, structural, technological, and quantitative standards of hospital care, including the volume of care above or below which the public and private hospitals may be accredited (or not) to provide specific healthcare interventions. OBJECTIVES To identify conditions/interventions for which an association between volume and outcome has been investigated. To identify conditions/interventions for which an association between volume and outcome has been proved. To analyze the distribution of Italian health providers by volume of activity. To measure the association between volume of care and outcomes of the health providers of the Italian National Health Service (NHS). METHODS Systematic review An overview of systematic reviews was performed searching PubMed, EMBASE, and The Cochrane Library up to November 2016. Studies were evaluated by 2 researchers independently; quality assessment was performed using the AMSTAR checklist. For each health condition and outcome, if available, total number of studies, participants, high volume cut-off values, and metanalysis have been reported. According to the considered outcomes, health topics were classified into 3 groups: positive association: a positive association was demonstrated in the majority of studies/participants and/or a pooled measure (metanalysis) with positive results was reported; lack of association: both studies and/or metanalysis showed no association; no sufficient evidence of association: both results of single studies and metanalysis do not allow to draw firm conclusions on the association between volume and outcome. Analysis of the distribution of Italian hospitals by volume of activity and the association between volume of activity and outcomes: the Italian National Outcome evaluation Programme 2016 The analyses were performed using the Hospital Information System and the National Tax Register (year 2015). For each condition, the number of hospitals by volume of activity was calculated. Hospitals with a volume lower than 3-5 cases/year were excluded. For conditions with more than 1,500 cases/year and frequency of outcome ≥1%, the association between volume of care and outcome was analyzed estimating risk-adjusted outcomes. RESULTS Bibliographic searches identified 80 reviews, evaluating 48 different clinical areas. The main outcome considered was intrahospital/30-day mortality. The other outcomes vary depending on the type of condition or intervention in study. The relationship between hospital volume and outcomes was considered in 47 out of 48 conditions: 34 conditions showed evidence of a positive association; • 14 conditions consider cancer surgery for bladder, breast, colon, rectum, colon rectum, oesophagus, kidney, liver, lung, ovaries, pancreas, prostate, stomach, head and neck; • 11 conditions consider cardiocerebrovascular area: nonruptured and ruptured abdominal aortic aneurysm, acute myocardial infarction, brain aneurysm, carotid endarterectomy, coronary angioplasty, coronary artery bypass, paediatric heart surgery, revascularization of lower limbs, stroke, subarachnoid haemorrhage; • 2 conditions consider orthopaedic area: knee arthroplasty, hip fracture; • 7 conditions consider other areas: AIDS, bariatric surgery, cholecystectomy, intensive care unit, neonatal intensive care unit, sepsis, and traumas; for 3 conditions, no association was demonstrated: hip arthroplasty, dialysis, and thyroidectomy. for the remaining 10 conditions, the available evidence does not allow to draw firm conclusions about the association between hospital volume and considered outcomes: surgery for testicular cancer and intracranial tumours, paediatric oncology, aortofemoral bypass, cardiac catheterization, appendectomy, colectomy, inguinal hernia, respiratory failure, and hysterectomy. The relationship between volume of clinician/surgeon and outcomes was assessed only through the literature re view; to date, it is not possible to analyze this association for Italian health provider hospitals, since information on the clinician/surgeon on the hospital discharge chart is missing. The literature found a positive association for 21 conditions: 9 consider surgery for cancer: bladder, breast, colon, colon rectum, pancreas, prostate, rectum, stomach, and head and neck; 5 consider the cardiocerebrovascular area: ruptured and nonruptured abdominal aortic aneurysm, carotid endarterectomy, paediatric heart surgery, and revascularization of the lower limbs; 2 consider the orthopaedic area: knee and hip arthroplasty; 5 consider other areas: AIDS, bariatric surgery, hysterectomy, intensive care unit, and thyroidectomy. The analysis of the distribution of Italian hospitals concerned the 34 conditions for which the systematic review has shown a positive volume-outcome association. For the following, it was possible to conduct the analysis of the association using national data: unruptured abdominal aortic aneurysm, coronary angioplasty, hip arthroplasty, knee arthroplasty, coronary artery bypass, cancer surgery (colon, liver, breast, pancreas, lung, prostate, kidney, and stomach), laparoscopic cholecystectomy, hip fracture, stroke, acute myocardial infarction. For these conditions, the association between volume and outcome of care was observed. For laparoscopic cholecystectomy and surgery of the breast and stomach cancer, the association between the volume of the discharge (o dismissal) operating unit and the outcome was analyzed. The outcomes differ depending on the condition studied. The shape of the relationship is variable among different conditions, with heterogeneous slope of the curves. DISCUSSION For many conditions, the overview of systematic reviews has shown a strong evidence of association between higher volumes and better outcomes. The quality of the available reviews can be considered good for the consistency of the results between the studies and for the strength of the association; however, this does not mean that the included studies are of good quality. Analyzing national data, potential confounders, including age and comorbidities, have been considered. The systematic review of the literature does not permit to identify predefined volume thresholds. The analysis of national data shows a strong improvement in outcomes in the first part of the curve (from very low to higher volumes) for most conditions. In some cases, the improvement in outcomes remains gradual or constant with the increasing volume of care; in other, the analysis could allow the identification of threshold values beyond which the outcome does not further improve. However, a good knowledge of the relationship between effectiveness of treatments and costs, the geographical distribution and the accessibility to healthcare services are necessary to choose the minimum volumes of care, under which specific health procedures could not been provided in the NHS. Some potential biases due to the use of information systems data should also be considered. The different way of coding among hospitals could lead to a different selection of cases for some conditions. Regarding the definition of the exposure (volume of care), a possible bias could result from misclassification of health providers with high volume of activity. Performing the intervention in different departments/ units of the same hospital would result in an overestimation of the volume of care measured for hospital rather than for department/unit. For the conditions with a further fragmentation within the same structure, the association between volumes of discharge department and outcomes has also been evaluated. In this case, the two curves were different. The limit is to attribute the outcome to the discharge unit, which in case of surgery may not be the intervention unit. A similar bias could occur if the main determinant of the outcome of treatment was the caseload of each surgeon. The results of the analysis may be biased when different operators in the same hospital/unit carried out the same procedure. In any case, the observed association between volumes and outcome is very strong, and it is unlikely to be attributable to biases of the study design. Another aspect on which there is still little evidence is the interaction between volume of the hospital and of the surgeon. A MEDICARE study suggests that in some conditions, especially for specialized surgery, the effect of the surgeon's volume of activity is different depending on the structure volume, whereas it would not differ for some less specialized surgery conditions. The data here presented still show extremely fragmented volumes of both clinical and surgical areas, with a predominance of very low volume structures. Health systems operate, by definition, in a context of limited resources, especially when the amount of resources to allocate to the health system is reduced. In such conditions, the rationalization of the organization of health services based on the volume of care may make resources available to improve the effectiveness of interventions. The identification and certification of services and providers with high volume of activity can help to reduce differences in the access to non-effective procedures. To produce additional evidence to guide the reorganization of the national healthcare system, it will be necessary to design further primary studies to evaluate the effectiveness and safety of policies aimed at concentrating interventions in structures with high volumes of activity.

[Literature review of childhood leukaemia cluster investigations]. / Revisione degli studi di cluster di leucemia infantile.

Since the first report of a possible cluster of childhood leukaemia in 1963, many studies have shown a tendency to clustering in space and/or in time of this disease. This paper summarizes the studies about clusters of childhood leukaemia in the international context and in Italy, and discusses the aetiological hypotheses particularly in reference to exposures in the area of residence. Thirty-three cluster studies have been identified through a literature search performed using the PubMed bibliographic database, websites of main national and international health authorities, and relevant reviews published on this topic. Most of leukaemia cluster studies were conducted following an alarm in the nearby areas of a point source of toxic substances as nuclear power plants, chemical-industrial sites, military bases, broadcasting antennas. As alternative explanation, in several clusters an infectious aetiology was hypothesized (population mixing or delayed infection hypothesis). The uncertainty associated with cluster investigations underlines the importance of applying rigorous methods and transparent decision making, involving parents of children with cancer and the local community, and taking into account all potential aetiological factors, especially those for which a biological plausibility exists.

[Audit and feedback, and continuous quality improvement strategies to improve the quality of care for type 2 diabetes: a systematic review of literature]. / Audit e feedback e interventi di continuous quality improvement per il miglioramento della qualità delle cure nella gestione del diabete di tipo 2: una revisione sistematica della letteratura scientifica.

OBJECTIVES: we analysed evidence on effective interventions to improve the quality of care and management in patients with diabetes type 2. This review focuses particularly on audit and feedback intervention, targeted to healthcare providers, and continuous quality improvement (CQI) involving health professionals and health care systems, respectively. METHODS: we searched The Cochrane Library, PubMed, and EMBASE (search period: January 2005-December 2015) to identify systematic reviews (SR) and randomized controlled trials (RCTs) considering patients' outcomes and process measures as quality indicators in diabetes care. Selection of studies and data extraction were carried out independently by two reviewers. Methodological quality of individual studies was assessed using the checklist «Assessment of methodological quality of systematic review¼ (AMSTAR) and the Cochrane's tool, respectively. We produced summaries of results for each study design. RESULTS: the search process resulted in 810 citations. One SR and 7 RCTs that compared any intervention in which audit and feedback and CQI was a component vs. other interventions were selected. The SR found that audit and feedback activity was associated with improvements of glycaemic (mean difference: 0.26; 95%CI 0.08;0.44) and cholesterol control (mean difference: 0.03; 95%CI -0.04;0.10). CQI interventions were not associated with an improvement of quality of diabetes care. The RCTs considered in this review compared a broad range of interventions including feedback as unique activity or as part of more complex strategies. The methodological quality was generally poor in all the included trials. CONCLUSIONS: the available evidence suggests that audit and feedback and CQI improve quality of care in diabetic patients, although the effect is small and heterogeneous among process and outcomes indicators.

Anticonvulsants for cocaine dependence.

BACKGROUND: Cocaine dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence, none is currently available for cocaine dependence, despite two decades of clinical trials primarily involving antidepressant, anticonvulsivant and dopaminergic medications. Extensive consideration has been given to optimal pharmacological approaches to the treatment of individuals with cocaine dependence, and both dopamine antagonists and agonists have been considered. Anticonvulsants have been candidates for use in the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction. OBJECTIVES: To evaluate the efficacy and safety of anticonvulsants for individuals with cocaine dependence. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1966 to June 2014), EMBASE (1988 to June 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to June 2014), Web of Science (1991 to June 2014) and the reference lists of eligible articles. SELECTION CRITERIA: All randomised controlled trials and controlled clinical trials that focus on the use of anticonvulsant medications to treat individuals with cocaine dependence. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included a total of 20 studies with 2068 participants. We studied the anticonvulsant drugs carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. Only one study had one arm by which the anticonvulsant was compared with the antidepressant desipramine. Upon comparison of anticonvulsant versus placebo, we found no significant differences for any of the efficacy and safety measures. Dropouts: risk ratio (RR) 0.95, 95% confidence interval (CI) 0.86 to 1.05, 17 studies, 20 arms, 1695 participants, moderate quality of evidence. Use of cocaine: RR 0.92, 95% CI 0.84 to 1.02, nine studies, 11 arms, 867 participants, moderate quality of evidence; side effects: RR 1.39, 95% CI 1.01 to 1.90, eight studies, 775 participants; craving: standardised mean difference (SMD) -0.25, 95% CI -0.59 to 0.09, seven studies, eight arms, 428 participants, low quality of evidence. AUTHORS' CONCLUSIONS: Although caution is needed when results from a limited number of small clinical trials are assessed, no current evidence supports the clinical use of anticonvulsant medications in the treatment of patients with cocaine dependence. Although the findings of new trials will improve the quality of study results, especially in relation to specific medications, anticonvulsants as a category cannot be considered first-, second- or third-line treatment for cocaine dependence.