Child abuse associates with an imbalance of oligodendrocyte-lineage cells in ventromedial prefrontal white matter.

Child abuse (CA) is a major risk factor for depression, and strongly associates with suicidal behavior during adulthood. Neuroimaging studies have reported widespread changes in white matter integrity and brain connectivity in subjects with a history of CA. Although such observations could reflect changes in myelin and oligodendrocyte function, their cellular underpinnings have never been addressed. Using postmortem brain samples from depressed suicides with or without history of CA and matched controls (18 per group), we aimed to characterize the effects of CA on oligodendrocyte-lineage (OL) cells in the ventromedial prefrontal white matter. Using immunoblotting, double-labeling immunofluorescence and stereological estimates of stage-specific markers, we found that CA is associated with increased numbers of mature myelinating oligodendrocytes, accompanied by decreased numbers of more immature OL cells. This was paralleled by an increased expression of transcription factor MASH1, which is involved in the terminal differentiation of the OL, suggesting that CA may trigger an increased maturation, or bias the populations of OL cells toward a more mature phenotype. Some of these effects, which were absent in the brain of depressed suicides with no history of CA, were also found to recover with age, suggesting that changes in the balance of the OL may reflect a transient adaptive mechanism triggered by early-life adversity. In conclusion, our results indicate that CA in depressed suicides is associated with an imbalance of the OL in the ventromedial prefrontal white matter, an effect that could lead to myelin remodeling and long-term connectivity changes within the limbic network.

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.

Modifiable and non-modifiable risk factors affecting walking recovery after hip fracture.

UNLABELLED: Modifiable and non-modifiable predictors of mobility recovery were analyzed on a sample of 774 hip fracture patients according to pre-fracture abilities. Overall predictors were mostly non-modifiable factors related to frailty of patients with the exception of 25-hydroxyvitamin D concentration which significantly affected walking recovery, especially in patients with higher pre-fracture performance. INTRODUCTION: This study aims to investigate mobility changes after hip fracture with the aim of identifying modifiable and non-modifiable predictors of mobility recovery according to different pre-fracture abilities. METHODS: This is a prospective inception cohort study of consecutive older patients, admitted with a fragility hip fracture in three Hospitals of Emilia Romagna (Italy). A sample of 774 patients alive at the sixth month was divided into three groups according to pre-fracture ambulation ability (group 1: mobile outdoors; group 2: mobile indoors; and group 3: mobile with help). The relationship between baseline characteristics of patients and the odds of walking recovery was analyzed using multivariate regression analysis. RESULTS: Mortality differed significantly among the three groups and was the highest in patients needing help to walk. Among the survivors, only 50.3 % of patients recovered walking ability. In a multivariate analysis, independent risk factors were different among the three groups. In group 1, older age, comorbidities, the use of walking devices before fracture, and low albumin level acted as negative factors while male gender, a pre-fracture high functional status, and higher 25-hydroxyvitamin D levels increased the probability of full recovery. In group 2, only pre-fracture functional status and 25-hydroxyvitamin D concentration were related to the recovery of walking ability. Pre-fracture functional status was also the only significant predictor for patients in group 3. CONCLUSIONS: Several baseline characteristics of patients are related to the likelihood of recovering walking ability after hip fracture. The 25-hydroxyvitamin D level seems to be the only relevant modifiable factor even if the effectiveness of its supplementation has yet to be demonstrated.

The fibroblast growth factor-23 and Vitamin D emerge as nontraditional risk factors and may affect cardiovascular risk.

OBJECTIVES: Fibroblast growth factor-23 (FGF-23) and vitamin D are hormones involved in phosphate homoeostasis. They also directly influence cardiomyocyte hypertrophy. We examined whether the relationships between levels of vitamin D or FGF-23, cardiac phenotype and outcome were independent of established cardiac biomarkers in a large cohort of community-dwelling elderly subjects. DESIGN AND SETTING: Plasma levels of FGF-23 and vitamin D were measured in 1851 men and women (65-84 years) resident in the Lazio region of Italy. Participants were referred to eight cardiology centres for clinical examination, electrocardiography, comprehensive Doppler echocardiography and blood sampling. All-cause mortality or hospitalizations were available after a median follow-up of 47 months with record linkage of administrative data. RESULTS: Vitamin D deficiency (<20 ng mL(-1) ) was found in 72.3% of subjects, but FGF-23 levels were normal [74 (58-97) RU per mL]. After adjustment for cardiovascular risk factors and morbidities, low concentrations of vitamin D and high levels of FGF-23 were associated with a higher left ventricular (LV) mass index. Levels of FGF-23 [hazard ratio (HR) (95% confidence interval (CI)) 1.71 (1.28-2.28), P < 0.0001] but not vitamin D [0.76 (0.57-1.01), P = 0.08] were independently associated with mortality after adjustment for clinical risk factors and two cardiac markers together (N-terminal pro-brain natriuretic peptide and high-sensitivity cardiac troponin T), but did not predict hospital admission. People with above median values of FGF-23 and below median values of vitamin D had greater LV hypertrophy and higher mortality. CONCLUSIONS: In community-dwelling elderly individuals with highly prevalent vitamin D deficiency, FGF-23 levels were associated with LV hypertrophy and predicted mortality independently of two robust cardiac biomarkers. A causal relationship was not demonstrated, but the hormones involved in mineral metabolism emerged as nontraditional risk factors and may affect cardiovascular risk.

Inequality in 30-day mortality and the wait for surgery after hip fracture: the impact of the regional health care evaluation program in Lazio (Italy).

INTERVENTIONS: that address inequalities in health care are a priority for public health research. We evaluated the impact of the Regional Health Care Evaluation Program in the Lazio region, which systematically calculates and publicly releases hospital performance data, on socioeconomic differences in the quality of healthcare for hip fracture. DESIGN: Retrospective cohort study. SETTING: and participants We identified, in the hospital information system, elderly patients hospitalized for hip fracture between 01 January 2006 and 31 December 2007 (period 1) and between 01 January 2009 and 30 November 2010 (period 2). MAIN OUTCOME MEASURES: We used multivariate regression models to test the association between socioeconomic position index (SEP, level I well-off to level III disadvantaged) and outcomes: mortality within 30 days of hospital arrival, median waiting time for surgery and proportion of interventions within 48 h. RESULTS: We studied 11 581 admissions. Lower SEP was associated with a higher risk of 30-day mortality in period 1 (relative risk (RR) = 1.42, P = 0.027), but not in period 2. Disadvantaged people were less likely to undergo intervention within 48 h than well-off persons in period 1 (level II: RR = 0.72, P < 0.001; level III: RR = 0.46, P < 0.001) and period 2 (level II: RR = 0.88, P = 0.037; level III: RR = 0.63, P < 0.001). We observed a higher probability of undergoing intervention within 48 h in period 2 compared with the period 1 for each socioeconomic level. CONCLUSION: This study suggests that a systematic evaluation of health outcome approach, including public disclosure of results, could reduce socioeconomic differences in healthcare through a general improvement in the quality of care.

Vitamin D supplementation is required to normalize serum level of 25OH-vitamin D in older adults: an observational study of 974 hip fracture inpatients.

BACKGROUND: Vitamin D deficiency is highly prevalent in older adults in all continents. In this study we assessed the vitamin D status of hip fracture subjects across different hospitals in a real word situation using the data from a multicenter cohort study on outcomes in orthogeriatric units. METHODS: We performed a prospective cohort study on 974 consecutive patients 75 yr or older admitted with fragility hip fracture over a 12 months period at 4 general hospitals of different districts in Emilia Romagna Region, Italy. Data collected included comorbidity, cognitive impairment, prefracture functional status, walking ability, living arrangement along with the use of antiosteoporotic drugs, serum intact PTH and serum 25-hydroxyvitamin D [25(OH)D]. RESULTS: Mean 25(OH)D serum levels were 12.2±9.4 ng/ml and 84.2% of patients had levels below recommended values. Male had a higher probability to have values within the reference range [odds ratio (OR): 1.74 (1.13-2.67); p=0.012] while living in nursing resulted negatively related even if only close to statistical significance [OR: 0.24 (0.06-1.02); p=0.051]. Vitamin D supplementation appeared to be the strongest factor associated with adequate level of vitamin D levels [OR: 4.50 (2.57-7.88); p<0.001). CONCLUSION: This study confirmed the very high rate of severe vitamin D deficiency in Italian subjects admitted with hip fracture. Our study also showed that supplementation of vitamin D is the strongest determinant influencing serum 25(OH)D level of older persons with hip fracture and these results should be taken into account when planning treatment in older persons.

Socio-demographic differences in adherence to evidence-based drug therapy after hospital discharge from acute myocardial infarction: a population-based cohort study in Rome, Italy.

WHAT IS KNOWN AND OBJECTIVE: Adherence to evidence-based drug therapy after acute myocardial infarction has increased over the last decades, but is still unsatisfactory. Our objectives are to set out to analyse patterns of evidence-based drug therapy after acute myocardial infarction (AMI), and evaluating socio-demographic differences. METHODS: A cohort of 3920 AMI patients discharged from hospital in Rome (2006-2007) was selected. Drugs claimed during the 12 months after discharge were retrieved. Drug utilization was defined as density of use (boxes claimed/individual follow-up; chronic use = 6+ boxes/365 days) and therapeutic coverage, calculated through Defined Daily Doses (chronic use: ≥80% of individual follow-up). Patterns of use of single drugs and their combination were described. The association between poly-therapy and gender, age and socio-economic position (small-area composite index based on census data) was analysed through logistic regression, accounting for potential confounders. RESULTS AND DISCUSSION: Most patients used single drugs: 90·5% platelet aggregation inhibitors (antiplatelets), 60·0%ß-blockers, 78·1% agents acting on the renin-angiotensin system (ACEIs/ARBs), 77·8% HMG CoA reductase inhibitors (statins). Percentages of patients with ≥80% of therapeutic coverage were 81·9% for antiplatelets, 17·8% for ß-blockers, 64·4% for ACEIs/ARBs and 76·1% for statins. The multivariate analysis showed gender and age differences in adherence to poly-therapy (females: OR = 0·84; 95% CI 0·72-0·99; 71-80 years age-group: OR = 0·82; 95% CI 0·68-0·99). No differences were observed with respect to socio-economic position. WHAT IS NEW AND CONCLUSION: The availability of information systems offers the opportunity to monitor the quality of care and identify weaknesses in public health-care systems. Our results identify specific factors contributing to non-adherence and hence define areas for more targeted health-care interventions. Our results suggest that efforts to improve adherence should focus on women and older patients.

A cost-utility analysis of increasing percutaneous coronary intervention use in elderly patients with acute coronary syndromes in six European countries.

AIMS: Percutaneous coronary intervention reduces mortality in acute coronary syndrome patients but the cost-utility of increasing its use in elderly acute coronary syndrome patients is unknown. METHODS: We assessed the efficiency of increased percutaneous coronary intervention use compared to current practice in patients aged ≥75 years admitted for acute coronary syndrome in France, Germany, Greece, Italy, Portugal and Spain with a semi-Markov state transition model. In-hospital mortality reduction estimates by percutaneous coronary intervention use and costs were derived from the EUROpean Treatment & Reduction of Acute Coronary Syndromes cost analysis EU project (n = 28,600). Risk of recurrence and out-of-hospital all-cause mortality were obtained from the Information System for the Development of Research in Primary Care (SIDIAP) database from North-Eastern Spain (n = 55,564). In-hospital mortality was modelled using stratified propensity score analysis. The 8-year acute coronary syndrome recurrence risk and out-of-hospital mortality were estimated with a multistate survival model. The scenarios analysed were to increase percutaneous coronary intervention use among patients with the highest, moderate and lowest probability of receiving percutaneous coronary intervention based on the propensity score analysis. RESULTS: France, Greece and Portugal showed similar total costs/1000 individuals (7.29-11.05 m €); while in Germany, Italy and Spain, costs were higher (13.53-22.57 m €). Incremental cost-utility ratios of providing percutaneous coronary intervention to all patients ranged from 2262.8 €/quality adjusted life year gained for German males to 6324.3 €/quality adjusted life year gained for Italian females. Increasing percutaneous coronary intervention use was cost-effective at a willingness-to-pay threshold of 10,000 €/quality adjusted life year gained for all scenarios in the six countries, in males and females. CONCLUSION: Compared to current clinical practice, broadening percutaneous coronary intervention use in elderly acute coronary syndrome patients would be cost-effective across different healthcare systems in Europe, regardless of the selected strategy.

Profiling hospital performance to monitor the quality of care: the case of COPD.

Comparative outcomes data are widely used to monitor quality of care in the cardiovascular area; little is available in the respiratory field. We applied validated methods to compare hospital outcomes for chronic obstructive pulmonary disease (COPD) exacerbation. From the hospital information system, we selected all hospital admissions for COPD exacerbation in Rome (for 2001-2005). Vital status within 30 days was obtained from the municipality mortality register. Each hospital was compared to a pool of hospitals with the lowest adjusted mortality rate (the benchmark). Age, sex and several potential clinical predictors were covariates in logistic regression analysis. 12,756 exacerbated COPD patients were analysed (mean age 74 yrs, 71% males). Diabetes, hypertension, ischaemic heart disease, heart failure and arrhythmia were the most common coexisting conditions. The average crude mortality in the benchmark group was 3.8%; in the remaining population it was 7.5% (range 5.2-17.2%). In comparison with the benchmark, the relative risk of 30-day mortality varied widely across the hospitals (range 1.5-5.9%). A large variability in 30-day mortality after COPD exacerbation exists even considering patients' characteristics. Although these results do not detect mechanisms related to worse outcomes, they may be useful to stimulate providers to revision and improvement of COPD care management.

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.

Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence.

BACKGROUND: Buprenorphine has been reported as an alternative to methadone for maintenance treatment of opioid dependence, but differing results are reported concerning its relative effectiveness indicating the need for an integrative review. OBJECTIVES: To evaluate the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use. SEARCH STRATEGY: We searched the following databases up to October 2006: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK , Alcohol and Drug Council of Australia, Australian Drug Foundation, Centre for Education and Information on Drugs and Alcohol, Library of Congress databases, reference lists of identified studies and reviews, authors were asked about any other published or unpublished relevant RCT. SELECTION CRITERIA: Randomised clinical trials of buprenorphine maintenance versus placebo or methadone maintenance. DATA COLLECTION AND ANALYSIS: Authors separately and independently evaluated the papers and extracted data for meta-analysis. MAIN RESULTS: Twenty four studies met the inclusion criteria (4497 participants), all were randomised clinical trials, all but six were double-blind. The method of allocation concealment was not clearly described in the majority (20) of the studies, but where it was reported the methodological quality was good. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR=1.50; 95% CI: 1.19 - 1.88), medium (RR=1.74; 95% CI: 1.06 - 2.87), and high doses (RR=1.74; 95% CI: 1.02 - 2.96). The high statistical heterogeneity prevented the calculation of a cumulative estimate. However, only medium and high dose buprenorphine suppressed heroin use significantly above placebo. Buprenorphine given in flexible doses was statistically significantly less effective than methadone in retaining patients in treatment (RR= 0.80; 95% CI: 0.68 - 0.95), but no different in suppression of opioid use for those who remained in treatment. Low dose methadone is more likely to retain patients than low dose buprenorphine (RR= 0.67; 95% CI: 0.52 - 0.87). Medium dose buprenorphine does not retain more patients than low dose methadone, but may suppress heroin use better. There was no advantage for medium dose buprenorphine over medium dose methadone in retention (RR=0.79; 95% CI:0.64 - 0.99) and medium dose buprenorphine was inferior in suppression of heroin use. AUTHORS' CONCLUSIONS: Buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is less effective than methadone delivered at adequate dosages.

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.

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.

Disrupted hippocampal neuregulin-1/ErbB3 signaling and dentate gyrus granule cell alterations in suicide.

This corrects the article DOI: 10.1038/tp.2017.132.

Disrupted hippocampal neuregulin-1/ErbB3 signaling and dentate gyrus granule cell alterations in suicide.

Neuregulin-1 (NRG1) and ErbB receptors have been associated with psychopathology, and NRG1-ErbB3 signaling has been shown to increase hippocampal neurogenesis and induce antidepressant-like effects. In this study, we aimed to determine whether deficits in NRG1 or ErbBs might be present in the hippocampus of suicide completers. In well-characterized postmortem hippocampal samples from suicides and matched sudden-death controls, we assessed gene expression and methylation using qRT-PCR and EpiTYPER, respectively. Moreover, in hippocampal tissues stained with cresyl violet, stereology was used to quantify numbers of granule cells and of glia. Granule cell body size was examined with a nucleator probe, and granule cell layer volume with a Cavalieri probe. Unmedicated suicides showed sharply decreased hippocampal ErbB3 expression and decreased numbers of ErbB3-expressing granule cell neurons in the anterior dentate gyrus; a phenomenon seemingly reversed by antidepressant treatment. Furthermore, we found ErbB3 expression to be significantly decreased in the dentate gyrus of adult mice exposed to chronic social defeat stress. Taken together, these results reveal novel suicidal endophenotypes in the hippocampus, as well as a putative etiological mechanism underlying suicidality, and suggest that antidepressant or NRG1 treatment may reverse a potential deficit in anterior dentate gyrus granule cell neurons in individuals at risk of dying by suicide.

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.

A novel missense mutation in the FGB gene (p.Gly302Arg) leading to afibrinogenemia. Predicted structure and function consequences.

Afibrinogenemia represents the rarest form of fibrinogen deficiency. Causative missense mutations occur rarely and may improve the understanding of fibrinogen structure and function. PATIENTS AND METHODS: The propositus was a 26-year-old Argentinian with afibrinogenemia. FGA, FGB and FGG exons and flanking regions were screened by sequencing and the mutant protein was analyzed in silico. RESULTS: A novel missense mutation in the FGB gene (Bbeta Gly272Arg, p.Gly302Arg) was identified. In silico analysis revealed its location in a highly conserved region, which preserves the core fold of the C-terminal beta-chain and is important for proper secretion. A substitution by a positively charged large Arg residue in this area would most likely disturb the core fold by additional interactions with adjacent residues (p.Asp291, p.Asp297, p.Asp311), or by forming of non-native interactions with other proteins, thereby hindering the action of molecular chaperones. Both alternatives would disturb the regular secretion of the beta-chain. CONCLUSIONS: The novel missense mutation in the FGB gene causes afibrinogenemia most probably by affecting the secretion of the fibrinogen beta-chain.