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Female density and distribution are dependent on resource phenology and female availability strongly influences male mating behaviour and success. When a male adopts a 'resource defence' tactic, his reproductive success depends on the location and attractiveness of his territory. Environmental factors associated with territory quality are expected to influence mating success, for example, through territory features or male–male competition. In a protected population of a mountain‐dwelling polygynous herbivore, the Alpine chamois Rupicapra r. rupicapra, we investigated the relationships among mating opportunities, some environmental variables (snow depth, topographic features and size of territories) and male intra‐sexual competition for mating. We recorded the mating behaviour and territory size of 15 GPS‐GSM radio‐tagged territorial males, during five rutting seasons (early November to early December: N = 8 individuals in 2011, N = 9 in 2012, N = 8 in 2015, N = 11 in 2016, N = 7 in 2017; 80% of them were observed for more than one mating season) and related them to snow depth and topography of territories. In ruts with deep snow cover, territorial males had smaller territories and higher number of mating opportunities than in ruts with lower snow cover. Smaller territories showed the highest values of terrain roughness, in turn with little or no snow cover in the mating season, and were visited by a greater number of females, than larger territories. Number of wins was positively influenced by snow depth and negatively related to the frequency of aggressions. The frequency of male–male aggressive interactions was greater during ruts with deep snow cover and for males with territories at higher elevations; additionally, it was negatively related to interactions won. Thus, snow depth, which influences resource distribution and female movements, is confirmed as a strong determinant of male mating opportunities and mating behaviour. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

AIM: To evaluate the efficacy of naltrexone maintenance treatment in preventing relapse in opioid addicts after detoxification. DESIGN: A systematic review according to the methodology developed by the Cochrane Collaboration based on either randomized controlled trials (RCTs) or controlled clinical trials (CCTs). PARTICIPANTS: Seven hundred and seven heroin dependent in- and out-patients, or former heroin addicts dependent on methadone and participating in a naltrexone treatment programme; 89% were male. INTERVENTION: Maintenance treatments on opiate dependent people after detoxification, comparing naltrexone with placebo, pharmacological or behavioural treatments. MEASUREMENTS: The outcomes considered were successfully completed treatment, opioid use under treatment (re)-incarcerations during the study period, mean duration of treatment. FINDINGS: The outcomes tended to be slightly although not significantly in favour of the naltrexone groups. Use of naltrexone in addition to behavioural treatment significantly decreased the probability of (re-)incarceration (OR=0.30; 95% CI 0.12, 0.76). The difficulties in producing a quantitative analysis were due mainly to the heterogeneity of the included studies. CONCLUSIONS: From the available clinical trials performed up to this time, there is insufficient evidence to justify the use of naltrexone in maintenance treatment of opioid addicts. [ABSTRACT FROM AUTHOR]

Aim. To analyse overall and cause-specific mortality among problem drug users (PDUs) attending treatment centres in Rome and to evaluate differences in mortality between genders. Methods. A cohort of 11 432 PDUs entering treatment in Rome between 1980 and 1995 was enrolled and followed-up as of May 31, 1997. Directly standardized mortality rates and standardized mortality ratios (SMRs) and their 95% confidence intervals (95% CI) were calculated. Results. The study population included mainly males (82%), heroin users (92%) and had a mean age of 26.6 (SD 5.9) at enrolment. At the end of the study period 1734 deaths were observed. Overall mortality rates began to increase in 1985-86 and decreased slightly afterwards. AIDS mortality peaked in 1991-92 (13.2/1000) and fell in the following years. A slight decrease in overdose mortality also occurred after 1989-90. Mortality for causes other than AIDS and overdose remained high and relatively steady for the whole study period. Women showed higher mortality rates for AIDS but lower mortality rates for overdose than males. Overall mortality risk among drug addicts was about 15 times higher compared to the general population of the same age among men, and 38 times higher among women. Conclusions. AIDS mortality among drug addicts began to decrease earlier than expected; the decrease was particularly significant in the period 1993-94 for both sexes. Afterwards a continuous but slight decrease was observed among males only. Even though overdose mortality has also decreased slightly in recent years, we still observe high mortality levels for both overdose and all other causes. These findings suggest that interventions directed specifically towards the reduction of baseline mortality are still needed. [ABSTRACT FROM AUTHOR]

Previous studies suggested that proteolysis lasting for many months after slaughtering could be responsible for excessive softness in dry-cured hams. Also, the long-term activity of muscle proteinases is mainly attributed to cathepsin B. Should an additive genetic component exist for the activity level of cathepsin B, such information could be used as a selection criterion for improving meat quality for dry-cured ham production. Data on the growth rate, carcass composition, and meat quality of 234 Large White pigs raised in a test station under a &lsquo|quasi ad libitum' nutritive level and slaughtered at around 160 kg live weight were analysed using a blup-mt-animal model. The cathepsin B activity level showed a moderate heritability (0.23–0.28) in all analyses, and negative genetic correlations with daily gain (- 0.34 to - 0.52) and backfat thickness (- 0.40 to - 0.86), but, with large standard errors. These results suggest that a genetic component exists in explaining the variability of the cathepsin B activity level. Further studies are necessary to confirm the outcome and to investigate genetic correlations with other traits currently under selection. [ABSTRACT FROM AUTHOR]

Introduction and Aims: To corroborate protective effects of a range of drug treatment modalities against overdose mortality risk., Design and Methods: Nested case-control study, with incidence density sampling, selecting controls retrospectively at each case event. Cases and controls came from a sub-cohort of opioid-dependent patients (n = 4444) from two Italian regions (Lazio and Piedmont). From 1998 to 2005, there were 91 overdose deaths (cases) matched to 352 controls. The primary outcome was overdose mortality and the primary exposure was drug treatment: opioid agonist treatment (OAT), opioid detoxification, residential community, psychosocial and other pharmacological treatment. Conditional logistic regression models generated intervention effects comparing mortality risk in and out of treatment, adjusting for confounding variables., Results: Overall, drug treatment reduced overdose mortality risk by 80% [adjusted odds ratio (AOR) 0.18, 95% confidence interval (CI) 0.10-0.33, P < 0.001] compared to being out of treatment. There was a particularly strong protective effect of OAT on overdose mortality (AOR 0.08, 95% CI 0.03-0.23, P < 0.001) compared to being out of treatment. There was evidence of a substantially elevated risk of overdose in the first month of leaving treatment (AOR 23.50, 95% CI 7.84-70.19, P < 0.001) compared to being in treatment., Discussion and Conclusions: The nested case-control design strengthened earlier findings that OAT in Italy has strong protective effects on overdose mortality risk, much stronger than has been previously seen in other Western European settings., (© 2020 Australasian Professional Society on Alcohol and other Drugs.)

Background: Real-time monitoring is used to the ends of postmarketing observational research on newly marketed drugs. We implemented a pilot near-real-time monitoring program on the test case of oral anticoagulants. Specifically, we evaluated the safety and effectiveness of direct oral anticoagulants compared to vitamin K antagonists in nonvalvular atrial fibrillation secondary prevention during 2013-2015 in the Lazio Region, Italy., Methods and Results: A cohort study was conducted using a sequential propensity-score-matched new user parallel-cohort design. Sequential analyses were performed using Cox models. Overall, 10 742 patients contributed to the analyses. Compared with vitamin K antagonists, direct oral anticoagulant use was associated with a reduction of all-cause mortality (0.81; 95% confidence interval [CI] 0.66-0.99), cardiovascular mortality (0.71; 95% CI 0.54-0.93), myocardial infarction (0.67; 95% CI 0.43-1.04), ischemic stroke (0.87; 95% CI 0.52-1.45), hemorrhagic stroke (0.25; 95% CI 0.07-0.88), and with a nonsignificant increase of gastrointestinal bleeding (1.26; 95% CI 0.69-2.30)., Conclusions: The present pilot study is a cornerstone to develop real-time monitoring for new drugs in our region., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Aims: The World Health Organization (WHO), and a growing number of other organizations, have adopted the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system in order to both assess the quality of research evidence and develop clinical practice guidelines. In 2009 WHO published a guideline on psychosocially assisted pharmacological treatment of opioid dependence, based on the results of Cochrane Reviews summarized using the GRADE methodology. The main features of this system are an a priori definition of outcomes and their relevance, and distinction between the quality of evidence (also referred to as confidence in the estimate of intervention effect) and the strength of recommendations. We consider how successful this approach has been., Analysis and Evidence: We discuss the merits and limitations of using Cochrane Reviews and GRADE framework in developing guidelines in the field of drug addiction. In 2009 a panel of multi-disciplinary international experts identified 15 clinical questions and eight relevant outcomes. Cochrane reviews were available for each clinical question and four outcomes. The panel formulated 15 recommendations. Eight recommendations were classified as strong, two of which were based on high-quality evidence and three on very low-quality evidence. For example, the strong recommendation to use methadone in adequate doses in preference to buprenorphine was based on high-quality evidence, while the strong recommendation not to use the combination of opioid antagonists with heavy sedation in the management of opioid withdrawal was based on low-quality evidence., Conclusions: An explicit stepwise process of moving from evaluation of the quality of evidence to the definition of the strength of recommendations is important in providing practical and clear clinical guidance for practitioners and policy-makers in addiction., (© 2014 Society for the Study of Addiction.)

Background and Objective: The Cochrane Drugs and Alcohol Group aims to produce, update, and disseminate systematic reviews on the prevention, treatment, and rehabilitation of problematic drug and alcohol use. This paper describes what the Group has done since the 1990s to produce evidence to guide policy, practice, and research., Method: We analyze the coverage of topics by our reviews, the body of studies they have included, and the evidence produced., Results: By July 2013, the Group had published 67 reviews, with 376 authors from 25 different countries. These reviews included 906 studies, of 3061 studies considered for inclusion. Most (90%) included studies were randomized trials. Considering the 'Implications for practice' section of each review, 41% interventions were classified as 'do it', 15% as 'do not do', and 44% as 'do only in research'. These proportions varied according to the type of substance of abuse studied. The proportion of 'do it' interventions were 46% for alcohol, 40% for opioids, 20% for psychostimulants, 40% for polydrugs, and 62% for prevention., Conclusion: Cochrane Reviews produced by the Drugs and Alcohol Group provide evidence on the effectiveness of several interventions, and identify areas of uncertainty where new research is needed., (© 2013 Chinese Cochrane Center, West China Hospital of Sichuan University and Wiley Publishing Asia Pty Ltd.)

Aims: To assess the incidence or prevalence of opioid dependence syndrome in adults (with and without previous history of substance abuse) following treatment with opioid analgesics for pain relief., Methods: Medline, Embase, CINHAL and the Cochrane Library were searched up to January 2011. Systematic reviews and primary studies were included if they reported data about incidence or prevalence of opioid dependence syndrome (as defined by DSM-IV or ICD-10) in patients receiving strong opioids (or opioid-type analgesics) for treatment of acute or chronic pain due to any physical condition. The data were abstracted, and the methodological quality was assessed using validated checklists., Results: Data were extracted from 17 studies involving a total of 88 235 participants. The studies included three systematic reviews, one randomized controlled trial, eight cross-sectional studies and four uncontrolled case series. Most studies included adult patients with chronic non-malignant pain; two also included patients with cancer pain; only one included patients with a previous history of dependence. Incidence ranged from 0 to 24% (median 0.5%); prevalence ranged from 0 to 31% (median 4.5%)., Conclusions: The available evidence suggests that opioid analgesics for chronic pain conditions are not associated with a major risk for developing dependence., (© 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.)

Issues: Cross-sectional surveys have revealed that cannabis is the most widely used illicit substance in Western countries. Cannabis intoxication can lead to acute, transient psychotic symptoms and the short-term exacerbation of pre-existing psychotic symptoms. However, controversy exists about whether cannabis can actually cause long-term psychosis., Approach: We summarised the findings of systematic reviews on the association between cannabis use and psychosis, searching MEDLINE, EMBASE and CINAHL up to August 2007. We assessed the methodological quality, selected the better quality reviews and analysed reasons for discordant results., Key Findings: We included five systematic reviews. Four of the reviews performed a meta-analysis and showed a consistent association between cannabis use and psychosis; the fifth review considered psychological problems more broadly, did not perform a meta-analysis and reported an inconsistent association. The reasons for discordance were: different outcomes (psychosis vs. psychological problems), different inclusion criteria for primary studies and different methods for summarising the results., Implications: This overview shows a consistent association between cannabis use and psychotic symptoms, though it is not possible to draw firm conclusions about a causal relationship. Reverse causality and residual confounding cannot be excluded. An interaction with other environmental and genetic factors is difficult to ascertain., Conclusion: We conclude that there is insufficient knowledge to determine the level of risk associated with cannabis use in relation to psychotic symptoms and that more information is needed on both the risks of cannabis use and the benefits of preventive interventions to support evidence-based approaches in this area.

Background: Specialist drug treatment is critical to overdose prevention; methadone maintenance is effective, but we lack evidence for other modalities. We evaluate the impact of a range of treatments for opiate dependence on overdose mortality., Methods: Prospective cohort study of 10,454 heroin users entering treatment 1998-2001 in Italy followed-up for 10,208 person-years in treatment and 2,914 person-years out of treatment. Standardized overall mortality ratios (SMR) estimate excess mortality risk for heroin users in and out of treatment compared to the general population. Cox models compare the hazard ratio (HR) of overdose between heroin users in treatment and out of treatment., Results: There were 41 overdose deaths, 10 during treatment and 31 out of treatment, generating annual mortality rates of 0.1% and 1.1% and SMRs of 3.9 [95% confidence interval (CI) 2.8-5.4] and 21.4 (16.7-27.4), respectively. Retention in any treatment was protective against overdose mortality (HR 0.09 95% CI 0.04-0.19) compared to the risk of mortality out of treatment, independent of treatment type and potential confounders. The risk of a fatal overdose was 2.3% in the month immediately after treatment and 0.77% in the subsequent period; compared to the risk of overdose during treatment the HR was 26.6 (95% CI 11.6-61.1) in the month immediately following treatment and 7.3 (3.3-16.2) in the subsequent period., Conclusions: We demonstrate that a range of treatments for heroin dependence reduces overdose mortality risk. However, the considerable excess mortality risk in the month following treatment indicates the need for greater health education of drug users and implementation of relapse and overdose death prevention programmes. Further investigation is needed to measure and weigh the potential benefits and harms of short-term therapies for opiate use.