Laura Amato

Background: The net health benefit of using antipsychotics in children and adolescents with ASD is unclear. This review was performed to provide the evidence necessary to inform the Italian national guidelines for the management of ASD. Methods: We performed a systematic review of randomized controlled trials (RCTs) comparing antipsychotics versus placebo for the treatment of ASD in children and adolescents. For efficacy, acceptability and safety we considered outcomes evaluated by the guideline panel critical and important for decision-making. Continuous outcomes were analyzed by using standardized mean difference (SMD), and dichotomous outcomes by calculating the risk ratio (RR), with their 95% confidence interval (95% CI). Data were analyzed using a random effects model. We used the Cochrane tool to assess risk of bias of included studies. Certainty in the evidence of effects was assessed according to the GRADE approach. Results: We included 21 RCTs with 1,309 participants, comparing antipsychotics to placebo. Antipsychotics were found effective on “restricted and repetitive interests and behaviors” (SMD − 0.21, 95% CI − 0.35 to − 0.07, moderate certainty), “hyperactivity, inattention, oppositional, disruptive behavior” (SMD − 0.67, 95% CI − 0.92 to − 0.42, moderate certainty), “social communication, social interaction” (SMD − 0.38, 95% CI − 0.59 to − 0.16, moderate certainty), “emotional dysregulation/irritability” (SMD − 0.71, 95% CI − 0.98 to − 0.43, low certainty), “global functioning, global improvement” (SMD − 0.64, 95% CI − 0.96 to − 0.33, low certainty), “obsessions, compulsions” (SMD − 0.30, 95% CI − 0.55 to − 0.06, moderate certainty). Antipsychotics were not effective on “self-harm” (SMD − 0.14, 95% CI − 0.58 to 0.30, very low certainty), “anxiety” (SMD − 0.38, 95% CI − 0.82 to 0.07, very low certainty). Antipsychotics were more acceptable in terms of dropout due to any cause (RR 0.61, 95% CI 0.48 to 0.78, moderate certainty), but were less safe in terms of patients experiencing adverse events (RR 1.19, 95% CI 1.07 to 1.32, moderate certainty), and serious adverse events (RR 1.07, 95% CI 0.48 to 2.43, low certainty). Conclusions: Our systematic review and meta-analysis found antipsychotics for children and adolescents with ASD more efficacious than placebo in reducing stereotypies, hyperactivity, irritability and obsessions, compulsions, and in increasing social communication and global functioning. Antipsychotics were also found to be more acceptable, but less safe than placebo.

Background: Autism Spectrum Disorder (ASD) is a neuro-developmental disorder that affects communication and behavior with a prevalence of approximately 1% worldwide. Health outcomes of interventions for ASD are largely Participant Reported Outcomes (PROs). Specific guidelines can help support the best care for people with ASD to optimize these health outcomes but they have to adhere to standards for their development to be trustworthy. Objective: The goal of this article is to describe the new methodological standards of the Italian National Institute of Health and novel aspects of this guideline development process. This article will serve as a reference standard for future guideline development in the Italian setting. Methods: We applied the new standards of the Italian National Institute of Health to the two guidelines on diagnosis and management of children/adolescents and adults with ASD, with a focus on the scoping, panel composition, management of conflict of interest, generation and prioritization of research questions, early stakeholders’ involvement, and PROs. Recommendations are based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence-to-Decision frameworks. Results: Following a public application process, the ISS established two multidisciplinary panels including people with ASD and/or their caregivers. Seventy-nine research questions were identified as potentially relevant for the guideline on children and adolescents with ASD and 31 for the one on adults with ASD. Questions deemed to have the highest priority were selected for inclusion in the guidelines. Other stakeholders valued their early involvement in the process which will largely focus on PROs. The panels then successfully piloted the development of recommendations using the methodological standards and process set by the ISS with a focus on PROs. Conclusions: In this article, we describe the development of practice guidelines that focus on PROs for the diagnosis and management of ASD based on novel methods for question prioritization and stakeholder involvement. The recommendations allow for the adoption or adaptation to international settings.

Recently, prescription opioids have been detected in up to 77% of opioid-related overdose fatalities, and the health, social, and economic costs associated with opioid use disorder (OUD) continue to increase.^1-3 Importantly, the quantities of opioids prescribed in different regions have been strongly associated with higher rates of subsequent opioid overdose.⁴ Nevertheless, despite the well-recognized harms of prescription opioids, recent data suggest that the number of opioid prescriptions is remaining stable, and while the United States has seen a decrease in the national opioid prescribing rate, in 2017, prescribing rates remained very high in most US jurisdictions.^5,6

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. Conclusion. 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.

SUMMARY. Stimulant use disorders are highly prevalent with a large burden of disease. Most clinical guidelines recommend psychosocial interventions, but there are no clear hierarchies or indications. Moreover, these interventions have been reported unevenly in the literature. Identifying the most suitable treatment for each patient therefore represents a major challenge. In this review, we describe all psychosocial interventions for stimulant use disorders investigated in randomized controlled trials – including contingency management, cognitive behavioral interventions, community reinforcement approach, 12-step program, meditation-based interventions and physical exercise, supportive expressive psychodynamic therapy, interpersonal psychotherapy, family therapy, motivational interviewing, drug counseling –, and we synthesize the main findings of these studies. Similarities and differences between treatments are highlighted, suggesting that distinct psychosocial interventions can be relevant for certain patients’ groups but not for others. Conversely, several interventions can be equally effective in similar clinical contexts, suggesting that a shared element such as therapeutic alliance is key. Finally, combined approaches emerge as a viable option for people with complex needs. Future studies will need to benchmark psychosocial interventions in stimulant use disorders and ascertain markers of response with a view to individualized treatment.

Packer1 says that the one who submits a research for public good should be ready to receive a request for data sharing for examination and re-analysis and that tax payers assume that a national agency is checking such data and analysis. Here we discuss Cochrane’s practice on data sharing. Open science, as endorsed by the G7,2 includes sharing data, computer code, and materials. It is essential for reproducibility, collaboration, and innovation. We support the work of Cochrane, but are concerned that Cochrane is not sharing all its reviews’ data. These data should be fully accessible for reuse by third parties. Cochrane, a non-profit private company3 and registered charity, produces and maintains systematic reviews in health and social care. Its work is undertaken by a global network of thousands of people,4 and its support largely comes from public funding.5 Most people producing Cochrane reviews are volunteers not specifically funded for this work,67 and Cochrane encourages “crowdsourcing” of work.8910 Cochrane editorial bases help volunteers obtain study reports and manually extract the wealth of data needed to generate systematic reviews.111213 Cochrane teams use RevMan software14 to produce files in standard format (XML), storing information on the studies, their methods, and results for publication in the Cochrane Library. Benefits of sharing extracted data from trials and systematic reviews are well known, as are the costs of not sharing.13151617 Sharing maximises transparency, reliability of data extraction, and syntheses. It improves access to data—saving time and money—and opens new avenues of inquiry.18 Sharing is associated with increased citations,19 more publications,20 and reuse for new purposes.16 Structured data from Cochrane should be fully accessible for download, reuse, and review (box 1). Currently, they are not. …

Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence and milder withdrawal symptoms than heroin. The evidence on withdrawal management of heroin might therefore not be exactly applicable for opium. To assess the effectiveness and safety of various pharmacologic therapies for the management of the acute phase of opium withdrawal. We searched the following sources up to September 2017: CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, regional and national databases (IMEMR, Iranmedex, and IranPsych), main electronic sources of ongoing trials, and reference lists of all relevant papers. In addition, we contacted known investigators to obtain missing data or incomplete trials. Controlled clinical trials and randomised controlled trials on pharmacological therapies, compared with no intervention, placebo, other pharmacologic treatments, different doses of the same drug, and psychosocial intervention, to manage acute withdrawal from opium in a maximum duration of 30 days. We used the standard methodological procedures expected by Cochrane. We included 13 trials involving 1096 participants. No pooled analysis was possible. Studies were carried out in three countries, Iran, India, and Thailand, in outpatient and inpatient settings. The quality of the evidence was generally very low. When the mean of withdrawal symptoms was provided for several days, we mainly focused on day 3. The reason for this was that the highest severity of opium withdrawal is in the second to fourth day. Comparing different pharmacological treatments with each other, clonidine was twice as good as methadone for completion of treatment (risk ratio (RR) 2.01, 95% confidence interval (CI) 1.69 to 2.38; 361 participants, 1 study, low-quality evidence). All the other results showed no differences between the considered drugs: baclofen versus clonidine (RR 1.06, 95% CI 0.63 to 1.80; 66 participants, 1 study, very low-quality evidence); clonidine versus clonidine plus amantadine (RR 1.03, 95% CI 0.86 to 1.24; 69 participants, 1 study); clonidine versus buprenorphine in an inpatient setting (RR 1.04, 95% CI 0.90 to 1.20; 1 study, 35 participants, very low-quality evidence); methadone versus tramadol (RR 0.95, 95% CI 0.65 to 1.37; 1 study, 72 participants, very low-quality evidence); methadone versus methadone plus gabapentin (RR 1.17, 95% CI 0.96 to 1.43; 1 study, 40 participants, low-quality evidence), and tincture of opium versus methadone (1 study, 74 participants, low-quality evidence). Comparing different pharmacological treatments with each other, adding amantadine to clonidine decreased withdrawal scores rated at day 3 (mean difference (MD) -3.56, 95% CI -5.97 to -1.15; 1 study, 60 participants, very low-quality evidence). Comparing clonidine with buprenorphine in an inpatient setting, we found no difference in withdrawal symptoms rated by a physician (MD -1.40, 95% CI -2.93 to 0.13; 1 study, 34 participants, very low-quality evidence), and results in favour of buprenorpine when rated by participants (MD -11.80, 95% CI -15.56 to -8.04). Buprenorphine was superior to clonidine in controlling severe withdrawal symptoms in an outpatient setting (RR 0.35, 95% CI 0.19 to 0.64; 1 study, 76 participants). We found no difference in the comparison of methadone versus tramadol (MD 0.04, 95% CI -2.68 to 2.76; 1 study, 72 participants) and in the comparison of methadone versus methadone plus gabapentin (MD -2.20, 95% CI -6.72 to 2.32; 1 study, 40 participants). Comparing clonidine versus buprenorphine in an outpatient setting, more adverse effects were reported in the clonidine group (1 study, 76 participants). Higher numbers of participants in the clonidine group experienced hypotension at days 5 to 8, headache at days 1 to 8, sedation at days 5 to 8, dizziness and dry mouth at days 1 to 10, and nausea at days 1 to 9. Sweating was reported in a significantly higher number of participants in the buprenorphine group at days 1 to 10. We found no difference between groups for all the other comparisons considering this outcome. Comparing different dosages of the same pharmacological detoxification treatment, a high dose of clonidine (1 to 1.2 mg/day) did not differ from a low dose of clonidine (0.5 to 0.6 mg/day) in completion of treatment in an inpatient setting (RR 1.00, 95% CI 0.84 to 1.19; 1 study, 68 participants), however a higher number of participants with hypotension was reported in the high-dose group (RR 3.25, 95% CI 1.77 to 5.98). Gradual reduction of methadone was associated with more adverse effects than abrupt withdrawal of methadone (RR 2.25, 95% CI 1.02 to 4.94; 1 study, 20 participants, very low-quality evidence). Results did not support using any specific pharmacological approach for the management of opium withdrawal due to generally very low-quality evidence and small or no differences between treatments. However, it seems that opium withdrawal symptoms are significant, especially at days 2 to 4 after discontinuation of opium. All of the assessed medications might be useful in alleviating symptoms. Those who receive clonidine might experience hypotension.

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. 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. 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. 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.