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BACKGROUND: Spasticity and chronic neuropathic pain are common and serious symptoms in people with multiple sclerosis (MS). These symptoms increase with disease progression and lead to worsening disability, impaired activities of daily living and quality of life. Anti‐spasticity medications and analgesics are of limited benefit or poorly tolerated. Cannabinoids may reduce spasticity and pain in people with MS. Demand for symptomatic treatment with cannabinoids is high. A thorough understanding of the current body of evidence regarding benefits and harms of these drugs is required. OBJECTIVES: To assess benefit and harms of cannabinoids, including synthetic, or herbal and plant‐derived cannabinoids, for reducing symptoms for adults with MS. SEARCH METHODS: We searched the following databases from inception to December 2021: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), CINAHL (EBSCO host), LILACS, the Physiotherapy Evidence Database (PEDro), the World Health Organisation International Clinical Trials Registry Platform, the US National Institutes of Health clinical trial register, the European Union Clinical Trials Register, the International Association for Cannabinoid Medicines databank. We hand searched citation lists of included studies and relevant reviews. SELECTION CRITERIA: We included randomised parallel or cross‐over trials (RCTs) evaluating any cannabinoid (including herbal Cannabis, Cannabis flowers, plant‐based cannabinoids, or synthetic cannabinoids) irrespective of dose, route, frequency, or duration of use for adults with MS. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane Risk of bias 2 tool for parallel RCTs and crossover trials. We rated the certainty of evidence using the GRADE approach for the following outcomes: reduction of 30% in the spasticity Numeric Rating Scale, pain relief of 50% or greater in the Numeric Rating Scale‐Pain Intensity, much or very much improvement in the Patient Global Impression of Change (PGIC), Health‐Related Quality of Life (HRQoL), withdrawals due to adverse events (AEs) (tolerability), serious adverse events (SAEs), nervous system disorders, psychiatric disorders, physical dependence. MAIN RESULTS: We included 25 RCTs with 3763 participants of whom 2290 received cannabinoids. Age ranged from 18 to 60 years, and between 50% and 88% participants across the studies were female. The included studies were 3 to 48 weeks long and compared nabiximols, an oromucosal spray with a plant derived equal (1:1) combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (13 studies), synthetic cannabinoids mimicking THC (7 studies), an oral THC extract of Cannabis sativa (2 studies), inhaled herbal Cannabis (1 study) against placebo. One study compared dronabinol, THC extract of Cannabis sativa and placebo, one compared inhaled herbal Cannabis, dronabinol and placebo. We identified eight ongoing studies. Critical outcomes • Spasticity: nabiximols probably increases the number of people who report an important reduction of perceived severity of spasticity compared with placebo (odds ratio (OR) 2.51, 95% confidence interval (CI) 1.56 to 4.04; 5 RCTs, 1143 participants; I(2) = 67%; moderate‐certainty evidence). The absolute effect was 216 more people (95% CI 99 more to 332 more) per 1000 reporting benefit with cannabinoids than with placebo. • Chronic neuropathic pain: we found only one small trial that measured the number of participants reporting substantial pain relief with a synthetic cannabinoid compared with placebo (OR 4.23, 95% CI 1.11 to 16.17; 1 study, 48 participants; very low‐certainty evidence). We are uncertain whether cannabinoids reduce chronic neuropathic pain intensity. • Treatment discontinuation due to AEs: cannabinoids may increase slightly the number of participants who discontinue treatment compared with placebo (OR 2.41, 95% CI 1.51 to 3.84; 21 studies, 3110 participants; I² = 17%; low‐certainty evidence); the absolute effect is 39 more people (95% CI 15 more to 76 more) per 1000 people. Important outcomes • PGIC: cannabinoids probably increase the number of people who report 'very much' or 'much' improvement in health status compared with placebo (OR 1.80, 95% CI 1.37 to 2.36; 8 studies, 1215 participants; I² = 0%; moderate‐certainty evidence). The absolute effect is 113 more people (95% CI 57 more to 175 more) per 1000 people reporting improvement. • HRQoL: cannabinoids may have little to no effect on HRQoL (SMD ‐0.08, 95% CI ‐0.17 to 0.02; 8 studies, 1942 participants; I(2) = 0%; low‐certainty evidence); • SAEs: cannabinoids may result in little to no difference in the number of participants who have SAEs compared with placebo (OR 1.38, 95% CI 0.96 to 1.99; 20 studies, 3124 participants; I² = 0%; low‐certainty evidence); • AEs of the nervous system: cannabinoids may increase nervous system disorders compared with placebo (OR 2.61, 95% CI 1.53 to 4.44; 7 studies, 1154 participants; I² = 63%; low‐certainty evidence); • Psychiatric disorders: cannabinoids may increase psychiatric disorders compared with placebo (OR 1.94, 95% CI 1.31 to 2.88; 6 studies, 1122 participants; I² = 0%; low‐certainty evidence); • Drug tolerance: the evidence is very uncertain about the effect of cannabinoids on drug tolerance (OR 3.07, 95% CI 0.12 to 75.95; 2 studies, 458 participants; very low‐certainty evidence). AUTHORS' CONCLUSIONS: Compared with placebo, nabiximols probably reduces the severity of spasticity in the short‐term in people with MS. We are uncertain about the effect on chronic neurological pain and health‐related quality of life. Cannabinoids may increase slightly treatment discontinuation due to AEs, nervous system and psychiatric disorders compared with placebo. We are uncertain about the effect on drug tolerance. The overall certainty of evidence is limited by short‐term duration of the included studies.

Objective to assess the inter-rater reliability (IRR) of the revised Cochrane risk-of-bias tool for randomised trials (RoB2). Methods Four raters independently applied RoB2 on critical and important outcomes of individually randomized parallel-group trials (RCTs) included in the Cochrane Review “Cannabis and cannabinoids for people with multiple sclerosis.” We calculated Fleiss’ Kappa for multiple raters and time to complete the tool; we performed a calibration exercise on five studies, then we developed an implementation document (ID) specific for the condition, and the intervention addressed by the review with instructions on how to answer the signalling questions of RoB2 tool. We measured IRR before and after the ID adoption Results Eighty results related to seven outcomes from 16 RCTs were assessed. During calibration exercise we reached no agreement for overall judgment (IRR -0.15); IRR for individual domains ranged from no agreement to fair. Mean time to apply the tool was 168.5 minutes per study. Time to complete the calibration exercise and develop the ID was about 40 hours. After the ID adoption ID, overall agreement increased to slightly (IRR 0.11) for the first five studies and moderate (IRR 0.42) for the remaining 11. IRR for individual domains ranged from no agreement to almost perfect. Mean time to apply the tool decreased to 41 minutes. Conclusion RoB2 tool is comprehensive but complex even for high experienced raters. The development of an ID specific for the review may improve reliability substantially.

Different forms of vaccines have been developed to prevent the SARS-CoV-2 virus and subsequent COVID-19 disease. Several are in widespread use globally. OBJECTIVES: To assess the efficacy and safety of COVID-19 vaccines (as a full primary vaccination series or a booster dose) against SARS-CoV-2.We searched the Cochrane COVID-19 Study Register and the COVID-19 L·OVE platform (last search date 5 November 2021). We also searched the WHO International Clinical Trials Registry Platform, regulatory agency websites, and Retraction Watch.We included randomized controlled trials (RCTs) comparing COVID-19 vaccines to placebo, no vaccine, other active vaccines, or other vaccine schedules.We used standard Cochrane methods. We used GRADE to assess the certainty of evidence for all except immunogenicity outcomes. We synthesized data for each vaccine separately and presented summary effect estimates with 95% confidence intervals (CIs). MAIN RESULTS: We included and analyzed 41 RCTs assessing 12 different vaccines, including homologous and heterologous vaccine schedules and the effect of booster doses. Thirty-two RCTs were multicentre and five were multinational. The sample sizes of RCTs were 60 to 44,325 participants. Participants were aged: 18 years or older in 36 RCTs; 12 years or older in one RCT; 12 to 17 years in two RCTs; and three to 17 years in two RCTs. Twenty-nine RCTs provided results for individuals aged over 60 years, and three RCTs included immunocompromized patients. No trials included pregnant women. Sixteen RCTs had two-month follow-up or less, 20 RCTs had two to six months, and five RCTs had greater than six to 12 months or less. Eighteen reports were based on preplanned interim analyses. Overall risk of bias was low for all outcomes in eight RCTs, while 33 had concerns for at least one outcome. We identified 343 registered RCTs with results not yet available. This abstract reports results for the critical outcomes of confirmed symptomatic COVID-19, severe and critical COVID-19, and serious adverse events only for the 10 WHO-approved vaccines. For remaining outcomes and vaccines, see main text. The evidence for mortality was generally sparse and of low or very low certainty for all WHO-approved vaccines, except AD26.COV2.S (Janssen), which probably reduces the risk of all-cause mortality (risk ratio (RR) 0.25, 95% CI 0.09 to 0.67; 1 RCT, 43,783 participants; high-certainty evidence). Confirmed symptomatic COVID-19 High-certainty evidence found that BNT162b2 (BioNtech/Fosun Pharma/Pfizer), mRNA-1273 (ModernaTx), ChAdOx1 (Oxford/AstraZeneca), Ad26.COV2.S, BBIBP-CorV (Sinopharm-Beijing), and BBV152 (Bharat Biotect) reduce the incidence of symptomatic COVID-19 compared to placebo (vaccine efficacy (VE): BNT162b2: 97.84%, 95% CI 44.25% to 99.92%; 2 RCTs, 44,077 participants; mRNA-1273: 93.20%, 95% CI 91.06% to 94.83%; 2 RCTs, 31,632 participants; ChAdOx1: 70.23%, 95% CI 62.10% to 76.62%; 2 RCTs, 43,390 participants; Ad26.COV2.S: 66.90%, 95% CI 59.10% to 73.40%; 1 RCT, 39,058 participants; BBIBP-CorV: 78.10%, 95% CI 64.80% to 86.30%; 1 RCT, 25,463 participants; BBV152: 77.80%, 95% CI 65.20% to 86.40%; 1 RCT, 16,973 participants). Moderate-certainty evidence found that NVX-CoV2373 (Novavax) probably reduces the incidence of symptomatic COVID-19 compared to placebo (VE 82.91%, 95% CI 50.49% to 94.10%; 3 RCTs, 42,175 participants). There is low-certainty evidence for CoronaVac (Sinovac) for this outcome (VE 69.81%, 95% CI 12.27% to 89.61%; 2 RCTs, 19,852 participants). Severe or critical COVID-19 High-certainty evidence found that BNT162b2, mRNA-1273, Ad26.COV2.S, and BBV152 result in a large reduction in incidence of severe or critical disease due to COVID-19 compared to placebo (VE: BNT162b2: 95.70%, 95% CI 73.90% to 99.90%; 1 RCT, 46,077 participants; mRNA-1273: 98.20%, 95% CI 92.80% to 99.60%; 1 RCT, 28,451 participants; AD26.COV2.S: 76.30%, 95% CI 57.90% to 87.50%; 1 RCT, 39,058 participants; BBV152: 93.40%, 95% CI 57.10% to 99.80%; 1 RCT, 16,976 participants). Moderate-certainty evidence found that NVX-CoV2373 probably reduces the incidence of severe or critical COVID-19 (VE 100.00%, 95% CI 86.99% to 100.00%; 1 RCT, 25,452 participants). Two trials reported high efficacy of CoronaVac for severe or critical disease with wide CIs, but these results could not be pooled. Serious adverse events (SAEs) mRNA-1273, ChAdOx1 (Oxford-AstraZeneca)/SII-ChAdOx1 (Serum Institute of India), Ad26.COV2.S, and BBV152 probably result in little or no difference in SAEs compared to placebo (RR: mRNA-1273: 0.92, 95% CI 0.78 to 1.08; 2 RCTs, 34,072 participants; ChAdOx1/SII-ChAdOx1: 0.88, 95% CI 0.72 to 1.07; 7 RCTs, 58,182 participants; Ad26.COV2.S: 0.92, 95% CI 0.69 to 1.22; 1 RCT, 43,783 participants); BBV152: 0.65, 95% CI 0.43 to 0.97; 1 RCT, 25,928 participants). In each of these, the likely absolute difference in effects was fewer than 5/1000 participants. Evidence for SAEs is uncertain for BNT162b2, CoronaVac, BBIBP-CorV, and NVX-CoV2373 compared to placebo (RR: BNT162b2: 1.30, 95% CI 0.55 to 3.07; 2 RCTs, 46,107 participants; CoronaVac: 0.97, 95% CI 0.62 to 1.51; 4 RCTs, 23,139 participants; BBIBP-CorV: 0.76, 95% CI 0.54 to 1.06; 1 RCT, 26,924 participants; NVX-CoV2373: 0.92, 95% CI 0.74 to 1.14; 4 RCTs, 38,802 participants). For the evaluation of heterologous schedules, booster doses, and efficacy against variants of concern, see main text of review.Compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID-19, and for some, there is high-certainty evidence that they reduce severe or critical disease. There is probably little or no difference between most vaccines and placebo for serious adverse events. Over 300 registered RCTs are evaluating the efficacy of COVID-19 vaccines, and this review is updated regularly on the COVID-NMA platform (covid-nma.com). Implications for practice Due to the trial exclusions, these results cannot be generalized to pregnant women, individuals with a history of SARS-CoV-2 infection, or immunocompromized people. Most trials had a short follow-up and were conducted before the emergence of variants of concern. Implications for research Future research should evaluate the long-term effect of vaccines, compare different vaccines and vaccine schedules, assess vaccine efficacy and safety in specific populations, and include outcomes such as preventing long COVID-19. Ongoing evaluation of vaccine efficacy and effectiveness against emerging variants of concern is also vital.

Objective The objective of the study is to assess the interrater reliability (IRR) and usability of the revised Cochrane risk of bias tool for randomized trials (RoB 2). Study Design and Setting This is a cross-sectional study. Four raters independently applied RoB 2 on the primary outcome of a random sample of individually randomized parallel-group trials (randomized controlled trials (RCTs)). We calculated the Fleiss’ kappa for multiple raters, the time needed to complete the tool, and discussed the application of RoB 2 to identify difficulties and reasons for disagreement. Results A total of 70 outcomes from 70 RCTs were included. IRR was slight for overall judgment (IRR 0.16, 95% confidence interval (CI) 0.08–0.24); individual domain analysis gave IRR as moderate for “randomization process” (IRR 0.45, 95% CI 0.37–0.53), slight for “deviations from intended intervention” for RCTs assessing the effect of the assignment to an intervention (IRR 0.04, 95% CI −0.06 to 0.14), fair for those assessing the effect of adhering (IRR 0.21, 95% CI 0.11–0.31), and fair for the other domains, ranging from 0.22 (95% CI 0.14–0.30) for “missing outcome data” to 0.30 (95% CI 0.22–0.38) for “selection of reported results”. Mean time to apply the tool was 28 minutes (standard deviation 13.4) per study outcome. The main difficulties were due to poor knowledge of the subject matter of primary studies, new terminology, different approaches for some domains compared with the previous tool, and way of formulating signaling questions. Conclusions RoB 2 is a detailed and comprehensive tool but difficult and demanding, even for raters with substantial expertise in systematic reviews. Calibration exercises and intensive training are needed before its application, to improve reliability.

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the efficacy of psychosocial interventions and medications to reduce or stop alcohol consumption during pregnancy.

to evaluate the impact of school closures, as a measure to contain the transmission of SARS-CoV-2 infection, on the psychological well-being of students of all levels starting from the 2020-2021 school year.a systematic literature review was conducted according to the PRISMA 2020 Guidelines. The literature search was conducted on 4 different databases: MedLine, Embase, PsycINFO, and L.OVE Platform. Quantitative observational studies published until 10.01.2022 were included. Studies conducted during the first pandemic wave, i.e., during the 2019-2020 school year and/or during the mandatory lockdown or confinement period, were excluded. The methodological quality of the studies was assessed with validated scales. Study selection, data extraction, and quality assessment were carried out independently by two authors.children, adolescents, and young people attending all levels of education (including universities) and, for reasons related to COVID-19, having a suspension of "in presence" school or attending classes remotely.a. outcomes directly related to mental health: suicides, emergency department visits, and hospitalizations for psychiatric problems; anxiety and depression, emotional difficulties, feelings of loneliness and isolation; b. well-being outcomes: sleep quality, perceived well-being (by child/adolescent/youth or referred by parents); c. health-related behaviours: tobacco smoking, alcohol, drug use. Outcomes related to school/academic performance, physical health, and those related to parents were not considered.after having removed duplicate articles, 2,830 records were retrieved with the bibliographic search. Twelve studies (2 uncontrolled before-after studies and 10 cross sectional surveys) were included, involving a total of 27,787 participants. Three studies involved university students, 2 involved high school students, and the remaining involved a mixed population of students attending primary and middle schools. The studies were conducted between September 2020 and April 2021. The methodological quality was rated as high in five studies and intermediate in the remaining studies. Due to the high heterogeneity of outcome measures and statistical analyses performed among the included studies, it was not possible to conduct a meta-analysis of the results of the considered publications. Nevertheless, the present review showed a clear signal of increase in mental health problems in relation to school closure or virtual instruction. In particular, results suggest evidence of association between school closure and risk of suicidal attempts or thoughts, mental health symptoms such as anxiety, depression, emotional disorders, psychological stress. Sleeping problems, drug and alcohol addiction were poorly studied.despite the limitations of the included studies and possible residual confounding and contamination due to restrictive measures and social isolation implemented during the pandemic, the available evidence confirms the negative impact on students' mental health associated with school closures and distance learning. Given the availability of vaccination also for young children, a long period of school closure should be avoided also in the case of the emergence of new pandemic waves.

Influenza is one of the most common respiratory viral infections worldwide. Numerous vaccines are used to prevent influenza. Their selection should be informed by the best available evidence. We aimed to estimate the comparative efficacy and safety of seasonal influenza vaccines in children, adults and the elderly.We conducted a systematic review and network meta-analysis (NMA). We searched the Cochrane Library Central Register of Controlled Trials, MEDLINE and EMBASE databases, and websites of regulatory agencies, through December 15th, 2020. We included placebo- or no vaccination-controlled, and head-to-head randomized clinical trials (RCTs). Pairs of reviewers independently screened the studies, abstracted the data, and appraised the risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was laboratory-confirmed influenza. We also synthesized data for hospitalization, mortality, influenza-like illness (ILI), pneumonia or lower respiratory-tract disease, systemic and local adverse events (AEs). We estimated summary risk ratios (RR) using pairwise and NMA with random effects. This study is registered with PROSPERO, number CRD42018091895.We identified 13,439 citations. A total of 231 RCTs were included after screening: 11 studies did not provide useful data for the analysis; 220 RCTs [100,677 children ( 18 years) and 329,127 adults (18-60 years) and elderly (≥ 61 years)] were included in the NMA. In adults and the elderly, all vaccines, except the trivalent inactivated intradermal vaccine (3-IIV ID), were more effective than placebo in reducing the risk of laboratory-confirmed influenza, with a RR between 0.33 (95% credible interval [CrI] 0.21-0.55) for trivalent inactivated high-dose (3-IIV HD) and 0.56 (95% CrI 0.41-0.74) for trivalent live-attenuated vaccine (3-LAIV). In adults and the elderly, compared with trivalent inactivated vaccine (3-IIV), no significant differences were found for any, except 3-LAIV, which was less efficacious [RR 1.41 (95% CrI 1.04-1.88)]. In children, compared with placebo, RR ranged between 0.13 (95% CrI 0.03-0.51) for trivalent inactivated vaccine adjuvanted with MF59/AS03 and 0.55 (95% CrI 0.36-0.83) for trivalent inactivated vaccine. Compared with 3-IIV, 3-LAIV and trivalent inactivated adjuvanted with MF59/AS03 were more efficacious [RR 0.52 (95% CrI 0.32-0.82) and RR 0.23 (95% CrI 0.06-0.87)] in reducing laboratory-confirmed influenza. With regard to safety, higher systemic AEs rates after vaccination with 3-IIV, 3-IIV HD, 3-IIV ID, 3-IIV MF59/AS03-adj, quadrivalent inactivated (4-IIV), quadrivalent adjuvanted (4-IIV MF59/AS03-adj), quadrivalent recombinant (4-RIV), 3-LAIV or quadrivalent live attenuated (4-LAIV) vaccines were noted in adults and the elderly [RR 1.5 (95% CrI 1.18-1.89) to 1.15 (95% CrI 1.06-1.23)] compared with placebo. In children, the systemic AEs rate after vaccination was not significantly higher than placebo.All vaccines cumulatively achieved major reductions in the incidence of laboratory-confirmed influenza in children, adults, and the elderly. While the live-attenuated was more efficacious than the inactivated vaccine in children, many vaccine types can be used in adults and the elderly.The directorate general of welfare, Lombardy region.

Objective To assess the inter-rater reliability (IRR) and usability of the risk of bias in nonrandomized studies of interventions tool (ROBINS-I). Study Design and Setting We designed a cross-sectional study. Five raters independently applied ROBINS-I to the nonrandomized cohort studies in three systematic reviews on vaccines, opiate abuse, and rehabilitation. We calculated Fleiss' Kappa for multiple raters as a measure of IRR and discussed the application of ROBINS-I to identify difficulties and possible reasons for disagreement. Results Thirty one studies were included (195 evaluations). IRRs were slight for overall judgment (IRR 0.06, 95% CI 0.001 to 0.12) and individual domains (from 0.04, 95% CI −0.04 to 0.12 for the domain “selection of reported results” to 0.18, 95% CI 0.10 to 0.26 for the domain “deviation from intended interventions”). Mean time to apply the tool was 27.8 minutes (SD 12.6) per study. The main difficulties were due to poor reporting of primary studies, misunderstanding of the question, translation of questions into a final judgment, and incomplete guidance. Conclusion We found ROBINS-I difficult and demanding, even for raters with substantial expertise in systematic reviews. Calibration exercises and intensive training before its application are needed to improve reliability.

The European Society of Gastrointestinal Endoscopy (ESGE) together with the United European Gastroenterology (UEG) recently developed a short list of performance measures for small-bowel endoscopy (i.e. small-bowel capsule endoscopy and device-assisted enteroscopy) with the final goal of providing endoscopy services across Europe with a tool for quality improvement. Six key performance measures both for small-bowel capsule endoscopy and for device-assisted enteroscopy were selected for inclusion, with the intention being that practice at both a service and endoscopist level should be evaluated against them. Other performance measures were considered to be less relevant, based on an assessment of their overall importance, scientific acceptability, and feasibility. Unlike lower and upper gastrointestinal endoscopy, for which performance measures had already been identified, this is the first time small-bowel endoscopy quality measures have been proposed. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:7 issue:5 pages:614-641 ispartof: location:England status: published

During the first semester 2020 almost all country implemented rigid measures of social distances, including schools closure, to limit the transmission of SARS-CoV-2 infection. Up to now, however, the efficacy of school closure to reduce the spread of the disease in the community still remains unclear and no much is known about the potential negative effects of such measures on physical health and psychological wellbeing of youths, mainly if protracted for long periods.To summarize the data of a systematic review on the impact of the 2020 school closure and social distances measures implemented in response to covid-19 pandemic on youths' physical health and psychological wellbeing. In the present paper we describe the impact on psychological wellbeing.We searched 11 international databases up to 1st September 2020 to retrieve cohort studies, cross sectional surveys, uncontrolled pre-post studies and modelling studies. Methodological quality of included studies has been assessed with validated checklists.Sixty-four studies have been included; 27 assessed the impact on psychological wellbeing. All the studies have been conducted during the first wave of pandemic and assessed the short-term effect of social distances measures implemented for relatively short periods. The majority of the studies were conducted in the UK (37,6%) and China (27%). The 42.3% has been judged of high methodological quality. Two studies reported an increase of suicides, while two studies reported a reduction of the access to Psychiatric Emergency Department, Maltreatment allegations decreased substantially, likely due to a reduction in reports rather than actual incidence. Prevalence of anxiety among adolescents ranged between 19% and 64%, depression between 22.3% and 43.7%. Among children 5-12 years old, prevalence of anxiety varied between 19% and 78%, while depression between 6.3% and 22.6%. Among pre-school children, some studies found worsening of behavioural and emotional problems while others did not.Most of the studies reported relevant worsening of the psychological wellbeing, mainly among adolescents. If school closure and rigid social distances measures will extend for a long time, an even more pronounced negative effect can be expected. Further studies are needed on the long-term effect of prolonged social distances measures, as well as a careful harm-benefit analysis of the impact of such measures.

During the first semester 2020 almost all country implemented rigid measures of social distances, including schools closure, to limit the transmission of SARS-CoV-2 infection. Up to now, however, the efficacy of school closure to reduce the spread of the disease in the community still remain unclear and no much is known about the potential negative effects of such measures on physical health and psychological wellbeing of children and adolescents, mainly if protracted for long periods.To summarize the most relevant data of a systematic review on the impact of the 2020 school closure and social distances measures implemented in response to covid-19 pandemic on youths physical health and psychological wellbeing. In the present paper we describe the review's methodology and the characteristics and methodological quality of the retrieved studies.We searched on 11 international databases up to 1st September 2020 to retrieve cohort studies, cross sectional surveys, uncontrolled pre-post studies and modelling studies. Methodological quality of included studies has been assessed with validated checklists.Sixty-four studies have been included; 42 assessed the effect of social distances measure of physical health and 27 on psychological wellbeing. All the studies have been conducted during the first wave of pandemic and assessed the short-term effect of social distances measures implemented for relatively short periods. The 32.4% of the studies has been conducted in the UK, 20.3% in Italy, 12.5% in China, 10.9% in developing countries and 9.4% in the US. 37.5% of the studies were cohort studies, 40.6% cross sectional surveys, 19.7% uncontrolled studies and 1 was a modeling study. 59.6% of the studies has been rated as high quality. The most important weakness of the cross-sectional surveys and uncontrolled studies was the scarce representativeness of the sample while 96% of the cohort studies were judged as high quality.A large number of acceptable quality studies have been published during the first months of pandemic to assess the impact of school closure and social distances measures on physical health and psychological wellbeing of youths. This highlights the relevance of the topic and the need to assess carefully the balance between harms and benefits of such measures in terms of actual reduction of transmission and youths' psychological and physical harms. Further studies are needed on the long-term effect of social distances measures extended over long periods.

Objective To discuss two alternative approaches for complementing the body of direct evidence from Randomized Controlled Trials (RCTs) when it is judged insufficient from a guideline panel making recommendations. The approaches included expanding the evidence's body to non-randomises studies on the population of interest or to RCTs on indirect populations. Study Design and Setting In this report, we adopt the perspective of an evidence review team developing guidelines following the GRADE approach. Our experience is based on the development of two evidence-based guidelines promoted by The Italian National Institute of Health (ISS) and focusing on diagnosis and treatment of Autism Spectrum Disorders (ASD) in children/adolescents and adults. Results We left panel members deciding case by case whether the direct evidence from RCTs was sufficient or not and indicating which alternative to implement. This strategy presented unanticipated challenges both from an organizational and methodological standpoint. Conclusion We suggest an early-stage production of a research protocol to define the criteria for expanding the body of evidence. These criteria should be informed by considerations around the certainty in the evidence, the clinical applicability of the results, feasibility and conflict of interest.

Background Patients treated with mechanical ventilation in intensive care units (ICUs) have a high risk of developing respiratory tract infections (RTIs). Ventilator-associated pneumonia (VAP) has been estimated to affect 5% to 40% of patients treated with mechanical ventilation for at least 48 hours. The attributable mortality rate of VAP has been estimated at about 9%. Selective digestive decontamination (SDD), which consists of the topical application of non-absorbable antimicrobial agents to the oropharynx and gastroenteric tract during the whole period of mechanical ventilation, is often used to reduce the risk of VAP. A related treatment is selective oropharyngeal decontamination (SOD), in which topical antibiotics are applied to the oropharynx only. This is an update of a review first published in 1997 and updated in 2002, 2004, and 2009. Objectives To assess the effect of topical antibiotic regimens (SDD and SOD), given alone or in combination with systemic antibiotics, to prevent mortality and respiratory infections in patients receiving mechanical ventilation for at least 48 hours in ICUs. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, PubMed, and Embase on 5 February 2020. We also searched the WHO ICTRP and ClinicalTrials.gov for ongoing and unpublished studies on 5 February 2020. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies. Selection criteria Randomised controlled trials (RCTs) and cluster-RCTs assessing the efficacy and safety of topical prophylactic antibiotic regimens in adults receiving intensive care and mechanical ventilation. The included studies compared topical plus systemic antibiotics versus placebo or no treatment; topical antibiotics versus no treatment; and topical plus systemic antibiotics versus systemic antibiotics. Data collection and analysis We used standard methodological procedures expected by Cochrane. Main results We included a total of 41 trials involving 11,004 participants (five new studies were added in this update). The minimum duration of mechanical ventilation ranged from 2 (19 studies) to 6 days (one study). Thirteen studies reported the mean length of ICU stay, ranging from 11 to 33 days. The percentage of immunocompromised patients ranged from 0% (10 studies) to 22% (1 study). The reporting quality of the majority of included studies was very poor, so we judged more than 40% of the studies as at unclear risk of selection bias. We judged all studies to be at low risk of performance bias, though 47.6% were open-label, because hospitals usually have standardised infection control programmes, and possible subjective decisions on who should be tested for the presence or absence of RTIs are unlikely in an ICU setting. Regarding detection bias, we judged all included studies as at low risk for the outcome mortality. For the outcome RTIs, we judged all double-blind studies as at low risk of detection bias. We judged five open-label studies as at high risk of detection bias, as the diagnosis of RTI was not based on microbiological exams; we judged the remaining open-label studies as at low risk of detection bias, as a standardised set of diagnostic criteria, including results of microbiological exams, were used. Topical plus systemic antibiotic prophylaxis reduces overall mortality compared with placebo or no treatment (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.73 to 0.96; 18 studies; 5290 participants; high-certainty evidence). Based on an illustrative risk of 303 deaths in 1000 people this equates to 48 (95% CI 15 to 79) fewer deaths with topical plus systemic antibiotic prophylaxis. Topical plus systemic antibiotic prophylaxis probably reduces RTIs (RR 0.43, 95% CI 0.35 to 0.53; 17 studies; 2951 participants; moderate-certainty evidence). Based on an illustrative risk of 417 RTIs in 1000 people this equates to 238 (95% CI 196 to 271) fewer RTIs with topical plus systemic antibiotic prophylaxis. Topical antibiotic prophylaxis probably reduces overall mortality compared with no topical antibiotic prophylaxis (RR 0.96, 95% CI 0.87 to 1.05; 22 studies, 4213 participants; moderate-certainty evidence). Based on an illustrative risk of 290 deaths in 1000 people this equates to 19 (95% CI 37 fewer to 15 more) fewer deaths with topical antibiotic prophylaxis. Topical antibiotic prophylaxis may reduce RTIs (RR 0.57, 95% CI 0.44 to 0.74; 19 studies, 2698 participants; low-certainty evidence). Based on an illustrative risk of 318 RTIs in 1000 people this equates to 137 (95% CI 83 to 178) fewer RTIs with topical antibiotic prophylaxis. Sixteen studies reported adverse events and dropouts due to adverse events, which were poorly reported with sparse data. The certainty of the evidence ranged from low to very low. Authors' conclusions Treatments based on topical prophylaxis probably reduce respiratory infections, but not mortality, in adult patients receiving mechanical ventilation for at least 48 hours, whereas a combination of topical and systemic prophylactic antibiotics reduces both overall mortality and RTIs. However, we cannot rule out that the systemic component of the combined treatment provides a relevant contribution in the observed reduction of mortality. No conclusion can be drawn about adverse events as they were poorly reported with sparse data.

BACKGROUND: The prevalence of opiate use among pregnant women can range from 1% to 2% to as high as 21%. Just in the United States alone, among pregnant women with hospital delivery, a fourfold increase in opioid use is reported from 1999 to 2014 (Haight 2018). Heroin crosses the placenta, and pregnant, opiate‐dependent women experience a six‐fold increase in maternal obstetric complications such as low birth weight, toxaemia, third trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neuro‐behavioural problems, increased neonatal mortality and a 74‐fold increase in sudden infant death syndrome. This is an updated version of the original Cochrane Review first published in 2008 and last updated in 2013. OBJECTIVES: To assess the effectiveness of any maintenance treatment alone or in combination with a psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions alone for child health status, neonatal mortality, retaining pregnant women in treatment, and reducing the use of substances. SEARCH METHODS: We updated our searches of the following databases to February 2020: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: Randomised controlled trials which assessed the efficacy of any pharmacological maintenance treatment for opiate‐dependent pregnant women. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We found four trials with 271 pregnant women. Three compared methadone with buprenorphine and one methadone with oral slow‐release morphine. Three out of four studies had adequate allocation concealment and were double‐blind. The major flaw in the included studies was attrition bias: three out of four had a high dropout rate (30% to 40%), and this was unbalanced between groups. Methadone versus buprenorphine: There was probably no evidence of a difference in the dropout rate from treatment (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.37 to 1.20, three studies, 223 participants, moderate‐quality evidence). There may be no evidence of a difference in the use of primary substances between methadone and buprenorphine (RR 1.81, 95% CI 0.70 to 4.68, two studies, 151 participants, low‐quality evidence). Birth weight may be higher in the buprenorphine group in the two trials that reported data MD;‐530.00 g, 95%CI ‐662.78 to ‐397.22 (one study, 19 particpants) and MD: ‐215.00 g, 95%CI ‐238.93 to ‐191.07 (one study, 131 participants) although the results could not be pooled due to very high heterogeneity (very low‐quality of evidence). The third study reported that there was no evidence of a difference. We found there may be no evidence of a difference in the APGAR score (MD: 0.00, 95% CI ‐0.03 to 0.03, two studies,163 participants, low‐quality evidence). Many measures were used in the studies to assess neonatal abstinence syndrome. The number of newborns treated for neonatal abstinence syndrome, which is the most critical outcome, may not differ between groups (RR 1.19, 95% CI 0.87 to1.63, three studies, 166 participants, low‐quality evidence). Only one study which compared methadone with buprenorphine reported side effects. We found there may be no evidence of a difference in the number of mothers with serious adverse events (AEs) (RR 1.69, 95% CI 0.75 to 3.83, 175 participants, low‐quality evidence) and we found there may be no difference in the numbers of newborns with serious AEs (RR 4.77, 95% CI 0.59, 38.49,131 participants, low‐quality evidence). Methadone versus slow‐release morphine: There were no dropouts in either treatment group. Oral slow‐release morphine may be superior to methadone for abstinence from heroin use during pregnancy (RR 2.40, 95% CI 1.00 to 5.77, one study, 48 participants, low‐quality evidence). In the comparison between methadone and slow‐release morphine, no side effects were reported for the mother. In contrast, one child in the methadone group had central apnoea, and one child in the morphine group had obstructive apnoea (low‐quality evidence). AUTHORS' CONCLUSIONS: Methadone and buprenorphine may be similar in efficacy and safety for the treatment of opioid‐dependent pregnant women and their babies. There is not enough evidence to make conclusions for the comparison between methadone and slow‐release morphine. Overall, the body of evidence is too small to make firm conclusions about the equivalence of the treatments compared. There is still a need for randomised controlled trials of adequate sample size comparing different maintenance treatments.

Objective To propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 weeks) in the clinical, public health, and health systems fields. Study design and setting We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the GRADE Rapid Guidelines project group, and obtained feedback from the larger GRADE working group. Results A request for developing recommendations within two weeks is the usual trigger for an urgent response. While the approach builds on the general principles of trustworthy guideline development, we highlight the following steps: (1) assess the level of urgency; (2) assess feasibility; (3) set up the organizational logistics; (4) specify the question(s); (5) collect the information needed; (6) assess the adequacy of identified information; (7) develop the recommendations using one of four potential approaches: adopt existing recommendations; adapt existing recommendations; develop new recommendations using existing adequate systematic review; or develop new recommendations using expert panel input; and (8) consider an updating plan. Conclusion An urgent response for developing recommendations requires building a cohesive, skilled and highly motivated multidisciplinary team with the necessary clinical, scientific, and methodological expertise, adapting to shifting needs, complying with the principles of transparency and properly managing conflicts of interest., Highlights • The proposed approach for developing trustworthy recommendations as part of urgent responses (1-2 weeks) builds on the general principles of trustworthy guideline development; • The approach proposes the following steps: (1) assess the level of urgency; (2) clarify and focus the scope of question(s); (3) prioritize and collect the information needed; (4) assess the adequacy of identified information; and then (5) develop recommendations; • Developing recommendations can consist of a) adopting existing recommendations; (b) adapting existing recommendations; c) developing new recommendations using existing systematic reviews; or d) developing new recommendations using identified information and panel input.

IntroductionSome recent randomized controlled trials (RCTs) assessed the efficacy and safety of polyunsaturated fatty acids (PUFAs) for the treatment of autism spectrum disorder (ASD). To optimally inform the Italian guideline for the management of ASD in children and adolescents, we reviewed the impact on equity, acceptability and feasibility for developing a pilot recommendation for PUFAs.MethodsWe performed a rapid systematic review of observational and experimental studies on PUFAs for children and adolescents with ASD, extracting data on resources required, equity, acceptability, and feasibility of PUFAs. We followed the framework provided by the grading of recommendations assessment, development and evaluation (GRADE) methodology, and we assessed risk of bias and methodological quality of included studies. Results were synthesized both narratively and quantitatively to address clinically relevant questions on equity, acceptability, and feasibility.ResultsWe found 14 papers related to equity. PUFAs did not seem to impact equity importantly. We did not find variation in effectiveness across subgroups and in a base case scenario, the cost of a 12 weeks cycle of therapy with 1.155 g/day of PUFAs was €65.51 euro.The acceptability of PUFAs was evaluated in 17 studies, 9 of which were RCTs. PUFAs were widely used among children and adolescents with ASD (18 to 51%), and 50% of parents considered nutritional supplementation as useful. Difficulty in swallowing capsules and bad taste were identified as possible causes of poor compliance, but treatment adherence, when measured in included RCTs, was judged to be good to excellent. Discontinuation due to any cause for PUFAs could not differ from placebo (low certainty of evidence).The feasibility of using PUFAs was assessed in 12 studies. PUFAs were probably sustainable, and no particular critical issue emerged from the feasibility assessment. However, the evidence appeared scarce and indirect.ConclusionsWe found the administration of PUFAs in children and adolescents with ASD to be potentially equitable, acceptable and feasible. These results are limited by the limited number and quality of retrieved documents, and need to be viewed in light of efficacy and safety data to formulate clinical recommendations.

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.

School closures as part of broader social lockdown measures during the COVID-19 pandemic may be associated with the health and well-being of children and adolescents.To review published reports on the association of school closures during broader social lockdown with mental health, health behaviors, and well-being in children and adolescents aged 0 to 19 years, excluding associations with transmission of infection.Eleven databases were searched from inception to September 2020, and machine learning was applied for screening articles. A total of 16 817 records were screened, 151 were reviewed in full text, and 36 studies were included. Quality assessment was tailored to study type. A narrative synthesis of results was undertaken because data did not allow meta-analysis.A total of 36 studies from 11 countries were identified, involving a total of 79 781 children and adolescents and 18 028 parents, which occurred during the first wave of the COVID-19 pandemic (February to July 2020). All evaluated school closure as part of broader social lockdown during the first COVID-19 wave, and the duration of school closure ranged from 1 week to 3 months. Of those, 9 (25%) were longitudinal pre-post studies, 5 (14%) were cohort, 21 (58%) were cross-sectional, and 1 (3%) was a modeling study. Thirteen studies (36%) were high quality, 17 (47%) were medium quality, and 6 (17%) were low quality. Twenty-three studies (64%) were published, 8 (22%) were online reports, and 5 (14%) were preprints. Twenty-five studies (69%) concerning mental health identified associations across emotional, behavioral, and restlessness/inattention problems; 18% to 60% of children and adolescents scored above risk thresholds for distress, particularly anxiety and depressive symptoms, and 2 studies reported no significant association with suicide. Three studies reported that child protection referrals were lower than expected number of referrals originating in schools. Three studies suggested higher screen time usage, 2 studies reported greater social media use, and 6 studies reported lower physical activity. Studies on sleep (10 studies) and diet (5 studies) provided inconclusive evidence on harms.In this narrative synthesis of reports from the first wave of the COVID-19 pandemic, studies of short-term school closures as part of social lockdown measures reported adverse mental health symptoms and health behaviors among children and adolescents. Associations between school closure and health outcomes and behaviors could not be separated from broader lockdown measures.

Acute pyelonephritis (aPN) is defined as a severe form of urinary tract infection. Despite its severity and the high incidence in the community setting, there is no consensus on the optimal duration of treatment. The aim was to compare effectiveness and tolerability of short- versus long-course treatment with the same antibiotic agent in patients with aPN. We searched MEDLINE (PubMed), EMBASE and CENTRAL up to June 2016 for randomized controlled trials (RCTs). Three pairs of authors independently extracted data and appraised risk of bias. We included 4 RCTs (439 participants). Short antibiotic treatment lasted from 4 to 14 days and long treatment from 7 to 42 days but was at least 2 days longer than the corresponding short-course. At the end of treatment, we did not find any significant differences in clinical success [risk ratio (RR) 1.01; 95% confidence interval (CI), 0.96-1.07, moderate quality evidence] as well as in microbiological success (RR 0.99; 95% CI, 0.92-1.07, very low-quality evidence). At 4-6 weeks after the end of treatment there were no significant differences in clinical relapses (RR 1.20, 95% CI 0.43-3.30, very low-quality evidence) and re-infection of other germs (RR 2.40; 95% CI, 0.68-8.49, very low-quality evidence), even if short-term therapy seemed to have more risk of recurrences (RR 2.39, 95% CI 1.19-4.83, very low quality of evidence). The incidence of any adverse effect seemed to be lower with the short-term therapy, though the results are not statistically significant (RR 0.63, 95% CI 0.39-1.02, low quality evidence). Short-term treatment for aPN seems to be equivalent to long-term treatment in terms of clinical and microbiological success at the end of treatment or tolerability. The only relevant difference is the frequency of recurrence of the same biological germ up to 4-6 weeks after the end of treatment, which is significantly higher with the short-term therapy.

The European Society of Gastrointestinal Endoscopy and United European Gastroenterology present a short list of key performance measures for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). We recommend that endoscopy services across Europe adopt the following seven key and one minor performance measures for EUS and ERCP, for measurement and evaluation in daily practice at center and endoscopist level: 1 Adequate antibiotic prophylaxis before ERCP (key performance measure, at least 90 %); 2 Antibiotic prophylaxis before EUS-guided puncture of cystic lesions (key performance measure, at least 95 %); 3 Bile duct cannulation rate (key performance measure, at least 90 %); 4 Tissue sampling during EUS (key performance measure, at least 85 %); 5 Appropriate stent placement in patients with biliary obstruction below the hilum (key performance measure, at least 95 %); 6 Bile duct stone extraction (key performance measure, at least 90 %); 7 Post-ERCP pancreatitis (key performance measure, less than 10 %). 8 Adequate documentation of EUS landmarks (minor performance measure, at least 90 %).This present list of quality performance measures for ERCP and EUS recommended by ESGE should not be considered to be exhaustive: it might be extended in future to address further clinical and scientific issues.

Objective To identify, synthesize, and categorize the methodological issues faced by the rehabilitation field. Data Sources A scoping review was conducted using studies identified in MEDLINE, the Cochrane Library, EMBASE, Web of Science, Scopus, Physiotherapy Evidence Database, and Google Scholar up to August 2018. Study Selection We included all type of publications describing methodological issues in rehabilitation research where rehabilitation is described as a multimodal process. The methodological issues have been categorized and classified. Data Extraction The synthesis included qualitative and quantitative analysis. To focus the attention on rehabilitation, we post hoc divided in “specific issues” (highly related to, even if not exclusive of, rehabilitation research) and “generic issues” (common in biomedical research). Data Synthesis Seventy-one publications were included: 68% were narrative reviews, 15% systematic reviews, 7% editorials, 4% meta-epidemiologic studies, and 5% others. Specific methodological issues include the following: problematic application of randomized controlled trials (32%), absent definition of core outcome sets (28%), poor interventions description (22%), weak methodological (conducting) and reporting quality (21%), scarce clinical practice applicability (14%), lack of blinding assessor (10%), inadequate randomization methods or inadequate allocation concealment (8%), and inadequate participants description and recruitment (8%). “Generic” issues included the following: data and statistical description (31%), authors’ methodological training (7%), peer review process (6%, n=4), funding declaration (6%), ethical statement (3%), protocol registration (3%), and conflict of interest declaration (1%). Conclusions Methodological and reporting issues might influence the quality of the evidence produced in rehabilitation research. The next steps to move forward in the field of rehabilitation could be to evaluate the influence of all these issues on the validity of trial results through meta-epidemiologic studies and to develop specific checklists to provide guidance to authors to improve the reporting and conduct of trials in this field.

AIMS: To estimate the effects of needle syringe programmes (NSP) and opioid substitution therapy (OST), alone or in combination, for preventing acquisition of Hepatitis C virus (HCV) in people who inject drugs (PWID). METHODS: Systematic review and meta-analysis. Bibliographic databases were searched for studies measuring concurrent exposure to current OST (within last 6 months) and/or NSP and HCV incidence among PWID. High NSP coverage was defined as regular NSP attendance or ≥100% coverage (receiving sufficient or greater number of needles/syringes per reported injecting frequency). Studies were assessed using the Cochrane risk of bias in non-randomised studies tool. Random effects models were used in meta-analysis. RESULTS: We identified 28 studies (n=6279) in North America (13), UK (5), Europe (4), Australia (5), and China (1). Studies were at moderate (2), serious (17) critical (7) and non-assessable risk of bias (2). Current OST is associated with 50% (risk ratio (RR) 0.50 95% CI 0.40-0.63) reduction in HCV acquisition risk, consistent across region and with low heterogeneity (I(2) =0, p=0.889). Weaker evidence was found for high NSP coverage (RR=0.79 95% CI 0.39-1.61) with high heterogeneity (I(2) =77%, p=0.002). After stratifying by region, high NSP coverage in Europe was associated with a 56% reduction in HCV acquisition risk (RR=0.44, 95% CI 0.24-0.80) with low heterogeneity (I(2) =12.3%, p=0.337) but not in North America (RR=1.58, I(2) =89.5%, p=

METHODS: After primary treatment, biochemical relapse (BCR) occurs in a substantial number of patients with prostate cancer (PCa). PET/CT imaging with prostate-specific membrane antigen based tracers (68Ga-PSMA) has shown promising results for BCR patients. However, a standardized image interpretation methodology has yet to be properly agreed. The aim of this study, which was promoted and funded by European Association of Nuclear Medicine (EANM), is to define standardized image interpretation criteria for 68Ga-PSMA PET/CT to detect recurrent PCa lesions in patients treated with primary curative intent therapy (radical prostatectomy or radiotherapy) who presented a biochemical recurrence. In the first phase inter-rater agreement between seven readers from seven international centers was calculated on the reading of 68Ga-PSMA PET/CT images of 49 patients with BCR. Each reader evaluated findings in five different sites of recurrence (local, loco-regional lymph nodes, distant lymph nodes, bone, and other). In the second phase the re-analysis was limited to cases with poor, slight, fair, or moderate agreement [Krippendorff's (K) alpha

The European Society of Gastrointestinal Endoscopy and United European Gastroenterology present a short list of key performance measures for lower gastrointestinal endoscopy. We recommend that endoscopy services across Europe adopt the following seven key performance measures for lower gastrointestinal endoscopy for measurement and evaluation in daily practice at a center and endoscopist level: 1 Rate of adequate bowel preparation (minimum standard 90 %); 2 Cecal intubation rate (minimum standard 90%); 3 Adenoma de-tection rate (minimum standard 25%); 4 Appropriate polypectomy technique (minimum standard 80%); 5 Complication rate (minimum standard not set); 6 Patient experience (minimum standard not set); 7 Appropriate post-polypectomy surveillance recommendations (minimum standard not set). Other identified performance measures have been listed as less relevant based on an assessment of their importance, scientific acceptability, feasibility, usability, and comparison to competing measures.

Background It is unclear whether the administration of antipsychotics to children and adolescents with autism spectrum disorders (ASD) is acceptable, equitable, and feasible. Methods We performed a systematic review to support a multidisciplinary panel in formulating a recommendation on antipsychotics, for the development of the Italian national guidelines for the management of ASD. A comprehensive search strategy was performed to find data related to intervention acceptability, health equity, and implementation feasibility. We used quantitative data from randomized controlled trials to perform a meta-analysis assessing the acceptability and tolerability of antipsychotics, and we estimated the certainty of the effect according to the GRADE approach. We extracted data from systematic reviews, primary studies, and grey literature, and we assessed the risk of bias and methodological quality of the published studies. Results Antipsychotics were acceptable (dropouts due to any cause: RR 0.61, 95% CI 0.48–0.78, moderate certainty of evidence) and well tolerated (dropouts due to adverse events: RR 0.99, 95% CI 0.55–1.79, low certainty of evidence) by children and adolescents with ASD. Parents and clinicians did not raise significant issues concerning acceptability. We did not find studies reporting evidence of reduced equity for antipsychotics in disadvantaged subgroups of children and adolescents with ASD. Workloads, cost barriers, and inadequate monitoring of metabolic adverse events were indirect evidence of concerns for feasibility. Conclusion Antipsychotics in children and adolescents with ASD were likely acceptable and possibly feasible. We did not find evidence of concern for equity.

Clinical practice guidelines need rigorous and transparent methods for summarizing the evidence, rate its certainty and moving from evidence to recommendations. We describe an intervention to support local efforts to provide optimal and safer care bridging the gap between researchers and local busy clinicians.A group of methodologists provided a wide range of research services to the medical community of a local non-teaching general hospital in Italy. Methodological support encompassed synthesis of evidence, rating of uncertainty and moving from evidence to recommendations. Local professionals were asked to judge GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology and its impact on patients' safety, professional liability, and guideline reliability. The research team then reflected on the barriers of implementing GRADE in local settings.Seven clinical recommendations about frequent complex medical conditions were produced. Few local clinicians completed the project. All clinicians found the GRADE methodology a guarantee for defending excellent standards of care. However, we identified a diffuse sense of inability to improve clinical behaviours as negative effects of general poor working conditions, in particular the strained health care workforce.Current financial constraints may be impeding the ability of clinicians in improving their clinical practice through adaptation and use of evidence. A successful integration of evidence-based guidelines cannot be separated from an activate promotion by the institutional management.

Background Organised cervical cancer (CC) screening programmes are delivered in many different ways across the European Union and its regions. Our aim was to systematically review the impact of these programs on CC mortality. Methods Two independent reviewers identified all eligible studies investigating the effect of organised screening on CC mortality in Europe. Six databases including Embase, Medline and Web of Science were searched (March 2018) with predefined inclusion and exclusion criteria. Only original studies with at least five years of follow-up were considered. Validated tools were used to assess the risk of bias of the included studies. Results Ten observational studies were included: seven cohort and three case-control studies. No randomised controlled trials were found, and there were no eligible studies from the eastern and southern part of Europe. Among the eligible studies, seven were conducted in the twentieth century; they scored lower on the risk of bias assessment. CC mortality reduction for women attending organised screening vs. non-attenders ranged from 41% to 92% in seven studies. Reductions were similar in Western (45–92%) and Northern (41–87%) Europe and were higher in the three more recent studies (66–92%). For invited vs. non-invited women, this reduction ranged from 17% to 79% in five studies. Conclusion Although data were lacking in Southern and Eastern Europe and the effect size varied between countries and studies, this systematic review provides evidence that organised CC screening reduces CC mortality in those parts of Europe where CC screening was implemented and monitored.

Objectives Rehabilitation interventions are usually complex and include different aspects that make difficult to accomplish with classical measures of methodological quality in clinical research. The aim of the present study was to identify, synthesize and categorize the main methodological issues in rehabilitation research to guide the development of methods for reporting and evaluating evidence in the rehabilitation field. Method A scoping review was conducted on PubMed, Cochrane Library, EMBASE, Web of Science, Scopus, Pedro and Google Scholar database up to August 2018. Methodological studies, special communications and literature reviews addressing any methodological issue in rehabilitation research were included. For each study, we identified the methodological issues addressed. Quantitative (frequencies of issues addressed in the studies) and qualitative (content analysis of the issues) synthesis have been conducted. Results After removing duplicates, we screened 2,879 citations, and 71 studies were finally included. Of these, 69% (n = 49) were narrative reviews, 14% (n = 11) systematic reviews, 7% (n = 5) editorials, 4% (n = 3) meta-epidemiological studies, 3% (n = 2) cross-sectional survey, 1% (n = 1) mapping review and 1% (n = 1) overview. The methodological problems in rehabilitation research included: poor data collection description and statistical analysis methods (56%); problematic application of randomized-controlled trials (38%); interventions description (35%); the definition of a core outcome sets for different clinical problems (31%); lack of blinding assessor (17%); clinical practice applicability (11%); randomization method description (10%); participants characteristics description and recruitment (8%); methodological and reporting quality (10% vs 8%). Studies also discussed other issues more related to the peer-review process, such as the methodology training need (7%), low-quality of the peer-review process (6%), funding (6%) and ethical statement (3%), lack of protocol registration (3%), and conflict of interest declaration (1%). Conclusions This study highlights several methodological and reporting issues in rehabilitation research and in the peer review process. Research looking at methods to improve reporting as well as improving the conduct of trials in the rehabilitation field is needed. The first step moving forward would be to evaluate the influence of all these issues on the validity of trial results and the development of a specific check-list for the evaluation of rehabilitation research specifically.

BackgroundRecent randomized controlled trials (RCTs) claimed PUFAs to be effective for autism spectrum disorder (ASD) but international guidelines have not considered yet this body of evidence. Our aim was to assess the effectiveness of PUFAs in children and adolescents with ASD, for the Italian national guidelines on the management of ASD in children and adolescents.MethodsWe performed a systematic review and meta-analysis of RCTs comparing PUFAs versus placebo or a healthy diet for the treatment of ASD in children and adolescents. The outcomes considered were deemed by the guideline panel to be highly relevant to children and adolescents with ASD and to their caregivers. The outcomes included hyperactivity, quality of sleep, self-harm, aggression, irritability, anxiety, attention, adaptive functioning, social interaction, restricted and repetitive interests and behavior, communication, hyperactivity and disruptive behaviors coexistent with core symptoms. The risk of bias of the included studies was assessed with the Cochrane tool, and the rating of the confidence in the effect estimates according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsWe included 9 studies with 405 participants. The strength of evidence ranged from low to very low. Six studies included preschoolers and school-age children, three studies included both children and adolescents. The majority of participants were males (83.8%), with a mean age of 6.7 years. PUFAs were superior compared to placebo in reducing anxiety in individuals with ASD (SMD -1.01, 95% CI − 1.86 to − 0.17; very low certainty of evidence). Moreover, PUFAs worsened quality of sleep compared to a healthy diet (SMD 1.11, 95% CI 0.21 to 2.00; very low certainty of evidence). PUFAs were not better than placebo in reducing aggression, hyperactivity, adaptive functioning, irritability, restricted and repetitive interests and behaviors and communication. Effects on some critical outcomes such as sleep, self-harm and disruptive behavior are currently unknown. The main limitations were the small number of participants included in the RCTs and the dosage which varied greatly (from 200 mg/day to 1540 mg/day), making it difficult to address causal inference.ConclusionsPUFAs did not show evidence of effect in children and adolescents with ASD and the certainty of evidence as measured with the GRADE was low to very low. Further research is needed on this topic because the available evidence is inconclusive.

BackgroundFalse-positive histological diagnoses have the same consequences of overdiagnosis in terms of unnecessary treatment. The aim of this systematic review is to assess their frequency at needle core biopsy (CB) and/or surgical excision of the breast.MethodsPubMed, Embase, Cochrane Library were systematically searched up to 30 October 2015. Eligibility criteria: cross-sectional studies assessing diagnostic accuracy of CB compared with surgical excision; studies assessing reproducibility of pathologists reading the same slides. Outcomes: false-positive rates; Misclassification of Benign as Malignant (MBM) histological diagnosis; K statistic. Independent reviewers extracted data and assessed quality using an adapted QUADAS-2 tool.ResultsSixteen studies assessed CB false-positive rates. In 10 studies (41 989 screen-detected lesions), the range of false-positive rates was 0%–7.1%. Twenty-seven studies assessed pathologists' reproducibility. Studies with consecutive, random or stratified samples of all the specimens: at CB the MBM range was 0.25%–2.4% (K values 0.83–0.98); at surgical excision, it was 0.67%–1.2% (K values 0.86–0.94). Studies with enriched samples: the MBM range was 1.4%–6.2% (K values 0.57–0.86). Studies of cases selected for second opinion: the MBM range was 0.29%–12.2% (K values 0.48 and 0.50).ConclusionsHigh heterogeneity of the included studies precluded formal pooling estimates. When considering studies of higher sample size or methodological quality, false-positive rates and MBM are around 1%. The impact of false-positive histological diagnoses of breast cancer on unnecessary treatment, as well as that of overdiagnosis, is not negligible and is of importance in clinical practice.

The general aim of this systematic review is to mitigate breast cancer (BC) overdiagnosis and overtreatment. The specific aim is to summarize available data on the occurrence and features of indolent invasive or in situ (DCIS) BC, and precisely survival of untreated cases, prevalence of occult cancers found in autopsies, frequency of regressive BC. PubMed, Embase and Cochrane Library were systematically searched up to 3/31/2014. Eligibility criteria were: cohort studies, case-control studies, uncontrolled case series assessing survival in women with a diagnosis of BC who did not receive treatment compared to treated women; case series of autopsies estimating the prevalence of undiagnosed BC; cohort studies, case-control studies, uncontrolled case series, case reports assessing the occurrence of spontaneous regression of BC in women with a confirmed histology diagnosis. Untreated BC: 8 cohort studies and 12 case series (3593 BC) were included. In three controlled cohort studies (diagnoses 1978-2006), the 5-years overall survival was 19-43%. Occult BC: 8 case series (2279 autopsies) were included. The prevalence of invasive BC undiagnosed during lifetime range was 0-1.5%, while for DCIS the range was 0.2-14.7%. Spontaneous regression: 2 cohort studies, 3 case reports, 1 case series included. In the cohort studies the relative risk of regression for screen detected compared with nonscreened BC was estimated as 1.2 and 1.1. It seems plausible that around 10% of invasive BC are not symptomatic during life, and that one fith of BC patients if untreated would be alive after 5 years. Around 1 of 10 screen-detected BC may regress according two studies.

BACKGROUND: Alcohol use disorder (AUD) and alcohol‐related impairments belong to the most widespread psychiatric disorders leading to specific psychophysical, affective and cognitive symptoms and consequences for psychosocial well‐being and health. Alcohol consumption is increasingly becoming a problem in many developing regions and AUD prevalence is estimated at 4.1% worldwide, with highest prevalence in European countries (7.5%), and the North America (6.0%). Therapeutic approaches, including pharmacotherapy, play an important role in treating patients with AUD. OBJECTIVES: To assess the efficacy and safety of baclofen for treating people with AUD, who are currently drinking, with the aim of achieving and maintaining abstinence or reducing alcohol consumption. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Specialised Register, CENTRAL, MEDLINE, Embase, two further databases and two clinical trials registries, conference proceedings, and the reference lists of retrieved articles. The date of the most recent search was 30 January 2018. SELECTION CRITERIA: Randomised controlled trials (RCTs) of at least four weeks' treatment duration and 12 weeks' overall study duration comparing baclofen for relapse prevention of AUD with placebo, no treatment or other treatments. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 12 RCTs (1128 participants). All studies but three recruited fewer than 100 participants. Participants had a diagnosis of alcohol dependence according the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV or the International Classification of Diseases (ICD)‐10 criteria who were currently drinking. The mean age of participants was 48 years, and there were more men (69%), than women. All studies compared baclofen to placebo, except for one study that evaluated baclofen versus acamprosate. The included studies considered baclofen at different doses (range 10 mg a day to 150 mg a day). In all but one of the studies, participants in both the baclofen and placebo groups received psychosocial treatment or counselling of various intensity. We judged most of the studies at low risk of selection, performance, detection (subjective outcome), attrition and reporting bias. We did not find any difference between baclofen and placebo for the primary outcomes: relapse‐return to any drinking (RR 0.88, 95% CI 0.74 to 1.04; 5 studies, 781 participants, moderate certainty evidence); frequency of use by percentage of days abstinent (MD 0.39, 95% CI ‐11.51 to 12.29; 6 studies, 465 participants, low certainty evidence) and frequency of use by percentage of heavy drinking days at the end of treatment (MD 0.25, 95% CI ‐1.25 to 1.76; 3 studies, 186 participants, moderate certainty evidence); number of participants with at least one adverse event (RR 1.04, 95% CI 0.99 to 1.10; 4 studies, 430 participants, high certainty evidence); the dropout rate at the end of treatment (RR 0.98, 95% CI 0.77 to 1.26, 8 studies, 977 participants, high certainty evidence) and dropout due to adverse events (RR 1.11, 95% CI 0.59 to 2.07; 7 studies, 913 participants, high certainty evidence). We found evidence that baclofen increases amount of use (drink per drinking days), (MD 1.55, 95% CI 1.32 to 1.77; 2 studies, 72 participants, low certainty evidence). Among secondary outcomes, there was no difference on craving (MD 1.38, 95% CI ‐1.28 to 4.03, 5 studies, 469 participants), and anxiety (SMD 0.07, 95% CI ‐0.14 to 0.28; 5 trials, 509 participants). We found that baclofen increased depression (SMD 0.27, 95% CI 0.05 to 0.48; 3 studies, 387 participants). Concerning the specific adverse events we found that baclofen increased: vertigo (RR 2.16, 95% CI 1.24 to 3.74; 7 studies, 858 participants), somnolence/sedation (RR 1.48, 95%CI 1.11 to 1.96; 8 studies, 946 participants), paraesthesia (RR 4.28, 95% CI 2.11 to 8.67; 4 studies, 593 participants), and muscle spasms/rigidity (RR 1.94, 95%CI 1.08 to 3.48; 3 studies, 551 participants). For all the other adverse events we did not find significant differences between baclofen and placebo. For the comparison baclofen versus acamprosate, we were only able to extract data for one outcome, craving. For this outcome, we found that baclofen increased craving compared with acamprosate (MD 14.62, 95% CI 12.72 to 16.52; 1 study, 49 participants). AUTHORS' CONCLUSIONS: None of the primary or secondary outcomes of the review showed evidence of a difference between baclofen and placebo. The high heterogeneity among primary studies results limits the interpretation of the summary estimate, the identification of moderators and mediators of baclofen's effects on alcohol use remains a challenge for further research. Even though some results from RCTs are promising, current evidence remains uncertain regarding the use of baclofen as a first‐line treatment for people with AUDs.

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology present a list of key performance measures for endoscopy services. We recommend that these performance measures be adopted by all endoscopy services across Europe. The measures include those related to the leadership, organization, and delivery of the service, as well as those associated with the patient journey. Each measure includes a recommendation for a minimum and target standard for endoscopy services to achieve. We recommend that all stakeholders in endoscopy take note of these ESGE endoscopy services performance measures to accelerate their adoption and implementation. Stakeholders include patients and their advocacy groups; service leaders; staff, including endoscopists; professional societies; payers; and regulators. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:7 issue:1 pages:21-44 ispartof: location:England status: published

The World Health Organization (WHO) estimates that depression affects about 121 million people in the world and in terms of years of illness, by the year 2020 could become the second most prevalent disease in the world population after cardiovascular diseases. Second-generation antipsychotics (SGAs) seems to induce remission in depression when added to an antidepressant.To evaluate the efficacy and safety of SGAs for the treatment of depression.We searched five bibliographic databases. We assessed the quality of evidence using Cochrane and GRADE criteria.We included 42 RCTs. Where possible, we made a statistical synthesis of results. For efficacy outcomes, in direct comparisons in unipolar and bipolar patients with acute depressive episode, and in unipolar patients who did not respond to previous treatments with antidepressants (non-responders), SGAs gave better results than placebo, moderate to low certainty of evidence. In the comparison with antidepressants, in unipolar and bipolar patients with acute depressive episode the evidence was in favour of SGAs high certainty of evidence; while in the non-responder unipolar patients (the included studies considered only this typology of patients) the evidence was in favour of the antidepressants, low certainty of evidence. For safety outcomes, the results were in favour of placebo for patients with at least one adverse event, and in favour of SGAs for the number of patients with serious adverse events, for both comparisons the certainty of evidence was moderate. Comparing the SGAs with antidepressants, no differences were observed for patients with at least one adverse event, high certainty of evidence; while serious adverse events were less acute in patients treated with SGAs, moderate certainty evidence. The results of direct and indirect comparisons made with the network meta-analysis showed no differences for most of the outcomes considered, not showing a clear superiority of a drug compared to the others.These results showed a moderate effect in favour of SGAs compared to antidepressants in patients, unipolar and bipolar, with a new acute depressive episode and confirm that in patients non-responders, antidepressants may remain more effective.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the impact of exposure to any form of alcohol marketing, compared to less exposure or no exposure, on alcohol consumption patterns among youth and young adults up to and including the age of 25 years (we want to be able to look at potential dose response relationships at different levels of exposure).

Programmes that promote dietary behaviour change for the prevention of chronic disease must include components that are rooted in best practice and associated with effectiveness. The purpose of this overview of systematic reviews was to examine the characteristics and dietary behaviour change outcomes of nutrition interventions among populations with or at risk of non-communicable chronic diseases. Systematic reviews of randomised controlled trials (RCTs) testing dietary behaviour change interventions published between January 2006 and November 2015 were identified via searches in Cochrane Library, PubMed, EMBASE and PsycINFO. Quality of reviews were appraised using AMSTAR. Dietary behaviour change and intervention details were extracted and systematically summarised. Fifteen articles met the inclusion criteria. Dietary behaviour changes in response to nutrition interventions were significant in over half of interventions. Reducing dietary fat and increasing fruits and vegetables were the most common behaviour changes. The characteristics of nutrition interventions and their relationship to effectiveness for dietary behaviour change among chronic disease or at-risk populations were reported inconsistently. However, associative evidence exists to support more frequent contacts and the use of specific behaviour change techniques. No clear relationships were found between effectiveness and intervention setting, mode of delivery or intervention provider, although some population-specific relationships were identified. Interventions that promote long-term maintenance of dietary behaviour changes are lacking in the literature. This comprehensive umbrella review identifies specific characteristics of interventions that are associated with effectiveness in interventions that promote dietary behaviour change among different at-risk populations. In order to maximise outcomes, public health, health promotion and healthcare organisations should consider these results in order to inform the development and improvement of nutrition programmes.

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology (UEG) have a vision to create a thriving community of endoscopy services across Europe, collaborating with each other to provide high quality, safe, accurate, patient-centered and accessible endoscopic care. Whilst the boundaries of what can be achieved by advanced endoscopy are continually expanding, we believe that one of the most fundamental steps to achieving our goal is to raise the quality of everyday endoscopy. The development of robust, consensus- and evidence-based key performance measures is the first step in this vision. ESGE and UEG have identified quality of endoscopy as a major priority. This paper explains the rationale behind the ESGE Quality Improvement Initiative and describes the processes that were followed. We recommend that all units develop mechanisms for audit and feedback of endoscopist and service performance using the ESGE performance measures that will be published in future issues of this journal over the next year. We urge all endoscopists and endoscopy services to prioritize quality and to ensure that these performance measures are implemented and monitored at a local level, so that we can provide the highest possible care for our patients.

The European Code Against Cancer is a set of recommendations to give advice on cancer prevention. Its 4th edition is an update of the 3rd edition, from 2003. Working Groups of independent experts from different fields of cancer prevention were appointed to review the recommendations, supported by a Literature Group to provide scientific and technical support in the assessment of the scientific evidence, through systematic reviews of the literature. Common procedures were developed to guide the experts in identifying, retrieving, assessing, interpreting and summarizing the scientific evidence in order to revise the recommendations. The Code strictly followed the concept of providing advice to European Union citizens based on the current best available science. The advice, if followed, would be expected to reduce cancer risk, referring both to avoiding or reducing exposure to carcinogenic agents or changing behaviour related to cancer risk and to participating in medical interventions able to avert specific cancers or their consequences. The information sources and procedures for the review of the scientific evidence are described here in detail. The 12 recommendations of the 4th edition of the European Code Against Cancer were ultimately approved by a Scientific Committee of leading European cancer and public health experts.\