Psychosocial interventions for stimulant use disorder.

BACKGROUND: Stimulant use disorder is a continuously growing medical and social burden without approved medications available for its treatment. Psychosocial interventions could be a valid approach to help people reduce or cease stimulant consumption. This is an update of a Cochrane review first published in 2016. OBJECTIVES: To assess the efficacy and safety of psychosocial interventions for stimulant use disorder in adults. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, three other databases, and two trials registers in September 2023. All searches included non-English language literature. We handsearched the references of topic-related systematic reviews and the included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing any psychosocial intervention with no intervention, treatment as usual (TAU), or a different intervention in adults with stimulant use disorder. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included a total of 64 RCTs (8241 participants). Seventy-three percent of studies included participants with cocaine or crack cocaine use disorder; 3.1% included participants with amphetamine use disorder; 10.9% included participants with methamphetamine use disorder; and 12.5% included participants with any stimulant use disorder. In 18 studies, all participants were in methadone maintenance treatment. In our primary comparison of any psychosocial treatment to no intervention, we included studies which compared a psychosocial intervention plus TAU to TAU alone. In this comparison, 12 studies evaluated cognitive behavioural therapy (CBT), 27 contingency management, three motivational interviewing, one study looked at psychodynamic therapy, and one study evaluated CBT plus contingency management. We also compared any psychosocial intervention to TAU. In this comparison, seven studies evaluated CBT, two contingency management, two motivational interviewing, and one evaluated a combination of CBT plus motivational interviewing. Seven studies compared contingency management reinforcement related to abstinence versus contingency management not related to abstinence. Finally, seven studies compared two different psychosocial approaches. We judged 65.6% of the studies to be at low risk of bias for random sequence generation and 19% at low risk for allocation concealment. Blinding of personnel and participants was not possible for the type of intervention, so we judged all the studies to be at high risk of performance bias for subjective outcomes but at low risk for objective outcomes. We judged 22% of the studies to be at low risk of detection bias for subjective outcomes. We judged most of the studies (69%) to be at low risk of attrition bias. When compared to no intervention, we found that psychosocial treatments: reduce the dropout rate (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.74 to 0.91; 30 studies, 4078 participants; high-certainty evidence); make little to no difference to point abstinence at the end of treatment (RR 1.15, 95% CI 0.94 to 1.41; 12 studies, 1293 participants; high-certainty evidence); make little to no difference to point abstinence at the longest follow-up (RR 1.22, 95% CI 0.91 to 1.62; 9 studies, 1187 participants; high-certainty evidence); probably increase continuous abstinence at the end of treatment (RR 1.89, 95% CI 1.20 to 2.97; 12 studies, 1770 participants; moderate-certainty evidence); may make little to no difference in continuous abstinence at the longest follow-up (RR 1.14, 95% CI 0.89 to 1.46; 4 studies, 295 participants; low-certainty evidence); reduce the frequency of drug intake at the end of treatment (standardised mean difference (SMD) -0.35, 95% CI -0.50 to -0.19; 10 studies, 1215 participants; high-certainty evidence); and increase the longest period of abstinence (SMD 0.54, 95% CI 0.41 to 0.68; 17 studies, 2118 participants; high-certainty evidence). When compared to TAU, we found that psychosocial treatments reduce the dropout rate (RR 0.79, 95% CI 0.65 to 0.97; 9 studies, 735 participants; high-certainty evidence) and may make little to no difference in point abstinence at the end of treatment (RR 1.67, 95% CI 0.64 to 4.31; 1 study, 128 participants; low-certainty evidence). We are uncertain whether they make any difference in point abstinence at the longest follow-up (RR 1.31, 95% CI 0.86 to 1.99; 2 studies, 124 participants; very low-certainty evidence). Compared to TAU, psychosocial treatments may make little to no difference in continuous abstinence at the end of treatment (RR 1.18, 95% CI 0.92 to 1.53; 1 study, 128 participants; low-certainty evidence); probably make little to no difference in the frequency of drug intake at the end of treatment (SMD -1.17, 95% CI -2.81 to 0.47, 4 studies, 479 participants, moderate-certainty evidence); and may make little to no difference in the longest period of abstinence (SMD -0.16, 95% CI -0.54 to 0.21; 1 study, 110 participants; low-certainty evidence). None of the studies for this comparison assessed continuous abstinence at the longest follow-up. Only five studies reported harms related to psychosocial interventions; four of them stated that no adverse events occurred. AUTHORS' CONCLUSIONS: This review's findings indicate that psychosocial treatments can help people with stimulant use disorder by reducing dropout rates. This conclusion is based on high-certainty evidence from comparisons of psychosocial interventions with both no treatment and TAU. This is an important finding because many people with stimulant use disorders leave treatment prematurely. Stimulant use disorders are chronic, lifelong, relapsing mental disorders, which require substantial therapeutic efforts to achieve abstinence. For those who are not yet able to achieve complete abstinence, retention in treatment may help to reduce the risks associated with stimulant use. In addition, psychosocial interventions reduce stimulant use compared to no treatment, but they may make little to no difference to stimulant use when compared to TAU. The most studied and promising psychosocial approach is contingency management. Relatively few studies explored the other approaches, so we cannot rule out the possibility that the results were imprecise due to small sample sizes.

Assessing the Adoption of One Health Approaches in National Plans to Combat Health Threats: The Pilot of a One Health Conceptual Framework in Armenia.

Due to several factors, such as environmental and climate changes, the risk of health threats originating at the human-animal-environment interface, including vector-borne diseases (VBDs) and zoonoses, is increasing. Low-resource settings struggle to counter these multidimensional risks due to their already-strained health systems and are therefore disproportionally affected by the impact caused by these changes. Systemic approaches like One Health (OH) are sought to strengthen prevention and preparedness strategies by addressing the drivers of potential threats with a multidisciplinary and multisectoral approach, considering the whole system at the human-animal-environment interface. The integration of OH in national plans can be challenging due to the lack of effective coordination and collaboration among different sectors. To support the process of knowledge coproduction about the level of OH integration in prevention and preparedness strategies against health threats in Armenia, a situation analysis was performed on Crimean-Congo hemorrhagic fever/virus and anthrax (identified by local stakeholders as priorities to be addressed with the OH approach), and actions to strengthen the national OH system were identified with the support of a OH conceptual framework. The study highlighted that multidisciplinary and multisectoral efforts towards prevention and preparedness against VBDs and zoonoses threats need to be strengthened in Armenia, and priority actions to integrate the OH approach were identified.

Mapping food surveillance chains through different sectors.

European countries are investing in strengthening disease surveillance from a One Health (OH) perspective. During the MATRIX project, in the context of the One Health European Joint Programme, existing surveillance chains across the sectors of animal health, food safety, and public health have been investigated through questionnaires. Provided information has then been selected to be displayed in a single slide using an implemented mapping template. Two real-life scenarios are presented as case studies: the surveillance activities in place in France for Salmonella in the pork meat food chain, and in Norway for Listeria monocytogenes in the dairy food chain. The results collected through the questionnaires and the lessons learnt during the mapping process are reported, to share the advantages and drawbacks of the methodology. Moreover, the presented template could be adjusted and applied to different contexts. Mapping the components of existing disease surveillance systems is a fundamental step in understanding the relationships between its components, and subsequently facilitating their collaboration and integration under a OH approach.

Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis.

BACKGROUND: Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder. METHODS: In this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. We included studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Primary outcomes were efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) both for acute and long-term treatment. We estimated summary standardised mean differences (SMDs) and odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with Open Science Framework, https://doi.org/10.17605/OSF.IO/PU4QJ. FINDINGS: We included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis. In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36-0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27-0·71 [moderate to very low]). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72 [95% CI 0·52-0·99; moderate], 0·70 [0·51-0·95; moderate] and 0·71 [0·52-0·98; moderate], respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00 [95% CI 1·28-3·13; very low]; zolpidem: 1·79 [1·25-2·50; moderate]); and zopiclone caused more dropouts than did eszopiclone (OR 1·82 [95% CI 1·01-3·33; low]), daridorexant (3·45 [1·41-8·33; low), and suvorexant (3·13 [1·47-6·67; low]). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27-2·78 [high to very low]). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63 [95% CI 0·36-0·90; very low]; lemborexant: 0·41 [0·04-0·78; very low]) and eszopiclone was more effective than ramelteon (0.63 [0·16-1·10; very low]) and zolpidem (0·60 [0·00-1·20; very low]). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43 [95% CI 0·20-0·93; very low]; zolpidem: 0·43 [0·19-0·95; very low]); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00 [95% CI 1·11-3·70; very low]). INTERPRETATION: Overall, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. These results should serve evidence-based clinical practice. FUNDING: UK National Institute for Health Research Oxford Health Biomedical Research Centre.

Epidemiological and genomic findings of the first documented Italian outbreak of SARS-CoV-2 Alpha variant of concern.

From 24 December 2020 to 8 February 2021, 163 cases of SARS-CoV-2 Alpha variant of concern (VOC) were identified in Chieti province, Abruzzo region. Epidemiological data allowed the identification of 14 epi-clusters. With one exception, all the epi-clusters were linked to the town of Guardiagrele: 149 contacts formed the network, two-thirds of which were referred to the family/friends context. Real data were then used to estimate transmission parameters. According to our method, the calculated Re(t) was higher than 2 before the 12 December 2020. Similar values were obtained from other studies considering Alpha VOC. Italian sequence data were combined with a random subset of sequences obtained from the GISAID database. Genomic analysis showed close identity between the sequences from Guardiagrele, forming one distinct clade. This would suggest one or limited unspecified viral introductions from outside to Abruzzo region in early December 2020, which led to the diffusion of Alpha VOC in Guardiagrele and in neighbouring municipalities, with very limited inter-regional mixing.

Italian guidelines on management of persons with multimorbidity and polypharmacy.

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

Effects of goal-oriented care for adults with multimorbidity: A systematic review and meta-analysis.

OBJECTIVE: To systematically review the evidence from randomized controlled trials comparing the effects of goal-oriented care against standard care for multimorbid adults. DATA SOURCES/STUDY SETTING: The literature presenting the results of randomized trials assessing the outcomes of goal-oriented care compared with usual care for adults with multimorbidity. STUDY DESIGN: Systematic review and meta-analysis. DATA COLLECTION/EXTRACTION METHODS: We searched the Cochrane Database of Systematic Reviews (CENTRAL), EMBASE, MEDLINE, CINHAL, trial registries such as ClinicalTrial.gov and World Health Organization International Clinical Trials Registry Platform (ICTRP), and the references of eligible trials and relevant reviews. Goal-oriented care was defined as an approach that engages patients, establishes personal goals, and sets targets for patients and clinicians to plan a course of action and measure outcome. We reviewed 228 trials, and 12 were included. We extracted outcome data on quality of life, hospital admission, patients' satisfaction, patient and caregiver burden. Risk of bias was assessed and certainty of evidence was evaluated using GRADE. PRINCIPAL FINDINGS: No study was fully free of bias. No effect was found on quality of life (standardized mean difference [SMD]: 0.05; 95% CI: -0.05 to 0.16) and hospital admission (risk ratio [RR]: 0.87; 95% CI: 0.65 to 1.17). There was a very small effect for patients' satisfaction (SMD: 0.15; 95% CI: 0.00 to 0.29) and caregiver burden (SMD: -0.13; 95% CI: -0.26 to 0.00). Certainty of evidence was low for all outcomes. CONCLUSIONS: No firm conclusions can be reached about the effects of goal-oriented care for multimorbid adults. Future research should overcome the shortcomings of trials assessed in this meta-analysis. Sound application of the indications for research of complex healthcare interventions is warranted.

Does letting adolescent and young adult inpatients share decisions in choosing the central-line insertion site reduce central-line-associated bloodstream infections? An empty systematic review.

To study whether allowing adolescents and young adults (AYA) with chronic or oncologic diseases admitted to tertiary or intensive care units to share decisions in choosing the insertion site for central-venous catheters (CVC) implanted for intravenous therapies or parenteral nutrition reduces central-line-associated and catheter-related bloodstream infections (CLABSI and CRBSI). Following the PRISMA guidelines, we systematically reviewed the literature by searching MEDLINE, Embase, CINAHL, CENTRAL, SCOPUS, Cochrane Library, and Web of Science up to December 2019. According to our aims, the review identified no study that could be included. This empty systematic review on healthcare teams allowing AYA with chronic or oncologic diseases admitted in tertiary or intensive care units to share decisions in choosing the site for implanting CVC prompts further research on clinical pathways on this hot-topic. By considering purportedly risk-taking behaviors in youngsters thus reducing CLABSI and CRBSI, healthcare teams should test specific strategies by engaging AYA empathetically in sharing decisions on the site for implanting CVC to improve quality in health care bundles.

[Reduce the distance between knowledge and practice.] / Ridurre la distanza tra la conoscenza e la pratica.

Ten years after the death of Alessandro Liberati - physician and researcher, founder of the Italian Cochrane Center - this article considers the changes that have taken place in international and Italian healthcare. In the first place, the authors regret the loss of cohesion of the group of researchers who have been working together for a long time in the Cochrane network, also due to the progressive change of the Collaboration, today more marketing-oriented than in the past. Evidence-based medicine is also suffering from the pressure of so-called "precision medicine" and from the bias that also affect randomized controlled trials: an important change in recent years is the greater importance given to the methodological quality of research, compared to theoretical value of the types of study. Alongside the bad news, there is also good news: the willingness to continue supporting the spread of evidence-based medicine among Italian professionals, which has given rise to several educational projects that discuss the opportunities and limits of innovation in medicine.

The Standard of Care Definitions on COVID-19 Pharmacological Clinical Trials: A Systematic Review.

Background: Standard of Care (SoC) has been used with different significance across Randomized Clinical Trials (RCTs) on the treatment of Covid-19. In the context of a living systematic review on pharmacological interventions for COVID-19, we assessed the characteristics of the SoC adopted in the published RCTs. Methods: We performed a systematic review searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to April 10, 2021. We included all RCTs comparing any pharmacological intervention for Covid-19 against any drugs, placebo, or SoC. All trials selected have been classified as studies with SoC including treatments under investigation for COVID-19 (SoC+); studies with SoC without specifications regarding the potential therapies allowed (SoC-); studies including as control groups Placebo (P) or active controls (A+). Results: We included in our analysis 144 RCTs, comprising 78,319 patients. Most of these trials included SoC (108; 75.0%); some in all arms of the study (69.7%) or just as independent comparators (30.3%). Treatments under investigation for COVID-19 in other trials were included in the SoC (SoC+) in 67 cases (62.0%), Thirty-one different therapeutic agents (alone or in combination) were counted within the studies with SoC+: mostly hydroxychloroquine or chloroquine (28), lopinavir/ritonavir (20) or azithromycin (16). No specification was given regarding treatment allowed in the control groups (SoC-) in 41 studies (38.0%). Conclusion: Our analysis shows that the findings emerging from several clinical trials regarding the efficacy and safety of pharmacological intervention for COVID-19 might be jeopardized by the quality of control arms.

PTEN Hamartoma Tumor Syndrome: Skin Manifestations and Insights Into Their Molecular Pathogenesis.

Germline PTEN pathogenic variants cause a spectrum of disorders collectively labeled PTEN Hamartoma Tumor Syndrome (PHTS) and featured by hamartomas, developmental anomalies and increased cancer risk. Studies on experimental models provided evidence that PTEN is a "haploinsufficient" tumor-suppressor gene, however, mechanisms involved in the pathogenesis of clinical manifestations in PHTS patients remain elusive. Beyond analyzing clinical and molecular features of a series of 20 Italian PHTS patients, we performed molecular investigations to explore the mechanisms involved in the pathogenesis of PTEN-associated manifestations, with special focus on mucocutaneous manifestations. Typical mucocutaneous features were present in all patients assessed, confirming that these are the most important clue to the diagnosis. The most frequent were papules located in the trunk or extremities (73.7%), oral mucosa papules (68.4%), acral/palmoplantar keratosis and facial papules (both 57.9%), according with literature data. Molecular analyses on one trichilemmoma suggested that the wild-type PTEN allele was retained and expressed, reinforcing the evidence that PTEN does not require a second somatic hit to initiate pathogenic processes. Unexpectedly, one patient also displayed a cutaneous phenotype consistent with atypical mole/melanoma syndrome; no variants were detected in known melanoma genes, but Whole Exome Sequencing showed the rare truncating variant c.495G>A in the CDH13 gene that might have cooperated with PTEN-haploinsufficiency to generate such phenotype. Our findings confirm the reproducibility of known PHTS manifestations in real-world practice, highlighting the role of mucocutaneous manifestations in facilitating prompt diagnosis of the syndrome, and provide some insights into the pathogenic process induced by PTEN alterations, which may contribute to its understanding.

GRADE Notes 2: Criteria for searching non-randomized or indirect evidence should be defined early in the guideline production process.

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.

Epidemiological Significance of SARS-CoV-2 RNA Dynamic in Naso-Pharyngeal Swabs.

From 16 March to 15 December 2020, 132,357 naso-pharyngeal/oropharyngeal swabs were collected in the province of Teramo, Abruzzo Region, Italy, and tested for the presence of SARS-CoV-2 genomic RNA by a commercially available molecular assay. A total of 12,880 swabs resulted positive. For 8212 positive patients (4.150 women and 4.062 men) the median age was statistically different between women (median: 49.55 ± 23.9 of SD) and men (median: 48.35 ± 23.5 of SD) while no differences were found in the comparison between the cycle threshold for the N protein-encoding gene (CT N) median values and gender. Differences were observed in the CT N gene median values of swabs collected from March to September as well as in the pairwise comparison between September and October and between November and December. The CT N gene median values observed in specific periods characterizing the SARS-CoV-2 epidemic in 2020 were also compared with the incidence of COVID-19 cases; a strong inverse correlation was highlighted (Pearson correlation coefficient = -0.978). Our findings confirm the usefulness of the CT N values as an indirect detection parameter to monitor viral loads in the population.

Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next?

The NBN gene has been included in breast cancer (BC) multigene panels based on early studies suggesting an increased BC risk for carriers, though not confirmed by recent research. To evaluate the impact of NBN analysis, we assessed the results of NBN sequencing in 116 BRCA-negative BC patients and reviewed the literature. Three patients (2.6%) carried potentially relevant variants: two, apparently unrelated, carried the frameshift variant c.156_157delTT and another one the c.628G>T variant. The latter was subsequently found in 4/1390 (0.3%) BC cases and 8/1580 (0.5%) controls in an independent sample, which, together with in silico predictions, provided evidence against its pathogenicity. Conversely, the rare c.156_157delTT variant was absent in the case-control set; moreover, a 50% reduction of NBN expression was demonstrated in one carrier. However, in one family it failed to co-segregate with BC, while the other carrier was found to harbor also a probably pathogenic TP53 variant that may explain her phenotype. Therefore, the c.156_157delTT, although functionally deleterious, was not supported as a cancer-predisposing defect. Pathogenic/likely pathogenic NBN variants were detected by multigene panels in 31/12314 (0.25%) patients included in 15 studies. The risk of misinterpretation of such findings is substantial and supports the exclusion of NBN from multigene panels.

Comparative Effectiveness of Pharmacological Interventions for Covid-19: A Systematic Review and Network Meta-Analysis.

Background: Several pharmacological interventions are now under investigation for the treatment of Covid-19, and the evidence is evolving rapidly. Our aim is to assess the comparative efficacy and safety of these drugs. Methods and Findings: We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We included 96 RCTs, comprising of 34,501 patients. The network meta-analysis showed in terms of all-cause mortality, when compared to SC or placebo, only corticosteroids significantly reduced the mortality rate (RR 0.90, 95%CI 0.83, 0.97; moderate certainty of evidence). Corticosteroids significantly reduced the mortality rate also when compared to hydroxychloroquine (RR 0.83, 95%CI 0.74, 0.94; moderate certainty of evidence). Remdesivir proved to be better in terms of SAEs when compared to SC or placebo (RR 0.75, 95%CI 0.63, 0.89; high certainty of evidence) and plasma (RR 0.57, 95%CI 0.34, 0.94; high certainty of evidence). The combination of lopinavir and ritonavir proved to reduce SAEs when compared to plasma (RR 0.49, 95%CI 0.25, 0.95; high certainty of evidence). Most of the RCTs were at unclear risk of bias (42 of 96), one third were at high risk of bias (34 of 96) and 20 were at low risk of bias. Certainty of evidence ranged from high to very low. Conclusion: At present, corticosteroids reduced all-cause mortality in patients with Covid-19, with a moderate certainty of evidence. Remdesivir appeared to be a safer option than SC or placebo, while plasma was associated with safety concerns. These preliminary evidence-based observations should guide clinical practice until more data are made public.

Multiple detection and spread of novel strains of the SARS-CoV-2 B.1.177 (B.1.177.75) lineage that test negative by a commercially available nucleocapsid gene real-time RT-PCR.

Several lineages of SARS-CoV-2 are currently circulating worldwide. During SARS-CoV-2 diagnostic activities performed in Abruzzo region (central Italy) several strains belonging to the B.1.177.75 lineage tested negative for the N gene but positive for the ORF1ab and S genes (+/+/- pattern) by the TaqPath COVID-19 CE-IVD RT-PCR Kit manufactured by Thermofisher. By sequencing, a unique mutation, synonymous 28948C > T, was found in the N-negative B.1.177.75 strains. Although we do not have any knowledge upon the nucleotide sequences of the primers and probe adopted by this kit, it is likely that N gene dropout only occurs when 28948C > T is coupled with 28932C > T, this latter present, in turn, in all B.1.177.75 sequences available on public databases. Furthermore, epidemiological analysis was also performed. The majority of the N-negative B.1.177.75 cases belonged to two clusters apparently unrelated to each other and both clusters involved young people. However, the phylogeny for sequences containing the +/+/- pattern strongly supports a genetic connection and one common source for both clusters. Though, genetic comparison suggests a connection rather than indicating the independent emergence of the same mutation in two apparently unrelated clusters. This study highlights once more the importance of sharing genomic data to link apparently unrelated epidemiological clusters and to, remarkably, update molecular tests.

[Impact of social distancing for covid-19 on youths' physical health: a systematic review of the literature.] / Impatto del distanziamento sociale per covid-19 sulla salute fisica dei giovani: una revisione sistematica della letteratura.

BACKGROUND: Schools' closure during covid-19 pandemic implemented almost all over the world, together with social distances measures and lockdown to reduce transmission, could have had negative impact on youths' health. AIM: Summarize the most relevant data from a literature systematic review on the impact on youths' physical health of the 2020 school closure and social distances measures implemented in response to covid-19 pandemic. METHODS: Authors of the original review 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 has been assessed with validated checklists. RESULTS: Forty-two studies reporting the impact on physical health have been finally included. They have been conducted in 14 countries, most of which in Italy (30.9%) and UK (30.9%). The majority were cohort studies (40.5%) and the overall methodological quality, irrespective of study designs, was high for the 71.4% of the studies. Twenty-seven studies assessed the impact on health services utilization, whose results showed a relevant reduction of Emergency Departments accesses (64%-89.3%) and hospital admissions (31%-85%); however, an increase of acute cases was observed together with delayed admission. An important reduction of vaccine services utilization was also noted during the first period of lockdown. Domestic accidents and head trauma for suspected domestic violence increased. Health related behaviours worsened, with a relevant increase of screen time (mean of 2.9 hours to 5.1 hours), an important reduction of physical activity (up to 64%). Finally, sleep problems and increase of food consumption, particularly the unhealthy food were reported. CONCLUSIONS: Relevant negative effects of school closure and social distances measures have observed. All the studies have been conducted during the first wave of pandemic and assessed the short-term effect of closures implemented for relatively short periods. If school closure and rigid social distances measures imposition will extend for a long time, an even more pronounced negative effect can be expected. In the context of health policies, in addition to the potential benefits of school closures and social distancing measures on the containment of infection, the potential damage on the physical health of young people should be taken into account by implementing policies to safeguard their health.

[Impact of social distancing for covid-19 on the psychological well-being of youths: a systematic review of the literature.] / Impatto del distanziamento sociale per covid-19 sul benessere psicologico dei giovani: una revisione sistematica della letteratura.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Impact of social distancing for covid-19 on young people: type and quality of the studies found through a systematic review of the literature.] / Impatto del distanziamento sociale per covid-19 sui giovani: tipologia e qualità degli studi reperiti attraversouna revisione sistematica della letteratura.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Infection sustained by lineage B.1.1.7 of SARS-CoV-2 is characterised by longer persistence and higher viral RNA loads in nasopharyngeal swabs.

Following the announcement on December 2020 about the emergence of a new variant (VOC 202012/ 01, B.1.1.7 lineage) in the United Kingdom, a targeted surveillance was put in place in the Abruzzo region (Italy), which allowed detection of 313 persons affected by lineage B.1.1.7, up to the 20th of February 2021. We investigated the results of RT-PCR on nasopharyngeal swabs tested from December 2020 to February 2021 to verify any difference on the viral load and persistence between people infected by lineage B.1.1.7 and others. Statistically significant lower values of CT associated with the detection of the N protein encoding gene (CT N) were observed in persons with lineage B.1.1.7 infection (median CT N = 15.8)in comparison to those infected by other lineages (median CT N = 16.9). A significantly longer duration of the persistence of SARS-CoV-2 RNA in nasopharyngeal swabs was observed in persons with lineage B.1.1.7 infection (16 days) in comparison to those infected by other lineages (14 days).