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and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials.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.

Competitive colonization of Legionella and Pseudomonas aeruginosa in water systems of residential facilities hosting closed communities Legionella versus Pseudomonas aeruginosa in water systems of residential facilities.

Legionella and Pseudomonas aeruginosa are pathogens that live and multiply in water systems and resist disinfection through biofilm formation. As suggested by some studies, we wanted to verify whether the presence of P. aeruginosa can lead to a less frequent presence of Legionella in water systems of retirement homes and group homes. We collected 123 hot water and biofilm samples from showerheads. Samples were tested by selective culture methods, and Heterotrophic Plate Counts were determined. Legionella and P. aeruginosa were found in 35% and 39% of distal points, respectively. The presence of P. aeruginosa was significantly inversely correlated with the presence of Legionella when considering both matrices together (p<0.01), water samples only (p=0.02), and biofilm samples only (p=0.04). The inverse relationship was strong for L. pneumophila sg1 (Odds Ratio 0.182, p=0.002), while it is no longer verified when only L. pneumophila serogroups 2-14 are considered. The implications for the development of environmental investigations and risk management are discussed.

Impact of antipsychotics in children and adolescents with autism spectrum disorder: a systematic review and meta-analysis.

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.

Equity, acceptability and feasibility of using polyunsaturated fatty acids in children and adolescents with autism spectrum disorder: a rapid systematic review.

INTRODUCTION: Some 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: We 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.

Introduction and methods of the evidence-based guidelines for the diagnosis and management of autism spectrum disorder by the Italian National Institute of Health.

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

Impact of polyunsaturated fatty acids on patient-important outcomes in children and adolescents with autism spectrum disorder: a systematic review.

BACKGROUND: Recent 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: PUFAs 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.

Acceptability, equity, and feasibility of using antipsychotics in children and adolescents with autism spectrum disorder: a systematic review.

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.

[Adverse reactions after repeated doses of anti-tetanus vaccine: scientific evidences]. / Reazioni avverse dopo dosi ravvicinate di vaccino anti-tetanico nell'adulto: una ricerca sulle evidenze scientifiche.

The possible risk of hyperimmunization after tetanus vaccination is currently discussed after the National Vaccine Prevention Plan 2017-2019 confirmed the recommendation of a booster dose every ten years. Due to the ubiquitous nature of tetanus spores and the inability to obtain herd-immunity through vaccination, efforts to reduce the incidence of tetanus aim at eliminating the disease. The only way to prevent infection is vaccination followed by recommended periodic booster doses. Between 2012 and 2016, Italy notified 45% (252/564) of all cases reported by the 26 EU Member States, most of them in the over 65 age group, generally women in the rural areas. The recommendation of the antipertussis vaccine, combined with anti-tetanus, in pregnancy and the indications for antitetanic prophylaxis by vaccination or specific immunoglobulins in emergency setting, gives rise to doubts about the risk of hyperimmunization. Studies generally agree on the safety of diphtheria-tetanus-pertussis combined vaccines during the third trimester of pregnancy, and the time elapsed since the previous tetanus vaccination seems not to be related to significant differences in the incidence of adverse events or obstetrical complications. In the emergency wards, given the relatively high incidence of tetanus in Italy, the risk/benefit ratio often leads to prefer vaccination to no-intervention. The administration of tetanus immunoglobulins in subjects not vaccinated in the last 10 years seems justified by the epidemiology of tetanus in Italy.

Comparative efficacy and acceptability of psychosocial interventions for individuals with cocaine and amphetamine addiction: A systematic review and network meta-analysis.

BACKGROUND: Clinical guidelines recommend psychosocial interventions for cocaine and/or amphetamine addiction as first-line treatment, but it is still unclear which intervention, if any, should be offered first. We aimed to estimate the comparative effectiveness of all available psychosocial interventions (alone or in combination) for the short- and long-term treatment of people with cocaine and/or amphetamine addiction. METHODS AND FINDINGS: We searched published and unpublished randomised controlled trials (RCTs) comparing any structured psychosocial intervention against an active control or treatment as usual (TAU) for the treatment of cocaine and/or amphetamine addiction in adults. Primary outcome measures were efficacy (proportion of patients in abstinence, assessed by urinalysis) and acceptability (proportion of patients who dropped out due to any cause) at the end of treatment, but we also measured the acute (12 weeks) and long-term (longest duration of study follow-up) effects of the interventions and the longest duration of abstinence. Odds ratios (ORs) and standardised mean differences were estimated using pairwise and network meta-analysis with random effects. The risk of bias of the included studies was assessed with the Cochrane tool, and the strength of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We followed the PRISMA for Network Meta-Analyses (PRISMA-NMA) guidelines, and the protocol was registered in PROSPERO (CRD 42017042900). We included 50 RCTs evaluating 12 psychosocial interventions or TAU in 6,942 participants. The strength of evidence ranged from high to very low. Compared to TAU, contingency management (CM) plus community reinforcement approach was the only intervention that increased the number of abstinent patients at the end of treatment (OR 2.84, 95% CI 1.24-6.51, P = 0.013), and also at 12 weeks (OR 7.60, 95% CI 2.03-28.37, P = 0.002) and at longest follow-up (OR 3.08, 95% CI 1.33-7.17, P = 0.008). At the end of treatment, CM plus community reinforcement approach had the highest number of statistically significant results in head-to-head comparisons, being more efficacious than cognitive behavioural therapy (CBT) (OR 2.44, 95% CI 1.02-5.88, P = 0.045), non-contingent rewards (OR 3.31, 95% CI 1.32-8.28, P = 0.010), and 12-step programme plus non-contingent rewards (OR 4.07, 95% CI 1.13-14.69, P = 0.031). CM plus community reinforcement approach was also associated with fewer dropouts than TAU, both at 12 weeks and the end of treatment (OR 3.92, P < 0.001, and 3.63, P < 0.001, respectively). At the longest follow-up, community reinforcement approach was more effective than non-contingent rewards, supportive-expressive psychodynamic therapy, TAU, and 12-step programme (OR ranging between 2.71, P = 0.026, and 4.58, P = 0.001), but the combination of community reinforcement approach with CM was superior also to CBT alone, CM alone, CM plus CBT, and 12-step programme plus non-contingent rewards (ORs between 2.50, P = 0.039, and 5.22, P < 0.001). The main limitations of our study were the quality of included studies and the lack of blinding, which may have increased the risk of performance bias. However, our analyses were based on objective outcomes, which are less likely to be biased. CONCLUSIONS: To our knowledge, this network meta-analysis is the most comprehensive synthesis of data for psychosocial interventions in individuals with cocaine and/or amphetamine addiction. Our findings provide the best evidence base currently available to guide decision-making about psychosocial interventions for individuals with cocaine and/or amphetamine addiction and should inform patients, clinicians, and policy-makers.

[Prevention of vector-borne diseases in Italy]. / Prevenzione delle Infezioni trasmesse da vettori in Italia.

In recent years, a constant increase of vector-borne diseases has been seen in Italy, due to various conditions including climate change, trade and international travel. These factors contribute to the diffusion on the Italian territory of newly introduced carriers and pathogens. These new pathogens can be an emerging cause of epidemics, as in the case of the Chikungunya virus in 2007 and in 2017, or can establish a true endemic disease, as in the case of the West Nile virus. It is even possible that diseases that had been endemic in the past, which were subsequently eliminated in Italy, could be reintroduced, as in the case of malaria. This review aims to illustrate the recent evolution of the diffusion of vectors and of the pathogens they convey, and to investigate which emerging pathogens could be responsible in the immediate future for new epidemics / endemics in Italy. Nowadays it is necessary to keep those neglected emerging diseases in mind, in order to establish a correct diagnostic-therapeutic approach at the individual level, and to identify the measures to avoid their diffusion at the community level. Preventive interventions, such as available vaccines or individual protection from vectors, are also discussed.

[Vaccine co-administration in clinical practice]. / Somministrazione contemporanea dei vaccini nella pratica clinica.

Vaccines are biological products designed to induce a protective immune response, mimicking natural infection without the development of disease and / or complications. Combined vaccine administration and vaccines co-administration is a safe and effective practice, the benefits of which outweigh the disadvantages. The operators should assess individual variations for the completion of the vaccination schedule, which may be necessary in clinical practice, case by case. Often there are myths to dispel, such as fears about the overload of the immune system, the remora to do more injections in the same session, excessive reactogenicity and some false contraindications. The operators, in order to resolve their doubt in performing non-routine co-administrations, can rely on the Summary of Product Characteristics (SPC) of the individual vaccines and on the new available evidence.

Occurrence of Legionella in showers at recreational facilities.

Critical environments, including water systems in recreational settings, represent an important source of Legionella pneumophila infection in humans. In order to assess the potential risk for legionellosis, we analyzed Legionella contamination of water distribution systems in 36 recreational facilities equipped with swimming pools. One hundred and sixty water samples were analyzed from shower heads or taps located in locker rooms or in bathrooms. By culture method and polymerase chain reaction, 41/160 samples were positive for Legionella from 12/36 recreational centers. Hotels (57.1%) and sports centers (41.2%) were the most contaminated. L. pneumophila serotypes 2-14 (25/41) were more frequently found than serotype 1 (10/41). Samples at temperature ≥30 °C were more frequently positive than samples at temperature <30 °C (n = 39 vs n = 2, p < 0.00001). The presence of L. pneumophila was investigated by comparison with heterotrophic plate count (HPC), an indicator of water quality. The presence of L. pneumophila was associated more frequently with high and intermediate HPC load at 37 °C, therefore should be considered a potential source when HPC at 37 °C is >10 CFU/mL. Maintenance, good hygiene practices, interventions on the hydraulic system and regular controls must be implemented to minimize exposure to L. pneumophila infection risk.

[Bacterial lysates: history and availability]. / Storia e diffusione dei lisati batterici utilizzati come "vaccini".

The use of bacterial lysates (BLs) can be traced back to the end of the nineteenth century, and they are currently available in several countries across all continents. Over the last few decades, BLs have been used, both in pediatric patients and in adults, mainly for the prevention and treatment of bacterial infections of the respiratory tract. BLs are produced from bacterial cultures that undergo cell lysis with two different methods: mechanical lysis and chemical lysis. The in vivo mechanism of action is still not fully understood, and the main hypotheses focus on mucosal immunity modulation. We searched PubMed for relevant papers on the use of BLs for the prevention and treatment of chronic obstructive pulmonary disease and recurrent respiratory infections both in adult and in pediatric patients. We retrieved 169 articles and after screening and selection, we analyzed 13 RCTs focusing on adult patients and 8 on pediatric patients. The outcomes assessed were mainly about the efficacy of BLs on exacerbations, hospitalizations, antibiotic treatment, fever, number of episodes and days of absence from work or school. Many aspects of BLs are still not well understood and the quality of available studies is not satisfactory; in order to place BLs within the scope of Public Health, further good quality studies are needed, keeping in mind the necessity to respond to the needs of patients for whom no alternative effective treatments are available.

[The Italian Immunization Plan 2017: analysis and starting point for the Regional Plans]. / Il nuovo Piano Nazionale Prevenzione Vaccinale 2017-2019: analisi e punto di partenza per i piani regionali.

The National Immunization Plan 2017-2019 has been approved on January 2017. This official document contains the new Italian guidelines to improve vaccination coverage in the country. We conducted an accurate and critical analysis of the document, highlighting its key points and critical issues, in order to offer an practical tool for writing the Regional Plans. The new immunization schedule and the establishment of a restricted panel for the vaccine vigilance are the most significant innovations of the Plan. The Plan addresses also the issues of mandatory vaccination and of penalties for physicians who advise against vaccinations. Together with the presence of qualifying aspects as information about the ethical value and the benefits of vaccination, the Plan contains other interesting proposals, such as the introduction of a computerized vaccination register and the targeted use of new technologies to reach the population extensively. The Plan is set up as a conceptually rich tool, suitable for the development of regional operational plans.

[HPV vaccination: active offer in an Italian region]. / Offerta attiva della vaccinazione anti-HPV nella Regione Lazio.

Human Papillomavirus is responsible for 4.8% of cancers, and is the main cause of cervical cancer. Cervical cancer can be reduced by mean of secondary prevention (PAP-test, HPV-DNA test), while through primary prevention (anti-HPV vaccine) the incidence of other HPV-attributable cancers can also be reduced. In Italy, anti-HPV vaccination is part of the immunization schedule in girls since 2008, and in 2017 it was extended to boys. However, vaccine coverage is decreasing nationwide. This study aims to examine anti-HPV vaccination practices in Health care services of Lazio Region, Italy. Questionnaires were sent or administered directly to those in charge of vaccinations. Data, collected from 11/12 (92%) Lazio Local Health Units and from 116 vaccination centers, show a remarkable diversity in the offer: 41% of the centers open only 1-2 days/week, 42% only in the morning, and only 7% are open on Saturday. Vaccination is available by reservation only in 62% of the centers, while vaccines are not administered to ≥18 years subjects in 33%; 93% of the centers call actively the girls in the target cohort, while 70% and 94% recall the patients who had not received the first or the second dose of vaccine, respectively. Collaboration with family physicians and/or pediatricians was declared by 80% of the centers. Vaccine coverage could probably be improved by addressing the highlighted critical issues and applying best practices widely.

[Zika virus: a public health overview on epidemiology, clinical practice and prevention]. / Virus Zika: una panoramica di sanità pubblica su epidemiologia, clinica e prevenzione.

Zika virus is an arbovirus mainly transmitted by mosquitoes bites. During the last months, the attention of Public Health Institutions has been drawn by a significant increase of microcephaly cases in Brasil and analyses highlighted a connection between Zika virus infection in pregnant women and fetal microcephaly. Since 2015, many Zika virus outbreaks have been identified in South America and there is concern about the spread of the virus in areas where competent vectors are present. Nowadays, vaccination is not available and prevention is based on individual measures and on vectors control. This review of the most recent studies give an overview on the Zika problem.

[Vaccines: history and stories between reality and imagination]. / La Storia e le storie sui vaccini. Un piano tra veridicità e fantasia.

Vaccinations and the controversy around them always go in parallel. We identified four categories blending in various amounts of truth and imagination: history, myths, shams and frauds. Over the years, they have alternated and sometimes transformed into one another. This sharp separation into categories is certainly academic and forced. In fact, the line between these aspects is not clear enough to allow a rigid and well-defined division. Our work starts from the category containing the most truthfulness: history, and goes on to analyze two categories that add fantasy to facts: myths and shams (or better, "old wives' tales"). The history deals with the topics of variolation and the first anti-vaccine activists' disputes. Myths that arose around immunization include immune overload, homeoprophylaxis, and excessive hygiene. In this context, immunization itself risked becoming a myth, being considered not amenable to improvements. In the category of old wives' tales we find rumors about the presence in the vaccines of considerable quantities of supposedly toxic components such as aluminum, squalene, Thimerosal and nanoparticles, as well as the existence of secret techniques of vaccine preparation that involve unethical procedures. The last category, fraud, is the poorest in both truth and fantasy but it is still hard to confront. The most famous fraud is the supposed link between vaccines and autism. In this frame, disinformation is certainly a fertile substrate for the emergence both of elements close to reality and of very imaginative ones. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and increasing the risk of vaccine-preventable disease outbreaks and epidemics. The role of communication in immunization is essential to its success, especially taking into account the deep transformations the world of information is going through. The great multitude of voices seem to carry the same weight, but it is not so in science. Web searches are influenced by the filter bubble phenomenon, which contributes to the radicalization of people's opinion through cognitive isolation. A new, more effective strategy of communication is required in order to regain the trust of populations in immunization in a context characterized by the presence of groups impervious to scientific evidence.

[Rare adverse events following immunization: coincidence]. / Eventi avversi rari successivi a vaccinazione: casualità o causalità?

The high standards of safety and effectiveness of vaccines have allowed them to get a prominent role in disease prevention and health protection. However, like any other intervention, vaccination is not free from risks. Rare adverse events occur after immunization in less than one in a thousand individuals and can be linked to vaccination by causality or coincidence. These events are reported on the SmPC (Summary of Product Characteristics). We have first divided the rare adverse events in local and generalized, and then we have analyzed them according to the type of vaccine linked to the event. Communication of the benefits of vaccines, that are surely greater than their risks, must take place in a conscious and scientific way, in order to avoid vaccinations being perceived as an imposition, instead of the great opportunity for everyone that they are.

[The public health importance of vaccinations in the elderly: an evidence-based guide]. / L'importanza delle vaccinazioni nell'anziano nell'ambito della Sanità Pubblica: una guida basata sulle prove scientifiche.

Ageing represents an extremely current issue globally, and involves especially European populations. It is estimated that in Europe by the year 2025, about a third of the population will be over 60 years of age, hence the imperative for "healthy ageing". Vaccinations in seniors, in contrast with paediatric vaccinations, are very often neglected even by health care workers. This article aims to provide an evidence-based guide to establish vaccinations in seniors as one of the pillars of Public Health in the future.

Bacterial Contamination of Healthcare Students' Mobile Phones: Impact of Specific Absorption Rate (SAR), Users' Demographics and Device Characteristics on Bacterial Load.

We quantitatively and qualitatively evaluated the bacterial contamination of mobile phones (MPs) in relation to users' demographics, habits, and device characteristics by administering questionnaires to 83 healthcare university students and sampling their MPs by following a cross-sectional design. The heterotrophic plate count (HPC) at 22 °C (HPC 22 °C) and 37 °C (HPC 37 °C), Enterococci, Gram-negative bacteria, and Staphylococci were evaluated. Higher bacterial loads were detected for HPC 37 °C and Staphylococci (416 and 442 CFU/dm2, respectively), followed by HPC 22 °C, Enterococci, and Gram-negative bacteria; the vast majority of samples were positive for HPC 37 °C, HPC 22 °C, and Staphylococci (98%), while Enterococci (66%) and Gram-negative bacteria (17%) were detected less frequently. A statistically significant positive correlation (r = 0.262, p < 0.02) was found between the European head specific absorption rate (SAR) and both HPC 37 °C and Staphylococci; Enterococci showed a strong, significant correlation with HPC 37 °C, HPC 22 °C, and Gram-negative bacteria (r = 0.633, 0.684, 0.884) and a moderate significant correlation with Staphylococci (r = 0.390). Significant differences were found between HPC 22 °C and the type of internship attendance, with higher loads for Medicine. Students with a daily internship attendance had higher HPC 22 °C levels than those attending <6 days/week. Our study showed that bacteria can survive on surfaces for long periods, depending on the user's habits and the device's characteristics.