Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program.

OBJECTIVE: This study was undertaken to assess the effectiveness/tolerability of adjunctive cenobamate, variations in the load of concomitant antiseizure medications (ASMs) and predictors of clinical response in people with focal epilepsy. METHODS: This was a retrospective study at 21 centers participating in the Italian Expanded Access Program. Effectiveness outcomes included retention and responder rates (≥50% and 100% reduction in baseline seizure frequency). Tolerability/safety outcomes included the rate of treatment discontinuation due to adverse events (AEs) and their incidence. Total drug load was quantified as the number of concomitant ASMs and total defined daily dose (DDD). Concomitant ASMs were also classified according to their mechanism of action and pharmacokinetic interactions to perform explorative subgroup analyses. RESULTS: A total of 236 subjects with a median age of 38 (Q1-Q3 = 27-49) years were included. At 12 months, cenobamate retention rate was 78.8% and responders were 57.5%. The seizure freedom rates during the preceding 3 months were 9.8%, 12.2%, 16.3%, and 14.0% at 3, 6, 9, and 12 months. A higher percentage of responders was observed among subjects treated with clobazam, although the difference was not statistically significant. A total of 223 AEs were recorded in 133 of 236 participants, leading to cenobamate discontinuation in 8.5% cases. At 12 months, a reduction of one or two concomitant ASMs occurred in 42.6% and 4.3% of the subjects. The median total DDD of all concomitant ASMs decreased from 3.34 (Q1-Q3 = 2.50-4.47) at baseline to 2.50 (Q1-Q3 = 1.67-3.50) at 12 months (p < .001, median percentage reduction = 22.2%). The highest rates of cotreatment withdrawal and reductions in the DDD were observed for sodium channel blockers and γ-aminobutyric acidergic modulators (above all for those linked to pharmacokinetic interactions), and perampanel. SIGNIFICANCE: Adjunctive cenobamate was associated with a reduction in seizure frequency and in the burden of concomitant ASMs in adults with difficult-to-treat focal epilepsy. The type of ASM associated did not influence effectiveness except for a favorable trend with clobazam.

Brivaracetam use in clinical practice: a Delphi consensus on its role as first add-on therapy in focal epilepsy and beyond.

BACKGROUND: Antiseizure medications remain the cornerstone of treatment for epilepsy, although a proportion of individuals with the condition will continue to experience seizures despite appropriate therapy. Treatment choices for epilepsy are based on variables related to both the individual patient and the available medications. Brivaracetam is a third-generation agent antiseizure medication. METHODS: We carried out a Delphi consensus exercise to define the role of brivaracetam in clinical practice and to provide guidance about its use as first add-on ASM and in selected clinical scenarios. A total of 15 consensus statements were drafted by an expert panel following review of the literature and all were approved in the first round of voting by panelists. The consensus indicated different clinical scenarios for which brivaracetam can be a good candidate for treatment, including first add-on use. RESULTS: Overall, brivaracetam was considered to have many advantageous characteristics that render it a suitable option for patients with focal epilepsy, including a fast onset of action, favorable pharmacokinetic profile with few drug-drug interactions, broad-spectrum activity, and being well tolerated across a range of doses. Brivaracetam is also associated with sustained clinical response and good tolerability in the long term. CONCLUSIONS: These characteristics also make it suitable as an early add-on for the elderly and for patients with post-stroke epilepsy or status epilepticus as highlighted by the present Delphi consensus.

Adjunctive brivaracetam and sustained seizure frequency reduction in very active focal epilepsy.

OBJECTIVE: This study aimed to explore the effectiveness of brivaracetam (BRV) according to baseline seizure frequency and past treatment history in subjects with focal epilepsy who were included in the Brivaracetam Add-On First Italian Network Study (BRIVAFIRST). METHODS: BRIVAFIRST was a 12-month retrospective, multicenter study including adults prescribed adjunctive BRV. Study outcomes included sustained seizure response (SSR), sustained seizure freedom (SSF), and the rates of treatment discontinuation and adverse events (AEs). Baseline seizure frequency was stratified as <5, 5-20, and >20 seizures per month, and the number of prior antiseizure medications (ASMs) as <5 and ≥6. RESULTS: A total of 994 participants were included. During the 1-year study period, SSR was reached by 45.8%, 39.3%, and 22.6% of subjects with a baseline frequency of <5, 5-20, and >20 seizures per month (p < .001); the corresponding figures for the SSF were 23.4%, 9.8%, and 2.8% (p < .001). SSR was reached by 51.2% and 26.5% participants with a history of 1-5 and ≥6 ASMs (p < .001); the corresponding rates of SSF were 24.7% and 4.5% (p < .001). Treatment discontinuation due to lack of efficacy was more common in participants with >20 seizures compared to those with <5 seizures per month (25.8% vs. 9.3%, p < .001), and in participants with history of ≥6 prior ASMs compared to those with history of 1-5 ASMs (19.6% vs. 12.2%, p = .002). There were no differences in the rates of BRV withdrawal due to AEs and the rates of AEs across the groups of participants defined according to the number of seizures at baseline and the number of prior ASMs. SIGNIFICANCE: The baseline seizure frequency and the number of previous ASMs were predictors of sustained seizure frequency reduction with adjunctive BRV in subjects with focal epilepsy.

Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures.

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32-56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12 months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy.

Brivaracetam as add-on treatment in focal epilepsy: A real-world time-based analysis.

The study assessed the clinical response to add-on brivaracetam (BRV) in real-world practice by means of time-to-baseline seizure count methodology. Patients with focal epilepsy who were prescribed add-on BRV were identified. Primary endpoint was the time-to-baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three-hundred eighty-seven patients were included. The overall median time-to-baseline seizure count was 150 (95% confidence interval [CI] = 130-175) days. The median time-to-baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV-naive patients, 126 (95% CI = 105-150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128-291) days for patients who discontinued LEV due to adverse events (P = .002). The number of prior antiseizure medications (adjusted hazard ratio [adj HR] = 1.07, 95% CI = 1.02-1.13, P = .009) and baseline monthly seizure frequency (adj HR = 1.004, 95% CI = 1.001-1.008, P = .028) were independently associated with the primary endpoint. Add-on BRV improved seizure control in LEV-naive and LEV-prior patients. The time-to-baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs.

Epilepsy in adult patients with tuberous sclerosis complex.

OBJECTIVES: Little is known about the evolution of epilepsy in individuals with tuberous sclerosis complex (TSC) in adulthood. This study aims at describing the characteristics of epilepsy in adult TSC patients attending a single multidisciplinary clinic. MATERIALS AND METHODS: We collected data about epilepsy (age at onset, seizure types, history of infantile spasms (IS), epilepsy diagnosis and outcome), genetic and neuroradiological findings, cognitive outcome and psychiatric comorbidities. RESULTS: Out of 257 adults with TSC, 183 (71.2%) had epilepsy: 121 (67.2%) were drug-resistant; 59 (32.8%) seizure-free, at a median age of 18 years. 22% of the seizure-free patients (13/59) discontinued medication. Median age at seizure onset was 9 months. Seventy-six patients (41.5%) had a history of IS. TSC2 pathogenic variants (p = 0.018), cortical tubers (p < 0.001) and subependymal nodules (SENs) (p < 0.001) were more frequent in those who developed epilepsy. Cognitive functioning was lower (p < 0.001) and psychiatric disorders more frequent (p = 0.001). We did not find significant differences regarding age, gender, mutation and tubers/SENs in seizure-free vs drug-resistant individuals. Intellectual disability (p < 0.001) and psychiatric disorders (p = 0.004) were more common among drug-resistant patients. CONCLUSIONS: Epilepsy in TSC can be a lifelong disorder, but one-third of individuals reach seizure freedom by early adulthood. In the long term, age at epilepsy onset has a crucial role in drug resistance and in developing intellectual disability, both in drug-resistant and drug-sensible patients. Patients with drug-refractory seizures tend to develop psychiatric issues, which should be recognized and adequately treated.

COVID-19 pandemic: health impact of staying at home, social distancing and 'lockdown' measures-a systematic review of systematic reviews.

BACKGROUND: To systematically review the evidence published in systematic reviews (SR) on the health impact of staying at home, social distancing and lockdown measures. We followed a systematic review approach, in line with PRISMA guidelines. METHODS: In October 2020, we searched the databases Cochrane Database of Systematic Reviews, Ovid Medline, Ovid Embase and Web of Science, using a pre-defined search strategy. RESULTS: The literature search yielded an initial list of 2172 records. After screening of titles and abstracts, followed by full-text screening, 51 articles were retained and included in the analysis. All of them referred to the first wave of the coronavirus disease 2019 pandemic. The direct health impact that was covered in the greatest number (25) of SR related to mental health, followed by 13 SR on healthcare delivery and 12 on infection control. The predominant areas of indirect health impacts covered by the included studies relate to the economic and social impacts. Only three articles mentioned the negative impact on education. CONCLUSIONS: The focus of SR so far has been uneven, with mental health receiving the most attention. The impact of measures to contain the spread of the virus can be direct and indirect, having both intended and unintended consequences.

The impact of perampanel treatment on quality of life and psychiatric symptoms in patients with drug-resistant focal epilepsy: An observational study in Italy.

An observational, prospective study has been conducted to evaluate the effects of adjunctive treatment with perampanel (PER) on psychological functioning and quality of life (QoL) in patients with drug-resistant focal epilepsy. Fifty-six adult patients treated with PER in addition to antiepileptic drugs (AEDs) were recruited in 2 Italian Epilepsy Centers. Irritability in Adult Patients with Epilepsy (I-EPI), Quality of Life in Epilepsy (QOLIE-31), Beck Depression Inventory II (BDI-II), and State-Trait Anxiety Inventory Y-1 and Y-2 (STAI) questionnaires were administered at baseline and 3 and 6 months after the treatment onset. Adverse events (AEs) were collected during the observational 6 months period. Retention rate of treatment with PER was 82.1% at 3 months and 64.3% at 6 months. Thirteen patients reported a significant seizure frequency reduction, and one seizure freedom case was observed after 4 months of PER treatment. Perampanel was stopped because of inefficacy or paradoxical effects in 28.6% of cases and because of AEs in 7.1%. The peak dose was not associated with discontinuation probability. Irritability, QoL, depression, trait, and state anxiety did not change significantly during the PER therapy. A tendency of association between higher level of irritability at baseline and PER discontinuation was found. The results of this observational study have shown that the addition of PER to AEDs may improve seizure control, does not increase levels of irritability, depression, and anxiety, and does not reduce patients' QoL. This study also confirms the importance of a comprehensive clinical assessment, including psychiatric symptoms evaluation before offering a new treatment, to improve therapy compliance.

Supporting access to healthcare for refugees and migrants in European countries under particular migratory pressure.

BACKGROUND: In 2015 the increased migratory pressure in Europe posed additional challenges for healthcare providers. The aim of this study was to inform the development of a "Resource Package" to support European Union (EU) member states in improving access to healthcare for refugees, asylum seekers and other migrants. METHODS: A mixed method approach was adopted: i) interviews and focus groups were carried out to gather up-to-date information on the challenges the different healthcare providers were facing related to the refugee crisis; ii) to complement the results of the FGs, a literature review was conducted to collect available evidence on barriers and solutions related to access to healthcare for refugees and migrants. RESULTS: The different actors providing healthcare for refugees and migrants faced challenges related to the phases of the migration trajectory: arrival, transit and destination. These challenges impacted on the accessibility of healthcare services due to legislative, financial and administrative barriers; lack of interpretation and cultural mediation services; lack of reliable information on the illness and health history of migrant patients; lack of knowledge of entitlements and available services; lack of organisation and coordination between services. These barriers proved particularly problematic for access to specific services: mental health, sexual and reproductive care, child & adolescent care and victim of violence care. CONCLUSIONS: The findings of this study show that solutions that are aimed only at responding to emergencies often lead to fragmented and chaotic interventions, devolving attention from the need to develop structural changes in the EU health systems.

Ictal signs in tuberous sclerosis complex: Clinical and video-EEG features in a large series of recorded seizures.

Epilepsy is the most common neurological symptom in tuberous sclerosis complex (TSC), occurring in 72-85% of affected individuals. Despite the large number of patients reported, their electroclinical phenotype has been rarely described. We analyzed seizure semiology through ictal video-electroencephalography (V-EEG) recordings in a large series of patients. In this multicenter study, we reviewed V-EEGs of 51 patients: ictal recordings were analyzed in correlation with their clinical variables. The median age of epilepsy onset was six months (one day-16 years), with onset in the first year of life in 71% patients (36/51), in 10 of them during the neonatal period. Sixty-five percent of patients (33/51) experienced epileptic spasms in their life, with late-onset (>two years) in five; 42% of the epileptic spasms persisted after age two years, despite the onset in the first year of life. We identified four different electroclinical subsets: focal epilepsy (35%, 18/51), Lennox-Gastaut Syndrome evolution (27%, 14/51), focal seizures with persisting spasms (33%, 17/51), and spasms only (4%, 2/51). We reviewed 45 focal seizures, 13 clusters of epileptic spasms, and seven generalized seizures. In 12 patients, we recorded different seizure types. In 71% of the focal seizures (32/45), the ictal pattern was focal without diffusion. In 38% of the patients (5/13) epileptic spasms were related to typical diffuse slow wave pattern associated with superimposed fast activity, with focal predominance. Focal seizures and focal spasms resulted as the most frequent seizure types in TSC. Seizure onset was variable but showing a predominant involvement of the frontocentral regions (40%). Discrete clinical signs characterized the seizures, and behavioral arrest was the predominant first clinical objective sign. Epileptic spasms were a typical presentation at all ages, frequently asymmetrical and associated with lateralizing features, especially in older patients.

Overuse in cancer care: do European studies provide information useful to support policies?

Health services overuse has been acknowledged as a relevant policy issue. In this study, we assessed the informative value of research on the quality of cancer care, exploring to what extent it is actually concerned with care overuse, thus providing policy-makers with sound estimates of overuse prevalence. We searched Medline for European studies, reporting information on the rate of use of diagnostic or therapeutic procedures/interventions in breast, colorectal, lung and prostate cancer patients, published in English between 2006 and 2016. Individual studies were classified with regards to their orientation towards overuse according to the quality metrics adopted in assessing rates of use of procedures and interventions.Out of 1882 papers identified, 100 accounting for 94 studies met our eligibility criteria, most of them on breast (n = 38) and colorectal (n = 30) cancer. Of these, 46 (49%) studies relied on process indicators allowing a direct measure of under- or overuse, the latter being addressed in 22 (24%) studies. Search for overuse in patterns of care did not increase over time, with overuse being measured in 24% of the studies published before 2010, and in only 13% of those published in 2015-2016. Information on its prevalence was available only for a relatively limited number of procedures/interventions. Overall, estimates of overuse tended to be higher for diagnostic procedures (median prevalence across all studies, 24%) than for drugs, surgical procedures or radiotherapy (median overuse prevalence always lower than 10%). Despite its increasing policy relevance, overuse is still an often overlooked issue in current European research on the quality of care for cancer patients.

Differentiating PNES from epileptic seizures using conversational analysis.

We applied conversation analysis in an unselected continuous series of 70 patients to discriminate patients with psychogenic nonepileptic seizures (PNES) from patients with epilepsy. Two psychologists examined the patients' recorded reports. Patients were also submitted to an extensive neuropsychological battery in order to verify whether specific cognitive deficits or mental health problems are typical of patients with PNES and whether some cognitive deficits could prevent the correct diagnosis. The results showed a good percentage of correct diagnosis, with a sensitivity of 0.795 and a specificity of 0.83, while no difference in the cognitive profile was found between patients with PNES and patients with epilepsy. The results also suggest that psychologists can apply the conversation analysis as well as linguists, which is an important finding since psychologists are employed in specialized centers, while linguists in general are not part of the team.

Lennox-Gastaut syndrome in adulthood: Long-term clinical follow-up of 38 patients and analysis of their recorded seizures.

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy with childhood onset that usually continues through adolescence and into adulthood. In the long term, patients with this condition still have intractable seizures, intellectual disability, behavioral problems, and physical comorbidities. The aim of this study was to describe the clinical and EEG characteristics of a group of adults with Lennox-Gastaut syndrome. We identified 38 (22 females, 16 males) patients with LGS older than age 18years at their last evaluation, with mean age of 43.3±10.6years. Median follow-up was 14.4years (range: 2-40). All of our patients had 3 or more seizure types during their clinical history. The most prevalent seizure types at follow-up were atypical absences (28/38), tonic (28/38), generalized tonic-clonic (17/38), focal (11/38), and myoclonic seizures (9/38). All patients had drug-resistant seizures. Besides epilepsy, intellectual disability and behavioral problems were prominent features. Surprisingly, paroxysmal nonepileptic seizures were reported in 3 patients. Our observations confirm the poor outcome of Lennox-Gastaut syndrome through adulthood, regardless of age at seizure onset, etiology, and history of previous West syndrome.

Assessing the impact of defining a global priority research agenda to address HIV-associated tuberculosis.

OBJECTIVES: In 2010, the WHO issued 77 priority research questions (PRQs) to address HIV-associated TB. Objective of the this study was to assess the impact of defining the research agenda in stimulating and directing research around priority research questions. METHODS: We used number and type of scientific publications as a proxy to quantitatively assess the impact of research agenda setting. We conducted 77 single systematic reviews - one for every PRQ - building 77 different search strategies using PRQs' keywords. Multivariate logistic regression models were applied to assess the quantity and quality of research produced over time and accounting for selected covariates. RESULTS: In 2009-2015, PRQs were addressed by 1631 publications (median: 11 studies published per PRQ, range 1-96). The most published area was 'Intensified TB case finding' (median: 23 studies/PRQ, range: 2-74). The majority (62.1%, n = 1013) were published as original studies, and more than half (58%, n = 585) were conducted in the African region. Original studies' publication increased over the study period (P trend = <0.001). They focused more on the 'Intensified TB case finding' (OR = 2.17, 95% CI: 1.56-2.93) and 'Drug-resistant TB and HIV infection' (OR = 2.12, 95% CI: 1.47-3.06) areas than non-original studies. Original studies were published in journals of lower impact factor and received a smaller number of citations than non-original studies (OR = 0.54, 95% CI: 0.42-0.69). CONCLUSION: The generation of evidence to address PRQs has increased over time particularly in selected fields. Setting a priority research agenda for HIV-associated TB might have positively influenced the direction and the conduct of research and contributed to the global response to such a major threat to health.

Laryngeal motility alteration: A missing link between sleep apnea and vagus nerve stimulation for epilepsy.

This study aimed to evaluate the prevalence and the relationship of sleep breathing disorders (SBDs) and laryngeal motility alterations in patients with drug-resistant epilepsy after vagus nerve stimulator (VNS) implantation. Twenty-three consecutive patients with medically refractory epilepsy underwent out-of-center sleep testing before and after VNS implantation. Eighteen eligible subjects underwent endoscopic laryngeal examination post-VNS implantation. Statistical analysis was carried out to assess an association between laryngeal motility alterations and the onset/worsening of SBDs. After VNS implantation, 11 patients showed a new-onset mild/moderate SBD. Half of the patients already affected by obstructive sleep apnea (OSA) showed worsening of SBD. All of the patients with a new-onset OSA had a laryngeal pattern with left vocal cord adduction (LVCA) during VNS stimulation. The association between VNS-induced LVCA and SBD was statistically significant. This study suggests an association between VNS and SBD, hinting to a pivotal role of laryngeal motility alterations. The relationship between SBD and VNS-induced LVCA supports the need to routinely investigate sleep respiratory and laryngeal motility patterns before and after VNS implantation.

The semiology of psychogenic nonepileptic seizures revisited: Can video alone predict the diagnosis? Preliminary data from a prospective feasibility study.

OBJECTIVE: To investigate if, when, and to what extent visual information contained in a video-recorded event allows experienced epileptologists to predict the diagnosis of psychogenic nonepileptic seizures (PNES) without the aid of electroencephalography (EEG). METHODS: Five neurologists actively practicing in epilepsy centers in Italy and the United States were asked to review 23 videos capturing representative events of 21 unselected consecutive patients admitted for long-term video-EEG monitoring (VEM). Four raters were blind to EEG and clinical information; one rater was not. They were requested to (1) rate the videos for quality and content; (2) choose among four diagnoses: (a) epileptic seizures (ES); (b) PNES; (c) Other nonepileptic seizures (NES; (syncope, movement disorder, migraine, etc.); (d) "Cannot Say"; and (3) explain in their own words the main reasons leading to the diagnosis of choice. RESULTS: All raters predicted the diagnosis correctly in 7 of 23 videos (all ES or PNES) (30.4%), whereas all raters failed in 5 of 23 cases (three Other NES, one PNES, one Cannot Say) (21.7%). The conditions that facilitate, and those that interfere with, a confident diagnosis were predictable. Degree of accuracy among raters was not uniform and was consistently better in three raters. Two among the four blind raters were as accurate as the rater who was not blinded. Interrater agreement was "moderate" (k = 0.52) for the overall group; "moderate" for ES (k = 0.53); "substantial" for PNES (k = 0.63); "fair" for Other NES (k = 0.21)-similar to the results obtained in a previous study evaluating the reliability of combined video-EEG. SIGNIFICANCE: In about one third of cases, a confident diagnosis of PNES/ES can be established on clinical grounds based on video data alone. Our results benefit all affected patients, particularly those with no access to video-EEG monitoring units.

Effects of chronic administration of valproic acid to epileptic patients on coagulation tests and primary hemostasis.

Valproic acid (VPA) is an antiepileptic drug that has been associated with impaired hemostasis and increased risk for postsurgical bleeding. However, the published reports provide controversial results. We measured parameters of primary hemostasis in VPA-treated patients with epilepsy, focusing on adenosine nucleotide-dependent platelet responses, which play a central role in primary hemostasis. We enrolled 20 cases (epileptic patients receiving treatment with VPA) and 20 controls (12 epileptic patients receiving treatment with drugs different from VPA and 8 healthy subjects). Measurements included prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count, platelet function analyzer (PFA)-100 closure times, plasma von Willebrand factor levels, platelet content of ADP, ATP, and serotonin (all stored in platelet dense granules), and platelet shape change and aggregation induced by ADP and other platelet agonists, including the ATP analog α,ß-methylene-ATP. The plasma concentration of VPA was in the therapeutic range in 17 patients and slightly above the upper limit in 3 patients. There were no statistically significant differences in any of the studied parameters in cases versus controls. Our thorough controlled study failed to show that chronic treatment with VPA induces significant abnormalities of coagulation and primary hemostasis. Therefore, VPA, when present in the circulation in the therapeutic range, does not impair hemostasis.

Influenza and immunization: a quantitative study of media coverage in the season of the «Fluad case¼.

BACKGROUND: Seasonal influenza generates serious health and economic losses. In the last influenza season, the report of three deaths originally blamed on the Fluad vaccine drew widespread attention from the media and is likely to have had a major negative impact on vaccine uptake. OBJECTIVE: We quantitatively analyzed media coverage on influenza and immunization-related topics on all published issues of the Italian newspaper ranking first in circulation, over one year. DESIGN: We retrieved relevant key words and articles, reporting on article topic, length, position, and approach to immunization, and on other selected indicators' summary statistics, trends, and correspondence with key events. RESULTS: Selected key words were retrieved 798 times over the study period, 34% specifically focusing on influenza. The average number of influenza-related key words per issue was 96%higher in the four-day «uncertainty¼ period from when the deaths were first reported to the release of the test results disproving any causal association between the deaths and the vaccine (time frame #1), as compared to the whole study period. Ninety relevant articles were included in the analysis, 51%focusing on influenza, the average number/issue being 97%higher during time frame #1. During time frame #1, articles were also longer and located in the main sections of the newspapers. No articles were published at the launch of the seasonal influenza immunization campaign. CONCLUSION: We propose an analytic model of media monitoring that could be effectively applied to support health authorities and representatives of the scientific community in conveying health education messages through the media.