Ursula Kirchmayer

Background: In the context of a comparative study of efficacy and safety of drugs used in rare neuromuscular and neurodegenerative diseases (CAESAR—call AIFA_FV_2012-13-14), we assessed the use patterns of drugs indicated for myasthenia gravis (MG). Methods: A retrospective cohort study was conducted based on administrative healthcare data. For a cohort of MG patients, prevalent and incident use of pyridostigmine (Py) and other indicated drugs in the first year after case identification was evaluated. Prevalent combined use of major therapies (azathioprine (Az), prednisone (Pr), vitamin D (Vd)) stratified by Py use was assessed, and a comparison between therapies at the time of MG identification and during the first year of follow-up was performed. Results: We included 2369 MG patients between 2013 and 2019. Among them, prevalent and incident Py users were 38.4% and 22.0%, respectively. In the first year of follow-up, the use of Pr was observed in 74.5% of Py prevalent users and in 82.0% of Py incident users, respectively; the use of Az was observed in 24.9% and 23.0%, respectively; and the use of Vd was observed in 53.3% and 48.2%, respectively. Among 910 Py prevalent users, 13.1% also used Az, Pr, and Vd, while 15.3% used none of these. Among 938 non-Py users, 2.7% used Az, Pr, and Vd, while 53.8% used none of these. During the first year, an increase in combined therapies was evident in incident Py users. Conclusions: Our results suggest that, for some MG patients, there may be a need for treatments that combine a rapid onset of benefit with long-term and consistent disease control. These issues may be addressed by the new treatments currently being developed. To date, more studies are needed to address the heterogeneity, quality, and generalizability of the existing data and to evaluate patterns of use, efficacy, and safety of new or emerging therapies for MG.

To investigate the association of the 2019–2020 influenza vaccine with prognosis of patients positive for SARS-CoV-2A, a large multi-database cohort study was conducted in four Italian regions (i.e., Lazio, Lombardy, Veneto, and Tuscany) and the Reggio Emilia province (Emilia-Romagna). More than 21 million adults were residing in the study area (42% of the population). We included 115,945 COVID-19 cases diagnosed during the first wave of the pandemic (February–May, 2020); 34.6% of these had been vaccinated against influenza. Three outcomes were considered: hospitalization, death, and intensive care unit (ICU) admission/death. The adjusted relative risk (RR) of being hospitalized in the vaccinated group when compared with the non-vaccinated group was 0.87 (95% CI: 0.86–0.88). This reduction in risk was not confirmed for death (RR = 1.04; 95% CI: 1.01–1.06), or for the combined outcome of ICU admission or death. In conclusion, our study, conducted on the vast majority of the population during the first wave of the pandemic in Italy, showed a 13% statistically significant reduction in the risk of hospitalization in some geographical areas and in the younger population. No impact of seasonal influenza vaccination on COVID-19 prognosis in terms of death and death or ICU admission was estimated.

Context and aim The spread of the new coronavirus SARS-CoV-2 is challenging many health and care systems around the globe [1]. Its onset constitutes a critical issue, especially for older and/or vulnerable people and patients with preexisting medical conditions being at risk for severe outcomes [2]. This new challenge puts care systems in need of answers: how can vulnerable populations be protected

Evidence available on the effectiveness and costs of biological therapies for the initial treatment of metastatic colorectal cancer (mCRC) is scarce and contrasting. We conducted a population-based cohort investigation for assessing overall survival and costs associated with their use in a real-world setting. Healthcare utilization databases were used to select patients newly diagnosed with mCRC between 2010 and 2016. Those initially treated with biological therapy (bevacizumab or cetuximab) added to chemotherapy were propensity-score-matched to those treated with standard chemotherapy alone, and were followed up to June 30th, 2018. Kaplan–Meier survival estimates, restricted mean survival time (RMST) and cumulative costs were compared between the two treatment arms. The study cohort included 1896 mCRC patients treated with biological therapy matched to 5678 patients treated with chemotherapy alone. Median overall survival was 21.8 and 20.2 months, respectively. After 84 months of follow-up, RMSTs were 30.9 and 31.9 months (p = 0.193), indicating no differences between the average survival time between treatment arms. Patients treated with biological therapy were associated with higher costs. Cumulative per capita costs were €59,663 and €44,399, respectively. In our study, first-line biological therapy did not improve long-term overall survival and was associated with higher costs as compared to standard chemotherapy.

Introduction: Despite recommendations from associations of geriatric and psychiatry societies and warnings from drug agencies, antipsychotic (AP) drugs are frequently used to control behavioral and psychological symptoms of dementia. APs are associated with a range of potential adverse events, including increased risk of cerebrovascular events and mortality. Evidence suggests limited efficacy of APs for aggression and psychosis. Our objectives were to investigate patterns and predictors for prescription of APs among older adults with dementia residing in a large region of central Italy, and to identify patient characteristics related to typical or atypical APs prescribing. Methods: This is a retrospective population-based cohort study using data from regional health information systems (HIS). We included dementia patients aged ≥65 years residing in the Lazio region. The exposure was defined as new use vs non-use of APs. Dementia patients with incident use of APs during 2015 were followed-up from the date of first prescription to the earliest among discontinuation of use, death, or end of study (December 31, 2016). Results: We enrolled 24,735 dementia patients, 1727 (6.7%) new users and 23,008 non-users of APs. Forty-four percent of AP users were treated for more than 3 months, and among these about 60% received APs continuously for at least 12 months. Individuals using antidepressant or anti-dementia drugs had higher odds of being prescribed with APs (OR: 1.67 and OR: 1.86, respectively). Patients exposed to polypharmacy were less likely to receive APs (OR: 0.82). Cardiovascular risk factors and comorbidities were not associated with APs use. Low socio-economic position was associated with lower odds of atypical AP prescribing (OR: 0.57). Conclusion: The study showed that a not negligible proportion of patients had a period of AP use longer than recommended by guidelines. We identified socio-demographic and clinical factors associated with first use of APs, providing insight into prescribing practices in a community setting and useful information to address areas of potential inappropriateness.

Background: Mortality and cardiorespiratory diseases are well-documented effects of atmospheric pollutants. Because epigenetic mechanisms are identified as interaction factors between environmental exposures and gene expression, as well as pathogenic factors of impaired immune tolerance, it seems relevant to study autoimmune diseases in relation to air pollution. Methods: To study whether daily increases of particulate matter (PM₁₀, PM_2.5) and nitrogen dioxide (NO₂) are associated with exacerbations of autoimmune diseases, a total of 23,898 residents of Rome (Italy) who were diagnosed in 2003–2014 with Hashimoto thyroiditis, systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and multiple sclerosis were enrolled. Exacerbations were defined as subsequent hospitalizations for the initial disease or its complications, or a different autoimmune disease, and as dose increases or time reductions between drug prescriptions for autoimmune diseases. Data were analyzed for 2006–2014. Daily concentrations of PM₁₀, PM_2.5, and NO₂ in Rome were available from a fixed monitoring network, during 2006–2014. A time-stratified case-crossover study was carried out. Results: All air pollutants were associated with more frequent changes than usual in treatment for all autoimmune diseases; the greatest increases in risk were observed for PM_2.5 (10 μg/m³ increase) in thyroiditis (3.31% [2.21%, 4.2%]), lupus (3.55% [0.70%, 6.49%]), arthritis (4.93% [2.11%, 7.83%]), and psoriasis (4.04% [0.21%, 8.01%]). No associations were observed for hospitalizations for all studied diseases, whereas changes toward lower corticosteroids’ dose in multiple sclerosis and less effective corticosteroids’ forms in psoriasis were observed. Conclusions: PM_2.5 and NO₂ might exacerbate autoimmune diseases. As detected with treatment changes especially in younger patients.

Drug consumption during pregnancy is a matter of concern, especially regarding drugs known or suspected to be teratogens. Little is known about drug use in pregnant women in Italy. The present study is aimed at examining the prevalence, and to detect potential inappropriateness of drug prescribing among pregnant women in Latium, a region of central Italy. This retrospective study was conducted on a cohort of women aged 18-45 years who delivered between 2008 and 2012 in public hospitals. Women were enrolled through the Regional Birth Register. After linking the regional Health Information Systems and the Regional Drug Claims Register, women’s clinical data and prescribed medications were analyzed. Italian Medicine Agency (AIFA) and US Food and Drug Administration (FDA) evidence were used to investigate inappropriate prescribing and teratogenic risk. Excluding vitamins and minerals, 80.6% (n = 153,079) of the women were prescribed at least one drug during pregnancy, with an average of 4.6 medications per pregnancy. Drugs for blood and hematopoietic organs were the most commonly prescribed (53.0%,), followed by anti-infectives for systemic use (50.7%). Among the inappropriate prescriptions, progestogen supplementation was given in 20.1% of pregnancies; teratogen drugs were prescribed in 0.8%, mostly angiotensin co-enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) (0.3%). In Latium, drugs are widely used in pregnancy. Prescriptions of inappropriate drugs are observed in more than a fifth of pregnancies, and teratogens are still used, despite their known risk. Continuous updates of information provided to practitioners and an increased availability of information to women might reduce inappropriate prescribing.

Background Real‐time monitoring is used to the ends of postmarketing observational research on newly marketed drugs. We implemented a pilot near‐real‐time monitoring program on the test case of oral anticoagulants. Specifically, we evaluated the safety and effectiveness of direct oral anticoagulants compared to vitamin K antagonists in nonvalvular atrial fibrillation secondary prevention during 2013‐2015 in the Lazio Region, Italy. Methods and Results A cohort study was conducted using a sequential propensity‐score–matched new user parallel‐cohort design. Sequential analyses were performed using Cox models. Overall, 10 742 patients contributed to the analyses. Compared with vitamin K antagonists, direct oral anticoagulant use was associated with a reduction of all‐cause mortality (0.81; 95% confidence interval [CI] 0.66‐0.99), cardiovascular mortality (0.71; 95% CI 0.54‐0.93), myocardial infarction (0.67; 95% CI 0.43‐1.04), ischemic stroke (0.87; 95% CI 0.52‐1.45), hemorrhagic stroke (0.25; 95% CI 0.07‐0.88), and with a nonsignificant increase of gastrointestinal bleeding (1.26; 95% CI 0.69‐2.30). Conclusions The present pilot study is a cornerstone to develop real‐time monitoring for new drugs in our region.

To describe NSAID utilization for musculoskeletal conditions in a large cohort of Italian elderly with cerebro/cardiovascular disease, a population in which NSAIDs should be generally avoided due to the prothrombotic potential.

According to scientific literature, antibacterials are prescribed for common pediatric conditions that do not benefit from antibiotic therapy. The link between antibiotic use and bacterial resistance is well known. Antibiotic overprescribing generates high social costs and severe consequences for children. Our objectives were to analyze antibiotic prescription patterns in pediatric outpatients residing in the Lazio region (Italy), to identify physicians’ characteristics associated with increased propensity for prescription, to identify the priority axes for action to improve the rational use of antibiotics. We enrolled all children aged 13 years or less in 2014. Antibiotic prescription patterns were analyzed during a one-year follow-up period. The main outcome measures were the antibiotic prescription prevalence, and the geographic variation in antibiotic prescribing. Multilevel models were performed to analyze variation. Variation was expressed as Median Odds Ratios (MORs). If the MOR is 1.00, there is no variation between clusters. If there is considerable between-cluster variation, the MOR will be large. We enrolled 636,911 children. Most of them were aged 6–13 years (57.3%). In 2015, the antibiotic prescription prevalence was 46% in the 0–13, 58% in the 0–5, and 37% in the 6–13 age group. Overall, penicillins were the most prescribed antibiotics, their consumption increased from 43% to 52% during the 2007–2015 period. In 2015, the antibiotic prescription prevalence ranged from 30% to 62% across local health districts (LHDs) of the region. Moreover, a significant (p < 0.001) variation was observed between physicians working in the same LHD: MORs were equal to 1.52 (1.48–1.56) and 1.46 (1.44–1.48) in the 0–5 and 6–13 age groups, respectively. The probability of prescribing antibiotics was significantly (p < 0.001) lower for more-experienced physicians. Pediatric antibiotic use in the Lazio region is much higher than in other European countries. The intra-regional drug prescribing variability underlines the lack of therapeutic protocols shared at regional level and raises equity issues in access to optimal care. Both LHD managers and individual physicians should be involved in training interventions to improve the targeted use of antibiotics and mitigate the effect of contextual variables, such as the spatial-related socioeconomic status of the patient/parent binomial.