Comparing clinical trial population representativeness to real-world users of 17 biologics approved for immune-mediated inflammatory diseases: An external validity analysis of 66,639 biologic users from the Italian VALORE project.

To date, no population-based studies have specifically explored the external validity of pivotal randomized clinical trials (RCTs) of biologics simultaneously for a broad spectrum of immuno-mediated inflammatory diseases (IMIDs). The aims of this study were, firstly, to compare the patients' characteristics and median treatment duration of biologics approved for IMIDs between RCTs' and real-world setting (RW); secondly, to assess the extent of biologic users treated for IMIDs in the real-world setting that would not have been eligible for inclusion into pivotal RCT for each indication of use. Using the Italian VALORE distributed database (66,639 incident biologic users), adult patients with IMIDs treated with biologics in the Italian real-world setting were substantially older (mean age ± SD: 50 ± 15 years) compared to those enrolled in pivotal RCTs (45 ± 15 years). In the real-world setting, certolizumab pegol was more commonly used by adult women with psoriasis/ankylosing spondylitis (F/M ratio: 1.8-1.9) compared to RCTs (F/M ratio: 0.5-0.6). The median treatment duration (weeks) of incident biologic users in RW was significantly higher than the duration of pivotal RCTs in almost all indications for use and most biologics (4-100 vs. 6-167). Furthermore, almost half (46.4%) of biologic users from RW settings would have been ineligible for inclusion in the respective indication-specific pivotal RCTs. The main reasons were: advanced age, recent history of cancer and presence of other concomitant IMIDs. These findings suggest that post-marketing surveillance of biologics should be prioritized for those patients.

Antidiabetic Therapy during Pregnancy: The Prescription Pattern in Italy.

Pregestational and gestational diabetes mellitus are relevant complications of pregnancy, and antidiabetic drugs are prescribed to obtain glycemic control and improve perinatal outcomes. The objective of this study was to describe the prescription pattern of antidiabetics before, during and after pregnancy in Italy and to evaluate its concordance with the Italian guideline on treatment of diabetes mellitus. A multi-database cross-sectional population study using a Common Data Model was performed. In a cohort of about 450,000 women, the prescribing profile of antidiabetics seemed to be in line with the Italian guideline, which currently does not recommend the use of oral antidiabetics and non-insulin injection, even if practice is still heterogeneous (up to 3.8% in the third trimester used oral antidiabetics). A substantial variability in the prescription pattern was observed among the Italian regions considered: the highest increase was registered in Tuscany (4.2%) while the lowest was in Lombardy (1.5%). Women with multiple births had a higher proportion of antidiabetic prescriptions than women with singleton births both in the preconception period and during pregnancy (1.3% vs. 0.7%; 3.4% vs. 2.6%) and used metformin more frequently. The consumption of antidiabetics in foreign women was higher than Italians (second trimester: 1.8% vs. 0.9%, third trimester: 3.6% vs. 1.8%).

Monitoring medicine prescriptions before, during and after pregnancy in Italy.

BACKGROUND: The use of medications during pregnancy is a common event worldwide. Monitoring medicine prescriptions in clinical practice is a necessary step in assessing the impact of therapeutic choices in pregnant women as well as the adherence to clinical guidelines. The aim of this study was to provide prevalence data on medication use before, during and after pregnancy in the Italian population. METHODS: A retrospective prevalence study using administrative healthcare databases was conducted. A cohort of 449,012 pregnant women (15-49 years) residing in eight Italian regions (59% of national population), who delivered in 2016-2018, were enrolled. The prevalence of medication use was estimated as the proportion (%) of pregnant women with any prescription. RESULTS: About 73.1% of enrolled women received at least one drug prescription during pregnancy, 57.1% in pre-pregnancy and 59.3% in postpartum period. The prevalence of drug prescriptions increased with maternal age, especially during the 1st trimester of pregnancy. The most prescribed medicine was folic acid (34.6%), followed by progesterone (19%), both concentrated in 1st trimester of pregnancy (29.2% and 14.8%, respectively). Eight of the top 30 most prescribed medications were antibiotics, whose prevalence was higher during 2nd trimester of pregnancy in women ≥ 40 years (21.6%). An increase in prescriptions of anti-hypertensives, antidiabetics, thyroid hormone and heparin preparations was observed during pregnancy; on the contrary, a decrease was found for chronic therapies, such as anti-epileptics or lipid-modifying agents. CONCLUSIONS: This study represents the largest and most representative population-based study illustrating the medication prescription patterns before, during and after pregnancy in Italy. The observed prescriptive trends were comparable to those reported in other European countries. Given the limited information on medication use in Italian pregnant women, the performed analyses provide an updated overview of drug prescribing in this population, which can help to identify critical aspects in clinical practice and to improve the medical care of pregnant and childbearing women in Italy.

Pattern of care of brain tumor patients in the last months of life: analysis of a cohort of 3045 patients in the last 10 years.

BACKGROUND: End-of-life in patients with brain cancer presents special challenges, and palliative care approach is underutilized. Patients with brain cancer, in the last months of life, receive frequent hospital readmissions, highlighting bad end-of-life care quality. Early integration of palliative care improves quality of care in advanced stage of disease and patient's quality of death. PURPOSE: We retrospectively analyzed a consecutive series of patients with brain cancer discharged after diagnosis to evaluate pattern of treatment and rate of hospital readmission in the last months of life. DESIGN: Data were collected from the Lazio Region Healthcare database. SETTING: Adult patients discharged with diagnosis ICD-9 191.* between January 1, 2010, and December 31, 2019 were included. RESULTS: A total of 6672 patients were identified, and 3045 deaths were included. In the last 30 days 33% were readmitted to the hospital and 24.2% to the emergency room. 11.7% were treated with chemotherapy and 6% with radiotherapy. Most indicators of end-of-life care showed wide variability by hospital of discharge. CONCLUSIONS: Strategies to improve quality of care at the end of life and to decrease re-hospitalization and futile treatments are becoming increasingly important to improve quality of death and reduce healthcare costs. Variability observed by hospital of discharge indicates the lack of a standard approach to end-of-life care.

An Italian multicentre distributed data research network to study the use, effectiveness, and safety of immunosuppressive drugs in transplant patients: Framework and perspectives of the CESIT project.

The goal of post-transplant immunosuppressive drug therapy is to prevent organ rejection while minimizing drug toxicities. In clinical practice, a multidrug approach is commonly used and involves drugs with different mechanisms of action, including calcineurin inhibitors (CNI) (tacrolimus or cyclosporine), antimetabolite (antimet) (mycophenolate or azathioprine), inhibitors of mechanistic target of rapamycin (mTOR) (sirolimus or everolimus), and/or steroids. Although evidence based on several randomized clinical trials is available, the optimal immunosuppressive therapy has not been established and may vary among organ transplant settings. To improve the knowledge on this topic, a multiregional research network to Compare the Effectiveness and Safety of Immunosuppressive drugs in Transplant patients (CESIT) has been created with the financial support of the Italian Medicines Agency. In this article, we describe the development of this network, the framework that was designed to perform observational studies, and we also give an overview of the preliminary results that we have obtained. A multi-database transplant cohort was enrolled using a common data model based on healthcare claims data of four Italian regions (Lombardy, Veneto, Lazio, and Sardinia). Analytical datasets were created using an open-source tool for distributed analysis. To link the National Transplant Information System to the regional transplant cohorts, a semi-deterministic record linkage procedure was performed. Overall, 6,914 transplant patients from 2009-19 were identified: 4,029 (58.3%) for kidney, 2,219 (32.1%) for liver, 434 (6.3%) for heart, and 215 (3.1%) for lung. As expected, demographic and clinical characteristics showed considerable variability among organ settings. Although the triple therapy in terms of CNI + antimet/mTOR + steroids was widely dispensed for all settings (63.7% for kidney, 33.5% for liver, 53.3% for heart, and 63.7% for lung), differences in the active agents involved were detected. The CESIT network represents a great opportunity to study several aspects related to the use, safety, and effectiveness of post-transplant maintenance immunosuppressive therapy in real practice.

Postmarketing active surveillance of myocarditis and pericarditis following vaccination with COVID-19 mRNA vaccines in persons aged 12 to 39 years in Italy: A multi-database, self-controlled case series study.

BACKGROUND: Myocarditis and pericarditis following the Coronavirus Disease 2019 (COVID-19) mRNA vaccines administration have been reported, but their frequency is still uncertain in the younger population. This study investigated the association between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccines, BNT162b2, and mRNA-1273 and myocarditis/pericarditis in the population of vaccinated persons aged 12 to 39 years in Italy. METHODS AND FINDINGS: We conducted a self-controlled case series study (SCCS) using national data on COVID-19 vaccination linked to emergency care/hospital discharge databases. The outcome was the first diagnosis of myocarditis/pericarditis between 27 December 2020 and 30 September 2021. Exposure risk period (0 to 21 days from the vaccination day, subdivided in 3 equal intervals) for first and second dose was compared with baseline period. The SCCS model, adapted to event-dependent exposures, was fitted using unbiased estimating equations to estimate relative incidences (RIs) and excess of cases (EC) per 100,000 vaccinated by dose, age, sex, and vaccine product. Calendar period was included as time-varying confounder in the model. During the study period 2,861,809 persons aged 12 to 39 years received mRNA vaccines (2,405,759 BNT162b2; 456,050 mRNA-1273); 441 participants developed myocarditis/pericarditis (346 BNT162b2; 95 mRNA-1273). Within the 21-day risk interval, 114 myocarditis/pericarditis events occurred, the RI was 1.99 (1.30 to 3.05) after second dose of BNT162b2 and 2.22 (1.00 to 4.91) and 2.63 (1.21 to 5.71) after first and second dose of mRNA-1273. During the [0 to 7) days risk period, an increased risk of myocarditis/pericarditis was observed after first dose of mRNA-1273, with RI of 6.55 (2.73 to 15.72), and after second dose of BNT162b2 and mRNA-1273, with RIs of 3.39 (2.02 to 5.68) and 7.59 (3.26 to 17.65). The number of EC for second dose of mRNA-1273 was 5.5 per 100,000 vaccinated (3.0 to 7.9). The highest risk was observed in males, at [0 to 7) days after first and second dose of mRNA-1273 with RI of 12.28 (4.09 to 36.83) and RI of 11.91 (3.88 to 36.53); the number of EC after the second dose of mRNA-1273 was 8.8 (4.9 to 12.9). Among those aged 12 to 17 years, the RI was of 5.74 (1.52 to 21.72) after second dose of BNT162b2; for this age group, the number of events was insufficient for estimating RIs after mRNA-1273. Among those aged 18 to 29 years, the RIs were 7.58 (2.62 to 21.94) after first dose of mRNA-1273 and 4.02 (1.81 to 8.91) and 9.58 (3.32 to 27.58) after second dose of BNT162b2 and mRNA-1273; the numbers of EC were 3.4 (1.1 to 6.0) and 8.6 (4.4 to 12.6) after first and second dose of mRNA-1273. The main study limitations were that the outcome was not validated through review of clinical records, and there was an absence of information on the length of hospitalization and, thus, the severity of the outcome. CONCLUSIONS: This population-based study of about 3 millions of residents in Italy suggested that mRNA vaccines were associated with myocarditis/pericarditis in the population younger than 40 years. According to our results, increased risk of myocarditis/pericarditis was associated with the second dose of BNT162b2 and both doses of mRNA-1273. The highest risks were observed in males of 12 to 39 years and in males and females 18 to 29 years vaccinated with mRNA-1273. The public health implication of these findings should be considered in the light of the proven mRNA vaccine effectiveness in preventing serious COVID-19 disease and death.

Drug Prescriptions among Italian and Immigrant Pregnant Women Resident in Italy: A Cross-Sectional Population-Based Study.

Ensuring drug safety for pregnant women through prescription drug monitoring is essential. The aim of this study was to describe the prescription pattern of medicines among pregnant immigrant women from countries with high migratory pressure (HMPCs) compared to pregnant Italian women. The prevalence of drug prescriptions among the two study populations was analysed through record linkage procedures applied to the administrative databases of eight Italian regions, from 2016 to 2018. The overall prevalence of drug prescription was calculated considering all women who received at least one prescription during the study period. Immigrants had a lower prevalence of drug prescriptions before (51.0% vs. 58.6%) and after pregnancy (55.1% vs. 60. 3%). Conversely, during pregnancy, they obtained a slightly higher number of prescriptions (74.9% vs. 72.8%). The most prescribed class of drugs was the blood and haematopoietic organs category (category ATC B) (56.4% vs. 45.9%, immigrants compared to Italians), followed by antimicrobials (31.3% vs. 33.7%). Most prescriptions were appropriate, while folic acid administration 3 months before conception was low for both study groups (3.9% immigrants and 6.2% Italians). Progesterone seemingly was prescribed against early pregnancy loss, more frequently among Italians (16.5% vs. 8.1% immigrants). Few inappropriate medications were prescribed among antihypertensives, statins and anti-inflammatory drugs in both study groups.

Temporal and spatial variability of immunosuppressive therapies in transplant patients: An observational study in Italy.

Background: In immunosuppression after transplantation, several multi-drug approaches are used, involving calcineurin inhibitors (CNI: tacrolimus-TAC or cyclosporine-CsA), antimetabolites (antiMs), mammalian target of rapamycin inhibitors (mTORis), and corticosteroids. However, data on immunosuppressive therapy by organ and its space-time variability are lacking. Methods: An Italian multicentre observational cohort study was conducted using health information systems. Patients with incident transplant during 2009-2019 and resident in four regions (Veneto, Lombardy, Lazio, and Sardinia) were enrolled. The post-transplant immunosuppressive regimen was evaluated by organ, region, and year. Results: The most dispensed regimen was triple-drug therapy for the kidneys [tacrolimus (TAC) + antiM + corticosteroids = 41.5%] and heart [cyclosporin + antiM + corticosteroids = 36.6%] and double-drug therapy for liver recipients (TAC + corticosteroids = 35.4%). Several differences between regions and years emerged with regard to agents and the number of drugs used. Conclusion: A high heterogeneity in immunosuppressive therapy post-transplant was found. Further studies are needed in order to investigate the reasons for this variability and to evaluate the risk-benefit profile of treatment schemes adopted in clinical practice.

Large-Scale Postmarketing Surveillance of Biological Drugs for Immune-Mediated Inflammatory Diseases Through an Italian Distributed Multi-Database Healthcare Network: The VALORE Project.

BACKGROUND: Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings. OBJECTIVE: The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID. METHODS: A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010-2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association. RESULTS: From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015-2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively. CONCLUSION: The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010-2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings.

Medication prescriptions before, during and after pregnancy in Italy: a population-based study.

BACKGROUND: Monitoring medicine prescriptions in pregnancy is an aspect of extreme interest in term of public health. METHODS: A retrospective prevalence study using administrative healthcare databases was performed in order to evaluate medication prescriptions in Italy. A cohort of 274,938 pregnant women (15-49 years) residing in three Italian regions (Emilia-Romagna, Lazio, Puglia), who delivered in 2014-2017, were enrolled. The prevalence of medication use was estimated as the proportion of pregnant women with any medication prescription in each of the following five trimesters: 1 before pregnancy (pre-T), 3 during pregnancy (1st TP, 2nd TP, 3rd TP) and 1 after pregnancy (post-T). RESULTS: About 80% of enrolled pregnant women received at least one prescription during pregnancy, 36.5% before pregnancy and 50.7% in the post-partum. The most prescribed medicine was folic acid (42%), mostly used in 1st TP (35%). Progesterone use was concentrated in 1st TP (19%) and increased as the number of previous abortions. Pregnancy use of antidiabetics, antihypertensives, and thyroid preparations were 24.1‰, 21.5‰, 101.8‰, respectively. CONCLUSIONS: At the national level, this study confirmed the prescriptive trend observed in other European studies, but a regional variability for all medication groups was found. Further studies are needed in order to identify determinants of medication prescriptions during pregnancy in Italy.

Association of Influenza Vaccination and Prognosis in Patients Testing Positive to SARS-CoV-2 Swab Test: A Large-Scale Italian Multi-Database Cohort Study.

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.

The Italian Network for Monitoring Medication Use During Pregnancy (MoM-Net): Experience and Perspectives.

There is an acute need for research to acquire high-quality information on the use of medicines in pregnancy, both in terms of appropriateness and safety. For this purpose, the Italian Medicines Agency established a Network for Monitoring Medication use in pregnancy (MoM-Net) through the conduction of population-based studies using administrative data available at regional level. This paper aimed to describe the experiences and challenges within the network. MoM-Net currently involves eight regions and several experts from public and academic institutions. The first study conducted aimed to identify drug use before, during and after pregnancy investigating specific therapeutic categories, analysing regional variability and monitoring drug use in specific subpopulations (i.e. foreign women/multiple pregnancies). Aggregated demographic, clinical, and prescription data were analysed using a distributed network approach based on common data model. The study population included all women delivering during 2016-2018 in the participating regions (n = 449,012), and corresponding to 59% of deliveries in Italy. Seventy-three per cent of the cohort had at least one drug prescription during pregnancy, compared to 57% before and 59% after pregnancy. In general, a good adherence to guidelines for pregnant women was found although some drug categories at risk of inappropriateness, such as progestins and antibiotics, were prescribed. A strong variability in the use of drugs among regions and in specific subpopulations was observed. The MoM-Net represents a valuable surveillance system on the use of medicines in pregnancy, available to monitor drug categories at high risk of inappropriateness and to investigate health needs in specific regions or subpopulations.

Direct and Indirect Impact of COVID-19 for Patients with Immune-Mediated Inflammatory Diseases: A Retrospective Cohort Study.

IMPORTANCE: Since the beginning of the Coronavirus Disease-19 (COVID-19) pandemic, Severe Acute Respiratory Syndrome-CoV-2 (SARS-CoV-2) infection has been a serious challenge for immune-compromised patients with immune-mediated inflammatory diseases (IMIDs). OBJECTIVE: Our aim was to investigate the impact of COVID-19 in terms of risks of infection, hospitalization and mortality in a cohort of patients with rheumatoid arthritis (RA), psoriasis (PSO) or inflammatory bowel disease (IBD). Furthermore, we studied the impact of SARS-CoV-2 infection on the prescribed drug regimen in these patients. METHODS: Through the record linkage between health information systems, a cohort of patients, ≥18 years old, assisted in the Lazio region and who had suffered from immune-mediated inflammatory diseases (RA, PSO, IBD) between 2007 and 2019, was identified. The risk of infection, hospitalization or mortality for COVID-19, was assessed by logistic regression models, and reported in an Odds Ratio (ORs; CI 95%), adjusting for sex, age and the Charlson Comorbidity Index. We also estimated these risks separately by IMID and in the subgroup of prevalent biologic drug users. We investigated deferral of biological treatments in the study population by comparing the prevalence of weekly use of biologicals (2019-2020) before and during the pandemic periods. FINDINGS: Within the 65,230 patients with IMIDs, the cumulative incidence for COVID-19 was 303/10,000 ab. In this cohort of patients, we observed a significantly higher risk of SARS-CoV-2 infection than the general population: OR = 1.17 (95% CI 1.12-1.22). The risk was higher even considering separately each disease and in the subgroup of prevalent biologic drug users. This last subgroup of patients showed a higher risk of death related to COVID-19 (OR 1.89; 95% CI 1.04-3.33) than the general population. However, no differences in terms of risks of hospitalization or death related to COVID-19 were recorded in patients with the IMIDs. Comparing the 2019-2020 prevalence of weekly biological drug treatments in prevalent biologic drug users, we found a decrease (-19.6%) during the lockdown, probably due to pandemic restrictions. CONCLUSIONS AND RELEVANCE: Patients with IMIDs seem to have a higher risk of SARS-CoV2 infection. However, other than for patients with prevalent biologic drug treatment, no significant differences in terms of hospitalization and mortality were reported compared to the general populations; further investigation is warranted on account of unmeasured confounding. In addition, during the lockdown period, the COVID-19 emergency highlighted a lower use of biologic drugs; this phenomenon requires strict pharmacological monitoring as it could be a proxy of forthcoming long-term clinical progression.

Real world data to identify target population for new CAR-T therapies.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma often refractory to currently available treatments (immuno-chemotherapy/autologous-stem-cell-transplantation-ASCT). Recently, new cell therapies have been approved for patients failing two conventional treatments, CAR-T (Chimeric-Antigen-Receptor-T-cell), committing payers in planning and implementing their use. We aim to define, using Real World Data (RWD), a reproducible procedure that allows identification of CAR-T target population for DLBCL. METHODS: Through the linking of electronic healthcare datasets (EHD), we identified patients with non-Hodgkin's Lymphoma (NHL), resident in Lazio region (2010-2015), aged ≥20 years. DLBCL patients were followed using pathological anatomy (PA) reports, up to 3 years. To be defined as relapsed after two treatment lines, patients must have had new chemotherapy and/or NHL hospitalization after ASCT or at the end of the second chemotherapy. The incident rate of second relapse (R2-rate) was extended to the population without PA reports. RESULT: NHL incident patients were 7384, 68% presented a PA report and, 29% of these had DLBCL codes. Patients who relapsed after two treatment lines were 47 (39%) in the subgroup of patients who received ASCT and 138 (41%) in that with second chemotherapy treatment. Patients in the two subgroups were very different in terms of age and comorbidity. The annual incident number of DLBCL was estimated to be 329 which multiplied by R2-rate (13.7%) gives 45 patients per year eligible for CAR-T. DISCUSSION: This study shows how RWD allows the identification of a target population with new advanced therapies. This approach is rigorous, transparent and verifiable over time.

Drug discontinuation in pregnant women with psoriasis: The PSO-MOTHER cohort study.

PURPOSE: To analyse the drug use pattern in women with psoriasis before, during and after pregnancy. METHODS: All children born (2009-2016) in a central Italian region (Lazio) to mothers with a diagnosis of psoriasis were identified. Drug use patterns (biologicals, systemic, and topical), and discontinuation and switching of drug therapies before, during, and after pregnancy were studied. Findings were compared with data from a population exposed to similar drug therapies (eg, antirheumatic drugs). RESULTS: Among 3499 deliveries by women affected by psoriasis, 1876 (53.6%) were diagnosed with this condition before the Last Menstrual Period (LMP). Of these, 525 (27.9%) had at least one drug prescription for psoriasis therapy during 6 months before LMP. For each class of drugs considered, there was a general decrease in its use during pregnancy. Considering the two trimesters preceding LMP and the three trimesters of pregnancy, the following percentages of prescriptions were observed: from 10.5% to 0% for biologicals, 7.2% to 2.5% for the conventional systemic drugs, and 51.1% to 9.4% for the topical treatments. After delivery, previous treatments were resumed. Similar results were observed for rheumatoid arthritis, a chronic condition. CONCLUSIONS: Majority of drugs come with warnings regarding potential embryo-fetotoxicity, which might play a role in the decision to continue treatments during pregnancy. According to our study pregnancy appears to have a significant influence on drug prescriptions of different pharmacological treatments for psoriasis.

Ethnic variation in the prevalence of depression and anxiety in primary care: a systematic review and meta-analysis.

Primary care plays a key role in the detection and management of depression and anxiety. At present it is not clear if the prevalence of depression and anxiety in primary care differs between migrants and ethnic minorities (MI) and natives and ethnic majorities (MA). A systematic review and a meta-analysis of studies comparing the prevalence of depression and anxiety in MI and MA in primary care were performed. Studies were identified by searching MEDLINE, PsychINFO, EMBASE and through hand-search. We included 25 studies, most of which had a relatively small sample size. Significant variations were found in the prevalence of anxiety and depression across studies. Pooled analyses were carried out for 23 studies, based on random-effects models. Pooled RR of depression and anxiety in MI were 1.21 (95% CI 1.04-1.40, p=0.012) and 1.01 (95% CI 0.76-1.32, p=0.971), with high heterogeneity (I²=87.2% and I²=73%). Differences in prevalence rates among studies can be accounted for by inclusion criteria, sampling methods, diagnostic instruments and study design. Further research on larger samples and with culturally adapted instruments is needed to estimate the prevalence of depression and anxiety in MI seeking help for these disorders.

Migrants referring to the Bologna Transcultural Psychiatric Team: reasons for drop-out.

BACKGROUND: Recent immigrants face various difficulties in adjusting to western countries and show a high prevalence of mental disorders. Access to a culturally appropriate community mental health centre (CMHC) is crucial for immigrants (Bhui et al., 2007). The Bologna West Transcultural Psychiatric Team (BoTPT, Tarricone et al., 2009) is one of the first projects in Italy that prioritizes cultural competence care. This paper aims to evaluate the effectiveness of this service and to describe what characteristics of patient and psychiatric intervention are related to 'drop-out'. METHOD: All migrants who consecutively attended the BoTPT between 1 July 1999 and 30 June 2008 were included and evaluated at first contact and again six months later. RESULTS: After six months we followed up 162 patients; 32 (17.9%) of these had interrupted treatment. Non-Asian origin, a recent history of migration and not receiving social intervention were the strongest predictors of drop-out cases. CONCLUSION: Psychiatric consultation services to migrants could be made more effective by enhancing: (a) cultural competence, through cultural mediator involvement; and (b) social support from the first psychiatric contact. These two characteristics of psychiatric consultation could be developed from resources ordinarily present in the context of a CMHC and could then become a cost-effective strategy for addressing mental health needs among first-generation immigrants.