Drug Use Patterns in Myasthenia Gravis: A Real-World Population-Based Cohort Study in Italy.

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.

Investigating socioeconomic disparities in lung cancer diagnosis, treatment and mortality: an Italian cohort study.

BACKGROUND: Lung cancer is one of the most lethal cancers worldwide and patient clinical outcomes seem influenced by their socioeconomic position (SEP). Since little has been investigated on this topic in the Italian context, our aim was to investigate the role of SEP in the care pathway of lung cancer patients in terms of diagnosis, treatment and mortality. METHODS: This observational retrospective cohort study included patients discharged in the Lazio Region with a lung cancer diagnosis between 2014 and 2017. In the main analysis, educational level was used as SEP measure. Multivariate models, adjusted for demographic and clinical variables, were applied to evaluate the association between SEP and study outcomes, stratified for metastatic (M) and non-metastatic (NM) cancer. We defined a diagnosis as 'delayed' when patients received their initial cancer diagnosis after an emergency department admission. Access to advanced lung cancer treatments (high-cost, novel and innovative treatments) and mortality were investigated within the 24-month period post-diagnosis. Moreover, two additional indicators of SEP were examined in the sensitivity analysis: one focusing on area deprivation and the other on income-based exemption. RESULTS: A total of 13,251 patients were identified (37.3% with metastasis). The majority were males (> 60%) and over half were older than 70 years. The distribution of SEP levels among patients was as follow: 31% low, 29% medium-low, 32% medium-high and 7% high. As SEP increased, the risks of receiving a delayed diagnosis ((high vs low: M: OR = 0.29 (0.23-0.38), NM: OR = 0.20 (0.16-0.25)) and of mortality ((high vs low M: OR = 0.77 (0.68-0.88) and NM: 0.61 (0.54-0.69)) decreased. Access to advanced lung cancer treatments increased in accordance with SEP only in the M cohort (high vs low: M: OR = 1.57 (1.18-2.09)). The primary findings were corroborated by sensitivity analysis. CONCLUSIONS: Our study highlighted the need of public health preventive and educational programs in Italy, a country where the care pathway of lung cancer patients, especially in terms of diagnosis and mortality, appears to be negatively affected by SEP level.

An epidemiological investigation of high-risk infants for Respiratory Syncytial Virus infections: a retrospective cohort study.

BACKGROUND: Respiratory Syncytial Virus (RSV) infections may lead to severe consequences in infants born preterm with breathing problems (such as bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS)) or congenital heart diseases (CHD). Since studies investigating the influence of different gestational age (WGA) and concomitant specific comorbidities on the burden of RSV infections are scarce, the present study aimed to better characterize these high-risk populations in the Italian context. METHODS: This retrospective, longitudinal and record-linkage cohort study involved infants born between 2017 and 2019 in Lazio Region (Italy) and is based on data extracted from administrative databases. Each infant was exclusively included in one of the following cohorts: (1) BPD-RDS (WGA ≤35 with or without CHD) or (2) CHD (without BPD and/or RDS) or (3) Preterm (WGA ≤35 without BPD (and/or RDS) or CHD). Each cohort was followed for 12 months from birth. Information related to sociodemographic at birth, and RSV and Undetermined Respiratory Agents (URA) hospitalizations and drug consumption at follow-up were retrieved and described. RESULTS: A total of 8,196 infants were selected and classified as 1,084 BPD-RDS, 3,286 CHD and 3,826 Preterm. More than 30% of the BPD-RDS cohort was composed by early preterm infants (WGA ≤ 29) in contrast to the Preterm cohort predominantly constitute by moderate preterm infants (98.2%), while CHD infants were primarily born at term (83.9%). At follow-up, despite the cohorts showed similar proportions of RSV hospitalizations, in BPD-RDS cohort hospitalizations were more frequently severe compared to those occurred in the Preterm cohort (p<0.01), in the BPD-RDS cohort was also found the highest proportion of URA hospitalizations (p<0.0001). In addition, BPD-RDS infants, compared to those of the remaining cohorts, received more frequently prophylaxis with palivizumab (p<0.0001) and were more frequently treated with adrenergics inhalants, and glucocorticoids for systemic use. CONCLUSIONS: The assessment of the study clinical outcomes highlighted that, the demographic and clinical characteristics at birth of the study cohorts influence their level of vulnerability to RSV and URA infections. As such, continuous monitoring of these populations is necessary in order to ensure a timely organization of health care system able to respond to their needs in the future.

Drug utilization in patients starting haemodialysis with a focus on cardiovascular and antidiabetic medications: an epidemiological study in the Lazio region (Italy), 2016-2020.

BACKGROUND: Entering dialysis is a critical moment in patients' healthcare journey, and little is known about drug therapy around it. A study funded by the Italian Medicines Agency offered the opportunity to leverage data from the Lazio Regional Dialysis and Transplant Registry (RRDTL) and perform an observational study on drug use patterns before and after initiating chronic dialysis. METHODS: Individuals initiating dialysis in 2016-2020 were identified from RRDTL, excluding patients with prior renal transplantation, stopping dialysis early, or dying within 12 months. Use of study drugs, predefined by clinicians, in the two years around the index date was retrieved from the drug claims register and described by semester. For each drug group, proportions of users (min 2 claims in 6 months) by semester, and intensity of treatment in terms of Defined Daily Doses (DDDs) for cardiovascular and antidiabetic agents were compared across semesters, stratifying by sex and age. RESULTS: In our cohort of 3,882 patients we observed a general increase in drug use after initiating dialysis, with the mean number rising from 5.5 to 6.2. Cardiovascular agents accounted for the highest proportions, along with proton pump inhibitors and antithrombotics over all semesters. Dialysis-specific therapies showed the most evident increase, in particular anti-anaemics (iron 4-fold, erythropoietins almost 2-fold), anti-parathyroids (6-fold), and chelating agents (4-fold). Use of cardiovascular and antidiabetic drugs was characterised by significant variations in terms of patterns and intensity, with some differences between sexes and age groups. CONCLUSIONS: Entering dialysis is associated with increased use of specific drugs and goes along with adaptations of chronic therapies.

Immunosuppression with Generics in Liver and Kidney Transplantation: A Real-World Evidence Study.

Purpose: This study evaluates the use, benefit-risk profile, and economic impact of generic immunosuppressants (tacrolimus-TAC, cyclosporine-CsA, and mycophenolate-MYC) in kidney and liver transplant recipients compared to brand-name drugs. Patients and Methods: A retrospective multicentre observational study, involving four Italian regions, was conducted based on the national transplant Information system and regional healthcare claims data. The analysis focused on incident patients who received kidney and liver transplants between 2013 and 2019 and evaluated the use of generic of CsA, TAC, and MYC during the 30-day period following discharge. For each type of transplant and immunosuppressive agent, the benefit-risk profile of generic vs branded drugs in a two-year window was estimated by multivariate Cox models (HR; 95% CI). Furthermore, the potential cost savings per person associated with one year of treatment using generics were calculated. Results: The utilization of generic drugs showed a significant increase; over the study years, the proportion of users among kidney recipients ranged from 14.2% to 40.5% for TAC, from 36.9% to 56.7% for MYC, and from 18.2% to 94.7% for CsA. A great variability in generic uptake for region was found. A comparable risk-benefit profile between generic and branded formulations was shown for all immunosuppressors considered. Choosing generic immunosuppressants during maintenance could result in yearly savings of around 2000 euros per person for each therapy ingredient. Conclusion: The study shows an increasing proportion of patients using generic immunosuppressive drugs over time suggesting a growing acceptance of generics within the transplant community and reveals comparable risk-benefit profiles between the generic and branded formulations of TAC, CsA, and MYC. A significant variability in the use of generics immunosuppressive agents was found both at the regional level and among transplant centers and future research should delve into regional prescribing variations.

Effectiveness and safety of immunosuppressive regimens used as maintenance therapy in kidney transplantation: The CESIT study.

Maintenance immunosuppressive therapy used in kidney transplantation typically involves calcineurin inhibitors, such as tacrolimus or cyclosporine, in combination with mycophenolate or mechanistic target of rapamycin (mTORi) with or without corticosteroids. An Italian retrospective multicentre observational study was conducted to investigate the risk-benefit profile of different immunosuppressive regimens. We identified all subjects who underwent kidney transplant between 2009 and 2019, using healthcare claims data. Patients on cyclosporine and tacrolimus-based therapies were matched 1:1 based on propensity score, and effectiveness and safety outcomes were compared using Cox models (HR; 95%CI). Analyses were also conducted comparing mTORi versus mycophenolate among tacrolimus-treated patients. Patients treated with cyclosporine had a higher risk of rejection or graft loss (HR:1.69; 95%CI:1.16-2.46) and a higher incidence of severe infections (1.25;1.00-1.55), but a lower risk of diabetes (0.66;0.47-0.91) compared to those treated with tacrolimus. Among tacrolimus users, mTORi showed non-inferiority to MMF in terms of mortality (1.01;0.68-1.62), reject/graft loss (0.61;0.36-1.04) and severe infections (0.76;0.56-1.03). In a real-life setting, tacrolimus-based immunosuppressive therapy appeared to be superior to cyclosporine in reducing rejection and severe infections, albeit with an associated increased risk of diabetes. The combination of tacrolimus and mTORi may represent a valid alternative to the combination with mycophenolate, although further studies are needed to confirm this finding.

Determinants of immunosuppressive therapy in renal transplant recipients: an Italian observational study (the CESIT project).

BACKGROUND: Very scanty evidence is available on factors influencing the choice of immunosuppressive drug therapy after kidney transplantation. METHODS: An Italian multiregional real-world study was conducted integrating national transplant information system and claims data. All patients undergoing kidney transplantation for the first time during 2009-2019 (incident patients) were considered. Multilevel logistic models were used to estimate Odds Ratio (OR) and corresponding 95% Confidence intervals. Factors with statistically significance were identified as characteristics associated with treatment regimens: cyclosporin-CsA vs tacrolimus-Tac and, within the latter group, mTOR inhibitors vs mycophenolate-MMF. RESULTS: We identified 3,622 kidney patients undergoing transplantation in 17 hospitals located in 4 Italian regions, 78.3% was treated with TAC-based therapy, of which 78% and 22% in combination with MMF and mTOR, respectively. For both comparison groups, the choice of immunosuppressive regimens was mostly guided by standard hospital practices. Only few recipient and donor characteristics were found associated with specific regimen (donor/receipt age, immunological risk and diabetes). CONCLUSIONS: The choice of post-renal transplant immunosuppressive therapy seems to be mostly driven by standard Centre practices, while only partially based on patient's characteristics and recognized international guidelines.

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.

Polytherapy and Multimorbidity Pattern of Users of Anti-VEGF Drugs and Dexamethasone for the Treatment of Age-Related Macular Degeneration and other Vascular Retinopathies in Clinical Practice.

Introduction: Our aim was to describe the polytherapy and multimorbidity pattern of users of anti-VEGF and dexamethasone drugs for the treatment of these conditions, and to investigate their polytherapy and multimorbidity profiles, together with adherence and the burden of care. Methods: Descriptive, population-based, pharmacoepidemiology study on the users of anti-VEGF drugs, and secondarily intravitreal dexamethasone, for the treatment of age-related macular degeneration and other vascular retinopathies in clinical practice, using administrative databases of Lazio region, Italy. We used a cohort of 50,000 residents in Lazio in 2019 with same age as comparison. Polytherapy was assessed using databases of prescribed drugs intended for outpatient use. Multimorbidity was investigated with additional sources, such as hospital discharge records, outpatient care records, and disease-specific exemptions from co-payment. Each patient was followed for 1 to 3 years from the first intravitreal injection received. Results: 16,266 residents in Lazio who received the first IVI from 1 January 2011 to 31 December 2019, with at least 1 year of observation before index date, were included. The proportion of patients with at least one comorbidity was 54.0%. Patients used an average 8.6 (SD 5.3) concomitant drugs other than anti-VEGF used for injections. A large percentage of patients (39.0%) used 10 or more concomitant drugs, including antibacterials (62.9%), drugs for peptic ulcers (56.8%), anti-thrombotics (52.3%), NSAIDs (44.0%), and anti-dyslipidaemics (42.3%). The same proportions were found across patients of all ages, probably due to high prevalence of diabetes (34.3%), especially in younger age groups. When stratified by diabetes, a comparison of multimorbidity and polytherapy with a sample of 50,000 residents of the same age found that patients receiving IVIs used more drugs and had more comorbidities, particularly in non-diabetics. Lapses of care, whether short (absence of any type of contact for at least 60 days in the first year of follow-up and 90 in the second year) or long (90 days in the first and 180 days in the second year) were common: 66% and 51.7%, respectively. Conclusions: Patients receiving intravitreal drugs for retinal conditions have high multimorbidity and polytherapy rates. Their burden of care is aggravated by the large number of contacts with the eye care system for examinations and injections. Pursuing Minimally Disruptive Medicine to optimise patient care is a difficult goal for health systems, and more research on clinical pathways and their implementation is warranted.

Impact of COVID-19 pandemic on outpatient visit volume in cancer patients: Results of COMETA multicenter retrospective observational study.

Objective: To evaluate the impact of the COVID-19 pandemic on first and follow-up visits for cancer outpatients. Methods: This is a multicenter retrospective observational study involving three Comprehensive Cancer Care Centers (CCCCs): IFO, including IRE and ISG in Rome, AUSL-IRCCS of Reggio Emilia, and IRCCS Giovanni Paolo II in Bari) and one oncology department in a Community Hospital (Saint'Andrea Hospital, Rome). From 1 January 2020 and 31 December 2021, we evaluated the volume of outpatient consultations (first visits and follow-up), comparing them with the pre-pandemic year (2019). Results were analyzed by quarter according to the Rt (real-time indicator used to assess the evolution of the pandemic). IFO and IRCCS Giovanni Paolo II were "COVID-free" while AUSL-IRCCS RE was a "COVID-mixed" Institute. Depending on the Rt, Sain't Andrea Hospital experienced a "swinging" organizational pathway (COVID-free/ COVID-mixed). Results: Regarding the "first appointments", in 2020 the healthcare facilities operating in the North and Center of Italy showed a downward trend. In 2021, only AUSL-IRCCS RE showed an upward trend. Regarding the "follow-up", only AUSL IRCCS RE showed a slight up-trend in 2020. In 2021, IFO showed an increasing trend, while S. Andrea Hospital showed a negative plateau. Surprisingly, IRCCS Giovanni Paolo II in Bari showed an uptrend for both first appointment and follow-ups during pandemic and late pandemic except for the fourth quarter of 2021. Conclusions: During the first pandemic wave, no significant difference was observed amongst COVID-free and COVID-mixed Institutes and between CCCCs and a Community Hospital. In 2021 ("late pandemic year"), it has been more convenient to organize COVID-mixed pathway in the CCCCs rather than to keep the Institutions COVID-free. A swinging modality in the Community Hospital did not offer positive results in term of visit volumes. Our study about the impact of COVID-19 pandemic on visit volume in cancer outpatients may help health systems to optimize the post-pandemic use of resources and improve healthcare policies.

Potentially inappropriate drug use in myasthenia gravis: a real-world population-based cohort study in Italy.

Introduction: To evaluate the use of pyridostigmine in presence of contraindications, and the use of concomitant potentially contraindicated drugs in a cohort of patients affected by Myasthenia Gravis (MG) in the Italian Regions of Lazio, Tuscany, and Umbria. Methods: This is a retrospective cohort study. A multivariate logistic regression model was used to evaluate the determinants of pyridostigmine and of potentially contraindicated drugs use in MG patients. Results: Among 591 incident pyridostigmine users affected by MG, 91 (15.4%) had at least one of the contraindications considered at the first prescription of pyridostigmine. Patients prescribed with pyridostigmine in presence of contraindications were more frequently affected by diabetes, obesity, and renal diseases. Age 75+ years (odds ratio, OR 4.94, 95% confidence interval, CI 1.60-15.22 for Latium; OR 3.78, 95%CI: 1.26-11.34 for Tuscany; OR 5.83, 95%CI 1.19-28.52 for Umbria), the presence of at least one specific comorbidity (OR 3.93; 95%CI 1.68-9.17 for Latium), and polytherapy (6+ drugs, OR 4.90, 95%CI: 1.35-17.85 for Tuscany) were found to be significantly associated with pyridostigmine use in presence of contraindications. Among patients affected by MG, 1,483 (62.6%) were treated with potentially contraindicated drugs in the first year of follow-up (67.06.9% in Latium; 59% in Tuscany; 57.6% in Umbria). Patients aged 75+ years, those with at least one specific complication or comorbidity, and those exposed to polytherapy were more likely to be treated with a potential contraindicated drug. Conclusion: Among incident users of pyridostigmine, more than 15% of patients have at least one of the contraindications considered, and among patients diagnosed with MG, in the first year of follow-up >60% of subjects were treated with potentially contraindicated drugs.

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.

Development of Approaches and Metrics to Measure the Impact and Improve the Clinical Outcomes of Patients With Frailty in the Era of COVID-19. The COMETA Italian Protocol.

The outbreak of the coronavirus 2 disease 2019 (COVID-19) puts an enormous burden on healthcare systems worldwide. This may worsen outcomes in patients with severe chronic diseases such as cancer, autoimmune diseases, and immune deficiencies. In this critical situation, only a few available data exist, which do not allow us to provide practical guides for the treatment of oncological or immunocompromised patients. Therefore, a further step forward is needed, addressing the specific needs and demands of frail patients in the pandemic era. Here we aim to present a protocol of a study approved by an ethical committee named "CO.M.E.TA". CO.M.E.TA protocol is a network project involving six Italian institutions and its goals are: i) to measure and compare the impact of the pandemic on the access of cancer and immunocompromised patients to therapies in three Italian regions; ii) to assess how reorganizational measures put in place in these different institutions have impacted specific metrics of performance; iii) to establish a COVID-19 Biobank of biological samples from SARS-CoV-2 infected patients to be used to study immunological alterations in patients with immune frailty.

[Presumed guilty. Falsification and fabrication of data in scientific publications.] / Presunti colpevoli. Falsificazione e fabbricazione di dati nelle pubblicazioni scientifiche.

The falsification of results and the fabrication of scientific research data are on the rise. Famous researchers see their articles pulled from leading journals. Often, however, this editorial malpractice does not harm the reputation of the authors, who continue to progress in their careers. The solution cannot come from a greater awareness of researchers, sponsors, regulatory agencies or research institutions: the incentives for malpractice are too strong. We need a new international governance of research and communication.

Effectiveness and safety of gonadotropins used in female infertility: a population-based study in the Lazio region, Italy.

PURPOSE: Infertility is a topic of growing interest, and female infertility is often treated with gonadotropins. Evidence regarding comparative safety and efficacy of different gonadotropin formulations is available from clinical studies, while real-world data are missing. The present study aims to investigate effectiveness and safety of treatment with different gonadotropin formulations in women undergoing medically assisted procreation treatments in Latium, a region in central Italy, through a real-world data approach. METHODS: A retrospective population-based cohort study in women between the ages of 18 and 45 years who were prescribed with at least one gonadotropin between 2007 and 2019 was conducted. Women were enrolled from the regional drug dispense registry, and data on their clinical history, exposure to therapeutic cycles (based on recombinant "REC" or extractives "EXT" gonadotropin, or combined protocol "CMD" (REC + EXT)), and maternal/infantile outcomes were linked from the regional healthcare administrative databases. Multivariate logistic regression models were applied to estimate the association between exposure and outcomes. RESULTS: Overall, 90,292 therapeutic cycles prescribed to 35,899 women were linked to pregnancies. Overall, 15.8% of cycles successfully led to pregnancy. Compared to extractives, recombinant and combined treatments showed a stronger association with conception rate (RRREC adj = 1.06, 95% CI: 1.01-1.12; RRCBD adj = 1.17, 95% CI: 1.11-1.24). Maternal outcomes occurred in less than 5% of deliveries, and no significant differences between treatments were observed (REC vs EXT, pre-eclampsia: RR adj = 1.24, 95% CI: 0.86-1.79, ovarian hyperstimulation syndrome: RR adj = 1.25, 95% CI: 0.59-2.65, gestational diabetes: RR adj = 1.06, 95% CI: 0.84-1.35). Regarding infantile outcomes, similar results were obtained for different gonadotropin formulations (REC vs EXT: low birth weight: RR adj = 0.98, 95% CI: 0.83-1.26, multiple births: RR adj = 1.06, 95% CI: 0.92-1.23, preterm birth: RR adj = 1.03, 95% CI: 0.92-1.26). CONCLUSIONS: Efficacy and safety profiles of REC proved to be similar to those of EXT. Regarding the efficacy in terms of conception rate and birth rate, protocols using the combined approach performed slightly better. Outcomes related to maternal and infantile safety were generally very rare, and safety features were overlapping between gonadotropin formulations.

Drug Prescriptions in the Outpatient Management of COVID-19: Evidence-Based Recommendations Versus Real Practice.

Background: Evidence-based recommendations for outpatient management of COVID-19 were published by the Italian Medicines Agency (AIFA) to limit the use of off-label treatments. The aim of this study is to measure the use of outpatient drug treatments in a COVID-19-positive population, taking into account the Italian regulatory agency's advices. Methods: A descriptive observational study was conducted. All patients testing positive for COVID-19 residing in Lazio region, Italy, with diagnosis date between March 2020 and May 2021 were selected, and outpatient medicine prescription patterns were identified. Results: Independent of AIFA recommendations, the use of drug therapy in the management of outpatient COVID-19 cases was frequent (about one-third of the cases). The most used drug therapy was antibiotics, specifically azithromycin, despite the negative recommendation of AIFA, while the use of corticosteroids increased after the positive recommendation of regulatory agency for the use in subjects with severe COVID-19 disease. The use of hydroxychloroquine was limited to the early pandemic period where evidence on its potential benefit was controversial. Antithrombotics were widely used in outpatient settings, even if their use was recommended for hospitalized patients. Conclusion: In this study, we show a frequent use of drug therapy in the management of outpatient cases of COVID-19, mainly attributable to antibiotics use. Our research highlights the discrepancy between recommendations for care and clinical practice and the need for strategies to bridge gaps in evidence-informed decision-making.

Orphan Drug Prices and Epidemiology of Rare Diseases: A Cross-Sectional Study in Italy in the Years 2014-2019.

INTRODUCTION: It is well acknowledged that the price of orphan drugs is normally higher than that resulting from the value-based pricing. A correlation between the cost of therapy for orphan drugs and the epidemiology (prevalence and incidence) of the related rare disease can be hypothesized. METHODS: This analysis includes all approved orphan drugs by European Medicines Agency whose reimbursement was granted for the first therapeutic indication in the years 2014-2019 in Italy. Regression and correlation analyses were performed to analyze the possible correlations between the logarithm of the annual therapy cost and the epidemiology of the rare diseases, between orphan drugs consumption and epidemiology of related rare disease and between therapy cost and the consumption. RESULTS: The regression analysis between the annual cost of therapy estimated on the published ex-factory price and the prevalence showed a slightly decreasing, not statistically significant, trend (coefficient: -0.10, p-value: 0.41). The results were similar when using the price resulting from the application of Managed Entry Agreements (coefficient: -0.11, p-value: 0.40). The regression analysis between sales volume and prevalence showed a positive slope without an acceptable level of significance (p-value: 0.04). The correlation analysis between the therapy cost and the sales volume highlighted again an absence of significant association, similarly if considering only ATC L orphan drugs, or the incidence. DISCUSSION: The definition of the price of an orphan drug seems not to depend on the rarity of the disease, and sales volumes do not correlate with the epidemiology of the rare disease and with the annual cost of therapy.