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.
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.
The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant ...chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm
2
) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8–13), median survival was 18 years (95 % CI 9–28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0–97.2 %) and 60.2 % (95 % CI 36.9–83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group).
Abstract
The fast reconstruction of charged particle tracks with high efficiency and track quality is an essential part of the online data selection for the ATLAS experiment at the High Luminosity ...LHC.
Dedicated custom designed hardware boards and software simulations have been developed to assess the feasibility of a Hardware Tracking Trigger (HTT) system.
The Pattern Recognition Mezzanine (PRM), as part of the HTT system, has been designed to recognize track candidates in silicon detectors with Associative Memory ASICs and to select and reconstruct tracks using linearized algorithms implemented in an Intel Stratix 10 MX FPGA.
The highly parallelized FPGA design makes extensive use of the integrated High-Bandwidth-Memory.
In this paper, the FPGA design for the PRM board is presented. Its functionalities have been verified in both simulations and hardware tests on an Intel Stratix 10 MX development kit.
Mercury (total and organic), cadmium, lead, copper, iron, manganese, selenium and zinc concentrations were measured in different organs of 6 different cetacean species stranded in an area of ...extraordinary ecological interest (Cetaceans’ Sanctuary of the Mediterranean Sea) along the coast of the Ligurian Sea (North-West Mediterranean). Stable-isotopes ratios of carbon (
13C/
12C) and nitrogen (
15N/
14N) were also measured in the muscle. A significant relationship exists between
15N/
14N, mercury concentration and the trophic level. The distribution of essential and non-essential trace elements was studied on several organs, and a significant relationship between selenium and mercury, with a molar ratio close to 1, was found in the cetaceans’ kidney, liver and spleen, regardless of their species. High selenium concentrations are generally associated with a low organic to total mercury ratio. While narrow ranges of concentrations were observed for essential elements in most organs, mercury and selenium concentrations are characterised by a wide range of variation. Bio-accumulation and bio-amplification processes in cetaceans can be better understood by comparing trace element concentrations with the stable-isotopes data.
The tenebrionid species
Blaps scabiosa
(tribe Blaptini) is redescribed and illustrated. This species was twice described under the same name by Baudi di Selve in 1874 from Tashkent (now Uzbekistan) ...and by Faust in 1875 from Tash (Iran, Semnan Province). In 1876 Faust synonymized his species with Baudi’s species. Nabozhenko interpreted these taxa as two distinct species and gave a new name
B. neoscabiosa
Nabozhenko, 2008 to the Iranian
B. scabiosa
Faust, 1875 to eliminate homonymy. This species has never been found in Tien Shan and occurs only in Eastern Alborz Mountains. The type locality “Tashk.” (Tashkent) should be corrected to “Tash” (Iran, Semnan). After examination of the type specimens we have established that the Baudi’s and Faust’s taxa are conspecific, and the following synonymy is proposed:
Blaps scabiosa
Baudi di Selve, 1874 =
B. scabiosa
Faust, 1875,
syn. resurr.
=
B. neoscabiosa
Nabozhenko, 2008,
syn. n.
The lectotype of
Blaps scabiosa
Faust, 1875 is designated.
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.
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.
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.
Breast surgery is associated with persistent postsurgical pain; usually related to poorly treated acute pain. Paravertebral block has been successfully employed in analgesic protocols for breast ...surgery; its impact on postdischarge pain (PDP) has not been investigated. The aim of this study was to assess characteristics of PDP after breast surgery, the development of chronic postoperative pain (CPP) and its impact on health care costs.
We conducted a retrospective, observational study on a continuous cohort of adult female patients undergoing local breast cancer surgery under combined anesthesia. All patients were interviewed 6 months after hospital discharge. The survey was specifically conceived to assess incidence, features and duration of PDP. The overall cost of additional healthcare resources consumed with a specific relationship to persistent PDP was estimated.
A database of 244 patients was preliminarily analyzed. Of these, 188 were included in the following statistical analysis; 123 patients (65.2%) reported significant PDP, with a median intensity on NRS of 6 (IQR=2), more frequently described as burning and associated with paresthesia and/or hyperalgesia (87 patients, 46%). One hundred and six patients (56.5%) reported this pain as interfering with their normal daily activities, work and sleep. In 26.8% of cases (50 patients) symptoms lasted more than 1 month and in 28 patients (15.0%) pain became chronic. The majority of patients self-treated their pain with non-steroideal anti-inflammatory drugs, but in 50 patients (26.8%) this therapy was reported as ineffective. This additional consumption of healthcare resources led to a significant economical impact.
PDP and CPP seem to be common complications after breast cancer surgery, even if a combined anesthesia technique with a thoracic paravertebral block is performed, leading to severe consequences on patients' quality of life and increasing consumption of healthcare resources after discharge.
NCT03618459 (www.clinicaltrials.gov).
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