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Introduction: Distance learning efficacy on physician performances and patient health outcomes has been demonstrated. This study explored the participation and evaluation of CME e-learning courses for Italian health care professionals addressing leading causes of maternal mortality identified by the Italian Obstetric Surveillance System (ItOSS) at the Italian National Health Institute, namely postpartum hemorrhage and pregnancy hypertensive disorders. Methods: A model for two online free 12-hour case-based training courses was used. Data on participants were collected, anonymized, and transferred to the Italian National Health Institute for later analysis. Participants were requested to sign an online informed consent form. Results: Twenty-one thousand five hundred thirty-two health care professionals enrolled to the courses from 2014 to 2017 as follows: midwives (14,187, 65.9%); obstetricians (3,716, 17.2%); anesthesiologists (1,896, 8.8%); and other medical specialists (1,733, 8.0%). Overall, 85% of participants acquired CME credits. Participants' satisfaction on quality, efficacy, and relevance was very high. Discussion: ItOSS courses were able to reach a substantial number of different professional profiles involved in perinatal care all over the country; ItOSS courses can be considered an effective way to spread evidence-based good clinical practices. Nevertheless, further studies are needed to verify the improvement in professional health care skills and patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The availability of cell lines releasing fluorescent viral particles can significantly support a variety of investigations, including the study of virus-cell interaction and the screening of antiviral compounds. Regarding HIV-1, the recovery of such biologic reagents represents a very hard challenge due to the intrinsic cytotoxicity of many HIV-1 products. We sought to overcome such a limitation by using a cell line releasing HIV-1 particles in an inducible way, and by exploiting the ability of a HIV-1 Nef mutant to be incorporated in virions at quite high levels. Results: Here, we report the isolation and characterization of a HIV-1 packaging cell line, termed 18-4s, able to release valuable amounts of fluorescent HIV-1 based Virus-Like Particles (VLPs) in an inducible way. 18-4s cells were recovered by constitutively expressing the HIV-1 NefG3C mutant fused with the enhanced-green fluorescent protein (NefG3C-GFP) in a previously isolated inducible HIV-1 packaging cell line. The G3C mutation creates a palmitoylation site which results in NefG3CGFP incorporation into virions greatly exceeding that of the wild type counterpart. Upon induction of 18-4s cells with ponasterone A and sodium butyrate, up to 4 μg/ml of VLPs, which had incorporated about 150 molecules of NefG3C-GFP per viral particle, were released into the culture supernatant. Due to their intrinsic strong fluorescence, the 18-4s VLPs were easily detectable by a novel cytofluorometric-based assay developed here. The treatment of target cells with fluorescent 18-4 VLPs pseudotyped with different glycoprotein receptors resulted in these becoming fluorescent as early as two hours post-challenge. Conclusion: We created a stable cell line releasing fluorescent HIV-1 based VLPs upon induction useful for several applications including the study of virus-cell interactions and the screening of antiviral compounds. [ABSTRACT FROM AUTHOR]

This study aimed to calculate Italy's first national maternal mortality ratio (MMR) through an innovative record-linkage approach within the enhanced Italian Obstetric Surveillance System (ItOSS). A record-linkage retrospective cohort study was conducted nationwide, encompassing all women aged 11–59 years with one or more hospitalizations related to pregnancy or pregnancy outcomes from 2011 to 2019. Maternal deaths were identified by integrating data from the Death Registry and national and regional Hospital Discharge Databases supported by the integration of findings from confidential enquiries conducted through active surveillance. Maternal Mortality Ratio (MMR), direct MMR (DMMR), and causes of maternal death are the study main outcomes. The MMR was found to be 8.4 per 100,000 live births (95% CI 7.5–9.3), significantly higher than the 3.9 per 100,000 (95% CI 3.3–4.5) calculated solely from the Death Registry, with a notable declining trend over the study period. Causes of death have been classified according to the 10th International Classification of Diseases. Within 42 days from pregnancy outcome, leading causes were obstetric haemorrhage, sepsis, and cardiovascular diseases. Late maternal deaths were primarily attributed to suicide, malignancies, and cardiovascular diseases. This integrated methodology provides a comprehensive understanding of maternal mortality trends and causes in Italy, offering valuable insights for countries utilizing or planning enhanced surveillance systems. [ABSTRACT FROM AUTHOR]

Suicide has been identified as one of the most common causes of death among women within 1 year after the end of pregnancy in several high-income countries. The aim of this study was to provide the first estimate of the maternal suicide ratio and a description of the characteristics of women who died by suicide during pregnancy or within 1 year after giving birth, induced abortion or miscarriage (i.e., maternal suicide) in 10 Italian regions, covering 77% of total national births. Maternal suicides were identified through the linkage between regional death registries and hospital discharge databases. Background population data was collected from the national hospital discharge, abortion and mortality databases. The previous psychiatric history of the women who died by maternal suicide was retrieved from the regionally available data sources. A total of 67 cases of maternal suicide were identified, corresponding to a maternal suicide ratio of 2.30 per 100,000 live births in 2006–2012. The suicide rate was 1.18 per 100,000 after giving birth (n = 2,876,193), 2.77 after an induced abortion (n = 650,549) and 2.90 after a miscarriage (n = 379,583). The majority of the women who died by maternal suicide (34/57) had a previous psychiatric history; 15/18 previously diagnosed mental disorders were not registered along with the index pregnancy obstetric records. Suicide is a relevant cause of maternal death in Italy. The continuity of care between primary, mental health and maternity care were found to be critical. Clinicians should be aware of the issue, as they may play an important role in preventing suicide in their patients. [ABSTRACT FROM AUTHOR]

Introduction: Peripartum hysterectomy is usually undertaken in cases of life-threatening obstetric hemorrhage to prevent the death of the mother. Near-miss events are still under-researched and inappropriate care continues to be a critical issue, even in countries with advanced obstetric surveillance systems. The aim of the present study was to estimate the prevalence, associated factors, management and intraoperative and postoperative complications of peripartum hysterectomy due to obstetric hemorrhage.Material and Methods: A prospective population-based study has been conducted in six Italian regions covering 49% of births in Italy. The study population comprised all women aged 11-59 years undergoing peripartum hysterectomy, from September 2014 to August 2016, due to obstetric hemorrhage within 7 days of delivery. In each maternity unit a trained reference person reported incident cases using electronic data collection forms. The background population comprised all women who delivered in the participating regions during the study period.Results: The overall peripartum hysterectomy prevalence was 1.09 per 1000 maternities, with a large variability among regions, ranging from 0.52 to 1.60. Previous cesarean section (relative risk [RR] 4.97, 95% CI 4.13-5.96), assisted reproductive technology (RR 5.99, 95% CI 4.42-8.11) multiple pregnancy (RR 5.03, 95% CI 3.57-7.09) and maternal age ≥35 years (RR 2.69, 95% CI 2.25-3.21) were the main associated factors for hysterectomy. The most common causes of peripartum hysterectomy were uterine atony (45.1%) and abnormally invasive placentation (40.2%). Intensive care unit admission was reported in 49.9% of cases, 16.8% of women suffered severe morbidity and 5 women died.Conclusions: The rate of peripartum hysterectomy in Italy was three times higher compared with the UK, the Netherlands and the Nordic countries. The wide difference may be associated with women's characteristics, such as age at delivery and previous cesarean section, and with different management options leading to peripartum hysterectomy. [ABSTRACT FROM AUTHOR]

Background: Despite the growing importance given to ensuring high-quality childbirth, perinatal good practices have been rapidly disrupted by SARS-CoV-2 pandemic. This study aimed at describing the childbirth care provided to infected women during two years of COVID-19 emergency in Italy. Methods: A prospective cohort study enrolling all women who gave birth with a confirmed SARS-CoV-2 infection within 7 days from hospital admission in the 218 maternity units active in Italy during the periods February 25, 2020-June 30, 2021, and January 1-May 31, 2022. Perinatal care was assessed by evaluating the prevalence of the following indicators during the pandemic: presence of a labour companion; skin-to-skin; no mother–child separation at birth; rooming-in; breastfeeding. Logistic regression models including women’ socio-demographic, obstetric and medical characteristics, were used to assess the association between the adherence to perinatal practices and different pandemic phases. Results: During the study period, 5,360 SARS-CoV-2 positive women were enrolled. Overall, among those who had a vaginal delivery (n = 3,574; 66.8%), 37.5% had a labour companion, 70.5% of newborns were not separated from their mothers at birth, 88.1% were roomed-in, and 88.0% breastfed. These four indicators showed similar variations in the study period with a negative peak between September 2020 and January 2021 and a gradual increase during the Alpha and Omicron waves. Skin-to-skin (mean value 66.2%) had its lowest level at the beginning of the pandemic and gradually increased throughout the study period. Among women who had a caesarean section (n = 1,777; 33.2%), all the indicators showed notably worse outcomes with similar variations in the study period. Multiple logistic regression analyses confirm the observed variations during the pandemic and show a lower adherence to good practices in southern regions and in maternity units with a higher annual number of births. Conclusions: Despite the rising trend in the studied indicators, we observed concerning substandard childbirth care during the SARS-CoV-2 pandemic. Continued efforts are necessary to underscore the significance of the experience of care as a vital component in enhancing the quality of family-centred care policies. [ABSTRACT FROM AUTHOR]

Introduction: Accurate estimates and reliable classification of maternal deaths are imperative steps in the chain of actions targeted at reducing avoidable maternal mortality. The aims of this study were to estimate the maternal mortality ratio (MMR) in 10 Italian regions covering 77% of total national births and to identify the most suitable approach to classify the causes of death.Material and Methods: Deaths during and within 1 year after pregnancy have been identified through linkage between death registry and hospital discharge database. Regional and national data sources from 2006 to 2012 were used. The MMR has been estimated and deaths were classified as direct or indirect and according to their primary causes.Results: A total of 277 maternal deaths within 42 days after pregnancy were identified: 149 direct, 102 indirect causes and 26 unclassified-resulting in a MMR of 9.18 per 100 000 live births. The under-reporting rate of official MMR figures in the participating regions is 60.3%. Hemorrhage (MMR 1.92), hypertensive disorders of pregnancy and cardiac diseases (MMR 1.06) were the leading causes of deaths occurring within 42 days after pregnancy, whereas malignancy (39%) and violent deaths (17%) were the most frequent of the 543 late maternal deaths.Conclusions: Record-linkage is an efficient and reliable method to estimate maternal mortality and to identify causes of maternal deaths. Both the indirect/direct and the classification by primary cause have a role in countries where direct deaths exceed indirect maternal mortality. Building upon linkage data, confidential enquiries further increase the likelihood of reducing maternal mortality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this before and after cross-sectional analysis, the authors aim to assess the impact of the bundle of research and training initiatives implemented between 2013 and 2018, and coordinated by the Italian Obstetric Surveillance System (ItOSS) to reduce obstetric haemorrhagic emergencies in five selected Italian Regions. To this purpose, the haemorrhagic Maternal Mortality Ratios (MMR) per 100,000 live births were estimated before and after implementing the bundle, through the ItOSS's vital statistic linkage procedures and incident reporting and Confidential Enquiries. The research and training bundle was offered to all health professionals involved in pregnancy and birth care in the selected regions, representing 40% of national live births, and participating in the ItOSS audit cycle since its institution. The haemorrhagic MMR significantly decreased from 2.49/100,000 live births [95% CI 1.75 to 3.43] in the years 2007–2013 prior to the bundle implementation, to 0.77/100,000 live births [95% CI 0.31 to 1.58] in the years 2014–2018 after its implementation. According to the study results, the bundle of population-based initiatives might have contributed to reducing the haemorrhagic MMR in the participating regions, thus improving the quality of care of the major obstetric haemorrhage. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Results: 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%).Conclusions: 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. [ABSTRACT FROM AUTHOR]

Abstract: For the first time in Europe hair and urine testing have been applied to assess drugs of abuse consumption in couples undergoing assisted reproductive technology and the eventual association of toxic habits with other lifestyle, health status and sociodemographic factors was also investigated. Couples attending five assisted reproduction centers in Rome were invited to join the study. When they presented at the Centre for the visit, they were asked to answer a structured questionnaire concerning sociodemographic characteristics and lifestyle habits, and at the same time to provide hair and urine samples. Hair and urine testing for drugs of abuse, urinary profile of principal endogenous steroids involved in fertility process (testosterone, epitestosterone, androsterone, etiocholanolone and dehydroepiandrosterone) and of alcohol and tobacco smoke biomarkers were performed with validated methodologies. Of the 594 enrolled individuals (297 couples), 352 (164 couples and 24 single individuals from the couple) completed the questionnaire and gave both hair and urine samples, apart from 3 bald men, who only gave urine samples. Urine testing showed an overall 4.8% (17 individuals) positivity to drugs of abuse: 4.2% to cannabinoids, 1.4% to cocaine and 0.85% to both drugs. Results of 4cm segment hair samples testing matched those from urine samples. Thus, taking together, results of urine and hair testing confirmed repeated use of cannabis, cocaine and both drugs in 3.7, 0.85 and 0.57% examined individuals, respectively. Drug consumers were in a statistically higher percentage active smokers and alcohol drinkers, less prone to physical activity and with a trend towards higher weight than non consumers. Finally, repeated drug consumption was associated with significant lower concentration of urinary testosterone in males and of urinary dehydroepiandrosterone in females. The findings of the present study confirm the suitability of urine testing to disclose recent drugs of abuse consumption and of hair analysis to verify repeated consumption. Association between different toxic habits and sedentary lifestyle is also substantiated by the obtained results in our cohort of couples attending assisted reproduction centers. [Copyright &y& Elsevier]

Abstract: For the first time in Europe hair and urine testing have been applied to assess drugs of abuse consumption in couples undergoing assisted reproductive technology and the eventual association of toxic habits with other lifestyle, health status and sociodemographic factors was also investigated. Couples attending five assisted reproduction centers in Rome were invited to join the study. When they presented at the Centre for the visit, they were asked to answer a structured questionnaire concerning sociodemographic characteristics and lifestyle habits, and at the same time to provide hair and urine samples. Hair and urine testing for drugs of abuse, urinary profile of principal endogenous steroids involved in fertility process (testosterone, epitestosterone, androsterone, etiocholanolone and dehydroepiandrosterone) and of alcohol and tobacco smoke biomarkers were performed with validated methodologies. Of the 594 enrolled individuals (297 couples), 352 (164 couples and 24 single individuals from the couple) completed the questionnaire and gave both hair and urine samples, apart from 3 bald men, who only gave urine samples. Urine testing showed an overall 4.8% (17 individuals) positivity to drugs of abuse: 4.2% to cannabinoids, 1.4% to cocaine and 0.85% to both drugs. Results of 4cm segment hair samples testing matched those from urine samples. Thus, taking together, results of urine and hair testing confirmed repeated use of cannabis, cocaine and both drugs in 3.7, 0.85 and 0.57% examined individuals, respectively. Drug consumers were in a statistically higher percentage active smokers and alcohol drinkers, less prone to physical activity and with a trend towards higher weight than non consumers. Finally, repeated drug consumption was associated with significant lower concentration of urinary testosterone in males and of urinary dehydroepiandrosterone in females. The findings of the present study confirm the suitability of urine testing to disclose recent drugs of abuse consumption and of hair analysis to verify repeated consumption. Association between different toxic habits and sedentary lifestyle is also substantiated by the obtained results in our cohort of couples attending assisted reproduction centers. [Copyright &y& Elsevier]

The Nef protein of human and simian immunodeficiency virus (HIV/SIV) is believed to interfere with T cell activation signals by forming a signaling complex at the plasma membrane. Composition and function of the complex are not fully understood. Here we report that Nef recruits the Polycomb Group (PcG) protein Eed, so far known as a nuclear factor and repressor of transcription, to the membrane of cells. The Nef-induced translocation of Eed led to a potent stimulation of Tat-dependent HIV transcription, implying that Eed removal from the nucleus is required for optimal Tat function. Similar to Nef action, activation of integrin receptors recruited Eed to the plasma membrane, also leading to enhanced Tat/Nef-mediated transcription. Our results suggest a link between membrane-associated activation processes and transcriptional derepression and demonstrate how HIV exploits this mechanism. [Copyright &y& Elsevier]

A highly conserved signaling property of Nef proteins encoded by human or simian immunodeficiency virus is the binding and activation of a PAK kinase whose function is unclear. Here we show that Nef-mediated p21-activated kinase (PAK) activation involves phosphatidylinositol 3-kinase, which acts upstream of PAK and is bound and activated by Nef similar to the manner of Polyoma virus middle T antigen. The Nef-associated phosphatidylinositol-3?PAK complex phosphorylated the pro-apoptotic Bad protein without involving the protein kinase B?Akt kinase, which is generally believed to inactivate Bad by serine phosphorylation. Consequently, Nef, but not a Nef mutant incapable of activating PAK, blocked apoptosis in T cells induced by serum starvation or HIV replication. Nef anti-apoptotic effects are likely a crucial mechanism for viral replication in the host and thus in AIDS pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: To compare mature human oocytes cryopreservation with slow freezing (SF) and vitrification (VT) in infertile couples. Design: Retrospective study of national Italian data submitted during the period 2007–2011. Setting: National ART registry. Patient(s): Infertile patients with supernumerary oocytes. Intervention(s): Thawing or warming of cryopreserved oocytes and ICSI. Main Outcome Measure(s): oocyte survival, fertilization, implantation and clinical pregnancy rate between SF and VT. Result(s): A total of 14,328 cycles with 11,599 transfers, 1,850 pregnancies, 1,168 deliveries and 1,342 babies born were analyzed from 146 reporting centers (range of cycles 1–1,255 per center). The SF oocytes' survival rate was lower than in VT (51.1% vs. 63.1%). Fertilization rate was significantly higher in SF than in VT (SF 71.6% vs. VT 70.1%). VT showed a significantly higher pregnancy rate, both per started cycle (14.4% vs. 12.0%) and per transfer (18.0% vs. 14.8%), and implantation rate (9.5% vs. 8.1%) than SF. However, the range and median pregnancy rate per started cycle were, respectively, 0%–50% and 7.7% in SF and 0%–100% and 6.7% in VT. Conclusion(s): VT showed a statistically significant higher performance than SF. As with other ART procedures, the results are not homogeneous among clinics and protocols, but the confirm the clinical value of oocyte cryopreservation in infertile patients. [ABSTRACT FROM AUTHOR]