Evaluation of adherence to pharmacological treatments by undocumented migrants with chronic diseases: a 10-year retrospective cohort study.

OBJECTIVES: To investigate the time course of medication adherence and some of the factors involved in this process in undocumented migrants with chronic diseases. DESIGN: Retrospective cohort study. SETTING: A big non-governmental organisation in Milano, Italy, giving medical assistance to undocumented migrants. PARTICIPANTS: 1918 patients, 998 females and 920 males, with at least one chronic condition (diabetes, cardiovascular diseases (CVDs), mental health disorders) seen over a period of 10 years (2011-2020). Their mean age was 49.2±13 years. RESULTS: Adherence to medications decreased over 1 year in all patients. This was more evident during the first 2 months of treatment. Patients on only one medication were less adherent than those on more than one medication; at 6 months the percentage of patients with high adherence was 33% vs 57% (p<0.0001) for diabetes, 15% vs 46% (p<0.0001) for mental disorders and 35% vs 59% (p<0.0001) for CVDs. Patients with mental disorders had the lowest adherence: 25% at 6 months and 3% at 1 year. Mental disorders, when present as comorbidities, greatly reduced the probability of being highly adherent: risk ratio (RR) 0.72 (95% CI 0.57 to 0.91; p=0.006) at 3 months, RR 0.77, (95% CI 0.59 to 1.01; p=0.06) at 6 months, RR 0.35 (95% CI 0.13 to 0.94; p=0.04) at 1 year. This was especially evident for patients with CVDs, whose percentage of high adherents decreased to 30% (p=0.0008) at 6 months and to 3% (p=0.01) at 1 year. We also noted that highly adherent patients usually were those most frequently seen by a doctor. CONCLUSIONS: Interventions to increase medication adherence of undocumented migrants with chronic diseases are necessary, particularly in the first 2 months after beginning treatment. These should be aimed at people-centred care and include more outpatient consultations. Educational interventions should especially be taken into consideration for patients on monotherapy.

Does preterm birth increase the initiation of antidepressant use during the postpartum? A population-based investigation.

Background: Preterm birth may affect maternal mental health. We explored the relationship between preterm birth and the risk of initiating antidepressant use during the year after birth. Methods: We conducted a population-based investigation using regional healthcare utilization databases. The exposure considered was preterm birth. The outcome was having at least one prescription for antidepressant medications during the year after birth. We used a log-binomial regression model including terms for maternal age at birth, nationality, educational level, parity, modality of conception, modality of delivery, use of other psychotropic drugs, and diabetes to estimate relative risk (RR) and 95% confidence intervals (CI) for the association between preterm birth and the initiation of antidepressant use. In addition, the absolute risk differences (ARD) were also computed according to the timing of birth. Results: The cohort included 727,701 deliveries between 2010 and 2020 in Lombardy, Northern Italy. Out of these, 6,522 (0.9%) women had at least one prescription for antidepressant drugs during the year after birth. Preterm births were related to a 38% increased risk of initiation of antidepressant use during the year after birth (adjusted RR = 1.38; 95% CI: 1.25-1.52) for moderate to late preterm and to 83% (adjusted RR = 1.83; 95% CI: 1.46-2.28) for extremely and very preterm. Excluding women with only one antidepressant prescription, the association was consistent (adjusted RR = 1.41, 95%CI: 1.23-1.61 for moderate to late preterm and adjusted RR = 1.81, 95% CI: 1.31-2.49 for extremely and very preterm). Also, excluding women who used other psychotropics, the association remained consistent (adjusted RR = 1.39, 95%CI: 1.26-1.54 and adjusted RR = 1.91, 95% CI: 1.53-2.38, respectively for moderate to late and extremely and very preterm). Conclusion: Women who delivered preterm may have an excess risk of initiation of antidepressant consumption during the first year after birth.

Estimating All-Cause Deaths Averted in the First Two Years of the COVID-19 Vaccination Campaign in Italy.

Comparing deaths averted by vaccination campaigns is a crucial public health endeavour. Excess all-cause deaths better reflect the impact of the pandemic than COVID-19 deaths. We used a seasonal autoregressive integrated moving average with exogenous factors model to regress daily all-cause deaths on annual trend, seasonality, and environmental temperature in three Italian regions (Lombardy, Marche and Sicily) from 2015 to 2019. The model was used to forecast excess deaths during the vaccinal period (December 2020-October 2022). We used the prevented fraction to estimate excess deaths observed during the vaccinal campaigns, those which would have occurred without vaccination, and those averted by the campaigns. At the end of the vaccinal period, the Lombardy region proceeded with a more intensive COVID-19 vaccination campaign than other regions (on average, 1.82 doses per resident, versus 1.67 and 1.56 in Marche and Sicily, respectively). A higher prevented fraction of all-cause deaths was consistently found in Lombardy (65% avoided deaths, as opposed to 60% and 58% in Marche and Sicily). Nevertheless, because of a lower excess mortality rate found in Lombardy compared to Marche and Sicily (12, 24 and 23 per 10,000 person-years, respectively), a lower rate of averted deaths was observed (22 avoided deaths per 10,000 person-years, versus 36 and 32 in Marche and Sicily). In Lombardy, early and full implementation of adult COVID-19 vaccination was associated with the largest reduction in all-cause deaths compared to Marche and Sicily.

Healthcare costs and resources utilization in children with difficult-to-control asthma treated with biologic therapies: A population-based cohort study.

INTRODUCTION: Asthma is one of the most common diseases in children, with a variable range of severity. In recent years, treatment for severe asthma has been largely improved by the availability of targeted biologic therapies. Nevertheless, studies reporting real-world data and cost-effectiveness analyses are lacking. The aim of this study was to evaluate, on a population-based cohort of children with asthma, the impact of the treatment with biologics on healthcare service utilization and associated costs. METHODS: Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). A cohort of 46 asthmatic children aged 6-11 in treatment with dupilumab, mepolizumab or omalizumab was identified during 2017-2021. We compared healthcare resources use between the year before ("baseline period") and the year after the treatment initiation ("follow-up period"). Average 1-year healthcare costs were also calculated. RESULTS: Comparing the baseline with the follow-up period, the number of patients with at least one exacerbation-related hospitalization and ER access decreased by 75.0% and 85.7%, respectively. The use of biologic agents, namely omalizumab, mepolizumab and dupilumab, significantly reduced oral corticosteroids (OCS), short-acting ß2-agonists and the association inhaled corticosteroids/long-acting ß2-agonists use. ER admissions for non-respiratory causes were also significantly reduced, while discontinuation rate was low (6.5%). The overall costs increased, due to the costs of the biologic agents, but the hospital admission-related costs due to respiratory causes reduced significantly. CONCLUSIONS: Our real-world investigation suggests that biologic agents reduced hospital admissions for respiratory causes and use of anti-asthmatic drugs, including OCS. However, long-term healthcare sustainability still needs more in-depth assessments.

Probability of second live birth after first natural and medically assisted reproduction-mediated live birth: A historical cohort study.

INTRODUCTION: Evidence on the role of medically assisted reproduction (MAR) in achieving the desired number of children is very limited. The aim of the current investigation was to assess the probability and the mode of conception of a second live birth according to the mode of conception of the first one. MATERIAL AND METHODS: This historical cohort study was based on administrative data from regional healthcare databases. Women hospitalized for childbirth in Lombardy between January 1, 2007 and December 31, 2017 were identified. The probability of a second live birth up to 2021 was estimated using the Kaplan-Meier method. We calculated this probability according to the mode of conception of the first birth, and the analysis was also performed in strata of maternal age at first birth. Cox proportional hazards models were fitted to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the association between mode of conception at first live birth and the probability of having a second live birth. Mothers were right-censored if they moved out of the region, died, or did not have a second live birth by the end of follow-up. RESULTS: We identified 431 333 women who had their first live birth after a natural conception and 16 837 who had their first live birth after MAR. The probability of having a second live birth was 58.6% and 32.1%, respectively in the two groups (HR = 0.68, 95% CI: 0.66-0.70). Considering solely women who naturally conceived their first live birth, the probability to have a second child with MAR was 1.1% and to have a second child naturally 59.3%. The corresponding values were 11.5% and 25.2% in the group of women with a first MAR-mediated live birth. CONCLUSIONS: In our cohort, one woman out of 10 having a first MAR-mediated live birth underwent MAR programs again. Considering women who had a first natural live birth, this proportion was drastically reduced. In the field of MAR, more attention should be given to the capacity of a couple to achieve the number of desired children.

Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study.

Purpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks. Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts. Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6-positive and HLA-Cw6-negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLA-Cw6-positive and HLA-Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings. Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile.

Spontaneous and induced abortions in women with a diagnosis of gestational related neoplasm: a population-based linkage study in Lombardy, 2010-2020.

BACKGROUND: A diagnosis of cancer during pregnancy or within one year after the end of pregnancy is a major clinical and public health issue. The current study aimed at estimating the incidence of pregnancy-associated cancer (PAC) and assessing whether the risk of abortion is increased in women diagnosed with cancer. METHODS: This population-based cohort study used the regional healthcare utilization (HCU) databases of Lombardy, the largest region in Italy, to identify the women who delivered between 2010 and 2020. PAC were identified by oncological ICD-9-CM codes reported in the hospital discharge forms. We computed the ratio of PAC cases to the total number of pregnancies. Following a diagnosis of PAC, the prevalence ratio (PR) of abortion and the corresponding 95% confidence interval (CI), was estimated using a log-binomial model adjusted for maternal age. RESULTS: During the study period, 926 women who gave birth (1.29 cases per 1000 births) and 341 women who had an abortion (1.52 cases per 1000 abortions) were diagnosed with PAC. Regardless of the outcome of pregnancy, the risk of PAC increased with increasing age. The rate of PAC was initially lower among births, but it came very close to the rate of PAC among abortions in the last two calendar years. The proportion of abortions among women with PAC gradually decreased from 27.7% in 2010-2012 to 18.5% in 2019-2020 (p-value < 0.001). Overall, a diagnosis of PAC was related to an approximately 10% increased risk of abortion (PR = 1.11, 95%CI:1.01-1.22). However, no association was observed in 2019-2020 (PR = 0.87, 95%CI:0.65-1.17). Considering only diagnoses made during the first trimester of pregnancy, the risk of abortion was about 2.5 times higher (PR = 2.53, 95%CI:2.05-3.11) and the risk of induced abortion was almost 4 times higher (PR = 3.71, 95%CI:2.82-4.90). CONCLUSION: In this population the risk of abortion was about 10% higher in women with PAC than in women without PAC. However, this association tended to decrease in more recent calendar periods. This trend seemed to be influenced more by spontaneous than by induced abortions.

Determinants of Admission to Critical Care Following Acute Recreational Drug Toxicity: A Euro-DEN Plus Study.

This study aimed to characterize patients admitted to critical care following Emergency Department (ED) presentation with acute recreational drug toxicity and to identify determinants of admission to critical care. A retrospective multicenter matched case-control study was conducted by the European Drug Emergency Network Plus (Euro-DEN Plus) over the period 2014-2021. The cases were ED presentations with acute recreational drug toxicity admitted to critical care, the controls consisted of ED presentations with acute recreational drug toxicity medically discharged directly from the ED. The potential determinants of admission to critical care were assessed through multivariable conditional stepwise logistic regression analysis and multiple imputation was used to account for the missing data. From 2014 to 2021, 3448 Euro-DEN Plus presentations involved patients admitted to critical care (76.9% males; mean age 33.2 years; SD 10.9 years). Patient age ≥35 years (as compared to ≤18 years) was a determinant of admission to critical care following acute recreational drug toxicity (adjusted odds ratio, aOR, 1.51, 95% confidence interval, CI, 1.15-1.99), along with polydrug use (aOR 1.39, 95% CI 1.22-1.59), ethanol co-ingestion (aOR 1.44, 95% CI 1.26-1.64), and the use of gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL, aOR 3.08, 95% CI 2.66-3.57). Conversely, lower odds of admission to critical care were associated with the use of cocaine (aOR 0.85, 95% CI 0.74-0.99), cannabis (aOR 0.44, 95% CI 0.37-0.52), heroin (aOR 0.80, 95% CI 0.69-0.93), and amphetamine (aOR 0.65, 95% CI 0.54-0.78), as was the arrival to the ED during the night (8 p.m.-8 a.m., aOR 0.88, 95% CI 0.79-0.98). These findings, which deserve confirmation and further investigation, could contribute to a more complete understanding of the decision-making process underlying the admission to critical care of patients with acute recreational drug toxicity.

Postoperative pulmonary complications and mortality after major abdominal surgery. An observational multicenter prospective study.

BACKGROUND: Postoperative pulmonary complications (PPCs) significantly contribute to postoperative morbidity and mortality. We conducted a study to determine the incidence of PPCs after major elective abdominal surgery and their association with early and 1-year mortality in patient without pre-existing respiratory disease. METHODS: We conducted a multicenter observational prospective clinical study in 40 Italian centers. 1542 patients undergoing elective major abdominal surgery were recruited in a time period of 14 days and clinically managed according to local protocol. The primary outcome was to determine the incidence of PPCs. Further, we aimed to identify independent predictors for PPCs and examine the association between PPCs and mortality. RESULTS: PPCs occurred in 12.6% (95% CI 11.1-14.4%) of patients with significant differences among general (18.3%, 95% CI 15.7-21.0%), gynecological (3.7%, 95% CI 2.1-6.0%) and urological surgery (9.0%, 95% CI 6.0-12.8%). PPCs development was associated with known pre- and intraoperative risk factors. Patients who developed PPCs had longer length of hospital stay, higher risk of 30-days hospital readmission, and increased in-hospital and one-year mortality (OR 3.078, 95% CI 1.825-5.191; P<0.001). CONCLUSIONS: The incidence of PPCs in patients without pre-existing respiratory disease undergoing elective abdominal surgery is high and associated with worse clinical outcome at one year after surgery. General surgery is associated with higher incidence of PPCs and mortality compared to gynecological and urological surgery.

Improved prediction of 5-year mortality by updating the chronic related score for risk profiling in the general population: lessons from the italian region of Lombardy.

Objective: The aim of this study was to improve the performance of the Chronic Related Score (CReSc) in predicting mortality and healthcare needs in the general population. Methods: A population-based study was conducted, including all beneficiaries of the Regional Health Service of Lombardy, Italy, aged 18 years or older in January 2015. Each individual was classified as exposed or unexposed to 69 candidate predictors measured before baseline, updated to include four mental health disorders. Conditions independently associated with 5-year mortality were selected using the Cox regression model on a random sample including 5.4 million citizens. The predictive performance of the obtained CReSc-2.0 was assessed on the remaining 2.7 million citizens through discrimination and calibration. Results: A total of 35 conditions significantly contributed to the CReSc-2.0, among which Alzheimer's and Parkinson's diseases, dementia, heart failure, active neoplasm, and kidney dialysis contributed the most to the score. Approximately 36% of citizens suffered from at least one condition. CReSc-2.0 discrimination performance was remarkable, with an area under the receiver operating characteristic curve of 0.83. Trends toward increasing short-term (1-year) and long-term (5-year) rates of mortality, hospital admission, hospital stay, and healthcare costs were observed as CReSc-2.0 increased. Conclusion: CReSC-2.0 represents an improved tool for stratifying populations according to healthcare needs.

The modest impact of assisted reproductive technology on the second birth: insights from a population-based study in Lombardy, Northern Italy.

BACKGROUND: In the field of assisted reproductive technology (ART), family rate is a neglected but emerging issue. The aim of the study was to investigate the epidemiological impact of ART on the second birth during the period 2007-2020 in Lombardy, Northern Italy. METHODS: We conducted a population-based study using administrative data from regional healthcare databases of Lombardy including first and second births occurred from 2007 to 2020. The proportion of deliveries after ART was calculated separately among first and second births. The probability of undergoing ART to achieve second birth compared to first one was estimated computing odds ratio (OR), crude and adjusted for maternal age, education, and nationality. We also assessed changes with age and calendar period. RESULTS: We obtained a cohort including 553,190 first births and 317,976 second births. The proportion of ART babies among first and second births was 4.3% and 1.0% respectively (p < 0.001). The probability of undergoing ART to achieve second birth compared to first one, adjusted for age, education, and nationality, was 0.14 (95%CI: 0.13-0.15). The proportion of deliveries after ART increased with maternal age and along the calendar period but remained always markedly higher among first births rather than among second births. CONCLUSION: ART played a significantly lower role in the determinism of the conception of a second birth in comparison to the conception of a first one.

Natural and vaccine-induced immunity are equivalent for the protection against SARS-CoV-2 infection.

OBJECTIVES: To compare the long-term cumulative risk of SARS-CoV-2 infection associated with natural and vaccine-induced immunity. METHODS: Retrospective population-based cohort study based on registry of COVID-19 vaccinations and SARS-CoV-2 infections among 9.1 million citizens of Lombardy, Italy, eligible for vaccination on 27th December 2020. Those who developed SARS-CoV-2 infection from 24th May to 14th September 2021, provided they did not yet receive the COVID-19 vaccine when infection was confirmed, and those who received the second mRNA vaccine dose, provided they had not yet developed the infection, were selected to be 1:1 matched for sex, age and index date. The latter corresponded to 90 days after confirmed infection or 14 days after vaccine administration. A control cohort including citizens who, on the index date, had neither developed infection nor received vaccination was also selected. Kaplan-Meier curves were used for comparing the cumulative incidence of new SARS-CoV-2 infection from the index date until 22nd June 2022. RESULTS: Overall, 19,418 1:1:1 risk-sets were included. After 9 months of follow-up, the cumulative risk of new SARS-CoV-2 infection was 21.8%, 22.0%, and 25.9%, respectively, among exposed to natural immunity, vaccine-induced immunity and unexposed. CONCLUSIONS: Equivalent potential for protecting against new SARS-CoV-2 infection was observed.

Characterizing non-communicable disease trends in undocumented migrants over a period of 10 years in Italy.

Undocumented migrants represent a large part of the population in Countries of the European Union (EU) such as Italy. Their health burden is not fully understood and likely to be related mainly to chronic conditions. Information on their health needs and conditions may help to target public health interventions but is not found in national public health databases. We conducted a retrospective observational study of non-communicable disease (NCD) burden and management in undocumented migrants receiving medical care from Opera San Francesco, a non-governmental organization (NGO) in Milan, Italy. We analyzed the health records of 53,683 clients over a period of 10 years and collected data on demographics, diagnosis and pharmacological treatments prescribed. 17,292 (32.2%) of clients had one or more NCD diagnosis. The proportion of clients suffering from at least one NCD increased from 2011 to 2020. The risk of having an NCD was lower in men than women (RR = 0.88, 95% CI 0.86-0.89), increased with age (p for trend < 0.001) and changed with ethnicity. African and Asian migrants had a lower risk than Europeans of cardiovascular diseases (RR 0.62 CI 0.58-0.67, RR 0.85 CI 0.78-0.92 respectively) and mental health disorders (RR 0.66 CI 0.61-0.71, RR 0.60 CI 0.54-0.67 respectively), while the risk was higher in Latin American people (RR 1.07 CI 1.01-1.13, RR 1.18 CI 1.11-1.25). There was a higher risk of diabetes in those from Asia and Latin America (RR 1.68 CI 1.44-1.97, RR 1.39 CI 1.21-1.60). Overall, migrants from Latin America had the greatest risk of chronic disease and this was true for diabetes, cardiovascular diseases and mental health disorders. Undocumented migrants demonstrate a significantly different health burden of NCDs, which varies with ethnicity and background. Data from NGOs providing them with medical assistance should be included in structuring public health interventions aimed at the prevention and treatment of NCDs. This could help to better allocate resources and address their health needs.

Paricalcitol and Extended-Release Calcifediol for Treatment of Secondary Hyperparathyroidism in Non-Dialysis Chronic Kidney Disease: Results From a Network Meta-Analysis.

CONTEXT: Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid hormone (PTH) production and parathyroid hyperplasia. OBJECTIVE: The objective of this analysis was to compare the efficacy and adverse effects of extended-release calcifediol (ERC) and paricalcitol (PCT) by assessing their effect on the biomarkers PTH, calcium, and phosphate in patients with non-dialysis CKD (ND-CKD). METHODS: A systematic literature research was performed in PubMed to identify randomized control trials (RCTs). Quality assessment was done with the GRADE method. The effects of ERC vs PCT were compared using random effects in a frequentist setting. RESULTS: Nine RCTs comprising 1426 patients were included in the analyses. The analyses were performed on 2 overlapping networks, due to nonreporting of outcomes in some of the included studies. No head-to-head trials were identified. No statistically significant differences in PTH reduction were found between PCT and ERC. Treatment with PCT showed statistically significant increases in calcium compared with ERC (0.2 mg/dL increase; 95% CI, -0.37 to -0.05 mg/dL). No differences in effects on phosphate were observed. CONCLUSION: This network meta-analysis showed that ERC is comparable in lowering PTH levels vs PCT. ERC displayed avoidance of potentially clinically relevant increases in serum calcium, offering an effective and well-tolerated treatment option for the management of SHPT in patients with ND-CKD.

Prevalence and Factors Associated With Intertwin Birth Weight Discordance Among Same-Sex Twins in Lombardy, Northern Italy.

This population-based cohort study investigated the prevalence, potential risk factors, and consequences of birth weight discordance (BWD) among same-sex twins. We retrieved data from the automated system of healthcare utilization databases of Lombardy Region, Northern Italy (2007-2021). BWD was defined as 30% or more disparity in birth weights between the larger and the smaller twin. Multivariate logistic regression was used to analyze the risk factors of BWD in deliveries with same-sex twins. In addition, the distribution of several neonatal outcomes was assessed overall and according to BWD level (i.e., ≤20%, 21-29, and ≥30%). Finally, a stratified analysis by BWD was performed to assess the relationship between assisted reproductive technologies (ART) and neonatal outcomes. We identified 11,096 same-sex twin deliveries; 556 (5.0%) pairs of twins were affected by BWD. Multivariate logistic regression analysis showed that maternal age ≥35 years (OR 1.26, 95% CI [1.05,5.51]), low level of education (OR 1.34, 95% CI [1.05, 1.70]), and ART (OR 1.16, 95% CI [0.94, 1.44], almost significant due to the low power) were independent risk factors for BWD in same-sex twins. Conversely, parity (OR 0.73, 95% CI [0.60, 0.89]) was inversely related. All the adverse outcomes observed were more common among BWD pairs than non-BWD ones. Instead, a protective effect of ART was observed for most neonatal outcomes considered among BWD twins. Our results suggest that conception after ART increases the risk of developing a high disparity between the weights of the two twins. However, the presence of BWD may complicate twin pregnancies, compromising neonatal outcomes, regardless of the modality of conception.

Effectiveness and economic impact of Dupilumab in asthma: a population-based cohort study.

RATIONALE: Severe asthma is burdened by relevant socio-economic and clinical impact. Randomized controlled trials on Dupilumab showed efficacy and a good safety profile, but post-market studies are needed. OBJECTIVES: To evaluate the impact of Dupilumab on (i) the use of anti-asthmatic drugs, including oral corticosteroids (OCS), (ii) the rates of asthma exacerbation-related hospital admissions, and (iii) the healthcare costs in patients with asthma. METHODS: Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). We compared healthcare resources use between the 6 months after Dupilumab initiation ("post-intervention period") and (i) the 6 months before Dupilumab initiation ("wash-out period") and (ii) the corresponding 6 months of the prior year ("pre-intervention period"). MAIN RESULTS: In a cohort of 176 patients, Dupilumab significantly reduced anti-asthmatic drugs use (including OCS and short-acting ß2-agonists, inhaled corticosteroids (ICS)/long-acting ß2-agonists and ICS alone) when comparing the "pre-intervention" to the "post-intervention" period. When considering hospital admissions, we observed a not statistically or marginally significant reduction between both periods before Dupilumab and the post-intervention period. Six-months discontinuation rate was 8%. Overall healthcare costs had a tenfold increase between the "pre-intervention" and "post-intervention" period, which was mainly led by the biologic drug cost. Conversely, expenditures connected to hospital admissions did not change. CONCLUSIONS: Our real-world investigation suggests that Dupilumab reduced anti-asthmatic drugs use, including OCS, in comparison to a corresponding period in the prior year. However, long-term healthcare sustainability remains an open issue.

Impact of the First and Second Lockdown for COVID-19 Pandemic on Preterm Birth, Low Birth Weight, Stillbirth, Mode of Labor, and of Delivery in Lombardy, Italy.

We investigated the effect of lockdown measures implemented in Lombardy on selected obstetric and perinatal outcomes. Births that occurred during the two lockdowns imposed (i.e., the first from 16 March to 2 June 2020 and the second from 3 November 2020 to 5 April 2021) and the comparison periods (i.e., the first from 16 March to 2 June 2018 and the second from 3 November 2018 to 5 April 2019) were identified using regional healthcare databases. The distribution of births according to the selected outcomes was computed and the Chi-square test was used for testing differences in the periods compared. During the two lockdowns, we observed a lower proportion of low birth weight, from 6.8% in the comparison period to 6.1% in the first lockdown (p = 0.019), and from 6.5% to 6.1% in the second one (p = 0.109). The proportion of preterm births decreased from 6.8% to 6.3% in the first lockdown (p = 0.097), and from 6.2% to 6.0% in the second one (p = 0.172). No differences in stillbirth rate emerged for both lockdowns. Induction of labor was more frequent during both lockdowns, from 28.6% to 32.7% in the first (p < 0.0001), and from 29.9% to 33.2% in the second one (p < 0.0001). Cesarean section was less frequent during the second lockdown.

[Extended release calcifediol and paricalcitol in the treatment of secondary hyperparathyroidism: a network meta-analysis of indirect comparison].

Introduction: Secondary hyperparathyroidism (SHPT) is a common and major complication of chronic kidney disease (CKD) among patients on dialysis and in patients with CKD stage G3 to G5. SHPT in CKD is caused by disturbances in metabolic parameters. Paricalcitol (PCT), other active vitamin D analogous (doxercalciferol and alfacalcidol), and active vitamin D (calcitriol) have been commonly used to treat SHPT in non-dialysis CKD (ND-CKD) for several years. However, recent studies indicate that these therapies adversely increase serum calcium, phosphate, and fibroblast growth factor 23 (FGF-23) levels. Extended release calcifediol (ERC) has been developed as an alternative treatment for SHPT in ND-CKD. The present meta-analysis compares the effect of ERC against PCT in the control of PTH and calcium levels. Methods: A systematic literature review was conducted, according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines to identify studies for inclusion in the Network Meta-Analysis (NMA). Results: 18 publications were eligible for inclusion in the network meta-analysis and 9 articles were included in the final NMA. The estimated PTH reduction from PCT (-59.5 pg/ml) was larger than the PTH reduction from ERC (-45.3 pg/ml), but the difference in treatment effects did not show statistical significance. Treatment with PCT caused statistically significant increases in calcium vs. placebo (increase: 0.31 mg/dl), while the marginal increase in calcium from treatment with ERC (increase: 0.10 mg/dl) did not reach statistical significance. Conclusions: The evidence suggests that both PCT and ERC are effective in reducing levels of PTH, whereas calcium levels tended to increase from treatment with PCT. Therefore, ERC may be an equally effective, but more tolerable treatment alternative to PCT.

Trends in the incidence of major birth defects after assisted reproductive technologies in Lombardy Region, Northern Italy.

PURPOSE: The incidence of birth defects is increased in children born after assisted reproductive technologies (ART). However, changes in ART over time could influence this incidence. To investigate this issue, we present the frequency and trends of birth defects in ART and natural pregnancies in Lombardy, Northern Italy, during the period 2014-2020. METHODS: This is a population-based study using automated system of healthcare utilization (HCU) databases. ART pregnancies included only those obtained with conventional IVF or ICSI. After identifying the total number of deliveries, the rate of newborns with birth defects was compared between natural and ART pregnancies. A logistic regression model was used to calculate the adjusted odd ratio (OR). Analyses were repeated for every calendar year. RESULTS: Overall, 508,421 deliveries were identified, of which 14,067 (2.8%) were achieved after IVF-ICSI. A decreasing trend in birth defects over time was highlighted. The adjusted OR dropped from 1.40 (95%CI: 1.03-1.91) in 2014 to 0.92 (95%CI: 0.69-1.22) in 2020. During the study period, a significant reduction in multiple pregnancy and in the ratio of ICSI to conventional IVF was also observed, explaining at least in part the positive trend observed for birth defects. CONCLUSION: The increased risk of birth defects in children born after IVF-ICSI is not steady over time. A decline of this risk emerged in our region. Policy changes in ART may explain this beneficial effect.