Effect of access to antenatal care on risk of preterm birth among migrant women in Italy: A population-based cohort study.

Objective: To evaluate the association between maternal migration status and preterm birth, and whether a better adherence to antenatal care during pregnancy mitigates the risk of preterm birth. Design: Population-based cohort. Setting: Administrative databases of the Lombardy region, Italy. Population: First singleton births of women aged 15-55 years at 22-42 gestational weeks, between 2016 and 2021. Methods: Assessed the risk of preterm birth (<37 weeks). Main outcome measures: A multivariable logistic regression mediation model calculated the mediation effect of adherence to antenatal care in the association between maternal migrant status and preterm birth and the residual effect not mediated by it. Analyses were adjusted for the socio-demographic and pregnant characteristics of the women. Results: Of 349,753 births in the cohort, Italian nationality accounted for 71 %; 28.4 % were documented migrants and 0.4 % undocumented migrants. Among them, 5.3 %, 6.4 %, and 9.3 % had a preterm birth, respectively. Using deliveries of Italian citizens as referent, migrants had a significantly increased risk of preterm birth (adjusted relative risk: 1.22, 95 % confidence interval: 1.18-1.27). Adherence to antenatal care mediated the 62 % of such risk. We have calculated that adherence to antenatal pathways set to the highest level for the whole population could lead to a 37 % reduction in preterm birth risk. Conclusion: Part of the excess of preterm birth among documented and undocumented migrants in Italy can be explained by a lack of adherence to the antenatal care path despite equal access to National Health care. The adherence of all pregnant women to antenatal care would reduce the risk of preterm birth by about one-third.

Predicting the risk of nursing home placement of elderly persons using a population-based stratification score.

OBJECTIVE: To develop and validate a novel score predictive of nursing home placement in elderly. STUDY DESIGN: Population-based case-control study based on healthcare utilization databases of Lombardy, a region of Northern Italy. METHODS: The 2.4 million citizens aged ≥65 years who on January 1, 2018 lived outside nursing home formed the target population. Cases were citizens who experienced nursing home admission (the outcome of interest) until December 31, 2019. Cases were matched 1:1 by gender, age, and municipality of residence to one control. Conditional logistic regression was fitted to select candidate predictors (the exposure to 69 clinical conditions and 11 social and healthcare services) independently associated with the outcome. The model was built from the 26,156 cases, and as many controls (training set), and applied to a validation set (15,807 case-control couples). Predictive performance was assessed by discrimination and calibration. RESULTS: Twenty-one factors were identified as predictive of nursing home admission and were included in the "Elderly Nursing Home Placement" (ENHP) score. Mental health disorders and chronic neurological illnesses contributed most to prediction of nursing home admission. ENHP performance showed an area under the receiver operating characteristic curve of 0.77 and a remarkable calibration of observed and predicted outcome risk. CONCLUSIONS: A simple score derived from data used for public health management may reliably predict the risk of nursing home placement in elderly. Its use by healthcare decision makers allows to accurately identify high-risk individuals who need home services, thereby avoiding admission to nursing homes.

Long-term exposure to antihypertensive drugs and the risk of cancer occurrence: evidence from a large population-based study.

OBJECTIVE: Available data on the association between antihypertensive drugs and cancer are characterized by a few years follow-up. Our aim has been to evaluate the association between long-term exposure to antihypertensive drugs and the risk of cancer occurrence. METHODS: Using the healthcare utilization databases of the Lombardy region (Italy), individuals aged 40-85 years who had no previous history of cancer and were newly dispensed with at least one antihypertensive drug from the major drug classes between 2009 and 2011 were followed from the first drug dispensation to December 31, 2020. Data were analyzed according to the first drug used and the intention to treat principle, but also via an "as treated" approach, that is, by considering changes of and exposure to drugs during follow-up. The association between the duration of exposure to each drug class and the risk of cancer occurrence was evaluated using the adjusted Cox regression models. RESULTS: The study cohort included 338 910 new drug users (median age, 59 years; 49.5% males). During a median follow-up of 10.2 years, 36 556 cancers occurred. There was no consistent significant association between the risk of cancer occurrence and angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, or thiazides. A progressive, weak increase in cancer occurrence was associated with progressive exposure to calcium channel blockers and, limited to long-term exposure, to beta-blockers. A modest progressive increase in risk was observed also for thiazide-like and loop diuretics in the as treated, although not in the intention to treat approach. CONCLUSIONS: Long-term evaluation of exposure to antihypertensive drugs did not show consistent associations between thiazides, angiotensin-receptor blockers, or angiotensin-converting-enzyme inhibitors and the risk of cancer occurrence. A weak association was observed between cancer and the duration of exposure to calcium channel blockers and beta-blockers.

Blood microRNA testing in participants with suspicious low-dose CT findings: follow-up of the BioMILD lung cancer screening trial.

Background: The proper management of suspicious radiologic findings is crucial to optimize the effectiveness of low-dose computed tomography (LDCT) lung cancer screening trials. In the BioMILD study, we evaluated the utility of combining a plasma 24-microRNA signature classifier (MSC) and LDCT to define the individual risk and personalize screening strategies. Here we aim to assess the utility of repeated MSC testing during annual screening rounds in 1024 participants with suspicious LDCT findings. Methods: The primary outcome was two-year lung cancer incidence in relation to MSC test results, reported as relative risk (RR) with 95% confidence interval (CI). Lung cancer incidence and mortality were estimated using extended Cox models for time-dependent covariates, yielding the respective hazard ratios (HR). Clinicaltrials.gov ID: NCT02247453. Findings: With a median follow-up of 8.5 years, the full study set included 1403 indeterminate LDCT (CTind) and 584 positive LDCT (CT+) results. A lung cancer RR increase in MSC+ compared to MSC- participants was observed in both the CTind (RR: 2.5; 95% CI: 1.4-4.32) and CT+ (RR: 2.6; 95% CI: 1.81-3.74) groups and was maintained when considering stage I or resectable tumors only. A 98% negative predictive value in CTind/MSC- and a 30% positive predictive value in CT+/MSC+ lesions were recorded. At seven years' follow-up, MSC+ participants had a cumulative HR of 4.4 (95% CI: 3.0-6.4) for lung cancer incidence and of 8.1 (95% CI: 2.7-24.5) for lung cancer mortality. Interpretation: Our study shows that MSC can be reliably performed during LDCT screening rounds to increase the accuracy of lung cancer risk and mortality prediction and supports its clinical utility in the management of LDCT findings of uncertain malignancy. Funding: Italian Association for Cancer Research; Italian Ministry of Health; Horizon2020; National Cancer Institute (NCI); Gensignia LifeScience.

Multiple births from medically assisted reproduction: contribution of different types of procedures and trends over time.

OBJECTIVE: To evaluate the relative impact of different strategies of medically assisted reproduction (MAR), i.e. first line treatment (ovarian stimulation with or without intrauterine insemination) and in vitro fertilization (IVF) procedures (conventional IVF or intracytoplasmic sperm injection), on the risk of multiple births. STUDY DESIGN: We utilized the health care utilization databases of the Lombardy region to identify births resulting from MAR between 2007 and 2022. We gathered data on the total number of multiple births and calculated the prevalence rate by dividing the number of multiples by the total number of births. To examine the temporal trend in the proportion of multiple births after MAR over time, a linear regression model was employed separately for different types of techniques and in strata of maternal age. RESULTS: A total of 30,900 births after MAR were included; 4485 (14.5 %) first line treatments and 26,415 (85.5 %) IVF techniques. Overall, 4823 (15.6 %) multiple births were identified. The frequency of multiple births over the study period decreased from 22.0 % in 2007 to 8.7 % in 2022 (p < 0.01). Multiple births from first line treatments were stable ranging from 13.5 % in 2007-2008 to 12.0 % in 2021-2022 (p = 0.29). Multiple births from IVF procedures decreased from 23.8 % in 2007-2008 to 8.4 % in 2021-2022 (p < 0.01). Stratifying for maternal age (i.e. < 35 and ≥ 35 years), the trends remained consistent. CONCLUSIONS: The reduction in multiple births has been influenced by changes in IVF strategy and procedures. The decline has been gradual but steady since 2009, when a law restricting embryo freezing was repealed in Italy. In contrast, the proportion of multiple births resulting from first line treatments has remained constant over time. Despite declining, multiple births from MAR remained about one order of magnitude higher than those from spontaneous pregnancies.

Cost-effectiveness of single-pill and separate-pill administration of antihypertensive triple combination therapy: a population-based microsimulation study.

BACKGROUND: Single-pill combination (SPC) of three antihypertensive drugs has been shown to improve adherence to therapy compared with free combinations, but little is known about its long-term costs and health consequences. This study aimed to evaluate the lifetime cost-effectiveness profile of a three-drug SPC of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic vs the corresponding two-pill administration (a two-drug SPC plus a third drug separately) from the Italian payer perspective. METHODS: A cost-effectiveness analysis was conducted using multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged ≥ 40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug dispensation until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies, assigning each of them to each cohort member. Costs and life-years gained were discounted by 3%. Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty. RESULTS: Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61-1.14), with a mean cost differential of -€12 (95% CI -9,719-8,131), making it the dominant strategy (ICER = -14, 95% CI -€15,871-€7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17-7,813) and €2,027 (95% CI 19-8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574-10,640 vs. €3,710, 95% CI 263-11,955). The cost-effectiveness profile did not significantly change according to age, sex, and clinical status. CONCLUSIONS: The SPC was projected to be cost-effective compared with the two-pill combination at almost all reasonable willingness-to-pay thresholds. As it is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system.

Cost-effectiveness of outpatient adherence to recommendations for monitoring of patients hospitalized for heart failure.

AIMS: A set of indicators to assess the quality of care for patients hospitalized for heart failure was developed by an expert working group of the Italian Health Ministry. Because a better performance profile measured using these indicators does not necessarily translate to better outcomes, a study to validate these indicators through their relationship with measurable clinical outcomes and healthcare costs supported by the Italian National Health System was carried out. METHODS AND RESULTS: Residents of four Italian regions (Lombardy, Marche, Lazio, and Sicily) who were newly hospitalized for heart failure (irrespective of stage and New York Heart Association class) during 2014-2015 entered in the cohort and followed up until 2019. Adherence to evidence-based recommendations [i.e. renin-angiotensin-aldosterone system (RAS) inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and echocardiograms (ECCs)] experienced during the first year after index discharge was assessed. Composite clinical outcomes (cardiovascular hospital admissions and all-cause mortality) and healthcare costs (hospitalizations, drugs, and outpatient services) were assessed during the follow-up. The restricted mean survival time at 5 years (denoted as the number of months free from clinical outcomes), the hazard of clinical outcomes (according to the Cox model), and average annual healthcare cost (expressed in euros per person-year) were compared between adherent and non-adherent patients. A non-parametric bootstrap method based on 1000 resamples was used to account for uncertainty in cost-effectiveness estimates. A total of 41 406 patients were included in this study (46.3% males, mean age 76.9 ± 9.4 years). Adherence to RAS inhibitors, beta-blockers, MRAs, and ECCs were 64%, 57%, 62%, and 20% among the cohort members, respectively. Compared with non-adherent patients, those who adhered to ECCs, RAS inhibitors, beta-blockers, and MRAs experienced (i) a delay in the composite outcome of 1.6, 1.9, 1.6, and 0.6 months and reduced risks of 9% (95% confidence interval, 2-14%), 11% (7-14%), 8% (5-11%), and 4% (-1-8%), respectively; and (ii) lower (€262, €92, and €571 per year for RAS inhibitors, beta-blockers, and MRAs, respectively) and higher costs (€511 per year for ECC). Adherence to RAS inhibitors, beta-blockers, and MRAs showed a delay in the composite outcome and a saving of costs in 98%, 84%, and 93% of the 1000 bootstrap replications, respectively. CONCLUSIONS: Strict monitoring of patients with heart failure through regular clinical examinations and drug therapies should be considered the cornerstone of national guidelines and audits.

Effects of acute carotid baroreceptor stimulation on sympathetic nerve traffic in resistant and uncontrolled hypertension: a systematic review and meta-analysis.

In resistant hypertensive patients acute carotid baroreflex stimulation is associated with a blood pressure (BP) reduction, believed to be mediated by a central sympathoinhbition.The evidence for this sympathomodulatory effect is limited, however. This meta-analysis is the first to examine the sympathomodulatory effects of acute carotid baroreflex stimulation in drug-resistant and uncontrolled hypertension, based on the results of microneurographic studies. The analysis included 3 studies assessing muscle sympathetic nerve activity (MSNA) and examining 41 resistant uncontrolled hypertensives. The evaluation included assessment of the relationships between MSNA and clinic heart rate and BP changes associated with the procedure. Carotid baroreflex stimulation induced an acute reduction in clinic systolic and diastolic BP which achieved statistical significance for the former variable only [systolic BP: -19.98 mmHg (90% CI, -30.52, -9.43), P < 0.002], [diastolic BP: -5.49 mmHg (90% CI, -11.38, 0.39), P = NS]. These BP changes were accompanied by a significant MSNA reduction [-4.28 bursts/min (90% CI, -8.62, 0.06), P < 0.07], and by a significant heart rate decrease [-3.65 beats/min (90% CI, -5.49, -1.81), P < 0.001]. No significant relationship was detected beween the MSNA, systolic and diastolic BP changes induced by the procedure, this being the case also for heart rate. Our data show that the acute BP lowering responses to carotid baroreflex stimulation, although associated with a significant MSNA reduction, are not quantitatively related to the sympathomoderating effects of the procedure. This may suggest that these BP effects depend only in part on central sympathoinhibition, at least in the acute phase following the intervention.

The COVID-19 Pandemic Was Associated with a Change in Therapeutic Management and Mortality in Heart Failure Patients.

Background: Heart failure (HF)-related mortality has been exacerbated by the COVID-19 pandemic; however, it is unclear how healthcare reassessment has contributed to the excess mortality versus SARS-CoV-2 infection itself. We aimed to assess how the pandemic affected the therapeutic management and prognosis of HF patients. Methods: We retrospectively reviewed the healthcare utilization databases of the Lombardy region (Italy) to identify all newly-diagnosed HF patients from January 2018 to December 2021. Outcomes were the utilization of HF therapies (Sacubitril/Valsartan; cardiac resynchronization therapy [CRT] and/or implantable cardioverter-defibrillator [ICD]; mechanical circulatory support [MCS]; heart transplantation [HTX]) and mortality. Cox regression models were fitted to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with the pandemic. Results: 36,130 and 17,263 patients were identified in the pre-pandemic and pandemic eras, respectively. The pandemic reduced Sacubitril/Valsartan utilization (HR = 0.77, 95% CI: 0.65-0.91) and CRT/ICD implantation (HR = 0.85, 95% CI: 0.78-0.92), but not MCS (HR = 1.11, 95% CI: 0.86-1.43) and HTX (HR = 0.88, 95% CI: 0.70-1.09). An increased mortality risk was observed during the pandemic (HR = 1.19, 95% CI: 1.15-1.23), which was attributable to SARS-CoV-2 infection (HR for non-COVID-19-related mortality = 1.01, 95% CI: 0.97-1.04). Conclusions: The COVID-19 pandemic was associated with a reduction in medical and interventional therapies for HF and an increase in mortality for HF patients.

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.

Comparing the effectiveness and cost-effectiveness of sulfonylureas and newer diabetes drugs as second-line therapy for patients with type 2 diabetes.

INTRODUCTION: We aimed to compare the effectiveness and cost-effectiveness profiles of glucagon-like peptide-1 receptor agonist (GLP-1-RA), sodium-glucose cotransporter 2 inhibitor (SGLT2i), and dipeptidyl peptidase-4 inhibitor (DPP-4i) compared with sulfonylureas and glinides (SU). RESEARCH DESIGN AND METHODS: Population-based retrospective cohort study based on linked regional healthcare utilization databases. The cohort included all residents in Lombardy aged ≥40 years, treated with metformin in 2014, who started a second-line treatment between 2015 and 2018 with SU, GLP-1-RA, SGLT2i, or DPP-4i. For each cohort member who started SU, one patient who began other second-line treatments was randomly selected and matched for sex, age, Multisource Comorbidity Score, and previous duration of metformin treatment. Cohort members were followed up until December 31, 2022. The association between second-line treatment and clinical outcomes was assessed using Cox proportional hazards models. The incremental cost-effectiveness ratios (ICERs) were calculated and compared between newer diabetes drugs and SU. RESULTS: Overall, 22 867 patients with diabetes were included in the cohort, among which 10 577, 8125, 2893 and 1272 started a second-line treatment with SU, DPP-4i, SGLT2i and GLP-1-RA, respectively. Among these, 1208 patients for each group were included in the matched cohort. As compared with SU, those treated with DPP-4i, SGLT2i and GLP-1-RA were associated to a risk reduction for hospitalization for major adverse cardiovascular events (MACE) of 22% (95% CI 3% to 37%), 29% (95% CI 12% to 44%) and 41% (95% CI 26% to 53%), respectively. The ICER values indicated an average gain of €96.2 and €75.7 each month free from MACE for patients on DPP-4i and SGLT2i, respectively. CONCLUSIONS: Newer diabetes drugs are more effective and cost-effective second-line options for the treatment of type 2 diabetes than SUs.

The sequential antifracturative treatment: a meta-analysis of randomized clinical trials.

Background: Subjects with a fragility fracture have an increased risk of a new fracture and should receive effective strategies to prevent new events. The medium-term to long-term strategy should be scheduled by considering the mechanisms of action in therapy and the estimated fracture risk. Objective: A systematic review was conducted to evaluate the sequential strategy in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines. Design: Systematic review and meta-analysis. Data sources and methods: PubMed, Embase, and the Cochrane Library were investigated up to February 2021 to update the search of a recent systematic review. Randomized clinical trials (RCTs) that analyzed the sequential therapy of antiresorptive, anabolic treatment, or placebo in patients with or at risk of a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Effect sizes were pooled in a meta-analysis using fixed-effects models. The primary outcome was the risk of refracture, while the secondary outcome was the bone mineral density (BMD) change. Results: In all, 17 RCTs, ranging from low to high quality, met our inclusion criteria. A significantly reduced risk of fracture was detected at (i) 12 or 24 months after the switch from romosozumab to denosumab versus placebo to denosumab; (ii) 30 months from teriparatide to bisphosphonates versus placebo to bisphosphonates; and (iii) 12 months from romosozumab to alendronate versus the only alendronate therapy (specifically for vertebral fractures). In general, at 2 years after the switch from anabolic to antiresorptive drugs, a weighted BMD was increased at the lumbar spine, total hip, and femoral neck site. Conclusion: The Task Force formulated recommendations on sequential therapy, which is the first treatment with anabolic drugs or 'bone builders' in patients with very high or imminent risk of fracture.

A systematic review to evaluate the sequential therapy of antiresorptive (denosumab and bisphosphonate, such as alendronate, minodronate, risedronate, and etidronate), anabolic treatment (such as romosozumab, teriparatide), or placebo in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines Subjects with previous fragility fractures should promptly receive effective strategies to prevent the risk of subsequent events. Indeed, patients with a fragility fracture have a doubled risk of a new fracture. For this reason, it is essential to provide adequate sequential therapy based on the mechanisms and the rapidity of action. A systematic review was performed to identify the sequential strategy in patients at high- or imminent-risk of (re)fracture and to support the Panel of the Italian Fragility Fracture Guideline in formulating recommendations. Our systematic review included seventeen studies mostly focused on women and enabled us to strongly recommend the anabolic drugs as first-line treatment. Specifically, for the sequential therapy from anabolic to antiresorptive treatment, there was a significant reduction in the risk of different types of fractures after the switch from romosozumab to denosumab versus placebo to denosumab. These findings were confirmed at 24 months after the switch. Considering the sequential treatment from antiresorptive to anabolic medications, there was a decreased risk of fracture 12 months after the switch from placebo to teriparatide versus bisphosphonate or antiresorptive to teriparatide. Moreover, a greater bone mineral density increase after the switch from anabolic to antiresorptive medications was shown in the lumbar spine, total hip, and femoral neck. The results of this systematic review and meta-analysis confirm that initial treatment with anabolic drugs produces substantial bone mineral density improvements, and the transition to antiresorptive drugs can preserve or even amplify the acquired benefit. These findings support the choice to treat very high-risk individuals with anabolic drugs first, followed by antiresorptive drugs.

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.

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.

Using real-world evidence in haematology.

Most new drug approvals are based on data from large randomized clinical trials (RCTs). However, there are sometimes contradictory conclusions from seemingly similar trials and generalizability of conclusions from these trials is limited. These considerations explain, in part, the gap between conclusions from data of RCTs and those from registries termed real world data (RWD). Recently, real-world evidence (RWE) from RWD processed by artificial intelligence has received increasing attention. We describe the potential of using RWD in haematology concluding RWE from RWD may complement data from RCTs to support regulatory decisions.

Risk of Dementia During Antihypertensive Drug Therapy in the Elderly.

BACKGROUND: Evidence exists that lowering high blood pressure reduces the risk of dementia. However, the generalizability of this evidence to old patients from the general population remains uncertain. OBJECTIVES: This study sought to evaluate the effect of antihypertensive drug treatment on the risk of dementia in a heterogeneous group of new users of antihypertensive drugs. METHODS: A nested case-control study was carried out by including the cohort of 215,547 patients from Lombardy, Italy, aged ≥65 years, who started taking antihypertensive drugs between 2009 and 2012. Cases were the 13,812 patients (age 77.5 ± 6.6 years; 40% men) who developed dementia or Alzheimer's disease during follow-up (up to 2019). For each case, 5 control subjects were selected to be matched for sex, age, and clinical status. Exposure to drug therapy was measured by the proportion of the follow-up covered by antihypertensive drugs. Conditional logistic regression was used to model the outcome risk associated with exposure to antihypertensive drugs. RESULTS: Exposure to treatment was inversely associated with the risk of dementia. Compared with patients with very low exposure, those with low, intermediate, and high exposure exhibited a 2% (95% CI: -4% to 7%), 12% (95% CI: 6%-17%), and 24% (95% CI: 19%-28%) risk reduction, respectively. This was also the case for very old (aged ≥85 years) and frail patients (ie, those characterized by a high mortality risk at 1 year). CONCLUSIONS: In the old fraction of the general population, antihypertensive drug treatment is associated with a lower risk of dementia. This was also the case in very old and frail patients.