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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.
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Antihipertensivos , Análisis Costo-Beneficio , Hipertensión , Humanos , Antihipertensivos/economía , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Italia , Hipertensión/tratamiento farmacológico , Adulto , Combinación de Medicamentos , Inhibidores de la Enzima Convertidora de Angiotensina/economía , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Bloqueadores de los Canales de Calcio/economía , Bloqueadores de los Canales de Calcio/uso terapéutico , Bloqueadores de los Canales de Calcio/administración & dosificación , Cadenas de Markov , Quimioterapia Combinada , Anciano de 80 o más Años , Simulación por Computador , Diuréticos/administración & dosificación , Diuréticos/economía , Diuréticos/uso terapéuticoRESUMEN
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.
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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.
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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.
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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.
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Cumplimiento de la Medicación , Trastornos Mentales , Migrantes , Humanos , Masculino , Femenino , Estudios Retrospectivos , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Enfermedad Crónica/tratamiento farmacológico , Italia , Adulto , Migrantes/estadística & datos numéricos , Migrantes/psicología , Trastornos Mentales/tratamiento farmacológico , Enfermedades Cardiovasculares/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
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.
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Análisis Costo-Beneficio , Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Hipoglucemiantes , Compuestos de Sulfonilurea , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/economía , Masculino , Femenino , Compuestos de Sulfonilurea/uso terapéutico , Compuestos de Sulfonilurea/economía , Estudios Retrospectivos , Hipoglucemiantes/economía , Hipoglucemiantes/uso terapéutico , Persona de Mediana Edad , Anciano , Inhibidores de la Dipeptidil-Peptidasa IV/economía , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/economía , Estudios de Seguimiento , Resultado del Tratamiento , Adulto , Glucemia/análisisRESUMEN
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.
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Barorreflejo , Presión Sanguínea , Hipertensión , Presorreceptores , Sistema Nervioso Simpático , Humanos , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Seno Carotídeo/inervación , Terapia por Estimulación Eléctrica/métodos , Frecuencia Cardíaca/fisiología , Hipertensión/fisiopatología , Hipertensión/terapia , Presorreceptores/fisiología , Sistema Nervioso Simpático/fisiopatología , Sistema Nervioso Simpático/fisiologíaRESUMEN
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.
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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.
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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.
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AIMS: To evaluate the impact of adherence to glucagon like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose transporter two inhibitors (SGLT2-I) on clinical outcomes and costs in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: The 121,115 residents of the Lombardy Region (Italy) aged ≥40 years newly treated with metformin during 2007-2015 were followed to identify those who started therapy with GLP1-RA or SGLT2-I. Adherence to drug therapy over the first year was defined as the proportion of days covered >80%. Within each drug class, for each adherent patient, one non-adherent patient was matched for age, sex, duration, adherence to metformin treatment and propensity score. The primary clinical outcome was a composite of insulin initiation, hospitalisation for micro- and macrovascular complications and all-cause mortality after the first year of drug treatment. Costs were evaluated based on reimbursements from the national healthcare system. RESULTS: After matching, 1182 pairs of adherent and non-adherent GLP1-RA users and 1126 pairs of adherent and non-adherent SGLT2-I users were included. In both groups, adherent patients experienced a significantly lower incidence of the primary outcome (HR: 0.85, 95% CI 0.72-0.98 for GLP1-RA and HR: 0.69, 95% CI 0.55-0.87 for SGLT2-I). A significant reduction in hospitalizations was found for adherent patients in the GLP1-RA group but not for the SGLT2-I group. Results were consistent when analyses were stratified by age and sex. While higher drug-related costs in the adherent group were counterbalanced by decreased hospitalisation costs in SGLT2-I treated patients, this was not the case for GLP1-RA. CONCLUSIONS: Higher adherence to drug treatment with GLP1-RA and SGLT2-I during the first year of the drug intake is associated with a lower incidence of adverse clinical outcomes in a real-world setting.
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Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Cumplimiento de la Medicación , Metformina , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Metformina/uso terapéutico , Transportador 2 de Sodio-Glucosa , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
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.
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Enfermedad de Alzheimer , Demencia , Hipertensión , Anciano , Masculino , Humanos , Femenino , Antihipertensivos/efectos adversos , Demencia/epidemiología , Demencia/complicaciones , Estudios de Casos y Controles , Enfermedad de Alzheimer/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipertensión/complicacionesRESUMEN
CONTEXT: Patients with diabetes are at increased risk of dying from liver-related events, but little is known on whether this increased risk changed in recent years. OBJECTIVE: The aim of the present study is to describe time trends in cause-specific liver-related mortality in people with and without diabetes from the general Italian population. METHODS: Data were retrieved from the healthcare utilization databases of Lombardy, a region of Italy that accounts for about 16% (almost ten million) of its population. Annual cause-specific mortality rates and proportionate mortality were computed among individuals with and without diabetes from 2010 to 2019. Liver-related deaths were categorized as viral, alcohol related and non-viral non-alcohol related (NVNA). RESULTS: Liver diseases were responsible for 2% and 1% of deaths in people with and without diabetes (2019). Among patients with diabetes, the crude mortality rate for liver diseases decreased from 1.13 to 0.64 deaths per 1,000 person-years from 2010 to 2019. The largest proportion of liver-related deaths was attributable to NVNA diseases and it increased from 63% in 2010 to 68% in 2019, with a corresponding relative reduction of viral causes (from 27% to 23%). The Standardized Mortality Ratio for patients with diabetes was 3.35 (95% CI 2.96-3.76) for NVNA, 1.66 (95% CI 1.33-2.01) for viral hepatitis and 1.61 (95% CI 1.13-2.17) for alcoholic liver disease and it remained relatively stable over time. Excess mortality risk in patients with diabetes for liver-related mortality was higher than for cardiovascular mortality and cancer. CONCLUSION: While liver-related mortality rates decreased significantly among patients with diabetes, NVNA causes comprised the majority of cases. Excess mortality for liver-related causes in patients with diabetes compared with controls remained constant in the studied period.
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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.
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Aprobación de Drogas , Hematología , HumanosRESUMEN
BACKGROUND: Compared with patients without evidence of psychiatric symptoms, those with mental disorders experience reduced adherence with recommended healthcare and poorer clinical outcomes. This study aimed to evaluate whether the worse prognosis of patients with mental disorders after experiencing acute myocardial infarction could be fully or partially mediated by their reduced adherence to recommended healthcare. METHODS: In this retrospective cohort population-based study, 103 389 residents in the Italian Lombardy Region who experienced acute myocardial infarction in 2007-19 were identified. Among them, 1549 patients with severe mental illness (SMI) were matched with five cohort members without evidence of mental disorders (references). Recommended healthcare (cardiac medicaments and selected outpatient services) was evaluated in the year after the date of index hospital discharge. The first occurrences of cardiovascular (CV) hospital admissions and any-cause-death were considered as endpoints. Mediation analysis was performed to investigate whether post-discharge use of recommended healthcare may be considered a mediator of the relationship between healthcare exposure and endpoints occurrence. RESULTS: Compared with references, patients with SMI had lower adherence with recommended healthcare and adjusted risk excesses of 39% and 73% for CV hospitalizations and all-cause mortality. Mediation analysis showed that 4.1% and 11.3% of, respectively, CV hospitalizations and deaths occurred among psychiatric patients was mediated by their worse adherence to specific healthcare. CONCLUSION: The reduced use of recommended outpatient healthcare by patients with SMI had only a marginal effect on their worse prognosis. Other key factors mediating the prognostic gap between patients with and without mental disorders should be investigated.
Asunto(s)
Trastornos Mentales , Infarto del Miocardio , Humanos , Masculino , Femenino , Trastornos Mentales/epidemiología , Estudios Retrospectivos , Infarto del Miocardio/mortalidad , Italia/epidemiología , Pronóstico , Persona de Mediana Edad , Anciano , Cooperación del Paciente/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , AdultoRESUMEN
This study aims at providing an accurate and up-to-date quantification of the dose-response association between cigarette smoking and gastric cancer (GC) risk, overall and by subsite. We conducted a systematic review and meta-analysis of case-control and cohort studies on the association between cigarette smoking and GC risk published up to January 2023. We estimated pooled relative risks (RR) of GC and its subsites according to smoking status, intensity, duration, and time since quitting. Among 271 eligible articles, 205 original studies were included in this meta-analysis. Compared with never smokers, the pooled RR for GC was 1.53 (95% confidence interval; CI 1.44-1.62; n = 92) for current and 1.30 (95% CI 1.23-1.37; n = 82) for former smokers. The RR for current compared with never smokers was 2.08 (95% CI 1.66-2.61; n = 21) for gastric cardia and 1.48 (95% CI 1.33-1.66; n = 8) for distal stomach cancer. GC risk nonlinearly increased with smoking intensity up to 20 cigarettes/day (RR:1.69; 95% CI 1.55-1.84) and levelled thereafter. GC risk significantly increased linearly with increasing smoking duration (RR: 1.31; 95% CI 1.25-1.37 for 20 years) and significantly decreased linearly with increasing time since quitting (RR: 0.65; 95% CI 0.44-0.95 for 30 years since cessation). The present meta-analysis confirms that cigarette smoking is an independent risk factor for GC, particularly for gastric cardia. GC risk increases with a low number of cigarettes up to 20 cigarettes/day and increases in a dose-dependent manner with smoking duration.