Evidence-based polytherapies and long-term mortality after acute myocardial infarction in very old subjects compared with elderly and adults: a nested case-control study

Background: Clinical trials have demonstrated that selected secondary prevention medications for patients after acute myocardial infarction (AMI) reduce mortality. Yet, these medications are generally underprescribed in daily practice, and older people are often absent from drug trials. Objectives: To examine the relationship between adherence to evidence-based (EB) drugs and post-AMI mortality, focusing on the effects of single therapy and polytherapy in very old patients (≥80 years) compared with elderly and adults (<80 years). Methods: Patients hospitalised for AMI between 01/01/2008 and 30/06/2011 and resident in the Local Health Authority of Bologna were followed up until 31/12/2011. Medication adherence was calculated as the proportion of days covered for filled prescriptions of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), β-blockers, antiplatelet drugs, and statins. We adopted a risk set sampling method, and the adjusted relationship between medication adherence (PDC≥75%) and mortality was investigated using conditional multiple logistic regression. Results: The study population comprised 4861 patients. During a median follow-up of 2.8 years, 1116 deaths (23.0%) were observed. Adherence to the 4 EB drugs was 7.1%, while nonadherence to any of the drugs was 19.7%. For both patients aged ≥80 years and those aged <80 years, rate ratios of death linearly decreased as the number of EB drugs taken increased. There was a significant inverse relationship between adherence to each of 4 medications and mortality, although its magnitude was higher for ACEIs/ARBs (adj. rate ratio=0.60, 95%CI=0.52–0.69) and statins (0.60, 0.50–0.72), and lower for β-blockers (0.75, 0.61–0.92) and antiplatelet drugs (0.73, 0.63–0.84). Conclusions: The beneficial effect of EB polytherapy on long-term mortality following AMI is evident also in nontrial older populations. Given that adherence to combination therapies is largely suboptimal, the implementation of strategies and initiatives to increase the use of post-AMI secondary preventive medications in old patients is crucial.

Psychiatric comorbidity, Restless Legs Syndrome and Nocturnal Eating Disorder: a case-control study

Objective: to evaluate the psychopathological profile in primary Restless Legs Syndrome (p-RLS) patients with and without nocturnal eating disorder (NED), analysing obsessive-compulsive traits, mood and anxiety disorder, and the two domains of personality proposed by Cloninger, temperament and character. Methods: we tested ten p-RLS patients without NED, ten p-RLS patients with NED and ten healthy control subjects, age and sex-matched, using Hamilton Depression and Anxiety Rating Scales, State-Trait Anxiety Inventory, Maudsley Obsessive Compulsive Inventory (MOCI) and Temperament and Character Inventory - revised (TCI). Results: p-RLS patients, particularly those with NED, had increased anxiety factor scores. MOCI-total, doubting and checking compulsion, and TCI-harm avoidance scores were significantly higher in p-RLS patients with NED. p-RLS patients without NED had significantly higher MOCI-doubting scores and a trend toward higher checking compulsion and harm avoidance scores with an apparent grading from controls to p-RLS patients without NED to p-RLS with NED. Conclusions: higher harm avoidance might predispose to display obsessive-compulsive symptoms, RLS and then, with increasing severity, compulsive nocturnal eating. RLS and NED could represent a pathological continuum in which a dysfunction in the limbic system, possibly driven by a dopaminergic dysfunction, could be the underlying pathophysiological mechanism.

Antiepileptic drugs and pregnancy. Population based pharmaco-epidemiological study on prescription patterns, pregnancy outcome and foetal health

Aims of the study: To assess the prevalence of Antiepileptic Drug (AED) exposure in pregnant women with or without epilepsy and the comparative risk of terminations of pregnancy (TOPs), spontaneous abortions, stillbirth, major congenital malformations (MCMs) and foetal growth retardation (FGR) following intrauterine AED exposure in the Emilia Romagna region (RER), Northern Italy (4 million inhabitants). Methods: Data were obtained from official regional registries: Certificate of Delivery Assistance, Hospital Discharge Card, reimbursed prescription databases and Registry of Congenital Malformations. We identified all the deliveries, hospitalized abortions and MCMs occurred between January 2009 and December 2011. Results: We identified 145,243 pregnancies: 111,284 deliveries (112,845 live births and 279 stillbirths), 16408 spontaneous abortions and 17551 TOPs. Six hundred and eleven pregnancies (0.42% 95% Cl: 0.39-0.46) were exposed to AEDs. Twenty-one per cent of pregnancies ended in TOP in the AED group vs 12% in the non-exposed (OR:2.24; CI 1.41-3.56). The rate of spontaneous abortions and stillbirth was comparable in the two groups. Three hundred fifty-three babies (0.31%, 95% CI: 0.28-0.35) were exposed to AEDs during the first trimester. The rate of MCMs was 2.3% in the AED group (2.2% in babies exposed to monotherapy and 3.1% in babies exposed to polytherapy) vs 2.0% in the non-exposed. The risk of FGR was 12.7 % in the exposed group compared to 10% in the non-exposed. Discussion and Conclusion: The prevalence of AED exposure in pregnancy in the RER was 0.42%. The rate of MCMs in children exposed to AEDs in utero was almost superimposable to the one of the non-exposed, however polytherapy carried a slightly increased risk . The rate of TOPs was significantly higher in the exposed women. Further studies are needed to clarify whether this high rate reflects a higher rate of MCMs detected prenatally or other more elusive reasons.

Determinants of cesarean delivery, a population-based study in the Emilia Romagna Region

Cesarean Delivery (CD) rates are rising in many parts of the world. In order to define strategies to reduce them, it is important to explore the role of clinical and organizational factors. This thesis has the objective to describe the contemporary CD practice and study clinical and organizational variables as determinants of CD in all women who gave birth between 2005 and June 2010 in the Emilia Romagna region (Italy). All hospital discharge abstracts of women who delivered between 2005 and mid 2010 in the region were selected and linked with birth certificates. In addition to descriptive statistics, in order to study the role of clinical and organizational variables (teaching or non-teaching hospital, birth volumes, time and day of delivery) multilevel Poisson regression models and a classification tree were used. A substantial inter-hospital variability in CD rate was found, and this was only partially explained by the considered variables. The most important risk factors of CD were: previous CD (RR 4,95; 95%CI: 4,85-5,05), cord prolapse (RR 3,51; 95% CI:2,96-4,16), and malposition/malpresentation (RR 2,72; 95%CI: 2,66-2,77). Delivery between 7 pm and 7 am and during non working days protect against CD in all subgroups including those with a small number of elective CDs while delivery at a teaching hospital and birth volumes were not statistically significant risk factors. The classification tree shows that previous CD and malposition/malpresentation are the most important variables discriminating between high and low risk of CD. These results indicate that other not considered factors might explain CD variability and do not provide clear evidence that small hospitals have a poor performance in terms of CD rate. Some strategies to reduce CD could be found by focusing on the differences in delivery practice between day and night and between working and no-working day deliveries.

Maternal Smoking Impact on the Delivery Cost: a population-based study in the Emilia-Romagna region

This doctoral thesis is devoted to the study of the causal effects of the maternal smoking on the delivery cost. The interest of economic consequences of smoking in pregnancy have been studied fairly extensively in the USA, and very little is known in European context. To identify the causal relation between different maternal smoking status and the delivery cost in the Emilia-Romagna region two distinct methods were used. The first - geometric multidimensional - is mainly based on the multivariate approach and involves computing and testing the global imbalance, classifying cases in order to generate well-matched comparison groups, and then computing treatment effects. The second - structural modelling - refers to a general methodological account of model-building and model-testing. The main idea of this approach is to decompose the global mechanism into sub-mechanisms though a recursive decomposition of a multivariate distribution.

NLGA based Active Control in Aerospace: fault tolerability, disturbance rejection, and parameter estimation

A new control scheme has been presented in this thesis. Based on the NonLinear Geometric Approach, the proposed Active Control System represents a new way to see the reconfigurable controllers for aerospace applications. The presence of the Diagnosis module (providing the estimation of generic signals which, based on the case, can be faults, disturbances or system parameters), mean feature of the depicted Active Control System, is a characteristic shared by three well known control systems: the Active Fault Tolerant Controls, the Indirect Adaptive Controls and the Active Disturbance Rejection Controls. The standard NonLinear Geometric Approach (NLGA) has been accurately investigated and than improved to extend its applicability to more complex models. The standard NLGA procedure has been modified to take account of feasible and estimable sets of unknown signals. Furthermore the application of the Singular Perturbations approximation has led to the solution of Detection and Isolation problems in scenarios too complex to be solved by the standard NLGA. Also the estimation process has been improved, where multiple redundant measuremtent are available, by the introduction of a new algorithm, here called "Least Squares - Sliding Mode". It guarantees optimality, in the sense of the least squares, and finite estimation time, in the sense of the sliding mode. The Active Control System concept has been formalized in two controller: a nonlinear backstepping controller and a nonlinear composite controller. Particularly interesting is the integration, in the controller design, of the estimations coming from the Diagnosis module. Stability proofs are provided for both the control schemes. Finally, different applications in aerospace have been provided to show the applicability and the effectiveness of the proposed NLGA-based Active Control System.