Analysis of Italian regulations on pathways of care for patients in a vegetative or minimally conscious state.

Different rehabilitation models for persons diagnosed with disorders of consciousness have been proposed in Europe during the last decade. In Italy, the Ministry of Health has defined a national healthcare model, although, to date, there is a lack of information on how this has been implemented at regional level. The INCARICO project collected information on different regional regulations, analysing ethical aspects and mapping care facilities (numbers of beds and medical units) in eleven regional territories. The researchers found a total of 106 laws; differences emerged both between regions and versus the national model, showing that patients with the same diagnosis may follow different pathways of care. An ongoing cultural shift from a treatment-oriented medical approach towards a care-oriented integrated biopsychosocial approach was found in all the welfare and healthcare systems analysed. Future studies are needed to explore the relationship between healthcare systems and the quality of services provided.

Assessment of human herpesvirus-6 infection in mesenchymal stromal cells ex vivo expanded for clinical use.

Infection or reactivation of human herpesvirus (HHV)-6 represents a potentially serious complication (often involving the central nervous system) in patients receiving either solid organ or hematopoietic stem cell transplantation. The objective of this study was to assess the risk of HHV-6 infection/reactivation in mesenchymal stromal cells (MSCs). MSCs are multipotent cells displaying immunomodulatory properties that have been already successfully used in the clinical setting to enhance hematopoietic stem cell engraftment and to treat steroid-refractory acute graft-versus-host disease. We analyzed 20 samples of ex vivo expanded MSCs, at different passages of culture, isolated both from bone marrow and from umbilical cord blood. Through Western blotting and immunocytochemistry techniques, we investigated the presence of the HHV-6 receptor (CD46) on cell surface, whereas the presence of HHV-6 DNA was evaluated by nested polymerase chain reaction assay. All of the MSC samples tested were positive for the virus receptor (CD46), suggesting their potential susceptibility to HHV-6. However, none of the MSC samples derived from cultures, performed in the perspective of clinical use, was found to harbor HHV-6. This preliminary observation on a consistent number of MSC samples, some of them tested at late in vitro passages, indicates a good safety profile of the product in terms of HHV-6 contamination. Nevertheless, it remains important to set up in vitro experimental models to study MSCs' susceptibility to HHV-6 (and HHV-7) infection, to verify their capacity to integrate the virus into cellular DNA, and to investigate which experimental conditions are able to induce virus reactivation.

Left ventricular and carotid structure in untreated, uncomplicated essential hypertension: results from the Assessment Prognostic Risk Observational Survey (APROS).

The impact of hypertension on left ventricular (LV) and vascular structure and the relation of left ventricular hypertrophy (LVH) with vascular changes in untreated essential hypertensives has not been fully explored. This study investigated the prevalence of structural abnormalities of LV and carotid arteries and their determinants in a large population of untreated, uncomplicated essential hypertensive patients. The Assessment of Prognostic Risk Observational Survey was a multicentre (44 centres) prospective study including 1142 untreated hypertensives classified as low or medium cardiovascular risk on the basis of the routine diagnostic work-up recommended by the 1999 World Health Organization/International Society of Hypertension guidelines. All patients underwent ultrasound examinations of the heart and carotid arteries. LVH and carotid structural changes were diagnosed when: (1) LV mass index exceeded 125 g/m(2) in men and 110 g/m(2) in women; (2) there was at least one plaque (focal thickening>1.3 mm) in any segment of either carotid artery or a diffuse common carotid intima-media thickness (IMT) (average of IMT>/=0.8 mm) was present. Overall, 1074 patients (504 women, mean age 48.1+/-11.4 years) completed the study with ultrasonographic examinations of good technical quality. The prevalences of LVH and LV concentric remodelling in the total population were 26.8 and 10.7%, respectively. Eccentric hypertrophy was more prevalent than concentric hypertrophy (15.2 vs 11.6%). One or more carotid plaques or thickening were present in 27.4% of the patients. A stepwise increase in IM thickness occurred from the lowest values in patients with normal cardiac mass and geometry (0.68 mm) to intermediate in those with LV remodelling (0.76 mm) and eccentric LVH (0.81 mm) and to the highest level in patients with concentric LVH (0.87 mm). Patients with LV concentric remodelling and concentric LVH had a significantly greater relative carotid wall thickness than those with normal geometry and eccentric LVH (0.25 and 0.26 vs 0.18 and 0.19, respectively, P<0.01). According to a multivariate analysis age, blood glucose, systolic BP and pulse pressure were the main independent predictors of LVH, while age, systolic BP and total cholesterol were the variables with the greatest impact on IM thickening. To conclude, this study shows that: (1) altered patterns of LV structure and geometry and carotid structural changes occur in a large fraction of patients with untreated essential hypertension; (2) there is a significant association between carotid wall thickening and LVH; (3) the probability of LVH or carotid thickening is significantly greater in elderly, in patients with higher systolic BP and in patients with associated metabolic risk factors.

Optimizing the assessment of the elderly patient with borderline hypertension: the Hypertension and Ambulatory Recording in the OLD (HAROLD) study.

This article describes the objectives and protocol of the HAROLD study, a trial designed to assess whether home blood pressure (BP), 24-hour ambulatory BP, left ventricular structure and function, and albumin excretion rate are more accurate predictors of outcome than traditional sphygmomanometric BP in elderly subjects with borderline hypertension. Development of sustained hypertension (BP > or = 160/95 mmHg) and incidence of morbid events over a 5-year follow-up are considered soft and hard endpoints, respectively. Patients with blood pressure values between 140/90 and 159/94 mmHg after three months of observation and who have never been treated, are eligible for the study; these subjects must be 60 to 79 years old, and free from other important risk factors for atherosclerosis. Baseline exams, which include plasma renin and insulin, 24-hour urine collection for detection of microalbuminuria, and echo-doppler cardiac examination are repeated after three and five years follow-up, or when subjects develop sustained hypertension. To recruit a large enough number of subjects to allow a sufficient number of endpoints (over 1000 subjects), the study is conducted as a multicenter trial. Ninety Italian Hospital Centers have agreed to participate in the study.

Hypertension, coronary artery and cerebrovascular diseases in the population. Has epidemiology changed in the last decades?

Life expectancy has significantly increased in the last decades in many western populations, due to the fall of total and cardiovascular death rate. However, morbidity from cardiovascular diseases has decreased to a smaller extent. The overall population risk profile has improved, but it is still unsatisfactory. This is true for blood pressure control (with only 20% of hypertensive patients achieving normotension with antihypertensive drugs), hypercholesterolemia (with borderline-high serum cholesterol levels in 50% of the population), and smoking habits. Other potential causes of the poor cardiovascular prevention are: 1) a limited knowledge of the optimal blood pressure goal with antihypertensive treatment, 2) scanty information on the long term effects of antihypertensive drugs on cerebral and coronary circulation. Finally, little is being done to improve primary prevention in youth, when the slowly progressing atherosclerotic plaque formation is already on the way. To improve the cost / effectiveness of cardiovascular prevention, efforts must concentrate on the early identification of the subjects at the highest risk and on health promotion among youngsters. Large epidemiological trials conducted from the early 50s have provided convincing evidence of the multifactorial origin of cardiovascular diseases and encouraged the implementation of population based primary and secondary preventive measures, including antihypertensive treatment, as well as dietary and life-style modifications. It is now time to start asking ourselves whether or not we are satisfied with the results obtained in terms of reduced morbidity and mortality, whether these results are the direct consequence of these measures and whether or not we can do even better. The present work reviews some of the most recent comparative reports on the epidemiology of cardiovascular diseases in different populations, and some intervention trials to answer these questions and to help in identifying the most cost-effective approach to cardiovascular disease prevention in the next few years.

[The cost/benefit of antihypertensive therapy]. / Costo/beneficio della terapia antipertensiva.

The prevalence of arterial hypertension is very high in the general population, ranging from 10% in people between 20 and 30 years of age to more than 50% in the elderly. However the great majority of hypertensive subjects belong to the mild hypertension range and are at relatively low risk for cerebrovascular and cardiac events. As it is impossible at the present time to identify subjects who are particularly inclined to develop complications, all hypertensives are put under treatment in the attempt to avoid a few events in a very vast population. This implies that enormous health care resources have to be allocated. In the present article a number of economic evaluation techniques of hypertension are reviewed with special focus on methods combining quantity and quality of life.

Ambulatory blood pressure monitoring in the assessment of antihypertensive treatment: 24-h blood pressure control with lacidipine once a day.

Ambulatory blood pressure monitoring gives a more representative blood pressure profile than office blood pressure measurements and is free of any placebo effect. It is therefore useful for studying the effect of antihypertensive agents. Although ambulatory blood pressure is less variable than office blood pressure, spontaneous fluctuations have been found in whole-day blood pressure when repeated measurements are taken. In the multicentre Triveneto Study, the mean difference between 24-h blood pressure recordings taken 3 months apart in 85 mild hypertensives was -0.1/-0.7 mmHg and the coefficient of repeatability (2 s.d.) was 17.3/12.6 mmHg. The corresponding values for office blood pressure were -8.7/-2.0 and 29.8/16.5 mmHg, respectively. This reduction in inter-measurement variability with ambulatory blood pressure monitoring makes it possible to reduce the sample size required to prove the effect of an antihypertensive agent in pharmacological trials. However, in the individual subject, the results of ambulatory blood pressure monitoring should be considered with caution, as 24-h blood pressure averages and profiles are subject to a degree of variability. This technique was used in 21 mild-to-moderate hypertensives to test the antihypertensive effect of lacidipine given once a day (4-6 mg) versus placebo. The drug proved effective throughout the day and night, showing a 24-h effect on blood pressure without reflex tachycardia or other intolerable side effects.