a possible role for hydrochlorothiazide hctz as enhancer of zofenopril activity at the tissue level

Background: Combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and a thiazide diuretic has proven to be effective in the treatment of hypertension with or without end-organ damage. Discussion: The mechanism of action of such a combination therapy may involve a opposite effect on the renin-angiotensinaldosterone system (RAAS) with possible "functional" synergistic effects. Indeed, while diuretics can initially reduce intravascular volume leading to an activation of the RAA system with consequent vasoconstriction and salt and water retention, the concomitant presence of an ACE inhibitor may prevent such a counterregulatory response on neurohumoral system. This creates the conditions for the achievement of a maximal antihypertensive effect for both the ACE inhibitor and the diuretic. In recent years, however, experimental evidence has suggested that in addition to the above described mechanism of action, which is common to all the combinations of ACE-inhibitors and diuretics, it can be possible to identify some additional and peculiar mechanisms involving some selected drugs. Such additional mechanisms would be essentially related to some differences in the pharmacokinetic profiles of ACE inhibitors. In particular, the extent of lipophilicity could play an important role in membrane penetration and tissue accumulation and has been correlated with the overall ACE-inibitory activity of various compounds, eg., tissue ACE inhibitory activity could increase with the increase of lipophilicity. For instance, in rats with myocardial infarction, volume depletion induced by concomitant administration of HCTZ can increase the tissue levels of zofenoprilat (the active metabolite of zofenopril, an highly lipophilic ACE inhibitor), but not those of the highly hydrophilic lisinopril. An interesting hypothesis is that associating HCTZ to a highly lipophilic ACE inhibitor translates into peculiar clinical profiles, therefore we suggest further studies on this matter. Conclusion: Experimental models have shown that hydrochlorothiazide (HCTZ) could act like a "tissue levels enhancer" of lipophilic ACE-inhibitors, eg., can increase tissue concentrations of zofenoprilat (active metabolite of zofenopril, an highly lipophilic compound), and consequently induce an enhancement of its tissue ACE inhibition. On the basis of available experimental data, we suggest a peculiar interaction between zofenopril and HCTZ, i.e., HCTZ could act as a "tissue levels enhancer" of zofenopril. This hypothesis, if confirmed, could imply a relevant therapeutic advantage for the treatment of arterial hypertension

Attitudes, knowledge and Practices of Nurses towards HIV/AIDS Patients. An Observational, Cross Sectional, Multicenter study

Background. Attitudes, knowledge and practices of nurses towards HIV/AIDS patients are of continuous interest, especially in developing countries. However, in Italy, this topic is still scarcely debated. Materials and methods. An observational, cross sectional, multicentre study was conducted on a sample of 144 nurses in two Italian Hospitals of the Puglia Region ("Vito Fazzi" Hospital in Lecce and "San Giuseppe da Copertino" Hospital in Copertino (Le)). Results. A large part of the sample (97.2%, n=140) stated that they never refused to take care of a patient with AIDS. Only 22.9%, (n=33), of the sample had attended a training course and almost half (63.2%, n=91) used the gloves regularly when performing blood samples or when administering therapy to patients. With regard to the assessment of HIV knowledge, the percentage of nurses who know the meaning of the terms " seropositive" (83.3%, n=120), "HIV-positive person" (91.7%, n=132) and "window period" (47.9%, n=69) decreased. Conclusions. The results of the study show that a non-negligible percentage of nurses could be considered at risk of infection due to non-routine use of gloves, incorrect handling of the patient's biological samples and not knowing how to decontaminate a surface with potentially infected blood

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Hyperuricemia and cardiovascular disease risk

Uric acid (UA) is the final end product of purine catabolism and is formed from xanthines and hypoxanthines. Hyperuricemia can be secondary to either an exaggerated production of UA that follows high cellular turnover conditions or, most frequently, to a low renal excretion in patients with impaired renal function. Recent data suggest that serum UA (SUA) at high–normal level is associated with cardiovascular disease risk factors and cardiovascular disease, often being a predictor of incident events. Preliminary data suggest that the reduction of SUA level in subjects with normal–high SUA could prevent at least a part of target-organ damage related to high SUA, especially when xanthine oxidase is selectively inhibited

Prevalence of proximal ascending aorta and target organ damage in hypertensive patients: the multicentric ARGO-SIIA project (Aortic RemodellinG in hypertensiOn of the Italian Society of Hypertension)

The aim of this study was to assess the prevalence of ascending aortic dilatation and to evaluate the possible association between proximal aorta dilatation and structural or functional markers of cardiac organ damage in hypertensive patients