Germana Montesi

Prevention of medication errors: detection and audit

1. Medication errors have important implications for patient safety, and their identification is a main target in improving clinical practice errors, in order to prevent adverse events. 2. Error detection is the first crucial step. Approaches to this are likely to be different in research and routine care, and the most suitable must be chosen according to the setting. 3. The major methods for detecting medication errors and associated adverse drug-related events are chart review, computerized monitoring, administrative databases, and claims data, using direct observation, incident reporting, and patient monitoring. All of these methods have both advantages and limitations. 4. Reporting discloses medication errors, can trigger warnings, and encourages the diffusion of a culture of safe practice. Combining and comparing data from various and encourages the diffusion of a culture of safe practice sources increases the reliability of the system. 5. Error prevention can be planned by means of retroactive and proactive tools, such as audit and Failure Mode, Effect, and Criticality Analysis (FMECA). Audit is also an educational activity, which promotes high-quality care; it should be carried out regularly. In an audit cycle we can compare what is actually done against reference standards and put in place corrective actions to improve the performances of individuals and systems. 6. Patient safety must be the first aim in every setting, in order to build safer systems, learning from errors and reducing the human and fiscal costs.

Intralymphocyte free magnesium in patients with primary aldosteronism: aldosterone and lymphocyte magnesium homeostasis.

It is known that hyperaldosteronism has been associated with magnesium deficiency, yet there are no data on the intracellular concentration of ionized magnesium ([Mg(2+)(i)]) in subjects with primary aldosteronism (PA). We measured intralymphocyte free magnesium ([Mg(2+)(i)]) and intralymphocyte free calcium ([Ca(2+)(i)]) in 16 patients with PA and 26 normotensive control subjects (NCs). [Mg(2+)(i)] and [Ca(2+)(i)] were also measured in blood lymphocytes incubated in vitro with aldosterone, according to a fluorimetric method. In subjects with PA, [Mg(2+)(i)] was significantly lower than that in NCs (mean+/-SD; PA 203+/-56 micromol/L, NCs 291+/-43 micromol/L, 95% confidence interval 57 to 119, P=0.001). In the patients, [Ca(2+)(i)] did not prove to be statistically different from that of NCs (mean+/-SD; PA 47.2+/-10.6 nmol/L, NCs 53.2+/-11 nmol/L). The lymphocytes exposed to the action of aldosterone showed a significant reduction in [Mg(2+)(i)] (n=15, NCs 271+/-28 micromol/L, aldosterone treatment 188+/-39 micromol/L, P=0.001, 95% confidence interval 57 to 108). The dose-effect curve of aldosterone on [Mg(2+)(i)] showed an EC(50) value of approximately 0.5 to 1 nmol/L aldosterone. The reduction in [Mg(2+)(i)] mediated by aldosterone is antagonized by the receptor inhibitor of aldosterone; it is inhibited by inhibitors of protein synthesis and is not measurable when the lymphocytes are incubated in an Na(+)-free medium. The data are consistent with the hypothesis that aldosterone affects the cellular homeostasis of magnesium, probably through modification of the activity of the Na(+)-Mg(2+) antiporter.

Erythrocyte Na(+)-H+ exchange activity in essential hypertensive and obese patients: role of excess body weight.

Introduction: Several authors have described increased Na + — H + exchanger activity in essential hypertension, and an increase in activity of this transport system has also been postulated in situations of hyperinsulinism, such as obesity and essential hypertension Methods: We measured Na + — H + exchanger activity in a group of 37 subjects with essential hypertension (18 obese, 19 non-obese), in a group of nine normotensive obese subjects and in a control group of 16 healthy volunteers. Plasma insulin and glucose values during an oral glucose tolerance test were evaluated, together with other variables such as plasma aldosterone, plasma renin activity and plasma potassium Results: Na+—H+ exchanger system activity did not appear to be abnormally raised in the hypertensive subjects, but was significantly increased in the normotensive obese group. Upon dividing the hypertensive subjects into two subgroups on the basis of body mass index, it was noted that, whereas the non-obese hypertensives showed Na+—H + exchanger activity patterns similar to those in controls, the obese hypertensive subjects exhibited increased activity of the transport system. Na+—H + activity correlates with body mass index and shows a significant inverse correlation with plasma potassium. No correlations were found between Na + — H + exchanger activity and the sum of plasma insulin values during the oral glucose tolerance test Conclusion: Na + — H + exchanger overactivity appears to be characteristic in overweight subjects, but would not appear to be a specific feature of essential hypertension. The increased Na + — H + exchanger activity observed in obese subjects may be postulated to be related to the hypermineralocorticoidism characteristic of this condition

Collagen I and III mRNA gene expression and cell growth potential of skin fibroblasts in patients with essential hypertension

Objectives Despite the claimed disregulation of extracellular matrix synthesis and the increased proliferation rate of different cell types in experimental models of hypertension, very few data are available on collagen synthesis and the proliferation rate of fibroblasts in essential hypertensive patients. Design We measured collagen I, collagen III, histone H3 mRNA gene expression, collagen protein concentration and thymidine incorporation in fibroblasts from 17 essential hypertensive patients (EH) and 13 healthy normotensive control subjects (NC). Methods A Northern blot analysis was performed on fibroblasts in culture obtained from skin biopsies. Collagen protein concentration and DNA synthesis were measured by means of incorporation of tritiated proline and tritiated thymidine, respectively. Results In cultivated fibroblasts from hypertensives, the expression of collagen III mRNA after addition of fetal calf serum was significantly increased in comparison with that of normotensive-derived cells. After addition of fetal calf serum, collagen protein was statistically increased in cultures from EH patients as compared to NC. In hypertensives, the expression of histone H3 mRNA as well as tritiated thymidine incorporation were both increased as compared to normotensives. Conclusions Our data suggest that cultivated fibroblasts from essential hypertensive patients are characterized by an increased expression of type III collagen mRNA and collagen protein synthesis in response to fetal serum, as compared to normotensive-derived cells. Cells from hypertensives are characterized by an increased rate of proliferation after addition of fetal serum, as ascertained by increased thymidine incorporation and increased histone H3 mRNA gene expression, as compared to normotensive-derived cells. This phenotype could be genetically determined and may have an important role in the pathogenesis of essential hypertension.

Intralymphocyte Free Magnesium in a Group of Subjects With Essential Hypertension

Despite the importance of magnesium in essential hypertension, few data are available on the ionized intracellular concentration of this ion. We therefore studied intralymphocyte free intracellular magnesium (Mgi) in 32 untreated essential hypertensive subjects and 27 normotensive control subjects by means of a fluorimetric technique based on the use of the new magnesium-sensitive dye furaptra. We also measured intralymphocyte ionized calcium (Cai) with fura 2. No statistically significant differences were found in Mgi in hypertensive compared with normotensive subjects (essential hypertensive, 0.291 +/- 0.053 mmol/L; normotensive, 0.293 +/- 0.043 [mean +/- SD]). A statistically significant inverse correlation was established between Mgi and plasma triglycerides in essential hypertensive subjects (r = -.521, P = .002). The hypertensive group was arbitrarily divided into two subgroups according to plasma triglyceride levels (> 2 [n = 10] or < 2 mmol/L [n = 22]), and Mgi proved to be significantly lower in the subgroup with high plasma triglyceride levels compared with either the subgroup with normal triglycerides (P = .009; 95% confidence interval, 0.013-0.088) or the normotensive control group as a whole (P = .03; 95% confidence interval, 0.003-0.069) (high-triglyceride hypertensive subgroup, Mgi = 0.256 +/- 0.045 mmol/L; normal-triglyceride hypertensive subgroup, Mgi = 0.307 +/- 0.049). No statistically significant differences were found in Cai in hypertensive compared with normotensive subjects (hypertensive, 53 +/- 12 nmol/L; normotensive, 54 +/- 14). We did not find statistically significant correlations between Cai and plasma triglycerides, nor did we find any differences in Cai between the subgroup of hypertensive subjects with high plasma triglyceride levels and either the subgroup of hypertensive subjects with normal triglycerides or the normotensive control group as a whole. The discrepancies between our results in lymphocytes and data relating to either erythrocytes or platelets emphasize the need for caution before the results are extrapolated from one tissue to the other. The decreased Mgi levels in the subgroup of high-triglyceride hypertensive subjects may suggest a role for magnesium in plurimetabolic syndrome.

Comparative Efficacy of Ketanserin and Pentoxiphylline in Treatment of Raynaud's Phenomenon

In a randomized, placebo-controlled, crossover study, 15 ambulatory pa tients with Raynauds phenomenon, treated for three weeks with ketanserin 80 mg/day and pentoxiphylline 1,200 mg/day, were evaluated by subjective symp tom scores, daily frequency and duration of attacks, and photoplethysmog raphy, at room temperature and after cold test. Reduced subjective symptoms and duration of attacks, together with improved cold test plethysmography, were significant only after ketanserin. All subjective symptom scores also im proved after ketanserin but only for cyanosis and paresthesia after pentoxiphyl line. Excellent results were obtained in 4 cases after ketanserin and in 1 case with pentoxiphylline. The authors discuss the greater importance of antivaso spastic action over antiaggregating and hemorheologic effects in Raynauds phenomenon therapy, as well as the pathogenetic role of serotonin.

Catecholamine-induced regulation in vitro and ex vivo of intralymphocyte ionized magnesium.

Despite the importance of the adrenergic activity and of the metabolism of magnesium in some important cardiovascular pathologies, very little is known about how intracellular ionized magnesium (Mgi2+) is regulated by catecholamines. We made an in-vitro study of the variations in the concentration of ionized magnesium in human lymphocytes using the fluorescent probe furaptra in response to different catecholamines. We also made an ex-vivo study of the changes in intracellular ionized magnesium in lymphocytes in 20 subjects with essential arterial hypertension, 10 treated with 120 mg/d of propranolol and 10 with placebo. Norepinephrine and isoproterenol significantly decrease Mgi2+ and this effect is blocked by β-blockers but not by α-blockers. The EC50 of the effect of norepinephrine is within the range of concentrations physiologically present in plasma. The substitution of extracellular sodium with choline blocks the decrease in intracellular ionized magnesium induced by norepinephrine, which leads us to suppose that the magnesium-reducing effect of catecholamines is a result of the activation of a Na+-Mg2+ exchanger. We were not able to demonstrate any change in intracellular ionized magnesium after 1 and 17 days of active treatment in essential hypertensives. The impossibility of demonstrating ex vivo the mechanism of catecholamine-mediated regulation that is evident in vitro is perhaps due to our experimental conditions or to substances which in vivo inhibit the action of the catecholamines on magnesium, such as insulin and/or glucose.

Efficacy of Ketanserin in the Therapy of Raynaud's Phenomenon: Thermometric Data

After a two-week washout (WO) period with placebo 1 capsule/ bid, 12 patients suffering from stable Raynauds phenomenon were treated with ketanserin (K) 40 mg/ bid for fifteen days. Blood pressure, heart rate, and laboratory parameters were evaluated at the end of each period. Patients used diary cards to record the number, duration, and intensity of attacks. Computerized thermometry of the fingers was evaluated at basal temperature after acclimatization, 23°C for thirty minutes; after cold test, 10°C for five minutes; and after thermal recovery, 23°C for eighteen minutes. Results were analyzed statistically by use of Students t-test for paired data (p<0.05). No marked changes were observed in the symptoms of the attacks, but K proved effective in significantly reducing the number and duration of daily attacks and in promoting their spontaneous regression. Thermometry revealed a parallel increase in temperatures, particularly basal and recovery values. The data suggest increased flow and decreased vasospasm following 5-HT2 receptor blockade.

Intralymphocyte free magnesium and plasma triglycerides

To evaluate the relative effect of hypertension and plasma triglycerides on intralymphocyte magnesium we measured ionized intralymphocyte magnesium (Mg(i)) concentration by means of a fluorimetric method based on the dye Furaptra in 4 groups of subjects: 18 normotensive normotriglyceridemic controls (NTNC), 9 hypertriglyceridemic normotensive patients (HTN), 8 hypertriglyceridemic essential hypertensive patients (HTEH), 17 normotriglyceridemic essential hypertensive patients (NTEH). Hypercholesterolemic, diabetic patients and alcoholics were excluded from the study. Mg(i) was found to be statistically reduced (ANOVA test F=10.41, P=0.0001) in both HTN and HTEH (M+/- SD, HTN: 0.235 +/- 0.01, HTEH: 0.236 +/- 0.01 mmol/l) as compared to both NTNC and NTEH (M +/- SD, NTNC: 0.294 +/- 0.008, NTEH: 0.297 +/- 0.009 mmol/l). A statistically significant negative correlation was found in the population as a whole between Mg(i) and plasma triglycerides (n=52, R= -541, P=0.00004). Our data suggest that hypertriglyceridemia per se and possibly the so-called plurimetabolic syndrome is characterized by low intralymphocyte free magnesium.

Effects of long-term nicardipine treatment on hemodynamics of large arteries in essential hypertension

SummaryThe effects of the calcium-entry blocker nicardipine on brachial hemodynamics were studied in 22 patients (18 male, 4 female) with essential hypertension, who were treated with 20 mg tid for 1 year. Compliance, characteristic impedance, vascular resistances, and tangential tension were measured before treatment and after 1, 3, and 12 months of treatment by an automatic recording from a B-mode, high-resolution, real-time scanner and pulsed Doppler velocimetry for the calculation of the flow volume. We observed statistically significant variations in compliance and impedance after 1 month (3.21±0.59 dyn−1 cm4 10−7 vs. 1.26±0.16 dyn−1 cm4 10−7 and 50.6±4.7 dyn s cm−5102 vs. 91.4 ±7.3 dyn s cm−5 102, respectively; mean±SEM; p<0.001), while tangential tension was significantly reduced after only 3 months (23.2±2.2 mmHg vs. 25.4±2.3 mmHg cm; p<0.05). The correlation between variations in mean blood pressure and in the hemodynamic parameters studied remained statistically significant throughout the study. Nicardipine improved the parameters of large-artery hemodynamics that favor a normal systolic pulse.