Efficacy, usability and sequence of operations of a workflow-integrated algorithm for basal-bolus insulin therapy in hospitalized type 2 diabetes patients.

AIMS: To evaluate glycaemic control and usability of a workflow-integrated algorithm for basal-bolus insulin therapy in a proof-of-concept study to develop a decision support system in hospitalized patients with type 2 diabetes. METHODS: In this ward-controlled study, 74 type 2 diabetes patients (24 female, age 68 ± 11 years, HbA1c 8.7 ± 2.4% and body mass index 30 ± 7) were assigned to either algorithm-based treatment with a basal-bolus insulin therapy or to standard glycaemic management. Algorithm performance was assessed by continuous glucose monitoring and staff's adherence to algorithm-calculated insulin dose. RESULTS: Average blood glucose levels (mmol/l) in the algorithm group were significantly reduced from 11.3 ± 3.6 (baseline) to 8.2 ± 1.8 (last 24 h) over a period of 7.5 ± 4.6 days (p < 0.001). The algorithm group had a significantly higher percentage of glucose levels in the ranges from 5.6 to 7.8 mmol/l (target range) and 3.9 to 10.0 mmol/l compared with the standard group (33 vs. 23% and 73 vs. 53%, both p < 0.001). Physicians' adherence to the algorithm-calculated total daily insulin dose was 95% and nurses' adherence to inject the algorithm-calculated basal and bolus insulin doses was high (98 and 93%, respectively). In the algorithm group, significantly more glucose values <3.9 mmol/l were detected in the afternoon relative to other times (p < 0.05), a finding mainly related to pronounced morning glucose excursions and requirements for corrective bolus insulin at lunch. CONCLUSIONS: The workflow-integrated algorithm for basal-bolus therapy was effective in establishing glycaemic control and was well accepted by medical staff. Our findings support the implementation of the algorithm in an electronic decision support system.

Mobile phone-based surveillance of cardiac patients at home.

We tested the reliability, acceptability and feasibility of a home-monitoring system for cardiac patients. Each participant was equipped with a mobile phone, an automatic blood pressure device and a digital weight scale. In total, 20 patients (14 patients with chronic heart failure, six patients with hypertension; mean age 50 years, standard deviation [SD] 14) were monitored for 90 days each. They were asked to measure their blood pressure, pulse and body weight every day, and to transfer the data together with the dosage of medication to the telemonitoring server using wireless Internet technology in the mobile phone. The physician in charge received email alerts when reported data fell outside pre-defined limits. The patients' compliance with the system was high. During a cumulative monitoring period of 1,735 days, there were 2,040 data transfer sessions, a mean of 102 per patient (SD 43). The mean percentage of successful data transfers was 83% (SD 22). The stability of the telemonitoring system was 98%, meaning that patient data transfer was almost always possible. The accessibility of the secure web server for physicians was above 99%. The web-based home-monitoring system was reliable and easy to handle for both patients and health care professionals. It may be a useful tool for patients with heart failure as well as hypertensive patients.

Increased neopterin in patients with chronic and acute coronary syndromes.

OBJECTIVES: The aim of our study was to determine neopterin levels in patients with chronic and acute coronary syndromes. BACKGROUND: In chronic and acute coronary syndromes the release of different cytokines activates cellular defense. Infiltration of neutrophils and monocytes/macrophages is detected in the vessel wall as well as in the myocardium. Neopterin, which is a by-product of the guanosine triphosphate-biopterin pathway, is a marker for those activated macrophages. METHODS: We studied 123 subjects: 1) 21 consecutive patients (17 men, 4 women; mean age +/- SD 66 +/- 15 years, range 31 to 87) with acute myocardial infarction (AMI); 2) 62 consecutive patients (50 men, 12 women; mean age 61 +/- 8 years, range 43 to 81) with signs and symptoms of clinically stable coronary artery disease (CAD); and 3) 40 healthy blood donors (28 men, 12 women; mean age 35 +/- 13 years). Neopterin levels were determined with a commercially available enzyme-linked immunosorbent assay method. RESULTS: In patients with AMI before thrombolytic therapy, neopterin levels were significantly higher than levels in patients with CAD and control subjects (13.7 vs. 8.6 and vs. 6.8 nmol/liter, p < 0.0001). Values also differed significantly between patients with CAD and control subjects (p < 0.0001). Neopterin levels in patients with AMI were measured seven times during a 72-h period. Within-group comparison showed significant differences over this period (p < 0.00001). The lowest value (11.4 nmol/liter) was observed after 4 h and differed significantly from the initial value and values after 24 and 72 h (p < 0.05). After 72 h, neopterin increased to 14.9 nmol/liter, a value significantly different from all values other than the initial one. There was no correlation between neopterin and creatine kinase (CK); CK, MB isoenzyme; or lactate dehydrogenase as markers for the extent of the myocardial infarction during the observation period. CONCLUSIONS: Our data support the hypothesis of an activation of monocytes and macrophages in patients with an acute or chronic coronary syndrome. Neopterin as a marker for macrophage activation is significantly increased in patients with chronic CAD and more pronounced in patients with AMI shortly after the onset of symptoms.

Transient reduction of autoantibodies against oxidized LDL in patients with acute myocardial infarction.

Fifteen consecutive patients (mean age 66 +/- 14, range 31-82) with an acute myocardial infarction (MI) suitable for thrombolytic therapy were included in this study. Autoantibodies against oxidized low-density lipoprotein (LDL) were determined by enzyme-linked immunosorbent assay (ELISA). Patients (n = 10) with marked elevation of the MB isoenzyme of creatinine kinase (CK-MB)-mass had significant decreases of oLDL-Ab during the acute phase, with a minimum after 8 h following the onset of thrombolytic therapy (within-group significance: p < .001; between groups: p = .01). Patients (n = 5) with CK-MB-mass values less than 70 ng/ml did not show this phenomenon. Furthermore, significant correlations existed between CK-MB-mass and oLDL-Ab after 6 and 8 h (n = 15; r = .72; p = .003) and the time of the highest CK-MB-mass values (after 12 h) and the time of the maximal decrease of oLDL-Ab (after 8 h) (r = .74; p = .003). Our observations provide further evidence for the release of free radicals and for increased lipid peroxidation during reperfusion after prolonged ischemia. The decrease of oLDL-Ab appears to be a marker for the severity of MI.

Comparison of wrist blood pressure measurement with conventional sphygmomanometry at a cardiology outpatient clinic.

OBJECTIVE: Oscillometric measurement of blood pressure at the wrist is becoming a widely used method for detection of hypertension and its control by treatment. The objective of the present study was to evaluate accuracy and suitability of wrist measurement in a clinical routine setting. PATIENTS AND METHODS: A series of 333 consecutive patients admitted to our cardiology outpatient clinic were included. Blood pressure was measured at both upper arms according to World Health Organization-International Society of Hypertension guidelines. Oscillometric measurement was performed at the contralateral wrist simultaneously. Blood pressure readings were taken by an oscillometric device applied at the wrist ('Klock'; Industrielle Entwicklung Medizintechnik, Stolberg, Germany) and a conventional mercury sphygmomanometer applied at the upper arm. RESULTS: Seventy-eight patients were excluded due to differences in blood pressure > 5 mmHg between both upper arms or due to 'error' messages of the wrist device. The data of the remaining 255 patients (149 males; mean age, 65 +/- 13 years; range, 18-95 years) are presented. Mean conventional blood pressure was significantly lower compared with the wrist device (137 +/- 20/80 +/- 11 mmHg versus 153 +/- 28/87 +/- 18 mmHg; P < 0.001 and P < 0.001). The mean difference was 16 +/- 25/6 +/- 17 mmHg. In clinical terms, differences in blood pressure exceeding +/-20/+/-10 mmHg reflecting classification of hypertension are considered important. Measurements of 101 (40%) patients were within these limits. Systolic readings of 110 (43%) and diastolic readings of 117 patients (46%) were beyond this scope. CONCLUSION: Due to low reliability of wrist blood pressure measurement, it cannot compete with the upper arm standard procedure. If ever, it should only be used if test readings in an individual comparing wrist and upper arm measurement show differences within a range of +/-20/+/-10 mmHg.

Differing beta-blocking effects of carvedilol and metoprolol.

BACKGROUND: Metoprolol is a beta(1)-selective beta-adrenergic antagonist while carvedilol is a non-selective beta-blocker with additional blockades of alpha(1)-adrenoceptors. Administration of metoprolol has been shown to cause up-regulation of beta-adrenoceptor density and to decrease nocturnal melatonin release, whereas carvedilol lacks these typical effects of beta-blocking drugs. AIMS: To compare beta-blocking effects of metoprolol and carvedilol when applied orally in healthy subjects. METHODS: We investigated the effects of single oral doses of clinically recommended amounts of metoprolol (50, 100 and 200 mg) and carvedilol (25, 50 and 100 mg) to those of a placebo in a randomised, double-blind, cross-over study in 12 healthy male volunteers. Two hours after oral administration of the drugs heart rate and blood pressure were measured at rest, after 10 min of exercise, and after 15 min of recovery. RESULTS: Metoprolol tended to decrease heart rate during exercise (-21%, -25% and -24%) to a greater extent than carvedilol (-16%, -16% and -18%). At rest, increasing doses of metoprolol caused decreasing heart rates (62, 60 and 58 beats/min) whereas increasing doses of carvedilol caused increasing heart rates (62, 66 and 69 beats/min), 50 and 100 mg carvedilol failed to differ significantly from the placebo (71 beats/min). CONCLUSIONS: We conclude that clinically recommended doses of carvedilol cause a clinically relevant beta-blockade in humans predominantly during exercise where it appears to be slightly (although not significantly) less effective than metoprolol. On the other hand, the effects of carvedilol on heart rate at rest appear rather weak, particularly in subjects with a low sympathetic tone. This might be caused by a reflex increase on sympathetic drive secondary to peripheral vasodilation resulting from the alpha-blocking effects of the drug. These results might be helpful in explaining why carvedilol, in contrast to metoprolol, may fail to cause up-regulation of beta-adrenoceptor density and does not decrease nocturnal melatonin release. This, in turn, may be a reason for the weak side-effects of carvedilol resulting from the beta-blockade. In addition, our data might be of interest in the interpretation of the forthcoming results of the COMET trial, although it has to be emphasised that they were derived from healthy subjects and, therefore, cannot be directly extrapolated to patients with heart failure.

Parasympathetic receptor blockade and the heart rate performance curve.

Parasympathetic receptor blockade and the heart rate performance curve. Med. Sci Sports Sci., Vol. 30. No. 2, pp. 229-233, 1998. The aim of the present study was to investigate the influence of parasympathetic receptor blockade on the heart rate performance curve (HRPC). Twenty healthy male subjects performed a first cycle ergometer test (F), showing a HRPC deflection of varying degree and direction. Subjects then in random order performed two additional cycle ergometer tests, one with atropine (A) and the other with placebo (P). Two lactate turn points (LTP1, and LTP2) were determined by means of linear regression turn point analysis. The degree and direction of the deflection of the HRPC was calculated mathematically as factor kHR (kHR>0 = downsloping of HPRC; kHR<0 = upsloping of HRPC). In comparison with that in F and P, HR in A was significantly higher at rest, LTP1, LTP2, and during recovery, but not at Power(max). An upsloping deflection of the HRPC was seen in only five cases in F and P, whereas in A 10 cases were observed (P < 0.05). In A, kHR was significantly lower than in F and P. A significant correlation for kHR was found among F, P, and A. Independent from parasympathetic receptor blockade and the HR at Power(max), the HR at LTP2 was lower in cases with negative kHR (upsloping). In A as well as in P a significant correlation was observed between kHR and HR at LTP2. The individual time course of HRPC is reproducible and may be independent of parasympathetic activity.

Change in left atrial and ventricular dimensions during and immediately after exercise.

PURPOSE: The aim of this study was to evaluate differences in the left atrial (LAD), total ventricular end-diastolic (TEDD), end-systolic diameters (TESD), and left ventricular shortening fraction (SF) compared with heart rate (HR) and systolic blood pressure (SBP) during exercise and recovery. METHODS: Healthy young male (N = 15) and female (N = 16) subjects performed an incremental cycle ergometer test in upright position, and three phases of energy supply were defined by means of blood lactate concentration (LA) and respiratory gas exchange variables (I: aerobic; II: aerobic-anaerobic transition; III: anaerobic). Subjects were required to rest their arms on a steering bar and to lean their upper body forward; two dimensional (2-D) echocardiograms were obtained over the left parasternal area at rest (R), at the end of each phase, immediately within 15 s post, and 6 min after exercise (6 min). By using VINGMED's "Anatomical M-Mode," it was possible to extract M-Mode Sweeps from stored 2-D-Loops and perform the M-Mode measurement. RESULTS: In contrast to the significant decrease in TEDD and TESD from III to 15 s up to resting values and the significant increase in SF from III to 15 s, the moderate decrease in HR immediately post exercise (15 s) was not significant. The SBP showed a significantly decrease from III to 15 s; in contrast to TEDD, TESD, and SF, the values at 15 s were comparable with the values at II. For LAD, significant increase during exercise and a decrease during recovery were observed. Sex-specific differences of changes in measured variables could not be found. CONCLUSION: We concluded that post exercise measurement of left ventricular and atrial dimensions or SF were not valid to describe heart function at maximal exercise although immediately post exercise HR was near maximal level.

Left ventricular function in response to the transition from aerobic to anaerobic metabolism.

The purpose of this investigation was to study myocardial function at rest, during three phases of energy supply, and during recovery. Radionuclide angiography was performed during the aerobic phase (phase I, rest-first lactate increase), the aerobic-anaerobic transition phase (phase II, first lactate increase-second lactate increase), the anaerobic phase (phase III, second lactate increase-maximal work performance (Pmax)), and during recovery. Thirty-eight male patients (59 +/- 7 d after myocardial infarction) were compared with 19 healthy control subjects and 21 sport students of comparable age. Left ventricular ejection fraction (LVEF) increased from rest to phase I and from phase I to phase II in sports students and control subjects. During phase III, LVEF did not change significantly in sports students, but it decreased significantly in control subjects. This is in contrast to the patients, who showed an increase of LVEF from resting values (47 +/- 3%) to phase I (50 +/- 1%), no change during phase II (51 +/- 2%), and a decrease to resting values (45 +/- 2) during phase III. All subjects showed an increase in stroke volume (SV) during phase I and II, reaching a maximum at phase II. This was evidenced by an improvement of the systolic function with a constant left ventricular end-diastolic volume (EDV) in control subjects and sports students. In contrast, an improved SV in patients was achieved through an increase in EDV and a less distinct increase in the left ventricular end-systolic volume (ESV). Maximal LVEF values were measured during the first 90 s of recovery in all subjects. Values during recovery are not representative of load dependent myocardial function. This increase in LVEF does not cause an increase in cardiac output but is a consequence of changes in the EDV and ESV, which decrease again immediately after the end of exercise performance.

Long-term outcome and prognostic factors in dilated cardiomyopathy. Preliminary results.

UNLABELLED: To investigate long-term follow-up and identify prognostic factors in patients with dilated cardiomyopathy (DCM) the authors investigated 167 consecutive patients on an outpatient basis. All patients underwent left- and right-heart catheterization; follow-up comprised clinical and echocardiographic investigations. RESULTS: After a mean follow-up period of ninety-three +/- thirty-six months 82 patients (49%; 71 men, 11 women, mean age fifty-five +/- eleven years) were alive. 29 of them (27 men, 2 women, mean age fifty-two +/- nine) showed normal left ventricular ejection fraction (LVEF) after a mean follow-up period of one hundred four +/- forty months. The remaining 53 patients (44 men, 9 women, mean age fifty-six +/- eleven) revealed LVEF similar to that of the first examination. Eighty-five patients died (51%; 73 men, 12 women). Causes of death were the following: progressive heart failure, 24; sudden death, 23; stroke, 3; pulmonary embolism, 2; noncardiac death, 4; unknown causes, 29. The median period from the onset of first symptoms until definite diagnosis was two months in patients with stable conditions, three months in those with normalization of LVEF and twenty-four months in those who died, respectively (P < 0.01). At the time of diagnosis, patients with stable outcome had a mean LVEF (LVEF 1) of 37%, those who returned to normal had 40% (ns). Patients who died had a mean LVEF 1 of 32% and therefore differed significantly from both groups of survivors (P < 0.001). Left ventricular end-diastolic pressure (LVEDP) at the time of diagnosis was highest in patients who died (22 mmHg) and therefore differed significantly from both groups of survivors (normalization: 16 mmHg, stable patients: 18 mmHg, P < 0.001). CONCLUSIONS: According to their results, time until diagnosis, LVEF, and LVEDP are prognostic indicators. No difference was noted between the groups concerning etiology, medical treatment, or functional classification according to the New York Heart Association.

[Thrombolytic therapy of acute myocardial infarct in advanced age (based on 2 case reports)]. / Thrombolytische Therapie des akuten Myokardinfarktes im hohen Alter (anhand von 2 Fallberichten).

The introduction of thrombolysis has reduced the mortality of acute myocardial infarction (MI) by 25%. Large-scale studies have revealed that especially patients over 65 benefit from this therapy. Nevertheless, many centers apply an age limit for thrombolytic therapy due to the higher risk of stroke or bleeding in elderly patients. In 1993 181 patients suffering from acute MI were admitted to the intensive care unit of the University Clinic of Internal Medicine, Graz, and 54 (29.4%) of them were treated with fibrinolytic drugs. In this paper we report on the successful thrombolytic management of acute MI in two male patients (87 and 88 years old) who were treated with 100 mg recombinant tissue-type plasminogen activator complex. As a sign of successful reperfusion a rapid increase in plasma creatinine kinase levels and fast amelioration of the ischemia-related ECG changes were observed. In the follow-up examination after four months the first patients showed only minimal exertional dyspnea and was otherwise well. The second patient died one month after MI following a laparotomy for ileus. We draw the conclusion that patients of advanced age also benefit from thrombolytic treatment of acute myocardial infarction, but the indications and contraindications have to be carefully observed.

A physiological oral magnesium supplement does not influence total serum magnesium, left ventricular ejection fraction and prognosis in patients with dilated cardiomyopathy.

It has been postulated that patients with congestive heart failure (CHF) benefit from physiological oral magnesium supplements. In order to study the effect of such supplements upon patients with idiopathic dilated cardiomyopathy (IDC) we studied a group of 23 patients with the salient characteristics of IDC (18 male, 5 female; mean age 51 +/- 13 years [range: 23-72]; Mg group), who received oral magnesium supplements (15 mmol/day). All patients received oral ACE inhibitors and 22 were receiving digitalis and diuretics. A control group of 27 patients, matched for age, sex, symptoms, and additional treatment (22 male, 5 female; mean age 52 +/- 13 years [range 22-71]) were not given oral magnesium supplements. All these patients also received oral ACE inhibitors, 25 were receiving digitalis, and 23 were receiving diuretics. Mean serum magnesium concentration (total serum Mg) in the Mg group was 0.83 +/- 0.06 mmol/litre [mean +/- SD, range 0.69-0.99], while in the control group it was 0.83 +/- 0.07 mmol/litre [range 0.70-0.96], P = NS. Left ventricular ejection fraction (LV-EF) improved from 32 +/- 11 per cent [range 13-51] to 42 +/- 14 per cent [range 15-66] in the Mg group and from 30 +/- 13 per cent [range 10-52] to 42 +/- 11 per cent [range: 25-64] in the control group. We found that physiological oral Mg supplements did not influence serum magnesium, LV-EF, or prognosis. Furthermore, we found that 56 per cent of all patients improved when subjected to strict guidance and therapy with ACE inhibitors, digitalis, and diuretics.

Near Field Communication-based telemonitoring with integrated ECG recordings.

OBJECTIVES: Telemonitoring of vital signs is an established option in treatment of patients with chronic heart failure (CHF). In order to allow for early detection of atrial fibrillation (AF) which is highly prevalent in the CHF population telemonitoring programs should include electrocardiogram (ECG) signals. It was therefore the aim to extend our current home monitoring system based on mobile phones and Near Field Communication technology (NFC) to enable patients acquiring their ECG signals autonomously in an easy-to-use way. METHODS: We prototypically developed a sensing device for the concurrent acquisition of blood pressure and ECG signals. The design of the device equipped with NFC technology and Bluetooth allowed for intuitive interaction with a mobile phone based patient terminal. This ECG monitoring system was evaluated in the course of a clinical pilot trial to assess the system's technical feasibility, usability and patient's adherence to twice daily usage. RESULTS: 21 patients (4f, 54 ± 14 years) suffering from CHF were included in the study and were asked to transmit two ECG recordings per day via the telemonitoring system autonomously over a monitoring period of seven days. One patient dropped out from the study. 211 data sets were transmitted over a cumulative monitoring period of 140 days (overall adherence rate 82.2%). 55% and 8% of the transmitted ECG signals were sufficient for ventricular and atrial rhythm assessment, respectively. CONCLUSIONS: Although ECG signal quality has to be improved for better AF detection the developed communication design of joining Bluetooth and NFC technology in our telemonitoring system allows for ambulatory ECG acquisition with high adherence rates and system usability in heart failure patients.

[Diagnosis of heart failure]. / Diagnostik der Herzinsuffizienz.

Heart failure is a clinical syndrome caused by various etiologic factors. The physician should undertake every effort to identify potentially reversible causes that lead to heart failure. Therefore one should go through various non-invasive as well as invasive diagnostic procedures. The diagnostic tests can be helpful in identifying patients with a poor prognosis.

[Drug therapy of chronic heart failure]. / Medikamentöse Therapie der chronischen Herzinsuffizienz.

Prevention of disease leading to cardiac dysfunction, improvement of quality of life and reduction of mortality are the primary objectives in the treatment of chronic heart failure. The therapeutic possibilities are various, including general advices, pharmacological therapy and surgical interventions. Standard medical treatment of systolic cardiac dysfunction contains ACE inhibitors, diuretics and cardiac glycosides. Beta-blocking agents, oral anticoagulation and antiarhythmic drugs can be used in addition. A therapeutic management of chronic heart failure tailored to the individual patient has nowadays become available due to multiple treatment options.

[Angiotensin I receptor blockers for heart failure]. / AT-I-Rezeptor-Blocker bei Herzinsuffizienz.

Angiotensin conversion enzyme inhibitors (ACE-inhibitors) have long been the only possibility to influence the renin angiotensin system (RAS) and its often fatal influences in heart failure. In the last few years specific blockers of the angiotensin 1 receptor (AT I blockers) offered a new possibility for this therapeutic target. In contrast to ACE inhibitors AT I blockers are relatively new and, therefore, few data on heart failure are available. The first head-to-head studies that compared AT I blockers and ACE-inhibitors and their effect on mortality did not show a reduced mortality in the AT I blocker groups. Based on the available data AT I blockers should be used in heart failure patients who are intolerant of ACE-inhibitors.

[Results of efficacy study with diclofenac/orphenadrine infusions in patients with musculoskeletal diseases and functional disorders]. / Ergebnisse einer Anwendungsbeobachtung mit Diclofenac/Orphenadrin-Infusionen bei Patienten mit muskuloskelettalen Krankheiten und Funktionsstörungen.

During a post-marketing surveillance study, 641 patients (age range 18 to 86 years) with painful rheumatic diseases, mostly of vertebral etiology, were given ready-for-use infusions containing a combination of the non-steroid antiphlogistic agent diclofenac (75 mg) and the muscle relaxing agent orphenadrine (30 mg) parenterally for 7 days. The goal of the study was to investigate efficacy, tolerability, and acceptance of this intravenous therapy in wide use in physicians' practices. At the end of treatment, the global evaluation resulted in a score of 1.6 on a scale of 1 (very good) to 4 (insufficient). The tolerability score was 1.3 and the acceptability score was 1.5. Only 20 patients (3.1%) had adverse effects, most of which were of gastrointestinal nature. The medication proved appropriate for use in the treatment of painful spine syndromes, inflammatory osteoarthritis, painful osteoporosis, post-operative conditions, and extra-articular rheumatism and could represent a first step towards multi-factorial therapeutic management of these diseases.