[Methods for organisational health services research]. / Methoden für die organisationsbezogene Versorgungsforschung.

On 1 July 2009, the German Network for Health Services Research [Deutsches Netzwerk Versorgungsforschung e. V. (DNVF e. V.)] approved the Memorandum III "Methods for Health Services Research", supported by the member societies mentioned below and published in this journal (Gesundheitswesen 2009; 71: 505-510). The focus of this part of the Memorandum III "Methods for health services research" is on the questions and methods of organisational health services research. In a first step, we describe the central questions which are at the core of organisational health services research. In a second step, we describe the methodological standards and requirements with regard to a) sampling, b) measurement and c) research design. We present a phase model for complex intervention trials. This model allows to conduct high quality organisational health services research, to integrate different methods of social research and to show in which phase they are of special importance.

Clopidogrel in addition to aspirin reduces in-hospital major cardiac and cerebrovascular events in unselected patients with acute ST segment elevation myocardial.

We sought to assess the effect of clopidogrel on in-hospital events in unselected patients with acute ST elevation myocardial infarction (STEMI). In a retrospective analysis of consecutive patients enrolled in the Acute Coronary Syndromes (ACOS) registry with acute STEMI we compared outcomes of either adjunctive therapy with aspirin alone or aspirin plus clopidogrel within 24 hours after admission.A total of 7,559 patients were included in this analysis, of whom 3,541 were treated with aspirin alone, and 4,018 with dual antiplatelet therapy. The multivariable analysis with adjustment for baseline characteristics and treatments showed that the rate of in-hospital MACCE (death, non-fatal reinfarction, non-fatal stroke) was significantly lower in the aspirin plus clopidogrel group,compared to the aspirin alone group in the entire cohort and all three reperfusion strategy groups (entire group odds ratio 0.60, 95% CI 0.49-0.72 , no reperfusion OR 0.69,95% CI 0.51-0.94,fibrinolysis OR 0.62,95% CI 0.44-0.88, primary PCI OR 0.54, 95% CI 0.39-0.74). There was a significant increase in major bleeding complications with clopidogrel (7.1% vs. 3.4%, p<0.001). In clinical practice early adjunctive therapy with clopidogrel in addition to aspirin in patients with STEMI is associated with a significant reduction of in-hospital MACCE regardless of the initial reperfusion strategy. This advantage was associated with an increase in major bleeding complications.

Volume-outcome relation for contemporary percutaneous coronary interventions (PCI) in daily clinical practice: is it limited to high-risk patients? Results from the Registry of Percutaneous Coronary Interventions of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK).

OBJECTIVE: The formerly observed volume-outcome relation for percutaneous coronary interventions (PCIs) has recently been questioned. DESIGN: We analysed data of the PCI registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte. PATIENTS: In 2003 a total of 27 965 patients at 67 hospitals were included. RESULTS: The median PCI volume per hospital was 327. In-hospital mortality was 1.85% in hospitals belonging to the lowest PCI volume quartile and 1.21% in the highest quartile (p for trend <0.001). Two groups of patients were then compared according to their treatment at hospitals with either <325 PCIs (n = 5754) or >325 PCIs (n = 22 211) per year. Logistic regression analysis showed that a PCI performed at hospitals with a volume of >325 PCI/year was independently associated with a lower hospital mortality (OR = 0.67, 95% CI: 0.52 to 0.87; p = 0.002). If PCI was performed in patients with acute myocardial infarction there was a significant decline in mortality with increasing volume (p for trend = 0.004); however, there was no association in patients without a myocardial infarction. CONCLUSIONS: This analysis of contemporary PCI in clinical practice shows a small but significant volume-outcome relation for in-hospital mortality. However, this relation was only apparent in high-risk subgroups, such as patients presenting with acute myocardial infarction.

[Predictive value of an ischemia test in men and women with stable angina pectoris in clinical practice. Results of the heart catheter registry of the Working Society of Senior Hospital Cardiologists]. / Prädiktiver Wert eines Ischämietests bei Männern und Frauen mit stabiler Angina pectoris im Klinikalltag. Ergebnisse des Herzkatheter-Registers der ALKK.

BACKGROUND AND OBJECTIVE: Symptoms of coronary artery disease (CAD) and the accuracy of non-invasive tests differ between men and women. This study sought to evaluate the difference between the predictive value of a stress test in clinical practice for the diagnosis of significant coronary heart disease (CHD: stenosis > 50%) between women and men with stable angina. PATIENTS AND METHODS: 143,848 consecutive patients undergoing diagnostic coronary angiography at 99 hospitals during 2002 were included in the prospective cardiac catheter registry of the Working Party of Senior Hospital Cardiologists (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte [ALKK]). All patients with stress test and stable angina CCS class I-III (n=27387; 20.4%) were included, 10,911 (39.8%) of them female. 70.6% of women and 73.2% of men had a positive stress test. RESULTS: In 46.1% of women and 71.5% of men with positive test and stable angina had relevant CHD (p<0,001). Diabetes increased the prevalence of CHD in patients with a positive test both in women (65.5%) and men (80.5%), with CCS class III angina to 63.3% and 85.8%, respectively. CONCLUSIONS: In clinical practice a positive stress test in women with stable angina is associated significantly less often with clinically relevant CHD than in men. The low positive predictive value of 46.1% underlines the need for additional clinical features like diabetes or cardiac symptoms (CCS class) before invasive diagnosis is performed.

[Which reasons may hinder Integrated Health Care from spreading as regular health care provision in cardiology?]. / Integrierte Versorgung sollte in der Kardiologie zur Regelversorgung werden--was steht dagegen?

Integrated Health Care may possibly be a training field for efficient patient and case management between different providers involved. In the medium term, those instruments should be developed further so that they are no longer merely tools for cost containment, risk transfer to the providers side and competition for the good risks in health care. In the present state Integrated Health Care--as many other new regulations--means a displacement of money from health care to administration. All participants are urged to check their contracts that the benefit for patients exceeds the price of the paper.

Beneficial effects of abciximab in patients with primary percutaneous intervention for acute ST segment elevation myocardial infarction in clinical practice.

OBJECTIVES: To assess the safety and effectiveness of abciximab in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) in clinical practice. METHODS: Data were analysed of 2184 consecutive patients treated with primary PCI for acute STEMI and either concomitant abciximab or no glycoprotein IIb/IIIa inhibitor (control group), who were prospectively enrolled in the Acute Coronary Syndromes (ACOS) registry between July 2000 and November 2002. RESULTS: Patients who were treated with abciximab were younger than the control group, and fewer of them had a history of stroke/transient ischaemic attack and systemic hypertension, but more of them had three-vessel coronary artery disease and cardiogenic shock. Cumulated mid-term survival for patients treated with abciximab was significantly higher than in the control group (91% v 79%, log rank p < 0.05, median observational time 375 days, range 12-34 months). The Cox proportional hazards model of mid-term mortality after admission with adjustment for baseline characteristics showed that mortality was significantly lower in the abciximab group than in the control group (hazard ratio 0.68, 95% confidence interval 0.49 to 0.95). Whereas overall there was no difference in bleeding complications, patients older than 75 years had more major bleeding events with abciximab (12.5% v 3.4%, p = 0.03). CONCLUSION: In clinical practice adjunctive treatment with abciximab in patients with primary PCI for acute STEMI was associated with a reduction in mid-term mortality. The subgroup of patients older than 75 years who were treated with abciximab had more major bleeding complications.

In-hospital time to treatment of patients with acute ST elevation myocardial infarction treated with primary angioplasty: determinants and outcome. Results from the registry of percutaneous coronary interventions in acute myocardial infarction of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausarzte.

OBJECTIVE: To determine the predictors of time between presentation and primary angioplasty and the influence of this delay time on in-hospital mortality in clinical practice. DESIGN: Analysis of data from the registry of percutaneous coronary interventions in acute myocardial infarction of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK). PATIENTS: Data of 4815 patients registered at 80 hospitals between 1994 and 2000 were analysed. RESULTS: Mean age of the patients was 61.4 (12.5) years. Cardiogenic shock was present in 14.1%. Mean time from admission to primary angioplasty ("door to angiography" time) was 83 (122) minutes. Logistic regression analysis showed the presence of a bundle branch block (odds ratio (OR) 1.95, 95% confidence interval (CI) 1.15 to 3.29), prior coronary artery bypass grafting (OR 1.67, 95% CI 1.08 to 2.59), pre-hospital delay > 3 hours (OR 1.61, 95% CI 1.37 to 1.89), and female sex (OR 1.21, 95% CI 1.01 to 1.45) to be independently associated with longer door to angiography times, whereas a higher hospital volume of performing primary angioplasty (OR 0.53, 95% CI 0.46 to 0.62) and the year of the investigation (OR 0.96, 95% CI 0.92 to 1.00) were independently associated with shorter door to angiography times. Independent predictors of in-hospital mortality were cardiogenic shock (41.6% v 4.0% without cardiogenic shock, p < 0.0001), technical success (29.2% with TIMI (thrombolysis in myocardial infarction) flow < 3 v 6.5% with TIMI flow 3, p < 0.0001), age (16.5% > or = 70 years v 6.6% < 70, p < 0.0001), three vessel disease (16.5% v 6.8% with < 3 vessel disease, p < 0.0001), anterior location of infarction (12% v 7.4% without anterior infarction, p < 0.0001), year of inclusion (adjusted OR 0.92 per year, p = 0.011), and volume of primary angioplasty at the hospital (11% for < 20 angioplasty procedures/year v 8.3% for > or = 20/year, p = 0.027) but not the door to angiography time (adjusted OR 1.14 per tertile, p = 0.397). CONCLUSIONS: In current clinical practice in Germany median door to angiography time is quite short (83 (122) minutes). Some patients and hospital factors are independently associated with a longer door to angiography time. Within the observed short in-hospital delays door to angiography time did not influence in-hospital mortality. However, efforts to keep them as short as possible should be continued.

Incications and complications of invasive diagnostic procedures and percutaneous coronary interventions in the year 2003. Results of the quality control registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK).

BACKGROUND: The ALKK registry contains about 20% of the invasive and interventional cardiological procedures performed in Germany. METHODS: In 2003 a total of 82,282 consecutive diagnostic invasive and 30,689 interventional procedures from 75 hospitals were centrally collected and analyzed. RESULTS: The main indication for an invasive diagnostic procedure was coronary artery disease in 92.5% of cases, myocardial disease in 1.6%, impaired left ventricular function in 4.0%, valve disease in 4% and other indications in 1.9%. An acute coronary syndrome was present in 25% of the patients. The rate of severe complications in patients with a lone diagnostic invasive procedure was low (<0.5%). The indication for percutaneous coronary intervention (n=30,689) was stable angina in 44.1%, ST elevation myocardial infarction in 22.3%, non ST elevation myocardial infarction in 14.8%, unstable angina in 10.0%, silent ischemia in 2.2%, prognostic in 5.2% of patients. The majority of interventions were performed directly after the diagnostic procedure (n=23,887=78.6%). The intervention was successful in 94.6% of cases. Stent implantation was performed in 77.2%, with 1 stent in 88.4%, two stents in 7.6% and 3 or more stents in 3.3%. A drug-eluting stent was implanted in 3.6% of the cases. The complication rate after PCI was influenced by the indication for the intervention. The in-hospital mortality in patients with cardiogenic shock was 33%, while in patients with stable angina, silent ischemia and prognostic indication only 0.2% died. CONCLUSION: There is an increase of invasive diagnostic and interventional procedures in patients with acute coronary syndromes, with 47% of PCIs performed in these patient. PCIs were performed in 75% of the cases directly after the diagnostic procedure. The rate of stent implantation seems to have reached a plateau at around 80%, while drug-eluting stents were implanted only in a minority of cases. The complication rate is mainly dependent on the clinical presentation of the patients and the indication for PCI.

[Mortality of patients who are older than 75 years after ST elevation myocardial infarction in clinical practice]. / Sterblichkeit bei über 75-jährigen Patienten mit akutem ST-Hebungsmyokardinfarkt im klinischen Alltag.

BACKGROUND: Patients who are older than 75 years are often excluded in clinical trials evaluating therapies for ST elevation myocardial infarction. Therefore there is a lack of prospective data for this steadily increasing number of elderly patients. PATIENTS AND METHODS: Between 07/2000 and 11/2002 a total of 16 823 patients with acute coronary syndromes in 154 hospitals were enrolled in the ACOS registry, with 8309 having a STEMI. Baseline characteristics, therapies during the hospital course and at discharge, hospital-mortality and 1-year mortality were prospectively collected. In this study we analysed the outcome of patients older than 75 years with STEMI of less than 24 duration. RESULTS: A total of 2045 patients > 75 years (median age 80.1 years, 53.9 % women) were included. Of the latter 51 % were treated conservatively, 19 % with fibrinolysis and 30 % with primary PCI. In-hospital mortality in the three groups was 23.4 %, 25.4 % und 10.2 %, while total mortality after one year was 52.4 %, 41.3 % und 19.3 %, respectively. In the multivariate analysis both primary PCI (odds ratio 0.36, 95 % CI 0.25 - 0.52) and fibrinolysis (odds ratio 0.65, 95 % CI 0.44 - 0.97) where associated with a lower mortality after discharge. CONCLUSION: Hospital- as well as 1-year mortality in patients with STEMI who are older than 75 years are high. Primary PCI is associated with a decrease of in-hospital and 1-year mortality, while fibrinolysis improves mortality after discharge. Therefore early reperfusion therapy, preferably with primary PCI should be considered in elderly patients, after taking in count biological age and major comorbidities.

[Rare cause of long QT and resuscitation-requiring torsade de pointes tachycardia]. / Seltene Ursache einer Prolongierung der QT-Zeit und reanimationspflichtigen Torsade-de-pointes-Tachykardie.

A 62 year old patient underwent an intraoperative pancreas biopsy because of a pancreas head process. On 13(th) and 20(th) postoperative day a short syncope episode occurred. On that days calcium blood levels were 1,82 and 1,74 mmol/l, respectively. On 13(th) postoperative day QT(c) interval was 565 ms. On 26(th) postoperative day the patient was resuscitated because of torsade de pointes tachycardia. His actual calcium blood level was 1,47 mmol/l and QT(c) interval 627 ms. An extensive diagnostic work-up revealed no evidence of cardiac disease. After calcium substitution QT interval normalised. During a follow-up period of 16 months the patient remained without symptoms.

Antibody levels against Chlamydia pneumoniae and outcome of roxithromycin therapy in patients with acute myocardial infarction. Results from a sub-study of the randomised Antibiotic Therapy in Acute Myocardial Infarction (ANTIBIO) trial.

BACKGROUND: Results of studies concerning prevention of cardiovascular disease by treatment with macrolide antibiotics targeting C. pneumoniae infection are still controversial. This study describes the results of different tests for infection with C. pneumoniae as well as the effect of treatment with roxithromycin in patients with acute myocardial infarction (AMI) in relation to their serostatus against C. pneumoniae. METHODS: We analysed blood of 160 patients who came from the ANTIBIOtic therapy after an AMI ( ANTIBIO-) study, a prospective, randomised, placebo-controlled, double-blind study to investigate the effect of roxithromycin 300 mg/OD for 6 weeks in patients with an AMI. Anti- Chlamydia IgG-, IgA-, and IgM-antibodies of these patients were analysed by means of different test systems. RESULTS: There was a good correlation between the two IgG and IgA methods (r = 0.900, p < 0.001 and r = 0.878, p < 0.001, respectively), but marked differences in the prevalence of positive tests. This resulted in only moderate concordance values, as expressed by the Kappa coefficients, for IgG kappa = 0.611 (95% CI = 0.498-0.724, p < 0.001) and for IgA kappa = 0.431 (95% CI: 0.322-0.540, p < 0.001). No significant association between positive C. pneumonia titers and the combined clinical endpoint during the 12 month follow-up could be found. In all test systems used, patients with positive anti- C. pneumoniae titers did not benefit from roxithromycin therapy (p = ns). CONCLUSION: Depending on the test system used, there are large differences in the prevalence of anti- C. pneumoniae seropositive patients. Clinical events during the 12 month follow-up after AMI did not depend on serostatus against C. pneumoniae and treatment with roxithromycin did not influence these events, independently of the serostatus against C. pneumoniae. However, the power of this subgroup analysis was low to detect small but significant differences.

[Too many heart catheter procedures in Germany ?]. / Zu viele Herzkatheteruntersuchungen in Deutschland?

BACKGROUND AND OBJECTIVE: Absolute numbers of cardiovascular procedures are higher in Germany as compared to other European countries. This fact is used as an argument for overuse. Therefore other indicators of an inappropriate use of these resources should be of interest. PATIENTS AND METHODS: The relationship between diagnostic cardiac catheterisations and consequent revascularisation procedures were compared in 8 European countries. In addition the indication criteria for cardiac catheterisations were reviewed in a German registry of 205.581 consecutive inpatients. RESULTS: Revascularisation procedures after diagnostic catheterisations in 8 countries range from 39,1 % to 57,9 %. Germany reaches 43,2 %. A relation between absolute numbers of diagnostic and percent subsequent revascularisation procedures does not exist. In a German registry the following indications for cardiac catheterisation could be identified: Acute Coronary Syndrome 22,9 %. Angina pectoris according to the Canadian Cardiac Society classification was present: CCS II/III in 80,3 %, CCS IV in 17,2 %. An exercise test was performed in 43 %. Final diagnoses were: significant coronary disease 69,5 %, exclusion of disease 9,4 %, lesions < 50 % 9 %, other cardiac disease 12,1 %. CONCLUSION: Absolute numbers cannot be used as an indicator of overuse of cardiovascular procedures. Instead standards for data acquisition should be established on European, national and regional levels. In addition a validation procedure for criteria has to be developed in order to judge the appropriateness of indications for invasive cardiac procedures in different health care systems.

Prognostic value of non-sustained ventricular tachycardias after acute myocardial infarction in the thrombolytic era: importance of combination with frequent ventricular premature beats.

PURPOSE: of this study was to re-evaluate the association between ventricular arrhythmias and long-term mortality after acute myocardial infarction (AMI) in the thrombolytic era. METHODS: MITRA (maximal individual therapy in patients with AMI) is a multicenter registry of 54 hospitals in Germany investigating patients with AMI. RESULTS: 2420 patients received Holter ECG. Positive Holter ECG was defined: > or =10 ventricular premature beats (VPB)/h, or > or =4 couplets/d, or > or =1 non-sustained ventricular tachycardia (nsusVT)/d, or their combination. Mortality rates (median 17 months) were 6.5% without ventricular arrhythmias, with > or =10 VPB/h 15.2% and with the combination of > or =10 VPB/h plus either > or =4 couplets/d or > or =1 nsusVT/d 23.4%. In multivariate analysis, none of the ventricular arrhythmias alone correlated with mortality. There was a significant association between mortality and the combination of > or =10 VPB/h plus > or =4 couplets/d (OR 2.3) or > or =10 VPB/h plus > or =1 nsusVT/d (OR 2.8). CONCLUSION: Non-sustained VTs are only associated with poor prognosis if combined with frequent VPBs.

Intensive treatment of coronary artery disease in diabetic patients in clinical practice: results of the MITRA study.

Patients with diabetes are at high risk for the development of coronary artery disease and have a significantly impaired prognosis after ST-elevation myocardial infarction (STEMI) as compared with non-diabetic patients. The beneficial effect of pharmaceutical treatment for secondary prevention after STEMI is proven also for diabetics, but little is known about its use in clinical practice. Between June 1994 and December 2000, consecutive patients with STEMI, admitted to hospital within 24 h of symptoms onset, were enrolled into the multicenter MITRA registry in 61 hospitals in Germany. We examined whether there were differences in the frequencies of pharmaceutical secondary prevention after STEMI and in long-term outcomes between diabetics and nondiabetics in 8206 patients who had been discharged alive and followed for a mean period of 17 months. The prevalence of diabetes in 8206 patients discharged alive after acute STEMI was 18%. Diabetics were older and more often female, and more often already had prior myocardial infarction (MI) and stroke than non-diabetics. As chronic discharge medication, diabetics received aspirin and betablockers less often, but more often ACE inhibitors than non-diabetics. The mortality rate 17 months after STEMI was nearly twice as high in diabetics than in non-diabetics (19.1% vs. 10.4%, p<0.01 at univariate analysis; OR=1.50 and 95% CI 1.27-1.77 at multivariate analysis). The combined endpoint of death, MI and stroke occurred in 25.8% of diabetics, but only in 15.8% of non-diabetics ( p<0.01). Long-term treatment with aspirin, betablockers and ACE inhibitors in diabetics was associated with a significant reduction of mortality. Diabetics received intensive pharmaceutical therapy for secondary prevention significantly less often than non-diabetics, although the beneficial effects of this treatment were similar or even more pronounced as compared with non-diabetics. Diabetes was an independent predictor of increased mortality in follow-up after acute STEMI. Intensifying secondary prevention by a more frequent use of established pharmaceutical regimes might improve the prognosis of diabetics after STEMI and prevent cardiovascular and cerebrovascular events.