[Disease management program (DMP) diabetes mellitus: simulation of therapeutic results of different guidelines. A new diabetes mellitus model (DMM)]. / DMP Diabetes mellitus: Simulation der Behandlungsergebnisse verschiedener Leitlinien. Ein neues Diabetes mellitus Modell (DMM).

BACKGROUND AND OBJECTIVE: In conjunction with the introduction of disease management programmes in Germany there is an ongoing scientific debate on the desirable goals for HbA1c in the management of patients with type 2 diabetes mellitus. PATIENTS AND METHODS: In this study, a novel computer-based simulation model (diabetes mellitus model = DMM) was used to estimate the consequences of different levels of metabolic control as assessed by HbA1c for the development of short- and long-term complications of this disease. RESULTS: At a mean difference of 1 % the rate of severe hypoglycaemic events over 10 years was by 32-84 % higher in those with a lower HbA1c. In contrast, the incidence of microvascular complications (proliferative retinopathy, end-stage kidney disease, clinical neuropathy) was by 20-33 % lower in the group with the lower as compared to the higher HbA1c level according to the scenario applied. The rates of myocardial infarction and stroke were reduced by 15-20 % under these conditions. CONCLUSIONS: This model calculation suggests that a more strict metabolic control in patients with type 2 diabetes mellitus results in a greater reduction of microvascular complications than of macrovascular complications, but is associated with a higher rate of hypoglycaemic episodes. The diabetes mellitus model is a non-expensive alternative to simulate clinically relevant questions on the management of type 2 diabetes and to provide rapid and realistic answers.

The importance of secondary mitral valve involvement in primary aortic valve endocarditis; the mitral kissing vegetation.

AIMS: Secondary involvement of the mitral valve is well documented in primary aortic valve endocarditis. A poorly considered, but probably important causative mechanism, involving both left-sided valves, is 'mitral kissing vegetation'. This results from large aortic vegetations prolapsing into the left ventricular outflow tract and making contact with the ventricular aspect of the anterior mitral leaflet thus causing secondary infection. METHODS AND RESULTS: In 192 consecutive patients with aortic valve endocarditis, two to 18 (7.6+/-2.6) serial transoesophageal echocardiographic examinations were analysed per patient to demonstrate the development of mitral kissing vegetation on initially competent, morphologically normal mitral leaflets. In 19 patients (9.9%) with aortic valve endocarditis, mitral kissing vegetation was diagnosed within 11.6+/-9.0 (range 1-31) days following primary transoesophageal echocardiography. In all patients with mitral kissing vegetation, vegetations attached to aortic cusps were >6 mm. On hospital admission, patients with aortic valve endocarditis plus mitral kissing vegetation presented more often with a positive sepsis score, embolic events, renal failure and had larger aortic valve vegetations (9.9+/-3.3 vs 5.7+/-2.3 mm). Prognosis of aortic valve endocarditis plus mitral kissing vegetation was unfavourable (P<0.005) when compared to patients with aortic valve endocarditis alone. CONCLUSION: In aortic valve endocarditis early echocardiographic detection of mitral kissing vegetation and timely surgery may preserve the mitral valve apparatus, and favourably influence the long-term prognosis.

Economic evaluation of collagenase-containing ointment and hydrocolloid dressing in the treatment of pressure ulcers.

OBJECTIVE: To evaluate the efficacy and cost effectiveness of two treatments of pressure sores on the heel: a collagenase-containing ointment and a hydrocolloid dressing. DESIGN: Study and cost data were collected prospectively in a randomised clinical trial in The Netherlands by counting the resource use for each patient until wound healing occurred. STUDY PARTICIPANTS: All 24 female study participants were inpatients from the same hospital with grade IV pressure sores on the heel following orthopaedic surgery. INTERVENTIONS: Two different treatment strategies were analysed: a collagenase-containing ointment (Novuxol) and a hydrocolloid dressing (Duoderm). PERSPECTIVE: Hospital perspective. MAIN OUTCOME MEASURES AND RESULTS: The average costs per patient for treatment with the hydrocolloid dressing were about 5% higher than those with the collagenase-containing ointment. The treatment costs were similarly distributed within both groups, with 34% for materials and 66% for personnel. The cost-effectiveness analysis revealed that cost savings of 899 Dutch guilders (1998 values) per successfully treated patient could be expected using the collagenase-containing ointment instead of the hydrocolloid dressing. In addition, wound healing was achieved, on average, within a shorter time period with the collagenase treatment (10 weeks) compared with the hydrocolloid treatment (14 weeks). The robustness of the results were also tested using sensitivity analyses. These analyses served to confirm that collagenase treatment provides a better cost-effectiveness ratio than hydrocolloid treatment. CONCLUSIONS: With regard to overall costs and costs per successfully treated patient, this study showed collagenase treatment to be more cost effective than the hydrocolloid treatment in patients with grade IV pressure sores on the heel and that the amount of time needed for wound healing was shorter.

[Is the estimation of the progression of valvular aortic stenosis possible?]. / Ist die Abschätzung der Progression valvulärer Aortenstenosen möglich?

BACKGROUND AND OBJECTIVE: It is of great importance to assess progression of aortic valvar stenosis (AVS) when cardiac surgery is planned for other indications when established criteria for aortic valve replacement are not fulfilled at that moment. These considerations have often been ignored in prospective planning of treatment, necessitating a second cardiac surgical intervention just a few years later. The aim of this study was to establish criteria for estimating the rate of progression of AVS. PATIENTS AND METHODS: Clinical, echocardiographic and haemodynamic data were analysed for 169 patients with aortic valvar stenosis (169 men, 88 women; mean age at first cardiac catheterization [CC] 55.2 +/- 15.7 years, at second CC 63.4 +/- 15.6 years. RESULTS: The degree of AVS increases exponentially in relation to the extent of calcification (graded 0-3) and the fall in transaortic gradient (TG), from a TG > 0.6 mmHg/ml stroke volume and can be sufficiently predictable for clinical purposes. But neither age, sex nor the aetiology/pathology of the valvar defect have a sustained influence on the progression of AVS. CONCLUSIONS: These data indicate that knowing the current reduction in TG and the degree of calcification makes it possible to assess the likely progression of previously asymptomatic AVS and thus greatly facilitate the decision of whether or not to combine aortic valve replacement with another indicated cardiac operation.

Economic evaluation of the treatment of chronic wounds: hydroactive wound dressings in combination with enzymatic ointment versus gauze dressings in patients with pressure ulcer and venous leg ulcer in Germany.

OBJECTIVE: The treatment costs for pressure ulcers and venous leg ulcers were estimated based on the hospital administrator's perspective in Germany. DESIGN: A spreadsheet model using input data from various hospitals in Germany was developed. INTERVENTIONS: Five currently used treatment strategies were analysed: gauze, impregnated gauze, calcium alginate and hydroactive wound dressing with enzymatic ointment. PARTICIPANTS: All cases used for and in the analysis were treated in the inpatient setting (4 hospitals and 120 patients were included). MAIN OUTCOME MEASURES AND RESULTS: The outcome distributions were calculated using the Monte Carlo method. For the whole treatment process, the attributable costs for the hospital were calculated for different cases (severity) and all treatment strategies (1997 values). The costs for treatment with gauze were the highest, whereas the costs for treatment with hydroactive wound dressings and enzymatic ointment were the lowest. The relation between personnel and material costs for gauze is approximately 95 to 5% and for hydroactive wound dressings 67 to 33%, respectively. The cost savings per case were between 1196 deutschmark (DM) and DM9826 using hydroactive wound dressings instead of gauze dressings (depending on the severity of the pressure ulcer), and between DM135 and DM677 for venous leg ulcers. The results were robust and did not change in any performed sensitivity analysis (parameter: 'personnel costs per minute', 'time required for changing a wound dressing', 'total number of wound dressing changes'). CONCLUSIONS: Despite the higher material costs of the hydroactive wound dressings in combination with enzymatic wound cleaning compared with other wound dressings, they should be recommended for the treatment of pressure ulcers and venous leg ulcers. This therapy alternative brings about significant reductions in total costs for hospitals because of significant reductions in personnel costs and the duration of treatment.

[Increased acceptance of the International Normalized Ratio (INR) as a monitoring parameter of oral anticoagulation therapy in Germany. GELIA Study Group]. / Zunehmende Akzeptanz der Internationalen Normalisierten Ratio (INR) als Uberwachungsparameter der oralen Antikoagulantientherapie in Deutschland. GELIA-Studiengruppe.

In 1994 the German Cardiac Society recommended the International Normalized Ratio (INR) instead of "Quick's test" for the long-term management of oral anticoagulation therapy. Parallel cardiac surgical centers in Germany and Switzerland started patient recruitment for the GELIA study (German Experience with Low Intensity Anticoagulation). By the end of 1996, 862 consecutive patients with mechanical heart valve replacement had been enrolled. According to the protocol of the GELIA study, intensity of anticoagulation, methods used to control the oral anticoagulation therapy as well as other factors relevant for the anticoagulation management are reported every three months. The so far accumulated data material of the GELIA study seemed, therefore, appropriate to analyze potential changes in the acceptance of INR during the time period 1993-1996. Potential differences in the anticoagulation management were analyzed separately according to the time of enrollment of patients and changes during the follow up period, e. g., a switch from "Quick's test" to INR. Taking the time of enrollment into account, the percentage of patients who had INR-controlled oral anticoagulation therapy increased from 0% (1993), 14.3% (1994), 63.2% (1995) to 74.2% in 1996. During the follow up, there was a change from "Quick's test" to INR controls in 7 patients (1994; 2.1%), 67 patients (1995; 10.5%) and 142 patients (1996; 17.3%) with a consequent increase of INR controlled patients to a total of 34.2% in 1994, 52.0% in 1995, and 73.9% in 1996.

[Emergency heart valve replacement after acute cerebral embolism during florid endocarditis]. / Dringlicher Herzklappenersatz nach akuter Hirnembolie während florider Endokarditis.

BACKGROUND: The indication for urgent cardiac surgical interventions in patients with active infective endocarditis has to be considered carefully following thromboembolic events, because of the high recurrence rate of such complications. In the case of brain embolisms the prognostic benefit of urgent surgery has been discussed controversially as effective anticoagulation during open heart surgery may result in secondary cerebral hemorrhages. PATIENTS AND METHODS: Between 1978 and 1993 infective endocarditis (IE) was proven in 288 consecutive and prospectively followed patients (131 females, 157 males; mean age 53.6 +/- 8.7 [9 to 81] years). To analyze potential benefits and risks of an urgent surgical intervention early after embolic cerebral infarction, cumulated survival rates were calculated for patients with and without surgical intervention with special reference to incremental risk factors and the timing of surgery. RESULTS: In 50 patients (17.4%) the clinical course was complicated by one, and in 58 patients (20.2%) by recurrent embolic events. In 80% the first embolism occurred within 33 days following the first manifestation of typical signs and symptoms of IE. 80% of recurrent events were observed within 32 days following the initial embolism. 71% of all embolic events were cerebral. In patients with cerebral embolism corroborated by computed tomography (CCT), the clinical course was complicated by intracranial hemorrhage in 12.5% while it was only 1.5% for patients without cerebral embolism. Because of a lack of therapeutic alternatives, 22 of 49 patients with recurrent embolic events, of which at least one was cerebral, underwent urgent cardiac surgery within 4 to 366 hours after the first cerebral manifestation. The cumulated survival rate of patients operated within 72 hours after the initial cerebral embolism was significantly more favorable (p < or = 0.000) than for unoperated patients or those who were operated after more than 8 days. CONCLUSION: An embolic event during IE carries a more than 50% risk of recurrence. In patients with short duration of signs and symptoms of IE and postembolic echocardiographic demonstration of persistent vegetations the probability is > 80%. At least for those patients urgent surgical intervention to remove the source of infection and embolic hazard seems to be beneficial. Surgical intervention using the heart-lung-machine should be performed within 72 hours. Such early timing results in a significant lower rate of secondary cerebral hemorrhages (p < or = 0.00) than a postponed operation. To exclude early reperfusion hemorrhage due to spontaneous thrombus fragmentation, CCT should be repeated directly preoperatively.

Efficacy and safety of low molecular weight heparin, unfractionated heparin and warfarin for thrombo-embolism prophylaxis in orthopaedic surgery: a meta-analysis of randomised clinical trials.

UNLABELLED: The efficacy and safety of low molecular weight heparin (LMWH), unfractionated heparin (UFH) and warfarin for prophylaxis of thrombo-embolism in orthopaedic surgery were compared using meta-analysis techniques. Twenty-two studies were included, 2 of which compared LMWH to warfarin. The mean probabilities to develop deep-vein thrombosis (DVT), pulmonary embolism and major and minor bleeding using UFH were: 0.21 (95% confidence interval, CI: 0.18-0.24); 0.01 (95% CI: 0.01-0.02); 0.05 (95% CI: 0.03-0.07), and 0.19 (95% CI: 0.17-0.22), respectively. The relative risk (RR) of DVT for LMWH vs. UFH was 0.76 (95% CI: 0.60-0.91), p < 0.05 and for LMWH vs. warfarin 0.78 (95% CI: 0.69-0.87), p < 0.05. The RR of minor bleeding for LMWH vs. UFH was 0.76 (95% CI: 0.64-0.92), p < 0.05. The RR of minor bleeding for LMWH vs. warfarin was 3.28 (95% CI: 2.21-4.70), p < 0.05. CONCLUSION: in orthopaedic surgery, LMWH is significantly superior to both UFH and warfarin in the prevention of DVT and results in significantly less minor bleeding complications when compared to UFH, but significantly more minor bleeding when compared to warfarin.

Low molecular weight heparin and unfractionated heparin for prevention of thrombo-embolism in general surgery: a meta-analysis of randomised clinical trials.

Low molecular weight heparin (LMWH), unfractionated heparin (UFH) and warfarin were compared with respect to efficacy and safety in the prevention of thrombo-embolism in general surgery. Meta-analysis (MA) with a priori definition of the MA protocol was used to combine the results from randomised trials with patients who underwent general surgery and deep-vein thrombosis (DVT) prophylaxis with LMWH, UFH or warfarin. Forty-four studies were identified for assessment and 33 were included, however, none for warfarin. For efficacy (DVT and pulmonary embolism) and major bleeding, no significant difference between the LMWH- and UFH-treated groups was demonstrated. The relative risk of minor bleedings for LMWH versus UFH was 0.75 (0.64-0.88; 95% confidence interval) and is significant (p < 0.05). Within the limitations of the MA, LMWH and UFH did not differ significantly in terms of prevention of thrombo-embolism, but LMWH had a significantly better safety profile. On this basis, LMWH may be preferable to UFH in the prevention of thrombo-embolism in general surgery.

Preventive treatment of chronic bronchitis: a meta-analysis of clinical trials with a bacterial extract (OM-85 BV) and a cost-effectiveness analysis.

Chronic bronchitis is a lifelong disease with significant effects on the patient and on the costs to health insurance institutions. Acute exacerbations in chronic bronchitic patients may have a negative impact on patients' quality of life and on the progression of the disease, particularly in more severe patients. The clinical efficacy of the immunoactive bacterial extract OM-85 BV has been shown in several clinical trials, a cost-effectiveness evaluation (CEA) of its use in chronic bronchitic patients has not been fulfilled so far. In this study a meta-analysis on the preventive treatment of acute exacerbations with OM-85 BV and a CEA, focusing on direct costs only, was performed. The meta-analysis showed a mean value of 0.6 prevented acute exacerbations per 6 months per patient, and a reduction of 9 days in antibiotic treatment per 6 months per patient. CEA evaluated the different cost elements. The mean direct cost (consultations, antibiotics, etc.) for the treatment of 1 acute exacerbation in chronic bronchitic patients was calculated as 143, 459 Lira. Thus for 0.6 prevented acute exacerbations per 6 months per patient a reduction in cost of 86,075 Lira (0.6-143,459) could be expected. The additional costs for the preventive treatment with OM-85 BV, based on prices for Italy, are 34,980 Lira per patient per 6 months. In conclusion, the effective cost savings per patient per 6 months are 51, 095 Lira. The sensitivity analysis revealed only one critical parameter, i.e. the clinical effectiveness of OM-85 BV. Even assuming 0.3 prevented exacerbations per 6 months per patient, the preventive treatment still proved to be cost effective.

Cost-effectiveness study of a lipid-lowering therapy in hyperlipoproteinaemia type IIb and type IV (Frederickson).

We performed a cost-effectiveness simulation of acipimox, bezafibrate, fenofibrate and gemfibrozil in patients with hyperlipoproteinaemia type IIb and IV (Frederickson). A distinction was made between patients with HLP type IIb and IV and HLP associated with diabetes mellitus type II (NIDDM). Direct costs were assessed as those incurred by social security for the treatment, and indirect costs were not taken into account. In appropriate dosages, all 4 substances can be considered equally efficacious in lowering lipid levels, although gallstones occur 3 times more frequently in patients treated with fibrates than in those treated with acipimox. Acquisition costs of the 4 drugs under consideration are comparable. Thus, when hospitalisation costs for treatment of gallstones are taken into account, therapy with acipimox is more cost effective than fibrate therapy.

[Improved glucose regulation and microalbuminuria/proteinuria in diabetic patients treated with ACE inhibitors. A meta-analysis of published studies of 1985-1990]. / Verbesserte Glucoseeinstellung und Mikroalbuminurie/Proteinurie bei Diabetikern unter ACE-Hemmer-Behandlung. Eine Metaanalyse publizierter Studien aus den Jahren 1985 bis 1990.

In patients with diabetes mellitus, metabolic control, hypertension and kidney function are important prognostic factors. In this respect ACE inhibitors exhibit, according to previous publications, a potentially beneficial effect on diabetic patients. To further clarify this effect of ACE inhibitors, a meta-analysis of 21 studies of type I and II diabetics under therapy with ACE inhibitors was performed. Altogether 325 cases were analyzed. The duration of diabetes varied between 2.5 and 22 years. Therapy with ACE inhibitors under long-term treatment (up to 12 months) reduced diastolic blood pressure (-25%) and, both for type I and II diabetics, fasting blood sugar (-14%) and HbA1 (-9%). Microalbuminuria/proteinuria was reduced by 33% under short-term treatment with ACE inhibitors (up to 3 months) and by 66% under long-term treatment. Analysis of the subgroups with microalbuminuria (30-300 mg/day, n = 48) or clinical proteinuria (greater than 300-1500 mg/day, n = 9) showed similar results. The outcome of this meta-analysis shows that the treatment of diabetic patients with ACE inhibitors not only effectively reduces high blood pressure but also reduces microalbuminuria/proteinuria and, in addition, exhibits an anti-hyperglycemic effect by improving blood sugar levels.