Efficacy and Safety of Alprostadil in Patients with Peripheral Arterial Occlusive Disease Fontaine Stage IV: Results of a Placebo Controlled Randomised Multicentre Trial (ESPECIAL).

OBJECTIVES: The aim was to assess the efficacy and safety of alprostadil in patients with peripheral arterial occlusive disease (PAOD) Fontaine Stage IV. METHODS: This was a multinational, prospective, randomised, double blind, placebo controlled, parallel group trial. Patients with Stage IV PAOD were equally randomised to either 4 weeks of alprostadil treatment twice daily or to placebo treatment twice daily. The primary efficacy variables were the rate of complete healing of all necrosis and ulceration 12 weeks after the end of treatment and the frequency of major amputations 24 weeks after the end of treatment. RESULTS: A total of 840 patients were randomised between 2004 and 2013. At baseline, no major differences between treatment groups were found. The rate of "complete healing" was 18.4% in patients on alprostadil and 17.2% in patients on placebo. The rates of "major amputations" were 12.6% in patients on alprostadil and 14.6% in patients on placebo. The adjusted difference between alprostadil and placebo including their 95% confidence intervals was 1.1 (-4.0 to 6.3) for "complete healing" and -2.1 (-6.7 to 2.5) for "major amputations." In the subgroup of diabetic patients the rates of major amputations were numerically lower in the alprostadil than placebo group (10.6% vs. 17.4%). Within the total cohort a non-significant difference in "decrease in ulcer area ≥50%" was reached in 30.2% of patients on alprostadil and in 24.3% of patients on placebo at end of treatment. CONCLUSIONS: In this study, superiority of alprostadil over placebo could not be shown. Nevertheless, a slight numerical but not clinically relevant advantage for alprostadil emerged from the "area decrease of ulcers by ≥ 50%," indicating that a healing effect may have started. The results have to be considered in the light of several limitations in study design and conduct.

[Prevention of infection with Streptococcus pneumoniae]. / Prophylaxe gegen Infektionen durch Streptococcus pneumoniae.

Streptococcus pneumoniae is the most common etiologic agent in outpatients pneumonia. Pneumococcal infections are often associated with high mortality risk in immunocompromised patients. An increasing resistance of Streptococcus pneumoniae to antibiotics is observed worldwide. This led to the official recommendation by the STIKO to use the vaccination in special risk groups. The commercially available 23-valent polysaccharide vaccine produces a reliable immune response against pneumococcal infection in children aged over 2 years and adults. The recommendation should be more realized in practice.

[Nosocomial infections with methicillin-resistant Staphylococcus aureus (MRSA) and epidermidis (MRSE) strains. Their importance, prophylaxis and therapy in orthopedic surgery]. / Nosokomiale Infektionen mit Methicillin-resistenten Staphylococcus aureus (MRSA) und -epidermidis (MRSE) Stämmen. Bedeutung, Prophylaxe und Therapie in der Knochenchirurgie.

MRSA/MRSE infections are a major problem in hospitals and although in orthopaedic units the incidence is low awareness of this problem is necessary. Once a MRSA strain has been isolated the strict use of the hygiene precautions has to be applied to avoid epidemic spread of the strain. The patient has to be isolated. The staff has to use gloves and gowns whilst treating the patient. A antimicrobiel hand wash solution has to be used after taking off the gloves and before leaving the isolation room. Patient and staff have to be informed about the pathogenicity and the way of infection spread so that infection precaution rules are fulfilled. Antibiotics should only be used in clinically well defined cases and the overall use of antibiotics should be reduced to lower the incidence of MRSA/E isolates. The problems of an MRSA case and its successful treatment are demonstrated.

Influence of Propionibacterium avidum KP-40 on the cellular immune system after intensive sport activity.

Intensive sport activities resulted in temporary downregulation of defined immune functions. To check its influence on the cellular immune system, 15 male professional ice hockey players of a German first league club were observed and a decrease of lymphocyte subset counts and activities was found after anaerobic exercise. To stabilize cellular immune functions, the players were orally treated with Propionibacterium avidum KP-40 (10 mg per administration; twice a day; 7 days), a well documented bacterial immunmodifier. After administration of Propionibacterium avidum KP-40, lymphocyte counts and activities after anaerobic exercise resembled normal values. For some subjects, defined lymphocyte subset counts and activities even exceeded normal values.

Precision of dual X-ray absorptiometry and peripheral computed tomography using mobile densitometry units.

Irrespective of the method used for noninvasive bone mass determination, data comparison between different centers is a major problem as significant interunit variation may occur. We, therefore, have employed mobile densitometry units to reduce interunit variability in two large epidemiologic studies in Germany. Two cars were equipped with either two dual X-ray absorptiometry (DXA) instruments (QDR 1000 Hologic, USA) (car I) or a special purposed scanner for peripheral quantitative computed tomography (pQCT) (XCT 900, Stratec, FRG) (car II). The cars were moved across Germany 11,090 km and 1651 km during the studies over a period of 30 and 7 months, respectively. Precision in vitro was determined using hydroxyapatite phantoms. Forty-eight patients underwent duplicate measurements at the lumbar spine (n = 22) and hip (n = 26) for assessing reproducibility in vivo. Between the two series of scans, the car was moved 63 km. Long-term precision in vitro of the QDR 1000 instruments were 0.41% and 0.59% for BMD with no evidence of machine drift (rate of change per year 0.04% and 0.05%, respectively). Short-term reproducibility in vivo showed a coefficient of variation (cv) of 1.02% for spinal BMD (L2-L4) and 1.72% for femoral neck. Long-term precision in vitro of the pQCT scanner was 0.9%. Our study shows precision in vivo and in vitro and stability of the mobile densitometers similar to that achieved with stationary equipment. In conclusion, mobile densitometry may become a useful tool not only for epidemiologic surveys and clinical trials but also for routine evaluation in less densely populated areas.

Dual-energy X-ray absorptiometry at the lumbar spine in German men and women: a cross-sectional study.

A cross-sectional, population-based study of 238 randomly selected females and 224 males with German ethnic background (aged 20-80 years) was carried out to establish lumbar spine bone mineral density (BMD) values, using dual X-ray absorptiometry (DXA), for a German population. Comparison was made to the reference range provided by the manufacturer of the DXA equipment. No sex difference in peak spine BMD was found in our study (1.091 +/- 0.114 g/cm2 for males versus 1.070 +/- 0.113 g/cm2 for females, n.s.). Different patterns of bone loss could be detected in both sexes. In premenopausal women there was no significant correlation between age and BMD (y = 1.044 + 0.00047x, r = 0.03, P = 0.73) whereas reduction of female BMD at the spine was demonstrated in postmenopausal women (y = 1.189-0.0041x, r = -0.28, P = 0.01), underscoring the important role of the menopause for later manifestation of spinal osteoporosis in women. In contrast, in males we found no significant change of BMD with aging (y = 1.071-0.0007x, r = -0.08, P = 0.25). Employing commonly used exclusion criteria, BMD values of the study subjects were found mostly within the normal range of BMD. The major finding of our study was good concordance between female data of our study population and the reference data provided by the manufacturer. Clinically significant discrepancies between our data and the Hologic reference range for males could be detected. Our data on males (30-39 years of age) were up to 7% lower than those provided by the manufacturer, probably due to differences in sampling procedures.