Werner Pölz

High ligation combined with stripping and endovenous laser ablation of the great saphenous vein: Early results of a randomized controlled study

OBJECTIVE This study compared postoperative patient comfort and the surgical outcome of endovenous laser ablation (EVLA) or stripping of the great saphenous vein, both performed in conjunction with high ligation. METHODS The study randomized 100 patients with primary trunk varicosities of the great saphenous vein (CEAP clinical class II to IV) to EVLA or stripping. The success of surgery was followed-up by duplex ultrasound imaging at 1, 4, and 16 weeks. Primary end points were the size of the hematoma 1 week after the operation and the preoperative disease-specific Chronic Venous Insufficiency Questionnaire (CIVIQ) quality of life score compared with 4 weeks postoperatively. Secondary end points were postoperative symptoms (pain, use of analgesics, paresthesia at the ankle, residual hematoma), complications, time taken to resume work, the patients satisfaction with the cosmetic outcome, and the CIVIQ quality of life score at 16 weeks. RESULTS The groups were well matched at baseline. In all, 95 patients could be followed up in accordance with the protocol. The treatment was successful in all patients. Endovenous laser ablation was associated with an occlusion rate of 100%. Hematomas were significantly smaller after EVLA (median [quartiles]) at 125 (55-180) cm(2) vs stripping 200 (123-269) cm(2) (P = .001). No difference was registered between groups for the CIVIQ quality of life score, with EVLA at -1.25 (-7.5-11.25) vs stripping at 4.38 (-5.94-14.38; P = .34). Several postoperative symptoms favored EVLA, but the only significant differences were seen in the minor side effects of surgery at 1 and 4 weeks and discomfort due to paresthesia at the ankle in the first postoperative week. EVLA was associated with a longer period of time until return to work (median [quartiles]) of 20 (14-25.5) days vs 14 (12.8-25) days (P = .054). CONCLUSION Endovenous laser ablation combined with high ligation is safe and effective. Postoperative hematomas are significantly smaller than those after stripping. Short-term quality of life is at least as good as that after stripping. The long-term results warrant further investigation.

Hydroxyethyl starch antibodies in humans: incidence and clinical relevance.

Hydroxyethyl starch (HES) is a plasma expander used for perioperative IV fluid management, as well as for resuscitation from trauma and shock.HES is very well tolerated, and the incidence of anaphylactic reactions is lower than with dextran or gelatin. Dextran anaphylaxis is caused by circulating dextran-reactive antibodies (ABs) of the immunoglobin G (IgG) class found in most adults. Histamine release from mast cells induces adverse reactions after gelatin infusion. The cause of adverse reactions due to HES is not yet clear. To investigate AB formation due to HES, we collected sera of 1004 patients at least 14 days after starch administration. Using a highly sensitive enzyme-linked immunoabsorbent assay technique, we found one patient with a low 1:10 titer of HES-reactive ABs (immunoglobin M [IgM] class). Despite repeated HES infusions, no clinical reaction could be detected in this patient. On the basis of a binomial distribution, a one-tailed confidence interval (99%) was used to calculate the percentage of the occurrence of ABs in general with maximum of 33 in 10,000 persons (IgM) and 23 in 10,000 persons (IgG). We suggest that HES-reactive ABs are extremely rare and that they do not necessarily induce anaphylaxis. Other mechanisms may be responsible for adverse reactions due to HES. Implications: The frequency of antibody formation due to hydroxyethyl starch, a commonly used plasma expander, was prospectively investigated in 1004 patients. Only one patient showed transient antibody formation, which was not harmful to the patient. This low antigenicity could explain the excellent tolerance of hydroxyethyl starch compared with other plasma expanders. (Anesth Analg 1998;86:1123-6)

Hypervolemic Hemodilution in Acute Ischemic Stroke: The Multicenter Austrian Hemodilution Stroke Trial (MAHST)

BACKGROUND AND PURPOSE Experimental studies suggest a beneficial effect of hemodilution on acute ischemic stroke. This was not proven by previous multicenter trials in the clinical setting. Various reasons have been suggested for the failure of these studies, which we attempted to consider in the Multicenter Austrian Hemodilution Stroke Trial (MAHST). METHODS MAHST is a randomized, double-blind, placebo-controlled study of hypervolemic hemodilution (HHD) within 6 hours of a clinically first ischemic stroke localized in the middle cerebral artery territory. The treatment consisted of 10% hydroxyethyl starch 200/0.5 (HES) and was tested against pure rehydration with Ringers lactate over a period of 5 days. Our primary outcome measure was clinical improvement within 7 days as measured by the Graded Neurologic Scale (GNS). We performed an adaptive interim analysis to reevaluate the study goal after entering half of the projected number of patients (n = 200). At least 600 patients per group would have been required for significant results, and therefore we decided to terminate the trial. RESULTS Ninety-eight patients received HHD and 102 patients placebo. The baseline characteristics were comparable between both groups. In the HHD group the absolute reduction of the hematocrit was 2.5% on day 2 with a maximum of 3.7% on day 5, which compares with a reduction in the placebo group of 1% and 1.9%, respectively. Intention-to-treat analysis showed no significant difference of the change of the GNS scores between HHD-treated (median, -8.5; 95% confidence interval, -14.2 to -4.0) and placebo-treated patients (median, -6.0; 95% confidence interval, -11.0 to 0.0) on day 7, and GNS scores remained similar in both treatment groups throughout the trial. At 3 months, slightly more HHD patients showed complete independence on the Barthel Index (28 versus 24), and fewer HHD than placebo patients had died (13 versus 17), but these differences were not statistically significant. HHD treatment was not associated with any specific adverse event. CONCLUSIONS Mild HHD is safe but failed to demonstrate a significant beneficial effect over the pure rehydration regimen in patients with acute ischemic stroke.

[Benefits of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain--a randomized controlled trial].

SummaryOBJECTIVE: The aim of this study was to investigate the efficacy and efficiency of an add-on treatment with the synthetic cannabinomimetic nabilone on patients with chronic pain. Of major interest were the evaluation of the influence the treatment had on pain and on quality of life as well as the subjective assessment of positive effects and side effects by the study participants. METHODS: The placebo-controlled double-blinded pilot study was divided into a 14 week cross-over period (two 4 week medication phases plus wash-out phases) followed by a 16 week medication switch period with free choice of the study drugs (drug A and drug B) by the study participants. The principal inclusion criterion was chronic therapy-resistant pain in causal relationship with a pathologic status of the skeletal and locomotor system. The study participants chose the dosage of the study drug themselves (between 1 und 4 capsules/day, in the case of nabilone this corresponds to ¼–1 mg/day). Pain intensity was assessed by a visual analogue scale (VAS), quality of life by the Mezzich & Cohen QOL-score. RESULTS: Altogether, 30 patients were included and analyzed. From the results, it is obvious that throughout the cross-over periods the nabilone treatment was superior (medians [25%-; 75%-percentiles]: nabilone/placebo): decrease of the average spinal pain intensity within the last 4 weeks (ΔVAS) 0.9 [0.0; 2.0] / 0.5 [0.0; 1.7], decrease of the current spinal pain intensity (ΔVAS) 0.6 [0.0; 2.5] / 0.0 [−1.0, 1.0] (p = .006), decrease of the average headache intensity within the last 4 weeks (ΔVAS) 1.0 [−1.0; 2.4] / 0.2 [−0.9; 1.0], increase of the number of days without headache within the last 4 weeks 2.0 [0.0; 6.5] / 0.0 [−5.0; 4.0], increase of the quality of life (ΔQOL-Score) 5.0 [0.8; 10.8] / 2.0 [−2.3; 8.0]. In the medication switch period, the number of study participants who favoured nabilone (nabilone intake ≥85% of all medication days) was more than 4 times higher than those who favoured placebo. The number of days with nabilone intake was clearly higher than the number with placebo intake (medians: 89% vs. 11% of all medication days, p = .003). CONCLUSION: In summary, the study results allow the conclusion that a majority of patients with chronic pain classify nabilone intake in addition to the standard treatment as a measure with a positive individual benefit-riskratio. Thus, this kind of treatment may be an interesting and attractive enrichment of analgetic therapy concepts.ZusammenfassungRATIONALE: Ziel der Studie war die Überprüfung der Wirksamkeit und Sinnhaftigkeit einer Add-On-Therapie mit dem synthetischen Cannabinomimetikum Nabilone bei Patienten mit chronischen Schmerzzuständen. Dabei standen die Evaluierung des Therapieeinflusses auf Schmerzzustand und Lebensqualität sowie die subjektive Abwägung von Wirkungen und Nebenwirkungen durch die Studienteilnehmer im Vordergrund. METHODEN: Die Placebo-kontrollierte doppelblinde Pilotstudie gliederte sich in einen 14-wöchigen Cross-Over-Abschnitt (2-mal 4-wöchige Medikationsphasen plus Wash-Out-Phasen) und einen anschließenden 16-wöchigen Medikations-Switch-Abschnitt mit freier Wahl der als Präparat A und Präparat B bekannten Prüfmedikation durch die Studienteilnehmer. Vorrangiges Einschlusskriterium waren chronische therapierefraktäre Schmerzzustände in kausalem Zusammenhang mit pathologischen Zuständen des Stütz- und Bewegungsapparates. Die Studienteilnehmer bestimmten die Prüfpräparat-Dosierung (zwischen 1 und 4 Kapseln/Tag, entspricht bei Nabilone ¼–1 mg/Tag) selbst. Schmerzintensitäten wurden mittels einer visuellen Analogskala (VAS), die Lebensqualität mittels des QOL-Scores von Mezzich & Cohen erhoben. ERGEBNISSE: Insgesamt wurden 30 Patienten in die Studie aufgenommen und ausgewertet. Die Ergebnisse zeigten im Cross-Over-Abschnitt durchwegs Vorteile der Nabilone-Therapie (Mediane [Quartile]: Nabilone/Placebo): Verringerung der durchschnittlichen Wirbelsäulen (WS)-Schmerzintensität in den letzten 4 Wochen (ΔVAS) 0,9 [0,0; 2,0] / 0,5 [0,0; 1,7], Verringerung der aktuellen WS-Schmerzintensität (ΔVAS) 0,6 [0,0; 2,5] / 0,0 [−1,0; 1,0] (p = 0,006), Verringerung der durchschnittlichen Kopfschmerzintensität in den letzten 4 Wochen (ΔVAS) 1,0 [−1,0; 2,4] / 0,2 [−0,9; 1,0], Erhöhung der Anzahl an kopfschmerzfreien Tagen in den letzten 4 Wochen 2,0 [0,0; 6,5] / 0,0 [−5,0; 4,0], Verbesserung der Lebensqualität (ΔQOL-Score) 5,0 [0,8; 10,8] / 2,0 [−2,3; 8,0]. Im Medikations-Switch-Abschnitt wurde eine mehrheitliche Nabilone-Einnahme (≥85% aller Medikationstage) von mehr als viermal so vielen Studienteilnehmern gewählt wie eine mehrheitliche Placebo-Einnahme. Die Anzahl der Tage mit Nabilone-Einnahme war klar höher als jene mit Placebo-Einnahme (Mediane: 89% vs. 11% aller Medikationstage, p = 0,003). SCHLUSSFOLGERUNGEN: Insgesamt lassen die Studienergebnisse den Schluss zu, dass die Nabilone-Einnahme zusätzlich zur Standardtherapie von einer Mehrheit an Patienten mit chronischen Schmerzzuständen als eine Maßnahme mit positiver individueller Nutzen-Risiko-Relation gesehen wird und somit eine interessante und attraktive Bereicherung des analgetischen Behandlungskonzepts darstellen kann.

Intestinal elimination of hydroxyethyl starch

Objective: Hydroxyethyl starch (HES) is mainly eliminated via the kidneys. Any information about extrarenal elimination obtained so far has been either incomplete or contradictory. The objective of this study was to quantify the intestinal excretion of infused HES with a mean molecular weight of 200,000 and a molar substitution of 0.5 (HES 200/0.5) and to compare the reappearance/recovery rate in urine and plasma.¶Design: Prospective clinical study without control group.¶Setting: The study was conducted at the Institute of Hypertension of the Society of Clinical Pharmacology, Vienna, Austria, which is an establishment for research in volunteers.¶Participants: The results of six out of seven healthy male volunteers were appropriate for analysis. One trial subject had to be excluded from the study because of severe protocol violation (mixing of stool and urine samples).¶Interventions and methods: Each volunteer was administered 500 ml of 10 % HES 200/0.5 in a 0.9 % NaCl solution intravenously within 1 h. A gut lavage with 6 l of a polysaccharide free solution was continuously administered from 3 h prior to until 2 h after the HES infusion to facilitate the collection of the samples and to exclude any source of error at analysis. HES was quantified with the hexokinase method.¶Measurements and results: Right from the beginning of the infusion until 10 h after its completion, the cumulative HES excretion with feces (principle parameter) and urine as well as selective plasma volume and HES plasma level were measured. Six and 14 h after the infusion had been completed, the recovery rates of HES in urine were about 30 % and 40 %, respectively, and in plasma about 23 % and 8 %, respectively. By contrast, not more than a kind of “background noise amount” of HES (about 0.2 %) could be recovered in feces ( mean value in % of the infused amount of the substance). Six and 14 h after the infusion had been completed, the total recovery rates of HES were 53 % and 49 %, respectively.¶Conclusion: In a physiologically unimpaired gut HES 200/0.5 is not, or only to an infinitesimal extent, eliminated via the intestine. The question if there is any alternative path to renal excretion for HES still remains to be answered. As the calculated reappearance/recovery rate of HES is only about 50 % of the administered dose, further investigations as to the final fate of HES appear necessary.

624 BENEFITS OF AN ADD‐ON TREATMENT WITH THE SYNTHETIC CANNABINOMIMETIC NABILONE ON PATIENTS WITH CHRONIC PAIN‐A RANDOMIZED CONTROLLED TRIAL

pediatric cleft lip and palate surgery for determining the efficacy of different doses of Fentanyl. Methods: 40 children aged 3mo-3 yrs were divided in 2 groups randomly (n = 20) after induction of general anesthesia with Thiopental 5mg/kg, Lidocaine 1mg/kg, Midazolam 0.2mg, Patients received 3m/kgfentanyl in group A, and Fentanyl 1m/kg + Acetaminophen rectal 20mg/kg in group B, repeated doses of rectal Acetaminophen was 10mg/kg/2 h. Intra operative pain was measured with change of vital signs from base and need to increase of halothane percentage. Results: Vital signs were more stable in group B than group A (P> 0.05). There was a need to increase halothane percentage during surgery in group A, rather than group B (P< 0.05). Conclusion: We conclude that low dose Fentanyl + repeated rectal Acetaminophen provides more effective analgesia and less side effects in children.

Optimal Scaling for Ordered Categories

When measuring the responses of individuals on scoring scales, it is usually necessary to assign numerical values to points on these scales and to proceed with statistical analyses based on these numerical scores. Generally, we can assume that the scale points are ordered. In common practice we consider points on scoring scales as evenly spaced, and we thus imply an arithmetic scale. But such an assignment of scale values may not be optimal. In order to find a solution to this problem we can use the method of correspondence analysis (optimal scaling).

Nutzen einer Add-On-Therapie mit dem synthetischen Cannabinomimetikum Nabilone bei Patienten mit chronischen Schmerzzuständen - eine randomisierte kontrollierte Studie

RATIONALE: Ziel der Studie war die Uberprufung der Wirksamkeit und Sinnhaftigkeit einer Add-On-Therapie mit dem synthetischen Cannabinomimetikum Nabilone bei Patienten mit chronischen Schmerzzustanden. Dabei standen die Evaluierung des Therapieeinflusses auf Schmerzzustand und Lebensqualitat sowie die subjektive Abwagung von Wirkungen und Nebenwirkungen durch die Studienteilnehmer im Vordergrund. METHODEN: Die Placebo-kontrollierte doppelblinde Pilotstudie gliederte sich in einen 14-wochigen Cross-Over-Abschnitt (2-mal 4-wochige Medikationsphasen plus Wash-Out-Phasen) und einen anschliesenden 16-wochigen Medikations-Switch-Abschnitt mit freier Wahl der als Praparat A und Praparat B bekannten Prufmedikation durch die Studienteilnehmer. Vorrangiges Einschlusskriterium waren chronische therapierefraktare Schmerzzustande in kausalem Zusammenhang mit pathologischen Zustanden des Stutz- und Bewegungsapparates. Die Studienteilnehmer bestimmten die Prufpraparat-Dosierung (zwischen 1 und 4 Kapseln/Tag, entspricht bei Nabilone ¼–1 mg/Tag) selbst. Schmerzintensitaten wurden mittels einer visuellen Analogskala (VAS), die Lebensqualitat mittels des QOL-Scores von Mezzich & Cohen erhoben. ERGEBNISSE: Insgesamt wurden 30 Patienten in die Studie aufgenommen und ausgewertet. Die Ergebnisse zeigten im Cross-Over-Abschnitt durchwegs Vorteile der Nabilone-Therapie (Mediane [Quartile]: Nabilone/Placebo): Verringerung der durchschnittlichen Wirbelsaulen (WS)-Schmerzintensitat in den letzten 4 Wochen (ΔVAS) 0,9 [0,0; 2,0] / 0,5 [0,0; 1,7], Verringerung der aktuellen WS-Schmerzintensitat (ΔVAS) 0,6 [0,0; 2,5] / 0,0 [−1,0; 1,0] (p = 0,006), Verringerung der durchschnittlichen Kopfschmerzintensitat in den letzten 4 Wochen (ΔVAS) 1,0 [−1,0; 2,4] / 0,2 [−0,9; 1,0], Erhohung der Anzahl an kopfschmerzfreien Tagen in den letzten 4 Wochen 2,0 [0,0; 6,5] / 0,0 [−5,0; 4,0], Verbesserung der Lebensqualitat (ΔQOL-Score) 5,0 [0,8; 10,8] / 2,0 [−2,3; 8,0]. Im Medikations-Switch-Abschnitt wurde eine mehrheitliche Nabilone-Einnahme (≥85% aller Medikationstage) von mehr als viermal so vielen Studienteilnehmern gewahlt wie eine mehrheitliche Placebo-Einnahme. Die Anzahl der Tage mit Nabilone-Einnahme war klar hoher als jene mit Placebo-Einnahme (Mediane: 89% vs. 11% aller Medikationstage, p = 0,003). SCHLUSSFOLGERUNGEN: Insgesamt lassen die Studienergebnisse den Schluss zu, dass die Nabilone-Einnahme zusatzlich zur Standardtherapie von einer Mehrheit an Patienten mit chronischen Schmerzzustanden als eine Masnahme mit positiver individueller Nutzen-Risiko-Relation gesehen wird und somit eine interessante und attraktive Bereicherung des analgetischen Behandlungskonzepts darstellen kann.

When is a clinical study non-commercial?

SummaryA non-commercial study is a research project not aiming at the protection of a commercial institution’s interests. The classification of a clinical study as non-commercial or commercial makes sense and is important especially for clinical research teams, ethics committees and hospital owners because of relevant differences in the image and cost fields. The support of non-commercial studies by commercial institutions like pharmaceutical companies is permissible, unless it is tied to conditions impairing impartiality in respect of design, publication of study results or ownership of the assessed data. Specific relationships between the investigator and a company of the health industry potentially profiting from the study results (e.g., major share holdings or financial dependences) favour the classification of a study as commercial. The reliable classification of a study as non-commercial is only possible if all aids and grants, all conflicts of interest and special agreements are disclosed.ZusammenfassungEine nicht-kommerzielle (akademische) Studie ist ein Forschungsprojekt, das nicht auf die Wahrung von Interessen einer kommerziell ausgerichteten Institution abzielt. Die Einstufung einer klinischen Studie als akademisch oder kommerziell ist sinnvoll bzw. vor allem für die forschende Ärzteschaft, Ethikkommissionen und Träger von Krankenanstalten wichtig, da durchaus relevante Unterschiede im Image- und Kostenbereich bestehen. Eine Unterstützung von akademischen Studien durch kommerzielle Institutionen wie z. B. pharmazeutische Unternehmen ist unproblematisch, sofern damit nicht Auflagen verbunden sind, die eine Beeinträchtigung der objektiven Studienplanung, der Ergebnisveröffentlichung oder der Rechte des akademischen Studieninitiators an den erhobenen Daten darstellen. Relevante direkte oder indirekte Verknüpfungen mit einem potentiell von den Projektergebnissen profitierenden Unternehmen der Gesundheitsbranche (z. B. größere Beteiligungen oder finanzielle Abhängigkeiten) sprechen für die Einstufung einer Studie als kommerziell. Ohne Offenlegung aller Unterstützungen, Interessenkonflikte und Sondervereinbarungen ist die verlässliche Einstufung einer Studie als akademisch nicht möglich.

When is a clinical study non-commercial?@@@Wann ist eine klinische Studie nicht-kommerziell?

SummaryA non-commercial study is a research project not aiming at the protection of a commercial institution’s interests. The classification of a clinical study as non-commercial or commercial makes sense and is important especially for clinical research teams, ethics committees and hospital owners because of relevant differences in the image and cost fields. The support of non-commercial studies by commercial institutions like pharmaceutical companies is permissible, unless it is tied to conditions impairing impartiality in respect of design, publication of study results or ownership of the assessed data. Specific relationships between the investigator and a company of the health industry potentially profiting from the study results (e.g., major share holdings or financial dependences) favour the classification of a study as commercial. The reliable classification of a study as non-commercial is only possible if all aids and grants, all conflicts of interest and special agreements are disclosed.ZusammenfassungEine nicht-kommerzielle (akademische) Studie ist ein Forschungsprojekt, das nicht auf die Wahrung von Interessen einer kommerziell ausgerichteten Institution abzielt. Die Einstufung einer klinischen Studie als akademisch oder kommerziell ist sinnvoll bzw. vor allem für die forschende Ärzteschaft, Ethikkommissionen und Träger von Krankenanstalten wichtig, da durchaus relevante Unterschiede im Image- und Kostenbereich bestehen. Eine Unterstützung von akademischen Studien durch kommerzielle Institutionen wie z. B. pharmazeutische Unternehmen ist unproblematisch, sofern damit nicht Auflagen verbunden sind, die eine Beeinträchtigung der objektiven Studienplanung, der Ergebnisveröffentlichung oder der Rechte des akademischen Studieninitiators an den erhobenen Daten darstellen. Relevante direkte oder indirekte Verknüpfungen mit einem potentiell von den Projektergebnissen profitierenden Unternehmen der Gesundheitsbranche (z. B. größere Beteiligungen oder finanzielle Abhängigkeiten) sprechen für die Einstufung einer Studie als kommerziell. Ohne Offenlegung aller Unterstützungen, Interessenkonflikte und Sondervereinbarungen ist die verlässliche Einstufung einer Studie als akademisch nicht möglich.