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DMW - Deutsche Medizinische Wochenschrift 06/2013; 138(25-26):1365-8. · 0.53 Impact Factor
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ABSTRACT: The novel melatonin agonist Neu-P11 is used in treatment of physiological insomnia. In animal studies Neu-P11 showed sleep-promoting effects. In a phase 1 study Neu-P11 was administered to cohorts of healthy young male volunteers in an ascending single dose study. Up to now the metabolism of this new drug in humans has not been investigated. The first aim of this study was to identify possible metabolites in pooled urine samples of the first collecting period (0-8h) of volunteers with the highest Neu-P11 oral dosage (200mg). The objective of the second part of the study was to estimate the concentrations of the main metabolites of Neu-P11 - in this urine sample. The analyte Neu-P11 and metabolites were separated from human urine using dilution and precipitation with acetonitrile. Samples were analyzed for formation of both phase I and phase II metabolites using LC-MS/MS in precursor ion mode, product ion mode, neutral loss mode and the multi-reaction monitoring mode (MRM). Urine samples were analyzed before and after addition of beta-glucuronidase and sulfatase. In the pooled urine sample eight metabolites could be proved. The parent drug, the sulfated demethylated Neu-P11, the sulfated 6OH-Neu-P11 and the di-oxygenated product gave the highest signals in these urine samples and probably had the highest concentration. But quantification without reference substances is not possible. So in the second part of the study the urine samples were additionally analyzed with UV-detection for a better estimation of the metabolite concentrations. The concentration of the sulfated metabolites was more than ten times higher than the concentration of the unchanged drug in urine. Other metabolites were not measurable with UV-detection. The di-oxygenated Neu-P11 and an additional mono-oxygenated Neu-P11 showed relatively high signals in MS/MS. Probably the other metabolites, namely glucuronides, unconjugated demethylated Neu-P11 and unconjugated 6OH-Neu-P11, were formed at a lesser extent.
Journal of chromatography. A 01/2013; · 4.19 Impact Factor
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ABSTRACT: Hintergrund und ZielDiabetes mellitus ist eine chronisch progrediente Erkrankung mit zunehmender Prävalenz und verursacht hohe Kosten für das
Gesundheitssystem. Seit 2003 wurden Disease-Management-Programme (DMP) Diabetes in Deutschland flächendeckend eingeführt.
2004 ist das Gesetzliche Krankenversicherungs-(GKV-)Modernisierungsgesetz (GMG) in Kraft getreten. Ziel der Studie war die
Untersuchung der Auswirkung von DMP und GMG auf die Antidiabetikaverordnungen im GKV-Bereich.
Material und MethodeDie Verordnungsdaten der Antidiabetika wurden aus den jährlichen „Arzneiverordnungs-Reports“ des Wissenschaftlichen Instituts
der AOK von 1993–2006 extrahiert. Die statistische Auswertung erfolgte deskriptiv bzw. bei ausreichender Datenbasis durch
Regressionsanalysen. Die Analyse umfasste die Verordnungstrends der Antidiabetika und die entsprechenden Kosten sowie die
möglichen Ausgabeneinsparungen.
ErgebnisseDie Verordnungszunahme der Antidiabetika war stärker als die Steigerung der Ausgaben während des beobachteten DMP-Zeitraums
(2003–2006) hierfür (8,2% vs. 0%). Die Insulinverordnungen sind inzwischen bei ca. 43% stabil bzw. die Ausgaben für Insuline
sind von 72,3% auf 70% aller Antidiabetika leicht gesunken. Die Anwendung der kurzwirkenden Humaninsuline stiegen schneller
als die der kurzwirkenden Insulinanaloga (+16,4 vs. +8,4Mio. standardisiert verschriebenen Tagesdosen („defined daily dose“,
DDD pro Jahr). Die führende therapeutische Klasse bei den oralen Antidiabetika (OAD) änderte sich 2006 von Sulfonylharnstoffen
(44%) zu Metformin (47%). Die Anwendung des Glimepirid (Amaryl®) hat von 28% auf 8,4% der OAD abgenommen. Die Verordnungen
der Glinide sind relativ stabil bei 36Mio.DDD geblieben. Die Verordnungen der Glitazone (ohne Kombinationsprodukte) zeigten
eine verhaltene Zunahme, die Rosiglitazon-Meformin-Kombination zeigte eine kontinuierliche Erhöhung (von 4,2 in 2004 auf 21,7Mio.DDD
in 2006). Die mittleren Kosten je DDD eines Antidiabetikums haben sich von 0,93EUR 2003 auf 0,86EUR 2004 um 0,07EUR (ca.
7,5%) vermindert und sind bis 2006 relativ konstant geblieben, unter diesen Bedingungen ergaben sich beträchtliche Einsparungen
bei allen Antidiabetika von ca. 306Mio.EUR. Die Ausgaben für sämtliche Antidiabetika sind inzwischen stabil geblieben.
SchlussfolgerungUnsere Analyse erbrachte Hinweise darauf, dass durch die Einführung von DMP und GMG eine leitlinienorientierte und wirtschaftlichere
Arzneimitteltherapie mit der entsprechenden Senkung der Kosten für Antidiabetika im gesamten GKV-Bereich erzielt wurde.
Background and PurposeDiabetes mellitus is a chronic progressive disease with increasing prevalence leading to high costs for Health care systems.
Since 2003 diabetes disease-management-programs (DMPs) have been universally introduced by the German statutory-health-insurance
(SHI). In 2004 the new regulations of modernization for SHI (RoM-SHI) came into force. The aim of this study was to examine
the impact of DMPs and RoM-SHI on antidiabetic prescription in the SHI in Germany.
Material and MethodsAntidiabetic prescription data were extracted from the German Drug-Prescription-Reports (1993 to 2006). We applied the auto-regression
analysis to assess the prescription trends of antidiabetics and related costs as well as the cost saving potential due to
DMPs.
ResultsDuring the observed DMPs period (2003–2006), the prescription of antidiabetic drugs increased more than its expenditure (8.2%
vs. 0%). The insulin use is stable at about 43% of total antidiabetics, the insulin expenditure slightly declined from 72.3%
of total expenditures of antidiabetic drugs to 70%. The use of ultrashort-acting human insulins increased more than the use
of ultrashort-acting insulin analogues (+ 16.4 million defined daily doses (DDD) vs. + 8.4 million DDD per year). Leading
therapeutic class in oral antidiabetics (OAD) has shifted in 2006 from sulfonylurea (44% of OAD) to metformin (47%). The glimepirid
(Amaryl®) use decreased from 28% of OAD to 8.4%. The glinide was relatively stable prescribed with 36 million DDD. Increasing
use of glitazones (excluding its combination product) was modest, the combination product use (rosiglitazon with metformin)
increased very rapidly, from 4.2 million DDD in 2004 to 21.7 million DDD in 2006. The mean cost per DDD of an antidiabetic
reduced from 0.93 Euro in 2003 to 0.86 Euro in 2004 by 0.07 Euro (7.5%) and then remained relatively constant to 2006, which
resulted in a considerable monetary-saving of approximately 306 million Euros. All antidiabetics expenditures were not changed
at the beginning and end of the observed DMPs period.
ConclusionOur analysis provided evidence that the introduction of DMPs and the new RoM-SHI led to a guideline-based and more economical
pharmacotherapy with the corresponding reduction in expenditures for antidiabetic agents in the whole SHI.
SchlüsselwörterAntidiabetika-Diabetes mellitus-Disease-Management-Programme-Krankenversicherungsmodernisierungsgesetz-Verordnungen
KeywordsAntidiabetics-Diabetes mellitus-Disease-Management- Programs-Regulations of modernization for the statutory-health-insurance-Prescriptions
Prävention und Gesundheitsförderung 04/2012; 5(2):159-168.
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ABSTRACT: HintergrundKörperliche Inaktivität ist charakteristisch für den Lebensstil der modernen westlichen Welt. Daraus resultiert die Zunahme
der Zivilisationskrankheiten. Mit Sport kann dem entgegengewirkt werden.
MethodeDer Nutzen und das Risiko von Sport sollen an Hand vorliegender Publikationen gegenüber gestellt werden. Dabei werden die
verschiedenen Sportarten und die Intensität des Trainings berücksichtigt.
ErgebnisseDer Nutzen des Sports für die Gesundheit ist vielfach belegt und übersteigt die Risiken weit. Ohne Hochleistungssport und
Extremsport mit ihren hohen Verletzungsrisiken, fällt die Nutzen-Risiko-Analyse noch günstiger aus. Ein relativ hohes Gesundheitsrisiko
haben Gelegenheitssportler, die sich bei schlechter Fitness aufgrund von Unerfahrenheit, Koordinationsproblemen und Selbstüberschätzung
leicht verletzen. Das Betreiben von Ballsportarten ist riskanter als Joggen, Schwimmen oder Wandern. Es ist meist einfacher,
sich für Mannschaftssportarten zu motivieren. Eine gute Alternative stellen Laufgruppen dar. Die Teilnehmer sind durch ein
gemeinsames Ziel (z.B. ein Marathonlauf) gut motiviert, trainieren dafür lange und kontinuierlich. Das Gesundheitsrisiko
im Sport ist sehr gering, wenn vorab eine ärztliche Kontrolle erfolgte und die Trainingsumfänge nur langsam gesteigert werden.
Kontinuierliches Training, besondere Vorsicht, wenn man bereits ermüdet ist, und Vermeidung von übermäßigem Ehrgeiz reduzieren
das Risiko noch weiter. Wer dann noch Ausdauersport bevorzugt, hat garantiert ein ausgezeichnetes Nutzen-Risiko-Verhältnis.
SchlussfolgerungKörperliche Aktivität begünstigt die Gesundheit. Das Risiko von Sportunfällen lässt sich minimieren. Das beste Nutzen-Risiko-Verhältnis
haben moderat betriebene Ausdauersportarten.
BackgroundPhysical inactivity is typical of the Western lifestyle. Therefore, an increase in the diseases of modern civilization has
been observed. But with the help of sports, health can be improved.
MethodThe literature was analysed to compare the benefits and risks of sport activities. The different kinds of sports and the intensity
of training are discussed.
ResultsThe risk-benefit analysis shows that taking part in sports is favourable for health. However, high-performance and extreme
sports have a high health hazard. Inexperienced recreational athletes with poor fitness, coordination problems, and an overestimation
of one’s abilities have a high risk of injuring themselves. Ball games are riskier than jogging, swimming, or hiking, but
team sports are better for motivation. A good alternative to ball games are running groups whose members have a common aim,
such as finishing a marathon; they train steadily with good motivation for a long time. In addition, some measures can minimise
the health risks in sports: a preventive medical check-up, continuous training, moderate increases in training intensity,
caution in the event of fatigue, and avoidance of excessive ambition. Athletes who follow these rules and who also prefer
endurance sports have an excellent benefit–risk ratio.
ConclusionPhysical activity is good for health, and the risk of sports injuries can be minimised. Moderate training in an endurance
sport has the best benefit–risk ratio.
Prävention und Gesundheitsförderung 04/2012; 4(4):240-244.
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ABSTRACT: Die wachsende Anzahl von Arzneimitteln und Innovationen führt zu einer Unübersichtlichkeit des Arzneimittelmarktes, bei der
die Vielfalt möglicher Neben- und Wechselwirkungen ad hoc kaum beachtet werden kann. Aus diesen Gründen ist es notwendig,
dem behandelnden Arzt mit effizienten und interessenunabhängigen Arzneimittelinfodiensten sichere und kritisch evaluierte
Unterstützung in der Pharmakotherapie zu geben. Daher hat sich in den letzten Jahren eine Reihe von Angeboten zur individualisierten
Arzneimittelinformation für Ärzte etabliert, deren Qualität und Nützlichkeit für die Pharmakotherapie aus Sicht dieser Nutzergruppe
positiv eingeschätzt wurden.
Auch auf Seiten der Patienten sind Informationsdefizite zur Arzneimitteltherapie zu verzeichnen, die auf generelle Mängel
in der Arzt-Patienten-Kommunikation zurückzuführen sind. An diesem Punkt knüpfen patientenorientierte Arzneimittelberatungsdienste
an, die dem Patienten ein verbessertes Selbstbewusstsein hinsichtlich seiner Erkrankung, dem Vertrauen in seine Arzneitherapie
und dem Selbstmanagement von Symptomen geben. In der Evaluation dieser Angebote wurde der Service von den Patienten als sinnvoller
Service bewertet.
The growing number of medicinal products and innovations has led to great complexity in the pharmaceutical market. The variety
of possible drug interactions and side effects can only be overviewed with difficulty. Therefore, it is necessary that services
for physicians be offered in order to provide critically evaluated and independent drug information for pharmacotherapy. In
recent decades, a series of hospital based drug information centres have been established. Their quality and usefulness for
patients have been positively evaluated by the users. Many patients are also insufficiently informed on their own drug therapy.
This deficit is based on a general lack in communication between the patient and physician. Patient-orientated drug information
services can help strengthen patients in their drug therapy and self management of symptoms, and to improve compliance. Such
services have also been positively evaluated by patients.
Der Internist 04/2012; 48(9):1029-1035. · 0.30 Impact Factor
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ABSTRACT: In legal medicine in many cases drugs are detected in autopsy material without connection to the cause of death, and until now no further investigations have taken place. In our study more than 50 drugs were measured directly in several compartments. The deceased had received continual therapeutic treatment, treatment during an operation or an unsuccessful emergency therapy. Liquid-liquid extraction and an LC-MS/MS method were developed for the determination of these drug concentrations. When measuring many transitions in a biological matrix, two problems should be excluded: ion suppression and too few measurement points per peak. A relatively short operation time and sufficient separation were achieved by column, eluent and gradient optimization with POPLC (phase-optimized liquid chromatography). Various autopsy materials from about 170 cases were investigated. In particular, in nine cases with four or more simultaneously determined drugs, their distribution in the compartments is very interesting for pharmacokinetic examinations. The distribution patterns of the drugs in the compartments of one individual deceased were compared. This meant that the great differences between subjects that are normally encountered these studies could be excluded. Measurements of drug concentrations in human autopsy material deepens knowledge of the respective drugs' pharmacokinetics. Copyright © 2012 John Wiley & Sons, Ltd.
Biomedical Chromatography 04/2012; 26(12):1608-16. · 1.97 Impact Factor
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ABSTRACT: Dietary supplements are a product group of foods, which are meant to supplement the general nutrition with micronutrients and other substances. They are widely used in Germany. We evaluated the frequency of their use and of information requirements concerning dietary supplements in patients who contacted the independent drug information service at TU Dresden.
All inquiries from 2008 to 2010 were evaluated regarding information requirement about dietary supplements, the kind of products used and characteristics of patients using supplements. Sociodemographic characteristics, kind and number of drugs and dietary supplements as well as underlying diseases were recorded from the inquiring patients.
23.3 % of persons looking for advice used dietary supplements. The most frequently used product groups included vitamins and minerals (52.5 %) as well as plant extracts (14.0 %). Information requirements were especially high for plant extracts and for products containing glucosamine/chondroitin and lutein/zeaxanthin. Users of dietary supplements were exposed to a higher number of different products than non-users.
Information requirements were primarily detected for products without clearly proven benefits or for supplements which are advertised to relieve certain diseases or symptoms although the product characteristics do not support such utilization. The frequency of use of dietary supplements among patients which already receive multiple medications substantiates the necessity to include dietary supplements in assessments of drug interactions and to scrutinize indications for supplement use.
DMW - Deutsche Medizinische Wochenschrift 04/2012; 137(17):881-6. · 0.53 Impact Factor
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ABSTRACT: The development of new drugs for the treatment of type 2 diabetes (T2DM) and metabolic disorders is currently one of the most innovative areas of drug development. However, a considerable number of newly developed drugs have either not reached the market and were stopped late in development or have been withdrawn after initial approval soon after market authorization due to serious safety concerns. How can drug safety problems be anticipated and, even more important, how can adverse events definitely caused by a drug be differentiated from incidences of naturally occurring diseases? This review article will provide an update about the state of the art treatment of type 2 diabetes and reflect on the newest available study evidence on glitazones, incretin mimetics (GLP-1 agonists and DPP-4 inhibitors), SGLT-2 inhibitors (gliflocines) and pan-PPAR agonists (glitazars). Furthermore, new and still experimental approaches for the treatment of T2DM, such as bardoxolone, salsalate and anakinra will be briefly reviewed.
Der Internist 03/2012; 53(4):478, 480-5, 487. · 0.30 Impact Factor
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DMW - Deutsche Medizinische Wochenschrift 01/2012; 137(3):78-82. · 0.53 Impact Factor
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DMW - Deutsche Medizinische Wochenschrift 04/2011; 136(17):910. · 0.53 Impact Factor
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ABSTRACT: In forensic medicine autopsy material is primarily investigated to find out the cause of death. But the results of corresponding toxicology measurements often involve more information. With screening methods drugs were detected not being related to the cause of death. Liquid/liquid extraction and LC/MS/MS methods were used for the determination of drug concentrations. In seven cases metoprolol could be determined in different autopsy materials. In all cases the dosage of the drug was unknown. In cases with oral application probably the patients took a normal customary continuous dosage. Intoxication with metoprolol could be excluded in all cases. The concentrations of metoprolol in blood were all in the therapeutic range. The time between oral intake and death was unknown. Therefore and because of the low number of cases statistic calculations were not meaningful and an individual case study was necessary. In three cases the highest concentration of metoprolol was found in the liver. Probably, metoprolol was taken shortly before the person died. In the other cases the highest concentration of metoprolol was found in urine. This means the elimination process of the drug predominated at the time of death. In all cases the concentrations of metoprolol were similar in the compartments heart blood, venous blood and brain. In this study it was possible to measure the distribution of metoprolol in human directly in several compartments. Measurement of drug concentrations in human autopsy material deepen the knowledge of its pharmacokinetics.
Pharmazie 02/2011; 66(2):115-8. · 1.01 Impact Factor
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ABSTRACT: In this study it was possible to measure the distribution of metoprolol, tramadol, and midazolam in human directly in several compartments. In the legal medicine autopsy material is normally investigated to find out the cause of death. But the results of corresponding toxicology measurements often involve more information. With screening methods drugs were detected without connection to the cause of death. The deceased had either a continual therapeutic treatment, a treatment during an operation, or an unsuccessful urgent therapy. A liquid/liquid extraction and a LC/MS/MS method were developed for the determination of the drug concentrations. Different autopsy materials of about 120 cases were investigated. Most frequently the drugs metoprolol, tramadol, and midazolam could be proved and determined simultaneously. Metoprolol was found in seven cases, tramadol in seven cases and midazolam in thirteen cases. The dosage of the drugs was unknown. Therefore and because of the low number of cases statistic calculations were not meaningful and an individual case study was necessary. In all cases with oral metoprolol application the patients probably took a normal customary continuous dosage. The concentrations of tramadol in blood were in the toxic range in three cases. The distribution of tramadol in the compartments was independent of the dosage. The time between oral intake of metoprolol or tramadol and death was unknown. With the distribution pattern of metoprolol in the compartments it was possible to estimate the duration between drug intake and death. In most cases midazolam was given intravenously during an operation or an unsuccessful urgent therapy. Sometimes the time between dosage and death was documented. The duration between application of the drug and death played the crucial role for the distribution of midazolam in the compartments. Measurements of drug concentrations in human autopsy material deepen the knowledge of the respective drugs' pharmacokinetics.
Journal of chromatography. A 01/2011; 1218(30):4988-94. · 4.19 Impact Factor
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ABSTRACT: A 71-year-old patient with a superficial carcinoma of the urinary bladder and high risk of recurrence was treated with intravesical instillation of Bacillus Calmette-Guérin (BCG) after transurethral resection. As a complication of the catheterization during BCG-instillation therapy the patient suffered from tuberculosis. The patient received a tuberculosis triple-therapy including rifampicin 600 mg once daily, isoniazid 300 mg once daily and ethambutol 400 mg thrice daily. The existing arterial hypertension had successfully been controlled by 3.75 mg bisoprolol medication once daily for the last 15 years. An increase of blood pressure and cardiac arrhythmia were seen after combining the β (1)-receptor blocker treatment with the triple-therapy.
The blood pressure was 160 / 90 mmHg. The heart rate reflected a value of 98 beats per minute. In the resting ECG monotopic ventricular extrasystoles could be diagnosed.
The dosage of bisoprolol was changed to 3.75 mg in the morning and additional 1.875 mg in the evening. Due to this increase of dosage the blood pressure could be controlled sufficiently.
Rifampicin is one of the best known potent enzyme inducing drugs. It strongly induces the expression of cytochrome P450 3A4 in the liver. The enzyme induction enhance the hepatic bisoprolol metabolism, hence the metabolic clearance of the drug increased. The maximal plasma level of bisoprolol decrease and in our use the arterial hypertension could not be treated sufficiently. It is well known that half the dose of bisoprolol undergoes oxidative metabolism in the liver and the rest eliminated unchanged in the kidney. A dosage adjustment of bisoprolol is necessary if the clinical status of the patient requires treatment with the antituberculosis drug rifampicin.
Aktuelle Urologie 11/2010; 41(6):372-4. · 0.27 Impact Factor
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ABSTRACT: A 71-year-old patient with a superficial carcinoma of the urinary bladder and high risk of recurrence was treated with intravesical instillation of Bacillus Calmette-Guérin (BCG) after transurethral resection. As a complication of the catheterization during BCG-instillation therapy the patient suffered from tuberculosis. The patient received a tuberculosis triple-therapy including rifampicin 600 mg once daily, isoniazid 300 mg once daily and ethambutol 400 mg thrice daily. The existing arterial hypertension had successfully been controlled by 3.75 mg bisoprolol medication once daily for the last 15 years. An increase of blood pressure and cardiac arrhythmia were seen after combining the β1-receptor blocker treatment with the triple-therapy.
The blood pressure was 160/90 mm Hg. The heart rate reflected a value of 98 beats per minute. In the resting ECG monotopic ventricular extrasystoles could be diagnosed.
The dosage of bisoprolol was changed to 3.75 mg in the morning and additional 1.875 mg in the evening. Due to this increase of dosage the blood pressure could be controlled sufficiently.
Rifampicin is one of the best known potent enzyme inducing drugs. It strongly induces the expression of cytochrome P450 3A4 in the liver. The enzyme induction enhance the hepatic bisoprolol metabolism, hence the metabolic clearance of the drug increased. The maximal plasma level of bisoprolol decrease and in our use the arterial hypertension could not be treated sufficiently. It is well known that half the dose of bisoprolol undergoes oxidative metabolism in the liver and the rest eliminated unchanged in the kidney. A dosage adjustment of bisoprolol is necessary if the clinical status of the patient requires treatment with the antituberculosis drug rifampicin.
DMW - Deutsche Medizinische Wochenschrift 10/2010; 135(40):1968-70. · 0.53 Impact Factor
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DMW - Deutsche Medizinische Wochenschrift 08/2010; 135(31-32):1561-2. · 0.53 Impact Factor
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ABSTRACT: In daily clinical practise, there is a lack of representative and robust data on the health-related quality of life (QoL) of patients with atrial fibrillation (AF).
In the non-interventional MOVE study, 638 physicians (predominantly cardiologists) in ambulatory care (78.0% of all centres) or hospital-based (12.7%), documented prospectively and retrospectively data from 3354 consecutive patients with ECG-confirmed AF in the previous 12 months (mean age 68.9 +/- 10.1 years; 62.4% males, mean CHADS (2) score 1.9 +/- 1.3). 1136 (33.9%) had paroxysmal, 899 (26.8%) persistent and 1295 (38.6%) permanent AF.
Symptoms within the previous 4 weeks were present in 89.9% of the cases and 43.1% of the patients reported palpitations in the range from sometimes to very frequently. As treatment aim, physicians reported rate control in 64%, rhythm control in 8%, and both in 19% of the cases (not stated: 8%). In the University of Toronto Atrial Fibrillation Severity Scale (AFSS), emergency room attendance or hospitalizations for AF or associated diseases in the previous 12 months were reported in 24.2% or 30.8%, respectively. Rhythm control was associated with higher emergency room admittance or hospitalization rates, respectively. The EQ-5D index (0.94 points) was near the maximum of 1; thus this index does not appear to reflect QoL of AF patients adequately. Analyses of the Visual Analogue Scale (VAS) of the EuroQol (EQ-5D), and the assessment scale or specific questions of AFSS, respectively, indicated an intermediate QoL or disease burden, respectively. No or only small differences were documented between subgroups with different AF types, or subgroups treated according to different aims.
The great majority of AF patients had one or more recent AF symptoms, and their overall QoL was limited. In daily practise, rate control is not inferior to rhythm control in AF patients with respect to QoL.
DMW - Deutsche Medizinische Wochenschrift 03/2010; 135 Suppl 2:S26-32. · 0.53 Impact Factor
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ABSTRACT: A male patient with severe chronic pain has been treated with a combined drug therapy scheme of morphine and clonidine. After cessation of clonidine the patient reported opiate-withdrawal symptoms with agitation, polyuria, diarrhea, and hyperalgesia. It is known that the combination of these two substances causes synergistic analgetic effects. The abrupt cessation of clonidine after a combined administration with morphine seems to lead to a relative decrease in opiate effects and furthermore excite opiate-withdrawal symptoms.
Der Internist 03/2010; 51(5):667-9. · 0.30 Impact Factor
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DMW - Deutsche Medizinische Wochenschrift 09/2009; 134(39):1956. · 0.53 Impact Factor
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DMW - Deutsche Medizinische Wochenschrift 08/2009; 134(31-32):1593-4. · 0.53 Impact Factor
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European Journal of Clinical Investigation 06/2009; 39 Suppl 2:1-2. · 3.02 Impact Factor
