Review & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms - an update on the evidence.

A systematic literature search revealed 35 clinical studies and one meta-analysis comprising 43,759 women, of which 13,096 were treated with isopropanolic Cimicifuga racemosa extract (iCR). Compared to placebo, iCR was significantly superior for treating neurovegetative and psychological menopausal symptoms, with a standardized mean difference of -0.694 in favor of iCR (p < 0.0001). Effect sizes were larger when higher dosages of iCR as monotherapy or in combination with St. John's wort (Hypericum perforatum [HP]) were given (-1.020 and -0.999, respectively), suggesting a dose-dependency. For psychological symptoms, the iCR+HP combination was superior to iCR monotherapy. Efficacy of iCR was comparable to low-dose transdermal estradiol or tibolone. Yet, due to its better tolerability, iCR had a significantly better benefit-risk profile than tibolone. Treatment with iCR/iCR+HP was well tolerated with few minor adverse events, with a frequency comparable to placebo. The clinical data did not reveal any evidence of hepatotoxicity. Hormone levels remained unchanged and estrogen-sensitive tissues (e.g. breast, endometrium) were unaffected by iCR treatment. As benefits clearly outweigh risks, iCR/iCR+HP should be recommended as an evidence-based treatment option for natural climacteric symptoms. With its good safety profile in general and at estrogen-sensitive organs, iCR as a non-hormonal herbal therapy can also be used in patients with hormone-dependent diseases who suffer from iatrogenic climacteric symptoms.

Factors associated with response in depressed elderly outpatients treated with escitalopram in a naturalistic setting in Germany.

BACKGROUND: An open, multi-centre study was designed to address the effectiveness and tolerability profile of treatment with escitalopram under naturalistic conditions, in elderly outpatients (above 65 years of age) with depression. PATIENTS AND METHODS: A total of 2 050 patients completed 8 weeks of treatment with escitalopram. Rating scales included a short version of the Montgomery-Asberg Depression Rating Scale (svMADRS), the Clinical Global Impression - Severity scale (CGI-S), and the Clinical Global Impression -Improvement scale (CGI-I) for the assessment of various clinical parameters. RESULTS: Most patients improved in their general state of health and showed a decrease in the severity of their depression. The majority (82.7%) of patients received initially 10 mg/day escitalopram. The mean svMADRS total score decreased from 31.9+/-7.9 at baseline to 14.2+/-8.5 at week 8. On completion, 63.9% of the patients were responders (> or =50% decrease of svMADRS total score from baseline) and 48.6% were remitters (svMADRS total score < or =12 at week 8). Statistically significantly more patients aged between 66 and 75 years responded to treatment and achieved remission than those aged >75 years. Logistic regression, using stepwise backward elimination, was used to model response to treatment. Statistically significant positive factors were having a current episode < or =1 month and duration of illness < or =1 year. Significant negative factors were being male, being older than 75 years, and having need of further psychotropic medication. Compared to patients diagnosed with unspecified dementia with other symptoms being predominantly depressive (F03, according to ICD-10), the response to escitalopram was significantly better for patients with depressive episodes (F32) or recurrent depressive episodes (F33), but significantly worse for patients with affective disorder (F31 or F34). The differences versus affective disorders were significant, while those for depressive episodes and recurrent depressive episodes vs. affective disorders were not significant. CONCLUSION: This observational study corroborates the effectiveness and tolerability of escitalopram treatment for elderly patients in a naturalistic treatment setting.

Initiation of hypertension treatment with a fixed-dose combination or its monocomponents -- does it really matter?

Despite efforts to diagnose and treat hypertension effectively, the goal of lowering blood pressure (BP) levels is rarely achieved, as treatment is often initiated with a single antihypertensive agent. The aim of this study was to assess the safety and efficacy of a first-line fixed-dose combination treatment compared with treatment with its monocomponents over a period of 4 weeks. Patients (n = 149) with essential hypertension were randomised to receive 2.5 mg of either ramipril or felodipine ER or the fixed-dose combination of ramipril 2.5 mg/felodipine ER 2.5 mg over a 4-week treatment period. BP and heart rate were measured by conventional methodology and 24-hour ambulatory blood pressure measurements. Treatment with the fixed-dose combination was significantly more effective in reducing systolic and diastolic BP (-15.8/-9.2 mmHg) compared with its monocomponents, ramipril (-7.6/-3.8 mmHg) and felodipine ER (-8.0/-5.0 mmHg). No significant difference could be observed in the occurrence of a greater fall in systolic and diastolic BP 6 h after the first dose of the three study medications. The adverse effects reported were mild, and less number of patients in the fixed-dose combination complained of adverse events. It can be concluded that initiating antihypertensive treatment with a low fixed-dose combination of ramipril/felodipine ER is more effective and safe when compared with treatment with its monocomponents.

[Uroprotection with mesna in the chemotherapy of malignant tumors with oxazaphosphorines. Biometric evaluation of a sequential clinical study]. / Uroprotektion mit Mesna bei der Chemotherapie maligner Tumoren mit Oxazaphosphorinen. Biometrische Auswertung einer sequentiellen klinischen Prüfung.

A multicentre, randomised, clinical study was performed by sequential analysis to quantify the uroprotective efficacy of sodium 2-mercaptoethane sulfonate (mesna, Asta D 7093, Uromitexan) during high-dosed chemotherapy with oxazaphosphorines. Patients were entered as matched pairs serially according to time of admission, trial centre, cytostatic therapy (cyclophosphamide, Endoxan; ifosfamide, Holoxan) and tumor diagnosis, and were given uroprotection at random either with mesna or standard prophylactic measures. The maximum number of erythrocytes in the urine (n/microliter) was chosen as effect variable in a qualitative manner: effective protection delta less than or equal to 15 erythrocytes/microliter urine ineffective protection delta greater than 15 erythrocytes/microliter urine. The scheme of sequential analysis was based on 1. a uroprotective efficacy of 70% of the standard prophylaxis, 2. an assumed efficacy of 95% of mesna treatment and 3. an alpha-error and beta-error of 0.05 and 0.10 respectively. The admission of the twentieth patient completed the eighth matched pair of patients. This pair proved to be the sixth discordant pair with regard to uroprotective efficacy. The significant uroprotective superiority (p less than 0.05) of mesna was proven in view of clear decisions in favour of the test compound.

[Prevention of urinary tract toxicity of oxazaphosphorines by a "uroprotector". Report on a field study (author's transl)]. / Verhütung der Harnwegstoxizität von Oxazaphosphorinen durch einen "Uroprotektor". Bericht über eine Feldstudie.

In an open multicenter phase III trial, prophylaxis of the urinary tract with sodium 2-mercaptoethanesulfonate (Mesnum) was carried out in 242 patients treated with oxazaphosphorines for various malignant tumors. Under the protection of Mesnum 29 patients were treated with cyclophosphamide (Endoxan), 195 with ifosfamide (Holoxan) and 8 with trofosfamide (Ixoten). Other cytostatics were also used (polychemotherapy) in 92 cases. On administration of Mesnum, 7 macrohematurias reappeared, only 3 of them however with correct application, and 22 microhematurias, 12 of them with correct application. Cylindrurias were re-established in 3 patients. In Mesnum we have a compound which can control the urotoxicity ("uroprotector") of oxazaphosphorines which limits their therapeutic use.