Elective vs. early elective surgery in diverticular disease: a retrospective study on the optimal timing of non-emergency treatment.

PURPOSE: This study set out to compare the in-hospital outcomes of early elective and elective laparoscopic sigmoidectomy due to diverticulitis. METHODS: We examined the data for 378 diverticulitis patients who received an elective laparoscopic sigmoid resection between 2008 and 2012. We divided the patients into two groups: elective (group A, n = 278) and early elective (group B, n = 100). Patients in group A received surgery during the inflammation-free interval, and those in group B immediately after treating the attack with IV antibiotics for a mean period of 8 days (IQR = 3). RESULTS: Overall mortality was 0%. The mean operation duration was the same in both groups being 77.5 and 80 min respectively. There was no significant difference in the outcomes between the two groups, measured using the Clavien-Dindo classification of surgical complication (CCSC; p = 0.992). A revision due to complications was necessary in 16 cases (group A) and six cases (group B) (p = 0.820). The conversion rate to open surgery was low (six individuals in group A, vs. four in group B; p = 0.331). Patients in group B suffered significantly fewer diverticulitis attacks (three in group A, vs. two in group B; p = 0.026). CONCLUSION: Our study showed no difference in outcome between elective and early elective cases. Operation durations were optimal in both cases and were 50% shorter than those recorded in the literature. An early elective operation represents a good treatment option, especially for patients suffering from complicated diverticulitis.

Results of a randomized, prospective, double-dummy, double-blind trial to compare efficacy and safety of a herbal combination containing Tropaeoli majoris herba and Armoraciae rusticanae radix with co-trimoxazole in patients with acute and uncomplicated cystitis.

OBJECTIVES: To demonstrate non-inferiority of an herbal combination (horseradish root and nasturtium herb) to an antibiotic (co-trimoxazole) in acute uncomplicated cystitis. DESIGN: Randomized, prospective, double-blind, double-dummy, multicenter, phase III clinical study, using block randomization of 4 blocks (size 2). SETTING: Twenty-six centers in Germany, from May 2011 to June 2013. PARTICIPANTS: Adult patients (median age, 38.5 years; 90% female) with acute uncomplicated cystitis confirmed via urinalysis and bacterial counts. INTERVENTIONS: Patients received the herbal combination (five tablets, four times per day) or the antibiotic (two tablets daily) for a period of 7 or 3 days, respectively, followed by a 21-days without drug treatment. Placebos ensured blinding. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the percentage of responders, expressed as reduction of germ count from >105 to <103 CFU/mL of pathogens between visit 1 (day 0) and 3 (day 15). Secondary endpoints included change of symptom scores, duration of symptoms, efficacy assessments, relapse frequency, and safety. A sample size of 178 patients per group was estimated. RESULTS: Of the 96 randomized patients (intent-to-treat; 45 in the phytotherapy group, 51 in the antibiotic group), 51 were considered per-protocol patients (22 in the phytotherapy group, 29 in the antibiotic group). Responder rates were 10/22 (45.5%) for the phytotherapy group and 15/29 (51.1%) for the antibiotic group (group difference: -6.27% [95% CI: -33.90%-21.3%]). The study was terminated prematurely due to slow recruitment rates. Non-inferiority could not be assumed by predefined criteria. During the follow-up period, one relapse occurred in each group. Both treatments were well tolerated. CONCLUSION: This clinical trial indicates comparable efficacy of the herbal combination and antibiotic, although non-inferiority was not proved. However, the results and lessons learned are important for the planning of future trials. Issues that led to the premature trial discontinuation were considered.

Influence of Tiopronin on the Metabolism of Alcohol in Healthy Subjects.

Drug safety- and drug-alcohol interaction studies have mainly been conducted for frequently prescribed drugs with high financial interests. Orphan drugs such as tiopronin (ORPHA25073) are often neglected in terms of clinical research. Tiopronin is a drug that is mainly used for the treatment of cystinuria. In this study, the interaction of tiopronin regarding the metabolism of alcohol (primary objective), and the safety of tiopronin in combination with alcohol was tested in healthy volunteers.In this randomised, double-blind, cross-over study, 13 healthy subjects received 500 mg tiopronin or an identical looking placebo 1 h before the intake of 0.8 g of alcohol per kg of bodyweight. Blood alcohol concentrations were measured over the course of 12 h after consumption. The experiment was repeated 7 days later with the previous placebo group receiving the active drug and vice-versa. Changes in blood alcohol AUC and elimination rate k were analysed using a 2-tailed t-test. Further acetaldehyde concentrations were measured. Additionally, the concentration ability of the subjects was tested and any adverse effects were recorded.There was no significant change in blood alcohol or acetaldehyde concentration. Significant differences in concentration tests refer presumably to learning effects. No serious adverse event occurred. All adverse events were reversible and there was no significant difference in occurrence between drug and placebo group.It was demonstrated that tiopronin does not affect the metabolism of alcohol. Intake of tiopronin in combination with alcohol has no safety implications on healthy subjects.

Large-scale Survey of the Impact of Complementary Medicine on Side-effects of Adjuvant Hormone Therapy in Patients with Breast Cancer.

BACKGROUND/AIM: The present clinical investigation was performed to confirm the benefit of complementary medicine in patients with breast cancer undergoing adjuvant hormone therapy (HT). PATIENTS AND METHODS: The patients (n=1561) were treated according to international guidelines. All patients suffered from arthralgia and mucosal dryness induced by the adjuvant HT. In order to reduce the side-effects, the patients were complementarily treated with a combination of sodium selenite, proteolytic plant enzymes (bromelaine and papain) and Lens culinaris lectin. On case report formulas, self assessment arthralgia and mucosal dryness were documented before and four weeks after complementary treatment. Validation was carried-out by scoring from 1 (no side-effects/optimal tolerability) to 6 (extreme side-effects/extremely poor tolerability). A total of 1,165 patients suffering from severe side-effects (symptom scores >3) were enrolled in this investigation. RESULTS: Overall, 62.6% of patients (729 out of 1,165) suffering from severe arthralgia and 71.7% of patients (520 out of 725) with severe mucosal dryness significantly benefited from complementary medicine. Mean scores of symptoms declined from 4.83 before treatment to 3.23 after four weeks of treatment for arthralgia and from 4.72 before treatment to 2.99 after four weeks of treatment for mucosal dryness, the primary aims of the present investigation. The reduction of side-effects of HT was statistically significant (p<0.001) after four weeks. CONCLUSION: This investigation confirms studies suggesting a benefit of complementary treatment with the combination of sodium selenite, proteolytic enzymes and L. culinaris lectin in patients with breast cancer.

Complementary medicine down-regulates side-effects of hormone therapy in prostate cancer patients.

AIM: The present clinical investigation was performed to evaluate the benefits of complementary medicine in prostate cancer patients undergoing hormone therapy (HT). PATIENTS AND METHODS: Patients (N=93) were treated according to international guidelines. All patients suffered from side-effects induced by the HT. To reduce the side-effects, the patients were complementarily treated with a combination of sodium selenite, proteolytic plant enzymes and Lens culinaris (Lc) lectin. On case report formulas (CRFs), self assessment of defined side-effects of HT (arthralgia, mucosal dryness, bone pain and hot flushes) were documented before (T-0) and on days 25 (T-1) and 50 (T-2) after complementary treatment. Validation was carried-out by scoring from 1 (no side-effects/optimal tolerability) to 6 (extreme side-effects/extremely bad tolerability), however, only patients suffering from severe side-effects (symptom scores >3) were enrolled in this investigation. RESULTS: The severity of side-effects of HT was reduced by complementary treatment with sodium selenite, proteolytic plant enzymes and Lc-lectin. The mean scores of side-effects declined for arthralgia from 4.72 (T-0) to 3.66 (T-1) to 2.76 (T-2), for mucosal dryness from 4.45 (T-0) to 3.65 (T-1) to 2.90 (T-2), for bone pain from 4.74 (T-0) to 3.44 (T-1) to 2.82 (T-2), for hot flushes from 4.97 (T-0) to 3.70 (T-1) to 3.15 (T-2). The reduced severity of the side-effects was statistically significant (p<0.001) for T-1 and T-2, compared to T-0. CONCLUSION: This investigation demonstrates benefits of indication-based complementary treatment with the combination of sodium selenite, proteolytic plant enzymes and Lc-lectin in prostate cancer patients, e.g. reduction of side-effects of HT.

Efficacy and safety of a herbal medicinal product containing myrrh, chamomile and coffee charcoal for the treatment of gastrointestinal disorders: a non-interventional study.

OBJECTIVE: This prospective observational postmarketing multicentre study was performed to collect data on the clinical efficacy, safety and tolerability of a licensed herbal combination of myrrh, coffee charcoal and chamomile extracts in patients with symptoms of acute diarrhoea. MATERIAL AND METHODS: Patients aged 12 years and above with symptoms of acute diarrhoea due to acute inflammatory disorders (AID) of the gastrointestinal tract, inflammatory bowel diseases (IBD) or irritable bowel syndrome (IBS) were treated with the herbal preparation either as monotherapy, add-on therapy or with other therapies. The primary outcome parameter was the pre-post change of total mean symptom score. Secondary outcome parameters were changes of score of single symptoms, physician's assessment of the clinical course and efficacy, and patient's satisfaction. RESULTS: 1062 patients (mean age 43.2±17.8 years, range 12-89, 42.3% men) were included. A decrease of the overall mean total symptom score was observed in all treatment groups (monotreatment: 1.33±0.51 to 0.15±0.34, add-on treatment: 1.39±0.41 to 0.30±0.37, other therapy: 1.31±0.43 to 0.24±0.33). No significant differences between three treatment options were observed within AID and IBD groups. However, in the IBS group, monotreatment with the herbal preparation resulted in a significantly better outcome when compared to either add-on treatment (mean difference 0.140; 95% CI 0.036 to 0.245; p=0.009) or other therapy (mean difference 0.217; 95% CI 0.085 to 0.349; p=0.001). Secondary efficacy criteria showed comparable results between different treatment options in the respective disorder groups. Patient satisfaction was generally higher with monotreatment in the AID and IBS groups, while add-on treatment was preferred in the IBD group. CONCLUSIONS: The combination of myrrh, coffee charcoal and chamomile flower extract is effective, well tolerated and safe for use in patients with symptoms of acute diarrhoea. The effects are comparable to conventional therapies used in routine care.

Complementary medicine on side-effects of adjuvant hormone therapy in patients with breast cancer.

BACKGROUND: This clinical investigation was performed in order to evaluate the benefit of complementary medicine in patients with breast cancer undergoing adjuvant hormone therapy (HT). PATIENTS AND METHODS: The patients (n=680) were treated according to international guidelines. All patients suffered from arthralgia and mucosal dryness induced by the adjuvant HT. In order to reduce side-effects, the patients were complementarily treated with a combination of sodium selenite, proteolytic plant enzymes (bromelaine and papain) and Lens culinaris lectin. On case report formulas, self assessment of defined side-effects of HT (namely arthralgia and mucosal dryness) were documented before and four weeks after complementary treatment. Validation was carried out by scoring from 1 (no side-effects/optimal tolerability) to 6 (extreme side-effects/extremely poor tolerability), however, only patients suffering from severe side-effects (symptom scores >3) were enrolled in this investigation. RESULTS: A total of 64% (316 out of 494) of patients suffering from severe arthralgia and 62% of patients (194 out of 310) with severe mucosal dryness significantly benefited from complementary medicine. The severity of side-effects of HT was reduced by complementary treatment. Mean scores of symptoms declined from 4.92 before treatment to 3.16 after four weeks of treatment for arthralgia and from 4.83 before treatment to 3.21 after four weeks of treatment for mucosal dryness, and these were the primary aims of this investigation. The reduction of side-effects of HT was statistically significant (p<0.001) after four weeks. CONCLUSION: This investigation further demonstrates benefits of indication-based complementary treatment with the combination of sodium selenite, proteolytic enzymes and L. culinaris lectin in patients with breast cancer.

Liver sinusoidal endothelial cells contribute to CD8 T cell tolerance toward circulating carcinoembryonic antigen in mice.

UNLABELLED: Immunity against cancer is impeded by local mechanisms promoting development of tumor-specific T cell tolerance, such as regulatory T cells, myeloid-derived suppressor cells, or immunosuppressive factors in the tumor microenvironment. The release of soluble antigens, such as carcinoembryonic antigen (CEA) from colorectal carcinoma (CRC) cells, has been investigated for diagnostic purposes, but not for its immunological consequences. Here, we address the question of whether soluble CEA influences tumor-specific immunity. Mice were injected with soluble CEA protein, and CEA-specific CD8 T cells were analyzed for their phenotype and functionality by means of restimulation ex vivo or antitumor efficacy in vivo. We furthermore characterized the CD8 T cell population in peripheral blood mononuclear cell (PBMCs) from healthy donors and colorectal carcinoma patients. In mice, circulating CEA was preferentially taken up in a mannose receptor-dependent manner and cross-presented by liver sinusoidal endothelial cells, but not dendritic cells, to CD8 T cells. Such systemically circulating CEA promoted tolerization of CEA-specific CD8 T cells in the endogenous T cell repertoire through the coinhibitory molecule B7H1. These CD8 T cells were not deleted but were rendered nonresponsive to antigen-specific stimulation and failed to control growth of CEA-expressing tumor cells. These nonresponsive CD8 T cells were phenotypically similar to central memory T cells being CD44(high) CD62L(high) CD25(neg) . We found T cells with a similar phenotype in PBMCs of healthy donors and at increased frequency also in patients with colorectal carcinoma. CONCLUSION: Our results provide evidence for the existence of an unrecognized tumor immune escape involving cross-presentation of systemically circulating tumor antigens that may influence immunotherapy of cancer.

Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany.

AIM: The aim of the study was to evaluate under praxis conditions the safety and efficacy of intravenous (i.v.) vitamin C administration in the first postoperative year of women with breast cancer. PATIENTS AND METHODS: Epidemiological multicentre cohort study, including 15 gynaecologists and general practitioners representatively distributed in Germany. Data from 125 breast cancer patients in UICC stages IIa to IIIb were selected for the study. A total of 53 of these patients were treated with i.v. vitamin C (supplied as Pascorbin® 7.5 g) additional to standard tumour therapy for at least 4 weeks (study group) and 72 without this additional therapy (control group). Main outcome measures were efficacy in regard to outcome and severity of disease- or therapy-induced complaints during adjuvant chemo- and radiotherapy and aftercare. RESULTS: Comparison of control and study groups revealed that i.v. vitamin C administration resulted in a significant reduction of complaints induced by the disease and chemo-/radiotherapy, in particular of nausea, loss of appetite, fatigue, depression, sleep disorders, dizziness and haemorrhagic diathesis. After adjustment for age and baseline conditions (intensity score before adjuvant therapy, chemotherapy, radiotherapy), the overall intensity score of symptoms during adjuvant therapy and aftercare was nearly twice as high in the control group compared to the study group. No side-effects of the i.v. vitamin C administration were documented. DISCUSSION: Oxidative stress and vitamin C deficiency play an important role in the etiology of adverse effects of guideline-based adjuvant chemo-/radiotherapy. Restoring antioxidative capacity by complementary i.v. vitamin C administration helps to prevent or reduce disease-, or therapy-induced complaints in breast cancer patients. CONCLUSION: Complementary treatment of breast cancer patients with i.v. vitamin C was shown to be a well tolerated optimization of standard tumour-destructive therapies, reducing quality of life-related side-effects.

[Justification of repeated animal experiments and determination of the required number of animals according to the German Animal Protection Act]. / Begründung der Wiederholung von Tierversuchen und Bestimmung der erforderlichen Tierzahl gemäss dem Deutschen Tierschutzgesetz.

The repetition of animal experiments requires justification according to the German Animal Protection Act (Tierschutzgesetz). On the other hand, repetition of experiments is considered necessary for the improvement of the precision and reliability of the results. In this paper it is shown that such improvement is not achieved by a repetition of the experiment but by repeated inclusion of animals into the experiment. The more animals are included, the more precisely and reliably the results can be generalized to further situations. The number of animals necessary for a proposed precision can be determined with statistical methods. The basic ideas are explained in the paper and demonstrated with two examples. In long term experiments the precision can be improved, if all experimental conditions are applied within temporally homogenous blocks to few animals and the blocks are repeated till the necessary number of animals is reached (block experiments). By sequential interim analyses, where at each analysis on the basis of all available data a decision on continuation or conclusion of the experiment is drawn, a further reduction of the number of animals can be achieved. These methods are discussed in the paper. Repetitions of total animal experiments are justified, if there exist legitimate doubts on the soundness of the published results or if in so called ring-experiments the variability of the results between different laboratories should be investigated.

Relation of gallbladder motility to viscosity and composition of gallbladder bile in patients with cholesterol gallstones.

BACKGROUND/AIMS: Increased viscosity and supersaturation of cholesterol in gallbladder bile, as well as an impaired motility of the gallbladder, are considered to be important factors in the pathogenesis of cholesterol gallstones. However, the relation of these parameters has not yet been determined. MATERIAL AND METHODS: Bile viscosity (mPa s) was measured by rotation viscosimetry and the composition of gallbladder bile was determined using standard methodology. Gallbladder motility was calculated as ejection fraction in percent of total volume 45 min after a test meal using ultrasonography in patients with gallstones prior to elective cholecystectomy. RESULTS: The study included 35 patients with cholesterol gallstones. Viscosity of gallbladder bile ranged between 0.9 and 12.5 mPa s (median 2.2 mPa s) and an ejection fraction of the gallbladder of 55.4 +/- 18.3% (mean +/- SD) was determined. No significant correlation (r = 0.19, p < 0.2) between the 2 parameters could be calculated. Analysis of the composition of gallbladder bile revealed a positive correlation of all components to biliary viscosity but not to the motility of the gallbladder, with the exceptions of a negative correlation (r = 0.39, p < 0.02) between mucin concentration and the ejection fraction at 45 min after the test meal. CONCLUSIONS: The motility of the gallbladder appears to be unrelated to the viscosity of gallbladder bile or gallbladder bile composition. The negative correlation between the ejection fraction of the gallbladder and mucin concentration of gallbladder bile suggests that chronic inflammation of the gallbladder wall is associated with both an impaired motility of the gallbladder and increased mucin release into gallbladder bile.

Myocardial infarction and stroke in early years after diagnosis of type 2 diabetes: risk factors and relation to self-monitoring of blood glucose.

BACKGROUND: The natural course of macrovascular events in patients with type 2 diabetes was analyzed: what are the risk factors, and what is the relationship to the use of self-monitoring of blood glucose (SMBG)? METHODS: Data were retrieved from ROSSO-a German retrospective observational study-which followed 3,268 patients from diagnosis of type 2 diabetes for 6.5 +/- 1.6 years. We compared patients with or without a nonfatal macrovascular event (myocardial infarction or stroke) and patients using or not using SMBG. RESULTS: At baseline, worse glycemic control and higher body mass index were not risk factors for macrovascular events. Moreover, there was no association with classic risk factors like blood pressure or total cholesterol. Overall, there was a higher incidence of stroke than of myocardial infarction (0.78% vs. 0.51%). Myocardial infarction was positively associated with male sex, and stroke with age (P < 0.001 for each). Patients using SMBG compared to patients not using SMBG had fewer myocardial infarctions (2.0% vs. 4.0%, P = 0.002) and strokes (3.6% vs. 5.7%, P = 0.005), experienced a stroke later after diagnosis of type 2 diabetes (5.1 +/- 1.9 vs. 3.8 +/- 2.1 years, P < 0.001), and had a higher mean hemoglobin A1c in the years before a myocardial infarction (7.8 +/- 1.8% vs. 6.8 +/- 1.1%, P = 0.003) or a stroke (8.0 +/- 1.8% vs. 7.1 +/- 1.2%, P = 0.003). However, classic cardiovascular risk factors did not differ between patients using or not using SMBG. CONCLUSIONS: In patients with type 2 diabetes SMBG was associated with a lower event rate of myocardial infarction (-50%) and stroke (-37%), although at baseline the classic risk factors for macrovascular events were not different in both groups.

Are type 2 diabetes patients who self-monitor blood glucose special? The role of confounders in the observational ROSSO study.

BACKGROUND: In the German multicenter, retrospective cohort study (ROSSO), those patients with type 2 diabetes who performed self-monitoring of blood glucose (SMBG) had a better long-term clinical outcome. We analyzed whether confounders accounted for the lower rate of clinical events in the SMBG cohort. METHODS: ROSSO followed 3268 persons from diagnosis of type 2 diabetes for a mean of 6.5 years. Data were retrieved from patient files of randomly contacted primary care practices. RESULTS: In total, more than 60 potential confounders were documented, including nondisease-associated parameters such as patient's health insurance, marital status, habitation, and characteristics of diabetes centers. There were only modest differences for these parameters between groups with versus without SMBG, and multiple adjustments did not weaken the association of SMBG use with better outcome (odds ratio 0.65, 95% confidence interval 0.53-0.81, p < .001). This was also true for subgroups of patients defined by type of antidiabetes treatment. Propensity score analysis confirmed the association of SMBG use with outcome. Using key baseline parameters, 813 matching pairs of patients were identified. The analysis again showed a better long-term outcome in the SMBG group (hazard ratio 0.67 p = .004). CONCLUSION: An influence of nonrecognized confounders on better outcome in the SMBG group is rendered improbable by similar results obtained with adjustments for disease-associated or disease-independent parameters, by the analysis of patient subgroups, by propensity score analysis and by performing a matched-pair analysis. The higher flexibility in pharmacological antidiabetes treatment regimens in the SMBG cohort suggests a different attitude of treating physicians and patients in association with SMBG.

The role of a homoeopathic preparation compared with conventional therapy in the treatment of injuries: an observational cohort study.

OBJECTIVES: To assess the use, effectiveness and safety of a homoeopathic preparation (Traumeel) compared with conventional therapies in the treatment of trauma and injuries. METHODS: Multi-centre, prospective, comparative observational cohort study of patients with various musculoskeletal injuries. German physicians who were using homoeopathy in addition to conventional medicine included patients. Patients treated with Traumeel were compared with patients managed conventionally. The primary outcome measure was the rate of resolution of the principal symptoms (i.e. pain and inflammatory symptoms) at the end of therapy. RESULTS: Sixty-nine Traumeel treated and 64 conventionally treated patients fitted the selection criteria. The most common diagnoses were acute injuries (sprains, strains, contusions, etc.) of the ankles, knees and hands. There were no significant differences between demographic and anamnestic baseline characteristics of both groups. Complete resolution of the principal symptom at the end of therapy occurred in 41 (59.4%) patients in the homoeopathy group versus 37 (57.8%) patients in the conventional group. No adverse events were reported in the Traumeel group compared to six adverse events (6.3%) in the conventional group. Physician-assessed tolerability was significantly better in the Traumeel group (P=0.001). CONCLUSION: Traumeel is as effective as conventional medicines in the management of mild to moderate injuries in this population. Traumeel was safe in use and judged by physicians to be better tolerated than conventional medicines. This study contributes to the case for a broad clinical effectiveness of Traumeel in the treatment of acute injuries and trauma.

Cost impact of blood glucose self-monitoring on complications of type 2 diabetes: a Swiss perspective (ROSSO study No.11).

QUESTION UNDER STUDY: despite the increasing prevalence of type 2 diabetes, its financial burden on the Swiss healthcare system remains unclear. Our aim was to determine the cost of self-monitoring of blood glucose (SMBG) in reducing diabetic complications by comparing the direct costs to the Swiss statutory health insurance system of diabetic complications in SMBG users vs. nonusers. METHOD: matched pair analysis of the average annual total cost of diabetes monitoring, treatment-related services, complications and followup in the RetrOlective Study Self-Monitoring of Blood Glucose and Outcome in Patients with Type 2 Diabetes (ROSSO) study cohort, updated to 2005 from the year of occurrence or diagnosis of diabetes, applying an annual inflation rate of 5%. RESULTS: in those patients treated with oral antidiabetic drugs only, total annual costs were CHF 5,140 in SMBG users and CHF 5,654 in non - users. In those patients treated with oral antidiabetic drugs plus insulin, total annual costs were CHF 8,254 and CHF 11,776, respectively. SMBG accounted for 1.6% to 1.7% of total costs. CONCLUSION: cost analysis indicates that SMBG provides a rapid return on initial investment.

A randomised, double-blind, placebo-controlled trial of a herbal medicinal product containing Tropaeoli majoris herba (Nasturtium) and Armoraciae rusticanae radix (Horseradish) for the prophylactic treatment of patients with chronically recurrent lower urinary tract infections.

OBJECTIVES: The aim of this study was to verify the efficacy and safety of a herbal medicinal product containing Tropaeoli majoris herba and Armoraciae rusticanae radix in the prophylactic treatment of chronically recurrent urinary tract infections (UTIs), and to test whether the medicinal product decreases the incidence of relapses over the study period. METHODS: A total of 219 adults aged between 18 and 75 years were screened and 174 patients enrolled. Of these 174 patients, a group of 45 patients were screening failures. Patients were randomised to receive either the study drug or placebo twice daily for 90 days. A UTI is confirmed by defined symptoms together with a laboratory result. The diagnosis of a new episode of a recurrent UTI included urine analysis from a central laboratory. The primary efficacy criterion - the number of recurrent UTIs over the study period - was tested between the treatment groups. RESULTS: For the per-protocol population, the mean number of recurrent UTIs in the study period was 0.43 versus 0.77 for the placebo group. This result is statistically significant (p = 0.035). A total of 36 patients in the test group and 37 patients in the placebo group reported adverse events. Two serious adverse events were reported in the placebo group and one serious adverse event in the treatment group (not associated with the study medication). CONCLUSION: This randomised, double-blind, placebo-controlled trial demonstrates the efficacy and safety of the herbal medicinal product Angocin Anti-Infekt N* in the prophylactic treatment of chronically recurrent UTIs.

[On-going investigations on efficacy and safety profile of a herbal drug containing nasturtium herb and horseradish root in acute sinusitis, acute bronchitis and acute urinary tract infection in children in comparison with other antibiotic treatments]. / Aktuelle Untersuchungen zur Wirksamkeit und Verträglichkeit eines pflanzlichen Arzneimittels mit Kapuzinerkressenkraut und Meerrettich bei akuter Sinusitis, akuter Bronchitis und akuter Blasenentztündung bei Kindern im Vergleich zu anderen Antibiotika.

PATIENTS AND METHODS: In this study which was carried out in the period between 1st May until 4th October 2006 in 65 study sites as a prospective cohort study in 858 children, adolescents and juveniles in the age between 4 and 18 years who consulted the physician due to an acute sinusitis, acute bronchitis or acute urinary tract infection (UTI). Data of in total 858 patients were recorded. The patients were treated either with the herbal drug preparation Angocin Anti-Infekt N (test group, n = 523, 61%) or with a standard antibiotic (control group, n = 335, 39%) according to the decision of the physician. The duration of treatment as well as the dosage was determined by the physician. 297 patients suffering from acute sinusitis (197 test group 66%, 100 control patients 34%), 290 patients suffering from acute bronchitis (178 test group 61%, 112 control patients 39%) and 271 patients with acute urinary tract infection (148 test group 55%, 123 control patients 45 %) were included. The patients recorded in a diary the utilization of the medication, concomitant procedures and adverse events (AEs). The physician recorded at study start and at the end of the study the compliance in a standardised form. Single symptoms were recorded according to their intensity with a score ranging from 0 = no symptom to 3 = severe symptoms. At the end of the study (disease free or after 7-14 days) the physicians finally judged on the course of the treatment as well on the efficacy as observed. The patients recorded their satisfaction with the treatment. Primary efficacy criterion was the change of the complaints quantified by the change of the relative symptom score average over all symptoms between result at study start and study end related to the baseline value. RESULTS: The two therapy groups differ in their basis data with regard to the mean age (test group 12.2 years, control group 13.5 years; p > 0.001) and the frequency of concomitant diseases (test group 6.3%, control group 2.4%; p = 0.008). At start of treatment the complaints in the test group were significantly less severe (mean of the complaint score 1.67) compared to the control group (mean 2.00; p > 0.001). At the end of treatment there were no significant differences in the mean complaint score between the groups (test group 0.41, control group 0.49; p = 0.722). The mean reduction of the complaint score expressed in percentages was for the indication acute sinusitis in the test group 84.8% and in the control group 85.5%, for the indication acute bronchitis in the test group 82.1% and in the control group 77.7% and for the indication acute urinary tract infection in the test group 89.9% and in the control group 93.1%. In total the mean reduction of the complaint score for the test group was 85.3% and in the test group 85.7% (p = 0.828). The 95% confidence interval for difference of the expected reductions between test group and control group ranged from -3.87% up to 3.10%. With a border of +/- 10% the mean reduction for both groups is equivalent, and more importantly non-inferior for the test group compared with the control group. Adverse events were recorded for 3 patients (0.6%) of the test group and for 14 patients (3.9%) of the control group (p = 0.001). In conclusion it was demonstrated that therapy with the herbal drug preparation in the indications acute sinusitis, acute bronchitis and acute urinary tract infection is--with regard to efficacy--comparable to a treatment with standard antibiotics. The test preparation displayed in all indications a significantly lower potential for adverse events compared to a treatment with standard antibiotics and, therefore, a better safety profile could be concluded.

Out-of-specification test results from the statistical point of view.

Although a generally accepted procedure has now been established for the organizational handling of out-of-specification test results, the uncertainty surrounding their statistical evaluation persists. Two statistical equations, the prediction and the confidence interval, are sufficient to examine whether data numbers indicate out-of-specification (OOS) results or not. This is demonstrated by means of 10 examples. These equations are usually sufficient to specify limit values as well. A number of consequences have been derived from a discussion of borderline cases: (A) If only one measured value is OOS, the same is true for the whole result (there are three exceptions: high data numbers, outliers, or the reportable result is not the single value but e.g. the mean). (B) The result is not automatically within specification, if this holds true for all measurements. If all measurements are close to the specification limit and the measurement error is high, an OOS result is still possible. (C) If it is clear that the obtained data will be close to the limit, a precisely working method and a relatively high data number is required. In order to obtain future measurements that remain within specification, the difference between the limit and the mean value must not become smaller than 1.65 times the standard deviation, even if very high numbers of measurements are provided. Procedures to deal with extreme values, so-called outliers, are not straightforward. The statistical evaluation is troublesome, because the probability distribution cannot be determined. This problem is discussed by another four examples. In several cases the outlier can be detected without doubt, for example, using Dixon's test or the box plot. However, there are a number of borderline cases, when a value is suspected to be an outlier, but this cannot be proven by statistics [7,9].

Interrelations between diabetes therapy, self-monitoring of blood glucose, blood glucose and non-fatal or fatal endpoints in patients with type 2 diabetes / results of a longitudinal cohort study (ROSSO 5).

The ROSSO study is a retrospective, longitudinal cohort study performed to obtain epidemiological data on self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes and to investigate the impact of SMBG on disease-related morbidity and mortality. 3,268 patients from 192 doctor's practices in Germany were included and their data from diabetes diagnosis (between 1995 and end of 1999) till drop-out (120 died, 17 drop-outs) or end of 2003 were collected from the medical records. The mean observational time was 6.5 years; total patient years of follow-up were 21.266 years. Based on these population data, questions about the motivation of patients with type 2 diabetes to start with SMBG, the changes in diabetes therapy and blood glucose associated with SMBG and the relationship of SMBG with non-fatal or fatal events during follow-up were evaluated. Use of SMBG is significantly associated with personal and baseline conditions. Patients using SMBG are more frequently treated by an internist, more often male, have more frequently a private health insurance, exhibit less frequently arterial hypertension, are younger, have lower systolic blood pressure and higher values of fasting blood glucose (FBG), HbA1c and triglycerides at diagnosis. The start of SMBG is preceded by a steady increase in blood glucose levels. It is accompanied by an intensification of diabetes therapy and followed by a significant reduction of blood glucose in the year after start of SMBG. 67% of the patients treated with diet only before SMBG began with antidiabetic medication concomitantly with SMBG (48% with oral antidiabetic agents (OAD), 9% with insulin and 10% with OAD and insulin) and 30% of the patients treated with OAD started on additional insulin treatment in parallel with SMBG. Switching from no antidiabetic medication to OAD reduced the mean FBG levels significantly from 9.31 to 8.70 mmol/l, from no medication to insulin from 10.05 to 6.93 mmol/l and from no medication to OAD and insulin from 10.85 to 8.92 mmol/l. Similar reductions of mean FBG levels were observed for switching from OAD to insulin therapy. Patients who stayed on OAD therapy also showed a significant reduction of FBG concentrations after the start of SMBG. The hazard for non-fatal events (particularly myocardial infarction and stroke) or overall mortality was significantly reduced for patients who performed SMBG during follow-up (p<0.001). SMBG-associated changes of antidiabetic therapy may contribute to the better clinical outcome of patients with SMBG.