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.

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.

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.

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.

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.

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].

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.

The morphology of perinecrotic tumor cell nuclei in glioblastomas shows a significant relationship with survival time.

A deeper knowledge about histopathological criteria with a significant impact on the prognosis of patients with glioblastomas is worthwhile, since these patients may show a considerable difference in the time of survival. Investigation of the morphology of perinecrotic tumor cell nuclei is a promising approach, because the expression of specific molecules in these cells has been associated with a more aggressive behaviour of the tumors. In our series of patients with documented clinical course, 11 patients had a survival of at least 24 months and we compared this group with a group of 10 patients with maximum survival of 12 months. Digital microscopic image analysis was performed in paraffin sections from the primary surgical specimen. Three hundred perinecrotic tumor cell nuclei per case and 300 nuclei per case from tumor cells lying more distant from the tumor necroses ('distant zone' nuclei) were measured. The ratio for the numerical nuclear density between both types of nuclei was significantly larger in cases with short survival indicating a more pronounced nuclear density of perinecrotic nuclei in relation to the 'distant zone' nuclei in these tumors. In cases with long survival, on the contrary, perinecrotic tumor cells exhibited an only slightly larger numerical density compared with 'distant zone' nuclei. Mean values and standard deviations from parameters of nuclear shape (Fourier-amplitudes) had significantly smaller values in short-time survivors indicating a tendency towards a more circular nuclear shape with less pronounced intratumoral variation in that group. Based on the morphometric results, all cases could be correctly reclassified as short- or long-time survivors by means of cross-validated discriminant analysis. In conclusion, the results confirm significant morphological differences between tumors from patients with short and with long survival regarding morphology of both types of tumor cell nuclei. It seems likely, that histomorphometry of tumor cell nuclei could be a promising approach for the assessment of the individual prognosis of patients with glioblastomas.

Morphology of tumor cell nuclei is significantly related with survival time of patients with glioblastomas.

PURPOSE: To investigate whether histomorphology of tumor cell nuclei has a significant and independent relation to survival time of patients with glioblastomas. EXPERIMENTAL DESIGN: Seventy-two tumors from 72 patients were investigated by means of digital image analysis. Proliferating and nonproliferating nuclei were separately measured and parameters of nuclear size, shape, texture, and spatial relationships (topometric parameters) were detected. Survival analysis was done regarding morphometric data together with the patients' age, the amount of resection (total or subtotal), and the classification of the tumor as a "primary" (de novo) or "secondary" glioblastoma. RESULTS: The overall relation of all morphometric data to the time of survival was highly significant (Cox analysis, P < 0.0001). Apart from the extent of surgical resection, parameters of nuclear shape and topometric variables, such as the distance between two nuclei lying nearest to each other, showed an independent and significant relation to survival time. The patients' age had also a significant but comparably slight relation to survival time. CONCLUSIONS: The morphology of tumor cell nuclei, as represented by morphometric data, shows a significant relation to survival time of patients with glioblastomas. This relation is statistically independent from the amount of surgical resection, from the patients' age and from the classification of the glioblastoma as being primary or secondary. The results support the view that histomorphometry of tumor cell nuclei is a valuable prognostic marker for patients with glioblastomas. We believe that such a marker ought to be incorporated into the formation of individual therapeutic decisions.

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.

Efficacy of Helicobacter pylori eradication in uninvestigated chronic dyspeptic staff members of a large factory: a prospective, long-term, follow-up, workplace outcome study.

BACKGROUND: Current European guidelines propose Helicobacter pylori eradication for the initial management of patients under 45 years with uninvestigated dyspepsia without alarm symptoms. Until now, no study has assessed this strategy in occupational medicine. AIM: To investigate the outcome of H. pylori eradication in staff members of a large factory with uninvestigated chronic dyspepsia in a prospective, open, controlled, workplace outcome study in terms of the 1 year follow-up of dyspepsia and quality of life. METHODS: In 267 subjects with uninvestigated chronic dyspepsia (229 males, mean age 42 years; range 22-62 years) H. pylori status was assessed by using the 13C-urea breath test at baseline. H. pylori-positive subjects were offered 1 week eradication therapy with omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d., and metronidazole 400 mg b.i.d., and were retested after 2 months. Subjects with a negative 13C-urea breath test at 2 months were H. pylori-responders; subjects still H. pylori-positive at this time were H. pylori-nonresponders. H. pylori-negative subjects at baseline were included as a reference. Dyspeptic symptoms, quality of life and health care utilization were assessed by questionnaires at baseline (T0), and at 2 (T2) and 12 months (T12). RESULTS: One hundred and eleven of 267 (41.65%) subjects were H. pylori-positive at baseline. The infection was cured in 85 of 94 (90.4%) subjects. Upper abdominal pain and dyspeptic symptoms were significantly reduced and quality of life significantly increased in H. pylori responder subjects at T12 compared to baseline and to reference subjects (P < 0.01). At T12 42.3% of H. pylori responder subjects showed complete relief of epigastric pain compared to 9.2% in the reference group (P < 0.001). Furthermore, disease-related absence from work, visits to family physicians, and antacid consumption significantly decreased in H. pylori responder subjects compared with reference subjects (P < 0.05). CONCLUSION: These data suggest that an H. pylori test-and-treat strategy in occupational medicine is effective for improving uninvestigated dyspepsia and quality of life and it may reduce dyspepsia related health care costs at a level of occupational medicine.

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 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.

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.

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.

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.