Effects and feasibility of an Integrative Medicine program for geriatric patients-a cluster-randomized pilot study.

BACKGROUND: Older adults often use complementary medicine; however, very few interventional studies have focused on them. The aim of this study was to evaluate the feasibility and to obtain preliminary data on effectiveness of an Integrative Medicine (IM) program compared to usual medical care. METHODS: The study consisted of older adults living in shared apartment communities including caregiving. The shared apartments were cluster-randomized to the IM program or Usual Care (UC). IM consisted of additional lifestyle modification (exercise and diet), external naturopathic applications, homeopathic treatment, and modification of conventional drug therapy for 12 months. The UC group received conventional care alone. The following outcomes were used: Nurses Observation Scale for Geriatric Patients (NOSGER); Assessment of Motor and Process Skills; Barthel Index; Qualidem; Profile of Wellbeing; and Mini-mental State Examination. Exploratory effect sizes (Cohen's d, means adjusted for differences of baseline values) were calculated to analyze group differences. RESULTS: A total of eight shared apartment communities were included; four were allocated to IM (29 patients, median seven patients; [mean ± standard deviation] 82.7 ± 8.6 years) and four to UC (29 patients, median eight patients; 76.0 ± 12.8 years of age). After 12 months, effect sizes ≥0.3 were observed for activities of daily living on the NOSGER-Activities of Daily Living subscale (0.53), Barthel Index (0.30), Qualidem total sum score (0.39), Profile of Wellbeing (0.36), NOSGER-Impaired Social Behavior (0.47), and NOSGER-Depressed Mood subscales (0.40). Smaller or no effects were observed for all other outcomes. The intervention itself was found to be feasible, but elaborate and time consuming. DISCUSSION: This exploratory pilot study showed that for a full-scale trial, the outcomes of Activities of Daily Living and Quality of Life seem to be the most promising. The results have to be interpreted with care; larger confirmatory trials are necessary to validate the effects.

Homeopathic drug proving of Okoubaka aubrevillei: a randomised placebo-controlled trial.

BACKGROUND: Homeopathic drug proving is a basic concept in homeopathy. This study aimed to record symptoms produced by a homeopathic drug compared with placebo. METHODS: This multicentre, randomised, double-blind, placebo-controlled phase 1 trial consisted of a 7-day run-in period, a 5-day intervention period and a 16-day post-intervention observation period. Subjects, investigators and statisticians were blinded for intervention groups and identity of the homeopathic drug. Subjects in the intervention group received Okoubaka aubrevillei (potency C12) and subjects in the placebo group received the optically identical sucrose globules. Dosage in both groups was five globules taken five times per day over a maximum period of 5 days. Subjects documented the symptoms they experienced in a semistructured online diary. The primary outcome parameter was the number of characteristic proving symptoms compared with placebo after a period of 3 weeks. Characteristic symptoms were categorised using content analysis. Secondary outcome parameters were the qualitative differences in profiles of characteristic and proving symptoms and the total number of all proving symptoms. The number of symptoms was quantitatively analysed on an intention-to-treat basis using analyses of covariance with the subject's expectation and baseline values as covariates. RESULTS: Thirty-one subjects were included (19 Okoubaka and 12 placebo). Data for 29 participants could be analysed. No significant differences in number of characteristic symptoms in both groups were observed between Okoubaka (mean±standard deviation 5.4±6.0) and placebo (4.9±5.6). The odds ratio for observation of a characteristic symptom was 1.11 (95% confidence interval 0.4 to 3.05, P=0.843). Females and subjects expecting a higher number of symptoms at baseline or feeling more sensitive to homeopathic drugs experienced more characteristic symptoms regardless of allocation. The qualitative analysis showed an inter-coder reliability of 0.69 (95% confidence interval 0.62 to 0.76). The qualitative comparison of symptom profiles was inconclusive. CONCLUSIONS: Combined results of qualitative and quantitative methods did not result in a significant difference of characteristic proving symptoms between O. aubrevillei C12 and placebo. The qualitative comparison of the symptom profiles leaves some open questions. The nocebo effect might be a plausible explanation for most of the phenomena observed in this trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01061229.

Protocol for a phase 1 homeopathic drug proving trial.

BACKGROUND: This study protocol adapts the traditional homeopathic drug proving methodology to a modern clinical trial design. METHOD: Multi-centre, randomised, double-blind, placebo-controlled phase 1 trial with 30 healthy volunteers. The study consists of a seven day run-in period, a five day intervention period and a 16 day post-intervention observation period. Subjects, investigators and the statisticians are blinded from the allocation to the study arm and from the identity of the homeopathic drug. The intervention is a highly diluted homeopathic drug (potency C12 = 1024), Dose: 5 globules taken 5 times per day over a maximum period of 5 days. The placebo consists of an optically identical carrier substance (sucrose globules). Subjects document the symptoms they experience in a semi-structured online diary. The primary outcome parameter is the number of specific symptoms that characterise the intervention compared to the placebo after a period of three weeks. Secondary outcome parameters are qualitative differences in profiles of characteristic and proving symptoms and the total number of all proving symptoms. The number of symptoms will be quantitatively analysed on an intention-to-treat basis using ANCOVA with the subject's expectation and baseline values as covariates. Content analysis according to Mayring is adapted to suit the homeopathic qualitative analysis procedure. DISCUSSION: Homeopathic drug proving trials using the terminology of clinical trials according GCP and fulfilling current requirements for research under the current drug regulations is feasible. However, within the current regulations, homeopathic drug proving trials are classified as phase 1 trials, although their aim is not to explore the safety and pharmacological dynamics of the drug, but rather to find clinical indications according to the theory of homeopathy. To avoid bias, it is necessary that neither the subjects nor the investigators know the identity of the drug. This requires a modification to the informed consent process and blinded study materials. Because it is impossible to distinguish between adverse events and proving symptoms, both must be documented together. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01061229.

Effects of abdominal hot compresses on indocyanine green elimination--a randomized cross over study in healthy subjects.

BACKGROUND: Hot compresses on the right upper abdomen are used as support for patients with liver diseases in Germany. The study was designed to determine, whether they affect hepatic blood flow. METHODS: Single dose kinetics of indocyanine green (ICG) were studied in 13 healthy subjects with or without hot compresses on the right upper abdomen over 40 minutes. The time interval between the investigations was 8 days, the sequence was randomly assigned. RESULTS: Within non-linear kinetic analyses the area under the curves (AUC) were 23% (95% confidence interval [CI]: 5-37%) lower with hot compresses. In the initial phase, however, no differences were detected (p = 0.295). The differences occurred only in the late phase after 30-40 minutes, when the genuine ICG is eliminated from the plasma and only the degradation product remains. CONCLUSION: Hot compresses have no effect on ICG elimination in healthy subjects but seem to affect the elimination of ICG metabolites. TRIAL REGISTRATION: ClinicalTrials.gov NCT00484913.

Effects of a comprehensive lifestyle modification program on quality-of-life in patients with ulcerative colitis: a twelve-month follow-up.

OBJECTIVE: To analyze the effects of a comprehensive lifestyle modification program on health-related quality-of-life, psychological distress, and clinical parameters in patients with ulcerative colitis (UC) 3- and 12 months after completion of the program. MATERIAL AND METHODS: Sixty patients with UC in clinical remission or with low disease activity were randomly assigned to an intervention group or a usual-care control group. Comprehensive lifestyle modification consisted of a structured 60-h training program over a period of 10 weeks which included stress management training, psychoeducational elements, and self-care strategies. Quality-of-life, psychological distress, and clinical disease activity were assessed with standardized questionnaires (Inflammatory Bowel Disease Questionnaire (IBDQ); the MOS Short-Form 36 (SF-36); the Brief Symptom Inventory (BSI), and the Colitis Activity Index (CAI)) at baseline, and 3 months and 12 months after comprehensive lifestyle modification. RESULTS: Three months after comprehensive lifestyle modification, patients in the intervention group showed significantly greater improvement in the SF-36 scale physical function (p=0.0175), and a significantly greater reduction in anxiety scores, measured with the BSI (p=0.0294). Use of relaxation techniques was a significant predictor of improvement in the psychological sum score after 3 months of therapy (p=0.034). Though 80% of patients with an initial IBDQ score <170 in the intervention group showed an improvement of >16 points after 3 months, no significant effects of the intervention were found on the IBDQ scales, or on clinical disease parameters, including CAI scores, self-assessed disease activity, hospitalizations, or medical consultations. CONCLUSIONS: These results are consistent with possible short-term benefits of a comprehensive lifestyle modification program on some aspects of quality-of-life and emotional well-being, but no effects were discernable 12 months after completion of therapy. Comprehensive lifestyle modification had no effect on clinical disease variables. The generalizability of these data is limited because of the inclusion of patients with a relatively low disease activity who were interested in integrative medicine.

Patterns of complementary and alternative medicine (CAM) use in patients with inflammatory bowel disease: perceived stress is a potential indicator for CAM use.

INTRODUCTION: The reasons for using complementary and alternative medicine (CAM) and the perception of stress in a group of patients with inflammatory bowel disease (IBD) who are actively interested in CAM were compared with those of a randomly selected group of IBD patients (controls). METHODS: Participants in a national lay workshop on CAM of the German Crohn's and Ulcerative Colitis Association (DCCV) (the study group) and a representative sample of the approximately 16,000 members and associates of the DCCV (the control group) were asked to complete a self-administered questionnaire that covered socio-demographic data, past medical history, stress perception, current conventional treatment, and interest in, and usage of, CAM. RESULTS: One-hundred and twelve (80%) of the approximately 140 participants of the lay workshop and 684 (68.8%) of the 994 IBD patients in the control group completed and returned the questionnaires. The duration of illness, taken as the time since diagnosis, was shorter for the participants of the lay workshop than for the control group (p=0.0035), and fewer workshop patients stated that their disease was currently "in remission" (p=0.0377). The two groups did not differ significantly in their experiences with CAM use. Among personal reasons given for CAM use, the "lack of success of conventional therapy" (p=0.014), the wish "to take a holistic therapeutic approach" (p=0.0008), and "a different point of view from that of my physician about the cause of, and treatment options for, IBD" (p=0.038) were chosen more often in the group of workshop participants than in the control patients. A total of 92% of the workshop patients perceived stress as having a negative effect on their IBD; this is a significantly greater percentage than in the control group (70.5%; p=0.0001). CONCLUSIONS: A group of IBD patients with an active interest in CAM showed distinct differences from a randomly selected group of IBD patients in their reasons for using CAM, particularly in their wish to take a holistic therapeutic approach. Patients who think that stress has a negative effect on their IBD appear to be more likely to use CAM.

Effects of mind-body therapy on quality of life and neuroendocrine and cellular immune functions in patients with ulcerative colitis.

BACKGROUND: The aim of this study was to investigate the effects of mind-body therapy on neuroendocrine and cellular immune measures, health-related quality of life and disease activity in patients with ulcerative colitis (UC) in remission. METHODS: Thirty UC patients in remission or with low disease activity were randomly assigned to an intervention group (n = 15) or a usual-care waiting control group (n = 15). Intervention consisted of a structured 60-hour training program over 10 weeks which included stress management training, moderate exercise, Mediterranean diet, behavioral techniques and self-care strategies. Quality of life, perceived stress and disease activity were assessed with standardized questionnaires (IBDQ, SF-36, PSS, CAI). In addition, the distribution of circulating lymphocytes and lymphocyte subsets as well as the beta-adrenergic modulation of TNF-alpha production in vitro were analyzed. Urine catecholamines and plasma cortisol, prolactin and growth hormone were measured pre- and postinterventionally, and were compared with a healthy control group (n = 10). RESULTS: In response to therapy, patients in the intervention group showed significantly greater improvement in the SF-36 scale Mental Health and the Psychological Health Sum score compared with changes observed in the usual-care waiting control group. Patients in the intervention group showed significantly greater improvement on the IBDQ scale Bowel Symptoms compared with the control group. However, no significant group differences in circulating lymphocyte subsets or endocrine parameters were observed in response to therapy. In addition, no significant effects of intervention on either the basal levels of TNF-alpha or the suppressive action of the beta-adrenergic agonist isoproterenol on TNF-alpha production were observed. CONCLUSION: Mind-body therapy may improve quality of life in patients with UC in remission, while no effects of therapy on clinical or physiological parameters were found, which may at least in part be related to selective patient recruitment.

Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary angiopathy caused by mutations in the NOTCH3 gene. The clinical course is highly variable. Little is known about the long-term prognosis and the causes of death in CADASIL patients. Likewise, the impact of gender and NOTCH3 genotype on disease progression remains largely unexplored. We identified 411 subjects (196 men, 215 women) with a definite diagnosis of CADASIL. Age at onset for stroke, immobilization and death as well as the causes of death and clinical status at onset of the cause of death were determined systematically. Weibull regression models were used to calculate times to event, with gender and NOTCH3 genotype as covariates. At the time of the study, 73 patients had died. The median age at onset for stroke was 50.7 years [95% confidence interval (CI) = 48.2-53.1 years] in men and 52.5 years (95% CI = 50.0-54.9 years) in women (P = n.s.). The median ages at onset for inability to walk without assistance [men 58.9 years (95% CI = 56.6-61.3 years); women 62.1 years (59.7-64.4 years)], bedriddenness [men 62.1 years (59.6-64.7 years), women 66.5 years (63.9-69.1 years); and death [men 64.6 years (61.7-67.6 years); women 70.7 years (67.6-73.9 years)] were significantly lower in men than in women (all P < or = 0.01). The median survival time of men was significantly shorter than expected from German life tables (64.6 versus 69.3 years, P = 0.01). In contrast, the median survival time of women was not significantly reduced (70.7 versus 72.2 years). The C117F mutation was associated with a lower age at death and the C174Y mutation with a lower age at onset for stroke, immobilization and death (adjusted P values <0.05). At onset of the cause of death, 78% of the subjects were completely dependent. Sixty-three per cent were confined to bed. Pneumonia was the most frequent cause of death (38%), followed by sudden unexpected death (26%) and asphyxia (12%). We conclude that male sex is a risk factor for early immobilization and death in CADASIL. Our findings suggest possible genotype-phenotype correlations with regard to disease progression. The data presented may serve as source material for counselling CADASIL patients and for designing future interventional trials.

Experience and attitudes towards CAM--a survey of internal and psychosomatic patients in a German university hospital.

Complementary and alternative medicine (CAM) is popular in Germany. In a consecutive survey the experiences with CAM and the need for a CAM consultation among inpatients of the departments of cardiology (CL), gastroenterology (GE), oncology (OL) and psychosomatics (PS) of the University Hospital Freiburg (FUH) were questionned. Exclusion criteria were inability to understand the questions or a Karnofsky Index < 30%. Four hundred thirty-five patients were included. Three hundred and fifty patients, 100 each in the departments of CL, GE and OL, and 50 in PS answered the questionnaires. Eighty-five patients (20%) refused. Among the 350 patients 26% had previously visited a CAM physician and 19% had visited a CAM therapist (Heilpraktiker). Information about CAM was obtained mainly by television, radio and family members. Frequently used therapies for the current disease were physical training (21%), diet (19%), massage (19%), vitamins/trace elements (19%), herbs (13%), acupuncture (10%) and homeopathy (7%). The highest frequency of CAM use had PS patients, followed by GE, OL and CL patients. High effectivity (> or = 70%) for the current disease, rated on a scale of 4 degrees, had for CL patients physical exercise and massage, for GE patients herbal treatment and for OL patients diet. Physical exercise, diet, massage and herbal treatment generally had better ratings than homeopathy, acupuncture and vitamins. 65% would welcome a CAM center and 53% asked for a consultation about CAM at FUH. OL and GE patients had the strongest (58%), PS patients a lower (52%) and patients with cardiovascular diseases the lowest (43%) interest in a CAM consultation. Twenty-five percent believed, that CAM can help to cope better with their disease. Predictors for a positive attitude towards CAM were young age, aversion to chemical medications (Spearman correlation r = 0.22), desire to participate in therapeutic decisions (r = 0.29), motivation to change, if recommended, the life style (r = 0.31) and desire for a holistic treatment (r = 0.37).