Severity of GERD and disease progression.

BACKGROUND: Many factors may play a role in the severity and progression of gastroesophageal reflux disease (GERD) since pathophysiology is multifactorial. Data regarding the progression of GERD are controversial: some reports of increased esophageal acid exposure (EAE) and mucosal damage were considered as evidence for a stable disease course, while others interprete these findings as disease progression. The aim of this study is to analyze a large patient-population with persisting symptoms indicative of GERD under protonpumpinhibitor-therapy and identify components characterizing disease severity and progression. METHODS: Patients with symptoms indicative of GERD were included in the study in a tertiary referral center (Frankfurt, Germany). All selected patients were under long-term protonpumpinhibitor-therapy with persistant symptoms. All patients underwent investigations to collect data on their physical status, EAE, severity of esophagitis, anatomical changes, and esophageal functional defects as well as their relation to the duration of the disease. Incidence over time was plotted as survival curves and tested with Log-rank tests for the four main disease markers. Multivariate modeling with COX-regression model was used to estimate the general impact of the four main disease markers on the time course of the disease. In order to elucidate possible causal relationships over time, a path analysis (structural equation model) was calculated. RESULTS: From the database with 1480 data sets, 972 patients were evaluated (542 males, 430 females). The mean age was 50.5 years (range18-89). The mean body mass index was 27.2(19-48). The mean time between the onset of symptoms and the diagnostic investigations was 8.2 years (1-50). A longer disease history for GERD was significantly associated with a higher risk for LES-incompetence. The mean duration from symptom onset to the time of clinical investigation was 9 years for patients with LES-incompetence (n = 563), compared to a mean of 6 years for those with mechanically intact LES (n = 95). A longer period from symptom onset to diagnostics was significantly associated with higher acid exposure. The pathway analysis was significant for the following model: 'history' (P < 0.001➔LES-incompetence & Hiatal Hernia➔(p < 0,001)➔pH-score (P < 0.001).Conclusion: LES-incompetence, the functional deterioration of the LES, and the anatomical alteration at the esophagogastric junction (Hiatal Hernia) as well as an increased EAE were associated with a long history of suffering from GERD. Path modeling suggests a causal sequence overtime of the main disease-parameters, tentatively allowing for a prediction of the course of the disease.

Recruitment and inclusion procedures as "pain killers" in clinical trials?

BACKGROUND: Recruitment and inclusion procedures in clinical trials are time critical. This holds particularly true for studies investigating patients with fluctuating symptom patterns, like those with chronic neck pain. In a feasibility study on neck pain, we found a clinically relevant decrease in pain ratings within the recruitment period. This paper analyses the phenomenon and gives recommendations for recruitment procedures in clinical trials on pain. METHODS: Changes in pain intensity scores of 44 chronic neck pain patients (6 males and 36 females; mean age: 45.3±13.2 years) between the first telephone contact and baseline assessment were analyzed. Inclusion criterion was a mean pain intensity of ≥40 on a 0-100 numerical rating scale during the last three months. Statistical analyses were performed using ANOVA and parametric/non-parametric correlation coefficients. RESULTS: Average pain intensity score decreased significantly from 60.3±13.3 at telephone interview to 38.1±21.7 at baseline assessment. This represents a relative change of 36.8%. A weak but significant negative correlation was found between number of days between assessments and pain rating differences. There was a positive correlation between change of pain intensity and the pain level at the first contact, indicating that the decreased pain ratings over time were also dependent on the initial pain rating. CONCLUSIONS: The clinically significant changes in pain intensity were weakly related to waiting time and moderately dependent on initial pain intensity, suggesting regression to the mean. The natural course of the disease and the Hawthorne effect are also discussed as contributing factors.

Foregut symptoms, somatoform tendencies, and the selection of patients for antireflux surgery.

A large variety of foregut symptoms can occur in patients with gastroesophageal reflux disease (GERD), which can overlap with other disorders such as somatoform disorders and dyspepsia. Due to unclear diagnostic situations, these patients are often not adequately treated. The aim of this study was the evaluation of patients with foregut symptoms, referred for possible antireflux surgery, regarding their relationship with GERD and somatization tendencies based on control data from an unselected population. Symptom evaluation and somatization screening were initiated both in volunteers and in patients with foregut symptoms and GERD. Unselected volunteers from a village population were also evaluated by symptom analysis and for somatisation tendency. In addition, patients with foregut symptoms were diagnosed for GERD, and symptom analysis and psychodiagnostic evaluation were performed. There is no major significant difference in the symptom-spectrum in patients with foregut symptoms, whether they have a proven pathologic acid exposure from GERD or not. The probability for the risk of somatization was 5.6% in the unselected population of nonpatient volunteers (n = 267). In patients with foregut symptoms (n = 750), the probability for the presence of somatoform tendencies was approximately 20%, independent whether these patients had a documented GERD or a normal esophageal acid exposure, implicating further diagnostic work-up for the selection of patients for antireflux surgery. There is a remarkable symptom load and variety in patients with GERD, in patients with foregut symptoms, and in an unselected population of volunteers. There is no difference in the risk for somatization between patients with foregut symptoms and those with documented GERD. Therapeutic decision making especially prior to antireflux surgery requires an awareness of mental and emotional challenges.

[Complementary and alternative therapies for fibromyalgia syndrome. Systematic review, meta-analysis and guideline]. / Komplementäre und alternative Verfahren beim Fibromyalgiesyndrom. Systematische Übersicht, Metaanalyse und Leitlinie.

BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. MATERIALS AND METHODS: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. The recommendations were based on level of evidence, efficacy (meta-analysis of the outcomes pain, sleep, fatigue and health-related quality of life), acceptability (total dropout rate), risks (adverse events) and applicability of treatment modalities in the German health care system. The formulation and grading of recommendations was accomplished using a multi-step, formal consensus process. The guidelines were reviewed by the boards of the participating scientific medical societies. RESULTS AND CONCLUSION: Meditative movement therapies (qi gong, tai chi, yoga) are strongly recommended. Acupuncture can be considered. Mindfulness-based stress reduction as monotherapy and dance therapy as monotherapy are not recommended. Homeopathy is not recommended. In a minority vote, homeopathy was rated as "can be considered". Nutritional supplements and reiki are not recommended. The English full-text version of this article is available at SpringerLink (under "Supplemental").

Reporting experiments in homeopathic basic research-description of the checklist development.

The objective of this study was to develop a criteria catalogue serving as a guideline for authors to improve quality of reporting experiments in basic research in homeopathy. A Delphi Process was initiated including three rounds of adjusting and phrasing plus two consensus conferences. European researchers who published experimental work within the last 5 years were involved. A checklist for authors provide a catalogue with 23 criteria. The "Introduction" should focus on underlying hypotheses, the homeopathic principle investigated and state if experiments are exploratory or confirmatory. "Materials and methods" should comprise information on object of investigation, experimental setup, parameters, intervention and statistical methods. A more detailed description on the homeopathic substances, for example, manufacture, dilution method, starting point of dilution is required. A further result of the Delphi process is to raise scientists' awareness of reporting blinding, allocation, replication, quality control and system performance controls. The part "Results" should provide the exact number of treated units per setting which were included in each analysis and state missing samples and drop outs. Results presented in tables and figures are as important as appropriate measures of effect size, uncertainty and probability. "Discussion" in a report should depict more than a general interpretation of results in the context of current evidence but also limitations and an appraisal of aptitude for the chosen experimental model. Authors of homeopathic basic research publications are encouraged to apply our checklist when preparing their manuscripts. Feedback is encouraged on applicability, strength and limitations of the list to enable future revisions.

Reporting experiments in homeopathic basic research (REHBaR)--a detailed guideline for authors.

BACKGROUND: Reporting experiments in basic research in homeopathy is an important issue as comprehensive description of what exactly was done is required. So far, there is no guideline for authors available, unlike criteria catalogues common in clinical research. METHODS: A Delphi Process was conducted, including a total of five rounds, three rounds of adjusting and phrasing plus two consensus conferences. European researchers who published experimental work within the last five years were involved. RESULTS: A checklist of 23 items was obtained and supplemented with detailed examples emphasizing what each item implies. Background, objectives and possible hypotheses should be given in the part 'introduction'. Special emphasis is put on the 'materials and methods' section, where a detailed description of chosen controls, object of investigation, experimental setup, replication, parameters, intervention, allocation, blinding, and statistical methods is required. The section 'results' should present sufficient details on analysed data, descriptive as well as inferential. Authors should discuss their results and give an interpretation in the context of current evidence. CONCLUSION: A guideline for Reporting Experiments in Homeopathic Basic Research (REHBaR) was compiled to be applied by authors when preparing their manuscripts, and to be used by scientific journals in the reviewing process. Furthermore the guideline is a commitment to a certain minimum quality level needed in basic research, e.g. blinding and randomisation. Feedback is encouraged on applicability, strength and limitations of the list to enable future revisions.

[Is the analgesic effect of acupuncture a placebo effect?]. / Ist die analgetische Wirkung der Akupunktur ein Placeboeffekt?

The German acupuncture trials ART and GERAC have shown that acupuncture and sham or minimal acupuncture were equally effective in the reduction of chronic pain symptoms. These results have prompted an ongoing discussion as to whether acupuncture exerts its effects through a placebo response. Increasing knowledge about the neurobiology of pain and its intrinsic control suggests a combination of acupuncture-specific neurophysiologic effects combined with effects that match those of expectation-induced placebo analgesia.

[Alternative and complementary therapies in fibromyalgia syndrome]. / Komplementäre und alternative Verfahren beim Fibromyalgiesyndrom.

INTRODUCTION: Interdisciplinary S3 level guidelines were devised in cooperation with 8 medical, 2 psychological and 2 patient support groups. Results were elaborated in a multilevel group process. METHODS: On the bases of the "Cochrane Library" (1993-2006), "Medline" (1980-2006), "PsychInfo" (2006) and "Scopus" (2006) controlled studies and meta-analyses of controlled studies were analyzed. RESULTS: Only few controlled studies were found supporting in part the effectiveness of CAM therapies in the treatment of fibromyalgia syndrome. Due to the lack of information on long term efficacy and cost-effectiveness, only limited recommendations for CAM therapies can be given. CONCLUSION: Within a multicomponent therapy setting, selective CAM therapies (acupuncture, vegetarian diet, homeopathy, Tai Chi, Qi Gong, music-oriented and body-oriented therapies) can be recommended for a limited period of time.

[Mind-body medicine as a part of German integrative medicine]. / Mind-Body Medicine als Bestandteil der Integrativen Medizin.

Mind-body medicine (MBM) as a holistic approach to health and healing has been shaped by research into stress physiology and stress psychology, by psychoneuro(endocrino)immunology and by Antonovsky's salutogenetic paradigm. MBM seeks to acknowledge physical, psychological as well as social and spiritual aspects of human beings. MBM constitutes one of the traditions, which the emerging field of integrative medicine in Germany draws upon, others being mainstream medicine, traditional European naturopathy and non-European methods like traditional Chinese medicine. The article outlines historical aspects of MBM, gives a brief review of research evidence, and introduces clinical MBM institutes in Germany. Especially the Clinic and Chair of Complementary and Integrative Medicine, Alfried Krupp von Bohlen und Halbach Foundation at the University Duisburg-Essen has been integrating MBM into the concept of integrative medicine. Considering that a growing number of health issues arises due to maladaptive lifestyles, MBM is being identified as a development that supports a shift from increasingly expensive treatments to more cost-effective preventive approaches.

[Psychophysiology of visceral pain]. / Psychophysiologie des Eingeweideschmerzes.

This paper reviews the most important research strategies in the context of the psychophysiology of visceral pain. These are disturbed gastrointestinal motility, visceral hypersensitivity and central nervous system mechanisms such as response bias, attentional bias and affective evaluation. The most prominent research methods and results are reviewed and methodological problems are discussed. From a psychophysiological perspective, visceral pain remains a complex and heterogeneous syndrome in which stress and coping may be etiologically as important as pathophysiological mechanisms of peripheral origin and central nervous system mechanisms like attentional bias.

[Therapy of fecal incontinence in elderly patients: Study of a home biofeedback training program]. / Therapie der Stuhlinkontinenz bei älteren Patienten: Untersuchung zur Wirksamkeit eines Biofeedback-Heimtrainingsprogramms.

UNLABELLED: The increased prevalence of urinary and fecal incontinence is one of the most important factors in the loss of independence and mobility in the elderly population. It is also one of the major reasons for elderly people to give up their household and move into a nursing home. Anorectal biofeedback therapy is a very effective treatment for fecal incontinence. However, due to the increased immobility of elderly people, ambulatory biofeedback training programs which require the participants to leave their homes and travel to the next available outpatient clinic on a regular basis, especially when depending on public transportation, may prove particularly difficult for elderly, incontinent subjects. Supervised home biofeedback training programs may offer an alternative for those patients, who are motivated enough and not mentally impaired. Two different age groups of women (between 49 and 63; and between 65 and 78 years old) suffering from fecal incontinence due to external anal sphincter impairment, received a supervised home biofeedback program, after extensive anorectal diagnostics including manometry. The program focused on improving voluntary sphincter contraction. After an average of 9 months, anorectal manometry was repeated, and anal resting and squeeze pressure as well as minimal rectal perception threshold were determined. There was no effect on anal resting pressure and rectal perception. However, anal maximum squeeze pressure as well as squeeze pressure over 10 s was substantially increased with no difference between the age groups. CONCLUSION: Supervised home biofeedback for sphincter insufficiency was effective in improving the voluntary contraction of the anorectum in both age groups. Therefore, biofeedback home training programs may offer an alternative to ambulatory programs for those individuals, who are not mobile enough to regularly attend an outpatient clinic.

A computer-controlled, long-term recording system for studying eating, drinking, and defecation behavior in miniature pigs.

The long-term observation of ingestive and excretory behaviors in freely ambulating and non socially isolated pigs is an important tool in the investigation of the physiological determinants of these behaviors. A computer-controlled laboratory setup for the recording of feeding, drinking, and defecation behavior in minipigs was developed, allowing for the observation of two pigs at a time for weeks. Four minipigs (29-52 kg) were conditioned to operate feeders with a precise food release per response and were then fed ad lib. The animals had up to 50% of their daily energy intake during the night. Meal size and time spent eating was highly correlated, meal size and the preprandial intermeal interval was moderately correlated, whereas meal size and the postprandial intermeal interval was not. Feeding facilitated defecation, supporting the assumption that the gastrocolonic response is present in the pig. The system has been shown to be highly reliable and valid, and thus provides an excellent tool for the investigation of the rhythmicity of ingestive and excretory behaviors in minipigs.

Influence of continuous, isobaric rectal distention on smooth muscle tone and cardiovascular activation in healthy volunteers.

UNLABELLED: Interactions between visceral, intestinal stimulation and autonomic cardiovascular function have received increasing attention over the last years. The aim of the study was to investigate the effect of long-term continuous rectal distention on rectal tone and cardiovascular function at the threshold for first sensation of distention and moderate urge to defecate compared to a resting period without distention. Continuous isobaric rectal distention was performed in 13 healthy volunteers with a ten minute pressure tracking procedure at each subject's predetermined individual threshold for either moderate urge or first sensation, separated by a ten minute resting period. Rectal volume, heart rate, systolic and diastolic blood pressure were determined continuously. RESULTS: Rectal tone decreased significantly over time at the threshold for moderate urge and first sensation. Cardiovascular measures remained stable over the distention procedures, except for a significant increase in systolic blood pressure at the threshold for moderate urge. DISCUSSION: The previously reported rectal accommodation response to rectal distention was confirmed. The increase in systolic blood pressure is most likely mediated through sympathetic efferent pathways.

Temporal analysis of feeding behavior in miniature pigs.

The feeding behavior of four Munich miniature pigs (29-43 kg) housed in pairs of two, was observed for two consecutive weeks. Pigs were conditioned to operate a computer-controlled recording system equipped with feeders delivering a precise food release per response and were then fed ad libitum. In addition to the descriptive analysis of feeding behavior, Walsh-Fourier Spectral Analysis was utilized to investigate the temporal patterns of food ingestion and the synchronisation of feeding patterns between the animals housed together. The pigs had up to 48% of their daily energy intake during the dark cycle and there was a substantial reduction of food intake from the first to the second week. Furthermore, pigs housed together synchronized feeding behavior from week 1 to week 2. The recording system has been shown to be highly reliable and valid and provides an excellent tool for the investigation of ingestive behaviors in miniature pigs.

Facial EMG responses to auditory stimuli.

Three studies were performed to investigate the effects of auditory stimuli (pure tones and environmental noise) of different intensities on surface EMG activity recorded over five facial muscle regions (M. frontalis lateralis, M. corrugator supercilii, M. orbicularis oculi, M. zygomaticus major, M. depressor anguli oris). The results show that with presentation of tones and noises of high intensity (> 85 dB) strong facial EMG reactions over muscles of the upper face (M. frontalis lateralis, M. corrugator supercilii, M. orbicularis oculi) were evoked. Among environmental noises of different valence but the same intensity, baby's crying evoked EMG reactions over facial muscles in the mouth region, possibly indicating that the subjects demonstrated expressions of dislike during this particular stimulation. It is also discussed whether facial EMG reactions to auditory stimulation of different intensities could be connected to changes in muscle tone of the middle ear muscles. The contraction of these muscles modulates sensitivity to auditory stimulation. Thus, facial EMG activity of the muscles of the upper face could serve as an indicator of sensitivity to external auditory stimuli. However, the evaluation of pleasant and unpleasant emotional reactions in response to auditory stimulation seems to be impossible.

Rectal adaptation to distention: implications for the determination of perception thresholds.

Chronic changes in rectal compliance and perception are often associated with constipation, but the mechanisms responsible for these changes are not known. These studies evaluated the dynamic response of the rectal wall to distention and, in a separate investigation, the influence of adaptive relaxation on perception thresholds. In Study 1, seven healthy volunteers were evaluated using a computer-controlled barostat to maintain continuous isobaric distention of the rectum at urge threshold over a 25-min period. Changes in intrabag volume were evaluated at minutes 1, 5, and 25. Study 2 investigated changes in perception thresholds with different interstimulus intervals (30 s vs. 60 s) in 16 healthy subjects. Pressure was incremented in steps of 2 mmHg up to discomfort threshold. The mean intrabag volume, pressure, and the compliance index for the first and second 5-s intervals were compared to the last 5 s interval. Statistical analyses were performed using the Wilcoxon Sign-Rank test with Bonferonni corrections. Study 1 showed a significant relaxation of the rectal wall in response to balloon distention with volumes consistently increasing from minute 1 to minute 25. Study 2 showed a significant change in the compliance index at the threshold for moderate urge and intense urge during the 60-s distention that resulted from progressive relaxation of the rectal wall. Study 1 showed an adaptive response of the rectum to distention. Study 2 confirmed these findings and implied a role for this adaptive response in the determination of rectal sensory thresholds.

Monitoring radio programs and time of day affect simulated car-driving performance.

Whether radio monitoring, task difficulty, and time of day affect driving performance was examined in a computer-controlled, simulated driving task. Driving performance was defined as the absolute deviation of the car position from road midline as displayed on the computer monitor. We found for 12 men and 8 women (i) an expected, marked deterioration of performance with increasing task difficulty, (ii) a deterioration of performance in the morning, and (iii) a deterioration of performance when subjects concurrently listened to radio programs except for the easy task conducted in the morning. The latter is supposed to be caused by a reactive increase of effort, which is induced by the concurrent radio monitoring and stimulated through a perceived impairment of attention.

Nutrient ingestion increases rectal sensitivity in humans.

To determine the effect of nutrient ingestion on rectal perception thresholds (first sensation, consistent urge to defecate, pain), rectosigmoid balloon distentions were performed with a computerized automated pump in eight healthy volunteers (four males, four females, 31.6 +/- 6.02 years). Two measurements of rectal balloon distention were performed on 2 separate days. Day 1 served as a control condition with no meal. On day 2 the subjects received a 600 kcal liquid meal. On the control day, determination of perception thresholds was performed two times with a 10-min break between measurements. On the experimental day, threshold determinations were made before and after the ingestion of the liquid standard meal. The order of the experimental days was counterbalanced. Distention volumes at the urge to defecate and the pain threshold (maximum tolerable volume) were significantly reduced following the meal. The average change from pre- to postprandial measurements of the threshold for urge to defecate was -20.55 +/- 4.22% and for the maximum tolerable volume it was -16.09 +/- 4.4%. These results extend data previously reported from animal studies using similar experimental methods.