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Lepage P.,University of Kiel | Lepage P.,French National Institute for Agricultural Research | Hosler R.,University of Kiel | Spehlmann M.E.,University of Kiel | And 8 more authors.
Gastroenterology | Year: 2011

Background & Aims: Interactions between genetic and environmental factors are believed to be involved in onset and initiation of inflammatory bowel disease. We analyzed the interaction between gastrointestinal mucosal microbiota and host genes in twin pairs discordant for ulcerative colitis (UC) to study the functional interaction between microbiota and mucosal epithelium. Methods: Biopsy were collected from sigmoid colon of UC patients and their healthy twins (discordant twin pairs) and from twins without UC. Microbiota profiles were determined from analysis of 16S ribosomal DNA libraries; messenger RNA profiles were determined by microarray analysis. Results: Patients with UC had dysbiotic microbiota, characterized by less bacterial diversity and more Actinobacteria and Proteobacteria than that of their healthy siblings; healthy siblings from discordant twins had more bacteria from the Lachnospiraceae and Ruminococcaceae families than twins who were both healthy. In twins who were both healthy, 34 mucosal transcripts correlated with bacterial genera, whereas only 25 and 11 correlated with bacteria genera in healthy individuals and their twins with UC, respectively. Transcripts related to oxidative and immune responses were differentially expressed between patients with UC and their healthy twins. Conclusions: The transcriptional profile of the mucosa appears to interact with the colonic microbiota; this interaction appears to be lost in colon of patients with UC. Bacterial functions, such as butyrate production, might affect mucosal gene expression. Patients with UC had different gene expression profiles and lower levels of biodiversity than their healthy twins, as well as unusual aerobic bacteria. Patients with UC had lower percentages of potentially protective bacterial species than their healthy twins. © 2011 AGA Institute.


Schaefer M.,Psychotherapy and Addiction Medicine | Sarkar R.,Asklepios Westklinikum Hamburg | Knop V.,Goethe University Frankfurt | Effenberger S.,Charité - Medical University of Berlin | And 18 more authors.
Annals of Internal Medicine | Year: 2012

Background: Depression is a major complication during treatment of chronic hepatitis C virus (HCV) infection with interferon-α (IFN-α). It is unclear whether antidepressants can prevent IFN-induced depression in patients without psychiatric risk factors. Objective: To examine whether preemptive antidepressant treatment with escitalopram can decrease the incidence or severity of depression associated with pegylated IFN-α in HCV-infected patients without a history of psychiatric disorders. Design: Randomized, multicenter, double-blind, prospective, placebo-controlled, parallel-group trial. (ClinicalTrials.gov registration number: NCT00136318) Setting: 10 university and 11 academic hospitals in Germany. Patients: 181 HCV-infected patients with no history of psychiatric disorders enrolled between August 2004 and December 2008. Intervention: Escitalopram, 10 mg/d (n = 90), or placebo (n = 91) administered 2 weeks before and for 24 to 48 weeks during antiviral therapy. Measurements: The primary end point was the incidence of depression, defined as a Montgomery-Asberg Depression Rating Scale (MADRS) score of 13 or higher. Secondary end points were time to depression, incidence of major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, quality of life, sustained virologic response, tolerability, and safety. Results: 32% (95% CI, 21% to 43%) of the patients in the escitalopram group developed a MADRS score of 13 or higher compared with 59% (CI, 48% to 69%) in the placebo group (absolute difference, 27 percentage points [CI, 12 to 42 percentage points]; P < 0.001). Major depression was diagnosed in 8% of the patients in the escitalopram group and 19% in the placebo group (absolute risk difference, 11 percentage points [CI, 5 to 15 percentage points]; P = 0.031). Tolerability and safety parameters did not differ between the groups. In the escitalopram group, 56% (CI, 46% to 66%) of patients achieved a sustained virologic response compared with 46% (CI, 37% to 57%) in the placebo group (P = 0.21). Limitations: Results might not be generalizable to patients with previous psychiatric disease. Some patients withdrew or developed temporary elevated MADRS scores after randomization but before the study medication was started. Conclusion: Prophylactic antidepressant treatment with escitalopram was effective in reducing the incidence and severity of IFN-associated depression in HCV-infected patients without previous psychiatric disease. Primary Funding Source: Roche Pharma and Lundbeck. © 2012 American College of Physicians.


Liebs T.R.,University of Kiel | Nasser L.,University of Kiel | Herzberg W.,Asklepios Westklinikum Hamburg | Ruther W.,Rheumaklinik Bad Bramstedt | Hassenpflug J.,University of Kiel
Bone and Joint Journal | Year: 2014

Several factors have been implicated in unsatisfactory results after total hip replacement (THR). We examined whether femoral offset, as measured on digitised post-operative radiographs, was associated with pain after THR. The routine post-operative radiographs of 362 patients (230 women and 132 men, mean age 70.0 years (35.2 to 90.5)) who received primary unilateral THRs of varying designs were measured after calibration. The femoral offset was calculated using the known dimensions of the implants to control for femoral rotation. Femoral offset was categorised into three groups: normal offset (within 5 mm of the height-adjusted femoral offset), low offset and high offset. We determined the associations to the absolute final score and the improvement in the mean Western Ontario and McMaster Universities osteoarthritis index (WOMAC) pain subscale scores at three, six, 12 and 24 months, adjusting for confounding variables. The amount of femoral offset was associated with the mean WOMAC pain subscale score at all points of follow-up, with the low-offset group reporting less WOMAC pain than the normal or high-offset groups (six months: 7.01 (SD 11.69) vs 12.26 (SD 15.10) vs 13.10 (SD 16.20), p = 0.006; 12 months: 6.55 (SD 11.09) vs 9.73 (SD 13.76) vs 13.46 (SD 18.39), p = 0.010; 24 months: 5.84 (SD 10.23) vs 9.60 (SD 14.43) vs 13.12 (SD 17.43), p = 0.004). When adjusting for confounding variables, including age and gender, the greatest improvement was seen in the low-offset group, with the normal-offset group demonstrating more improvement than the high-offset group. © 2014 The British Editorial Society of Bone & Joint Surgery.


Liebs T.R.,University of Kiel | Herzberg W.,Asklepios Westklinikum Hamburg | Roth-Kroeger A.M.,Asklepios Westklinikum Hamburg | Ruther W.,Rheumaklinik Bad Bramstedt | And 2 more authors.
Clinical Orthopaedics and Related Research | Year: 2011

Background: Specific anatomic differences are believed to account for gender-specific function and health-related quality of life after TKA. However, there are conflicting data in the literature regarding these gender-specific outcomes, especially as woman appear to have surgery later in the course of the disease compared with men. Questions/purposes: We asked whether (1) women had worse knee function and health-related quality of life after TKA compared with men, (2) lower improvements in scores, and (3) slower recovery after surgery. Methods: Using a cohort study design, we retrospectively analyzed prospectively collected data from three multicenter randomized controlled trials evaluating rehabilitation measures after standard unisex knee arthroplasty in 494 patients (141 men and 353 women). The primary outcome was self-reported physical function as measured by the WOMAC at 3, 6, 12, and 24 months after surgery. Secondary outcomes included the pain and stiffness scales of the WOMAC and the physical and mental component summaries of the SF-36. At the time of surgery, the women were on average older (70.8 versus 67.8 years), had lower mean physical function (55 versus 47), higher mean pain scores (54 versus 48), and greater stiffness (54 versus 46) as measured by the WOMAC. Results: At the 3-, 6-, 12-, and 24-month followups, men and women had similar WOMAC scores. Improvements were greater for women compared with men for WOMAC function and pain subscale scores at the 3-month (function, 28 versus 23; pain, 32 versus 25) and 6-month followups (function, 32 versus 27; pain, 36 versus 31). At the 12- and 24-month followups we noted no differences in improvement between men and women. Conclusion: Although women had greater functional limitations at the time of surgery than men, they recover faster early after standard TKA although function is similar at 12 and 24 months. Women also had greater improvement of WOMAC scores after standard TKA than men. Level of Evidence: Level II, prognostic study. See the guidelines for authors for a complete description of levels of evidence. © 2011 The Association of Bone and Joint Surgeons.


Seidel D.,Witten/Herdecke University | Mathes T.,Witten/Herdecke University | Lefering R.,Witten/Herdecke University | Storck M.,Sta dtisches Klinikum Karlsruhe gGmbH | And 2 more authors.
Trials | Year: 2014

Background: In August 2010, the Federal Joint Committee (G-BA) decided that negative pressure wound therapy (NPWT) would not be reimbursable in German ambulatory care. This decision was based on reports from the Institute for Quality and Efficiency in Health Care (IQWiG), which concluded that there is no convincing evidence in favor of NPWT. The aim of this diabetic foot study (DiaFu study) is to evaluate whether the clinical, safety and economic results of NPWT are superior to the results of standard wound treatment. Methods/Design: The DiaFu study is designed as a national, multicenter, randomized controlled clinical superiority trial with a special focus on outpatient care in Germany. Competent patients in inpatient and outpatient care suffering from a chronic diabetic foot wound for a minimum of four weeks may be included in the study. The trial evaluates the treatment outcome of the application of a technical medical device which is based on the principle of NPWT (intervention group) in comparison to standard moist wound therapy (control group). All treatment systems used in the intervention group bear the symbol of free trade capacity in the European Union (CE mark) and will be operated within normal conditions of clinical routine and according to manufacturer's instructions. Primary endpoints are the time to complete wound healing and the rate of wound healing achieved in each group within the maximum study treatment time of 16 weeks. Primary endpoints will be confirmed by blinded assessment of wound photographs. Discussion: The DiaFu study will provide solid evidence regarding the efficacy and effectiveness of NPWT until 31 December 2014, the date when G-BA plans to decide on future reimbursement of NPWT in both ambulatory and in-hospital care. The study is designed to comply with all quality requirements of G-BA and IQWiG and will contribute to evidence-based wound care in Germany. The study has been initiated by the statutory health insurance companies in Germany and is co-funded by two manufacturers of NPWT systems. Trial registration: Clinical Trials.gov registration number: NCT01480362 (date of registration: 23 November 2011).German Clinical Trials Register number: DRKS00003347 (date of registration: 22 November 2011). © 2014 Seidel et al.


Liebs T.R.,University of Kiel | Herzberg W.,Asklepios Westklinikum Hamburg | Rther W.,Klinikum Bad Bramstedt | Rther W.,University of Hamburg | And 3 more authors.
Archives of Physical Medicine and Rehabilitation | Year: 2012

Objective: To evaluate if the timing of aquatic therapy influences clinical outcomes after total knee arthroplasty (TKA) or total hip arthroplasty (THA). Design: Multicenter randomized controlled trial with 3-, 6-, 12-, and 24-month follow-up. Setting: Two university hospitals, 1 municipal hospital, and 1 rural hospital. Participants: Patients (N=465) undergoing primary THA (n=280) or TKA (n=185): 156 men, 309 women. Intervention: Patients were randomly assigned to receive aquatic therapy (pool exercises aimed at training of proprioception, coordination, and strengthening) after 6 versus 14 days after THA or TKA. Main Outcome Measures: Primary outcome was self-reported physical function as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3-, 6-, 12-, and 24-months postoperatively. Results were compared with published thresholds for minimal clinically important improvements. Secondary outcomes included the Medical Outcomes Study 36-Item Short-Form Health Survey, Lequesne-Hip/Knee-Score, WOMAC-pain and stiffness scores, and patient satisfaction. Results: Baseline characteristics of the 2 groups were similar. Analyzing the total study population did not result in statistically significant differences at all follow-ups. However, when performing subanalysis for THA and TKA, opposite effects of early aquatic therapy were seen between TKA and THA. After TKA all WOMAC subscales were superior in the early aquatic therapy group, with effect sizes of WOMAC physical function ranging from.22 to.39. After THA, however, all outcomes were superior in the late aquatic therapy group, with WOMAC effect sizes ranging from.01 to.19. However, the differences between treatment groups of these subanalyses were not statistically significant. Conclusions: Early start of aquatic therapy had contrary effects after TKA when compared with THA and it influenced clinical outcomes after TKA. Although the treatment differences did not achieve statistically significance, the effect size for early aquatic therapy after TKA had the same magnitude as the effect size of nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis of the knee. However, the results of this study do not support the use of early aquatic therapy after THA. The timing of physiotherapeutic interventions has to be clearly defined when conducting studies to evaluate the effect of physiotherapeutic interventions after TKA and THA. © 2012 American Congress of Rehabilitation Medicine.


Liebs T.R.,University of Kiel | Herzberg W.,Asklepios Westklinikum Hamburg | Ruther W.,University of Hamburg | Haasters J.,Ostseeklinik Damp | And 2 more authors.
Journal of Bone and Joint Surgery - Series A | Year: 2010

Background: The optimal treatment strategy following primary total hip or knee replacement remains unknown. The purpose of this study was to evaluate the effect of ergometer cycling after hip or knee replacement surgery on health-related quality of life and patient satisfaction. Methods: Three hundred and sixty-two patients were randomly assigned to either perform or not perform ergometer cycling beginning two weeks after total hip or knee replacement. The primary outcome was self-reported physical function as measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at three, six, twelve, and twenty-four months postoperatively. Results were compared with published thresholds for minimal clinically important improvements. Results: The baseline characteristics of the two groups were similar. After the hip arthroplasties, all of the outcome parameters were superior in the ergometer cycling group at all follow-up intervals, and the primary outcome, physical function as measured with the WOMAC, was significantly better at three months (21.6 compared with 16.4 points, effect size = 0.33, p = 0.046) and twenty-four months (14.7 compared with 9.0 points, effect size = 0.37, p = 0.019). After the hip arthroplasties, a higher percentage of the ergometer cycling group was ''very satisfied'' at all follow-up intervals (for example, 92% compared with 80% at three months; p = 0.027). The significant differences in the primary outcome exceeded the absolute minimal clinically important improvement threshold by a factor of 2.0. No significant differences between the study groups were seen after the knee arthroplasties. Conclusions: Ergometer cycling after total hip arthroplasty is an effective means of achieving significant and clinically important improvement in patients' early and late health-related quality of life and satisfaction. However, this study does not support the use of ergometer cycling after knee arthroplasty. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence. Copyright © 2010 by The Journal of Bone and Joint Surgery, Incorporated.


Lawall H.,Asklepios Westklinikum Hamburg | Zemmrich C.,Institute For Pharmakologie Und Praventive Medizin | Bramlage P.,Institute For Pharmakologie Und Praventive Medizin | Amann B.,Asklepios Westklinikum Hamburg
Vasa - Journal of Vascular Diseases | Year: 2012

Critical limb ischemia (CLI) is the terminal stage of peripheral artery disease. Research in recent years has been largely focussed on treatment options such as bypass surgery / endovascular treatment, surgery / primary amputation and additional benefi ts of supportive pharmacotherapy. Despite this plethora of treatment options, however, patients continue to have a reduced health related quality of life (HRQoL). Aim of the present work was to review the available evidence of improvement of HRQoL with regard to diff erent treatment options. We found that a number of clinical studies have been conducted using HRQoL measures mostly as secondary outcomes in patients with CLI and other less severe forms of peripheral arterial disease. The studies demonstrate a consistent improvement of HRQoL over baseline within the first few months aft er the intervention. Prostaglandins, but no other pharmacotherapies, appear to be eff ective in patients without an option for revascularization. Due to a largely diff ering patient population under investigation and the diff erent degrees of disease progression it appears difficult however to compare diff erent treatment options with respect to their impact on HRQoL. HRQoL improvement as a predefined endpoint of novel therapeutic approach studies should be considered more consequently. © 2012 Hans Huber publishers, Hogrefe AG, Bern.


Liebs T.R.,University of Kiel | Herzberg W.,Asklepios Westklinikum Hamburg
Clinical Orthopaedics and Related Research | Year: 2013

Background: The number of unicompartmental knee arthroplasties (UKAs) is growing worldwide. Because lateral UKAs are performed much less frequently than medial UKAs, the limited information leaves unclear whether UKAs have comparable survival and health-related quality of life (HRQoL) of the lateral UKA to medial UKAs. Questions/purposes: We therefore compared the (1) survivorship and (2) HRQoL after lateral versus medial cemented mobile-bearing UKAs and (3) determined whether there is an association of survival to modifications of surgical technique in one of three phases. Methods: We retrospectively reviewed 558 patients who underwent mobile-bearing UKAs from 2002 to 2009. From the records we determined revision of the joint for any reason and revision for aseptic loosening. Patients reported their physical function, pain, and stiffness as measured by the WOMAC, SF-36 physical-component summary (PCS), and Lequesne knee score. Information regarding implant survival was collected for 93% of the patients. We analyzed the patients separately by three phases based on surgical changes associated with each phase (1: initial technique; 2: improved cementing; 3: additional bone resection to ensure backward sliding of the inlay without impingement). The minimum followup was 2.1 years (mean, 6 years; range, 2.1-9.8 years). Results: Implant survival was 88% at 9 years. We found similar implant survival rates for medial (90%) and lateral UKAs (83%). In all HRQoL measures, patients receiving a medial UKA had better mean scores compared with patients who had a lateral UKA: WOMAC physical function (23 versus 34, respectively) and pain (21 versus 34) and SF-36 PCS (41 versus 38). There were no survival differences by surgical phase. Conclusions: Our observations suggest a medial UKA is associated with superior HRQoL when compared with a lateral UKA, although implant survival is similar. Level of Evidence: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. © 2013 The Association of Bone and Joint Surgeons®.


Spehlmann M.E.,University of Kiel | Begun A.Z.,University of Kiel | Saroglou E.,Asklepios Westklinikum Hamburg | Hinrichs F.,Asklepios Westklinikum Hamburg | And 3 more authors.
Journal of Crohn's and Colitis | Year: 2012

Introduction: Environmental factors may play an important role in the pathogenesis of IBD. The history of patients of the German IBD twin study was analyzed by questionnaires and interviews. Methods: Randomly selected German monozygotic (MZ) and dizygotic (DZ) twins with at least one sibling suffering from IBD (n = 512) were characterized in detail including demography, medical history and concomitant medications. Controls comprised of non-twin IBD patients (n = 392) and healthy subjects (n = 207). Results: The most significant variables that were associated with Crohn's disease (CD) or ulcerative colitis (UC) included living abroad before time of diagnosis (OR, 4.32; 95% CI, 1.57-13.69), high frequency of antibiotic use (MZ CD OR, 5.03; 95% CI 1.61-17.74, DZ CD OR, 7.66; 95% CI, 3.63-16.82, MZ UC OR, 3.82; 95% CI, 1.45-10.56, DZ UC OR, 3.08; CI, 1.63-5.92), high consumption of processed meat including sausage (MZ CD OR, 7.9; 95% CI, 2.15-38.12, DZ CD OR, 10.75; 95% CI, 4.82-25.55, MZ UC OR, 5.69; 95% CI, 1.89-19.48, DZ UC OR, 18.11; 95% CI, 7.34-50.85), and recall of bacterial gastrointestinal infections (MZ CD OR, 15.9; 95% CI, 4.33-77.14, DZ CD OR, 17.21; 95% CI, 4.47-112.5, MZ UC OR, 5.87; 95% CI, 1.61-28.0, DZ UC OR, 11.34; 95% CI, 4.81-29.67). Conclusions: This study reinforced the association of life style events, in particular a specific dietary and infections history, with IBD. Alteration of gut flora or alterations of the mucosal immune system in reactivity to the flora could be an important factor to explain the relationship between life-style and disease. © 2011 European Crohn's and Colitis Organisation.

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