Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study.

BACKGROUND: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. OBJECTIVE: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. METHODS: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. RESULTS: An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine. CONCLUSION: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.

Cytokine levels in children and adults with wheezing and asthma show specific patterns of variability over time.

Levels of cytokines are used for in-depth characterization of patients with asthma; however, the variability over time might be a critical confounder. To analyze the course of serum cytokines in children, adolescents and adults with asthma and in healthy controls and to propose statistical methods to control for seasonal effects. Of 532 screened subjects, 514 (91·5%) were included in the All Age Asthma Cohort (ALLIANCE). The cohort included 279 children with either recurrent wheezing bronchitis (more than two episodes) or doctor-diagnosed asthma, 75 healthy controls, 150 adult asthmatics and 31 adult healthy controls. Blood samples were collected and 25 µl serum was used for analysis with the Bio-Plex Pr human cytokine 27-Plex assay. Mean age, body mass index and gender in the three groups of wheezers, asthmatic children and adult asthmatics were comparable to healthy controls. Wheezers (34·5%), asthmatic children (78·7%) and adult asthmatics (62·8%) were significantly more often sensitized compared to controls (4·5, 22 and 22·6%, respectively). Considering the entire cohort, interleukin (IL)-1ra, IL-4, IL-9, IL-17, macrophage inflammatory protein (MIP)-1- α and tumor necrosis factor (TNF)- α showed seasonal variability, whereas IL-1ß, IL-7, IL-8, IL-13, eotaxin, granulocyte colony-stimulating factor (G-CSF), interferon gamma-induced protein (IP)-10, MIP-1 ß and platelet-derived growth factor (PDGF)-BB did not. Significant differences between wheezers/asthmatics and healthy controls were observed for IL-17 and PDGF-BB, which remained stable after adjustment for the seasonality of IL-17. Seasonality has a significant impact on serum cytokine levels in patients with asthma. Because endotyping has achieved clinical importance to guide individualized patient-tailored therapy, it is important to account for seasonal effects.

Combined-modality 125J-seed-brachytherapy, external beam radiation and androgen deprivation therapy of unfavorable-risk prostate cancer: report of outcomes and side-effects.

PURPOSE: To analyze outcomes and complication rates in an unselected cohort of men with unfavorable (NCCN intermediate and high-risk) PCa receiving combined-modality radiation treatment (CRT). METHODS: Patients received androgen deprivation therapy for 1 year and combined-modality radiation treatment (CRT) consisting of external-beam radiotherapy (EBRT, 59.4 Gy, 33 fractions) and 125J seed-brachytherapy (S-BT, 100 Gy). Subgroups, including WHO group 3-5, and initial PSA (iPSA) < 20 and > 20 ng/ml were identified. Biochemical recurrence-free (BRFS), metastasis-free (MFS), cancer-specific (CSS) and overall survival (OS) were calculated at 5 and 10 years using the Kaplan-Meier method. Subgroups were compared using log-rank test and Cox proportional hazards regression. Urogenital and gastrointestinal side-effects were reported according to the CTCAE classification. RESULTS: After a median of 6.9 years (range 2-13) calculated 5- and 10-year rates for the whole cohort of 425 men were 92.8% and 82.5% for BRFS, 95.1%, and 88.8% for MFS, 98.2%, and 95.1 for CSS, and 95.4%, and 80.1% for OS, respectively. Univariate (UVA) and multivariate analysis (MV) identified a group with unfavorable outcome with iPSA > 20 ng/ml, comprising 24% of all patients, in which 55% of recurrences, 54% of metastases and 71% of cancer-specific deaths occurred. Side-effects were limited, with < 5% of patients complaining of genitourinary and 0.5% of gastrointestinal AEs after 5 years. CONCLUSION: CRT is an excellent treatment option for men with unfavorable PCa. In a subgroup of patients with iPSA > 20 ng/ml further, possibly systemic, treatment options should be identified.

[Clinical trials with medical devices: lack of quality illustrated for faecal incontinence]. / Therapiestudien mit Medizinprodukten: Mangelnde Qualität illustriert anhand analer Inkontinenz.

BACKGROUND: Medical devices must be safe and functioning states the law. Treatments with medical devices need not be efficacious to be allowed. We investigated special requirements and problems arising from the law. METHODS: The market for medical devices is contrasted with that for drugs. The requirements of relevant laws are discussed. Finally, published clinical studies on anal incontinence are analysed with respect to their methodological quality. RESULTS: Clinical trials of medical devices for treat-ing anal incontinence are of poor methodological quality thus preventing evaluation of the devices' utility. CONCLUSION: Large, high quality clinical studies of the efficacy of medical devices for treating anal incontinence are urgently needed. Only such studies enable health technology assessment and comprehensible decisions on reimbursement by health insurance.

Botulinum toxin for Frey's syndrome: a closer look at different treatment responses.

OBJECTIVE: Botulinum toxin is a widely accepted, effective treatment for Frey's syndrome. While some patients need only one injection, others require repeated treatments. We aimed to describe the clinical features of patients with a more challenging treatment course. DESIGN: Literature review and retrospective analysis of eight consecutive patients treated at a university hospital. SUBJECTS: These patients' treatment responses were categorised (using our own system) and compared with those of 25 published cases. RESULTS: Combined analysis identified no significant correlation between treatment response and age, gender or the extent of primary salivary gland surgery. There was no significant correlation between botulinum toxin dosage and time between treatments. CONCLUSION: Frey's syndrome should be viewed as a dynamic process in which the stimulus for aberrant reinnervation of parasympathetic nerve fibres can be reduced, in some patients, with higher botulinum toxin dose injections to the treated areas. However, responses are unpredictable, and relapses may occur at different time points and in different areas.

[A prospective evaluation of psychometric items in patients with nasal deformities]. / Psychosoziale Leistungseinschätzung bei Patienten mit Nasendeformitäten.

BACKGROUND: Patient satisfaction with surgical outcome is essential in plastic reconstructive surgery, yet no German-language psychometrically validated instrument exist for assessing satisfaction with surgery in the head and neck area. Previously, the short form of the "Frankfurter Selbstkonzeptskalen/FSKN" showed mixed results in a sample of patients undergoing correction of microtia. MATERIAL AND METHODS: This short form was tested in 22 patients following septorhinoplasty and in 24 following tonsillectomy, regarding its psychometric characteristics. RESULTS: While showing good practical characteristics and content validity, there were disappointing results in responsiveness to change and known group's discriminant validity. CONCLUSIONS: Beside sample size, different psychological mechanisms in more common malformations of the head neck area, especially in patients with nasal deformities, have to be further explored as they are not sufficiently represented in the short form of FSKN.

Polymorphisms in the Renin-Angiotensin system and outcome of very-low-birthweight infants.

BACKGROUND: The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE-ins/del) and the angiotensin II type 1 receptor 1166A/C polymorphism (ATR1166A/C) were reported to be associated with several unfavorable outcome parameters in preterm infants like bronchopulmonary dysplasia, persistent ductus arteriosus and impaired insulin sensitivity. OBJECTIVE: To confirm the above-mentioned associations in a large cohort of very-low-birthweight (VLBW) infants. METHOD: Clinical data of VLBW infants were prospectively recorded. The ACE-ins/del polymorphism and the ATR1166A/C polymorphism were determined by polymerase chain reaction in 1,209 and 1,168 infants, respectively. RESULTS: There was no significant association between ACE-ins/del or ATR1166A/C genotype and outcome parameters (death, intraventricular hemorrhage, sepsis, bronchopulmonary dysplasia, ventilation, supplemental oxygen at discharge, postnatal treatment with insulin, surgery for intestinal perforation/necrotizing enterocolitis/retinopathy of prematurity/persistent ductus arteriosus. CONCLUSION: Both known functional polymorphisms of the renin-angiotensin system do not seem to be associated with the outcome of VLBW infants.

Distal and proximal interleukin (IL)-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case--control study.

Inherited promoter polymorphisms of the interleukin (IL)-10 gene resulting in altered IL-10 production may contribute to a genetic susceptibility for melanoma. We investigated the role of a haplotype from distal as well as proximal polymorphic sites [-7400InDel, -6752AT (rs6676671), -3538AT (rs1800890), -1087AG (rs1800896), -597AC (rs1800872)] of the IL-10 5'-flanking region in a hospital-based case-control study of 165 Caucasian patients with cutaneous melanoma from Germany in comparison with 162 healthy cancer-free Caucasian control participants from the same area matched by age. Using multivariate analysis for the number of nevi and skin type, the IL-10 'higher producing' haplotype ITAGC was found to be significantly associated with a reduced risk of developing melanoma (adjusted P=0.02). Although our findings need to be confirmed by independent and larger multicenter studies, we have described for the first time the association of distal gene variants of the IL-10 gene as an independent risk factor for melanoma.

Manganese superoxide dismutase (MnSOD) polymorphism, alcohol, cigarette smoking and risk of oesophageal cancer.

AIMS: Alcohol, tobacco smoke and Barrett's oesophagus as a consequence of gastro-oesophageal reflux are the main risk factors in oesophageal carcinogenesis. All risk factors may induce oxidative stress. Manganese superoxide dismutase (MnSOD) is one important repair enzyme for reactive oxidative stress (ROS)-induced damage. MnSOD polymorphisms in the -9 position of the signal sequence of the protein may lead to critical enzyme deficiency. The aim of the present study was to investigate the role of polymorphisms of MnSOD in patients with oesophageal cancer [n = 170, 61 patients with adenocarcinoma (AC), 109 patients with squamous cell carcinoma (SCC)] compared to heavy drinkers (n = 160) and healthy blood donors (n = 400). METHODS: Genotyping was performed by PCR-RFLP analysis using genomic DNA extracted from whole blood. RESULTS: The Ala/Ala genotype was 27.7% in cancer patients (29.5% AC, 26.6% SCC), 23.1% in patients with heavy alcohol abuse and 12.5% in the group of healthy blood donors. These results were not statistically significant after multivariate analysis controlling for age, sex, alcohol, cigarettes and interactions (odds ratio 0.92, 95% confidence interval = 0.63-1.36, for cancer patients versus heavy drinkers; odds ratio 1.02, 95% confidence interval = 0.51-2.03, for cancer patients versus blood donors; analysis by logistic regression). Subjects with an Ala/Ala genotype (81.3 g/day) had a significantly higher alcohol intake than those with Val/Ala (63.9 g/day) or Val/Val (53.8 g/day) genotype (P < 0.00001 by the Kruskal-Wallis test). CONCLUSIONS: MnSOD polymorphisms play no role in the genetic predisposition to oesophageal cancer. However, our data suggest a complex gene-to-phenotype interaction between the MnSOD genotype and alcohol misuse.

p53 Mutations in carcinoma of the esophagus and gastroesophageal junction.

BACKGROUND: Recent studies suggested p53 mutations as a prognostic factor. Tumors of the esophagus and gastroesophageal (GE) junction show raising incidence with a general poor prognosis. METHODS: p53 Mutational spectra in 103 patients (68 squamous cell carcinoma/SCC and 35 adenocarcinoma/AC) were compared to clinical and pathologic data. RESULTS AND CONCLUSIONS: p53 Mutations were found in 26 of 68 SSC (38.2%) and in 12 of 35 AC (34.5%). We only found G > T transversions in smokers with SCC. The survival of patients was not affected by p53 mutational status. In our study, the frequency and mutational spectrum of mutant p53 is similar in both histological types without prognostic relevance.

[Analysis of psychosocial changes following ear reconstruction with rib cartilage - development of a short test]. / Analyse psychosozialer Parameter nach Ohrrekonstruktionen mit Rippenknorpel - Entwicklung eines Kurztests.

BACKGROUND: The improvement of psychosocial well being in patients with microtia after ear reconstruction with rib cartilage is mainly assessed clinically. There are first prospective studies with established psychological questionnaires showing promising results but these tests are too extensive for everyday-use in clinical routine. Therefore, we examined a self-designed short version for the specific use in the head-neck-region. METHODS AND PATIENTS: The clinically established psychological questionnaire "Frankfurter Selbstkonzeptskalen/FSKN" consists of 78 items for self-assessment of performance abilities, self-esteem, and psychosocial attitude. We downsized the FSKN to 13 items that might be relevant for plastic reconstructive surgery in the head-neck-region. The pre- and postoperative development after ear reconstruction with rib cartilage was analyzed retrospectively in 68 patients and prospectively in 21 patients. The preoperative data of the prospective study group were compared with the results of 23 patients with microtia who declined any type of reconstruction after consultation. RESULTS: Especially the results of the psychosocial competence improved after ear reconstruction as well in the retrospective (median values 138,5 to points; p<0,01) as well as in the prospective study group (median values 126 to 141 points; p=0,01). We were able to demonstrate changes in the short version of the FSKN (median values 51,5 to 58,5 points; p<0,01 respectively, 50 to 56 points; p=0,02). Patients who declined ear surgery showed higher values in psychosocial competence (median values 126 to 154 points; p<0,01). Again, the short form displayed this difference clearly (median values 50 to 65 points; p<0,01). CONCLUSIONS: The short version of the FSKN has promising potential for the preoperative assessment and the documentation of psychological changes following reconstructive surgery. Further studies are necessary to validate the new instrument to obtain a valuable test for use in clinical routine in plastic surgery in the head-neck-region.

Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism.

OBJECTIVES: To study the frequency of different gene mutations in patients with early-onset parkinsonism and bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and the short- and long-term surgical outcome in mutation-positive (MUT+) and -negative (MUT-) patients. METHODS: Eighty patients with disease onset at age

Preliminary report on elective preterm delivery at 34 weeks and primary abdominal closure for the management of gastroschisis.

INTRODUCTION: We aimed to critically evaluate elective preterm delivery and immediate abdominal wall closure and other techniques for the management of gastroschisis, hypothesizing that the advantages of an elective preterm delivery outweigh possible complications related to prematurity at birth. PATIENTS AND METHODS: 13 gastroschisis patients were enrolled in the elective preterm delivery program (Group 1) since 1999. Patients were delivered by cesarean section in the 34th gestational week, with immediate primary closure of the defect. Data regarding parameters at and after birth were compared with a historical control group of 10 patients conventionally managed for gastroschisis in a similar period (1994 - 1999) (Group 2). The primary endpoints of this study were the initiation of oral feeding and the length of hospital stay. RESULTS: There was a significantly faster initiation of oral feeding (p = 0.0012) and a shorter hospital stay (p = 0.0160) in Group 1. The postoperative outcome was excellent in all patients. Acute and late complications were fewer and less severe in Group 1 and none were related to prematurity. CONCLUSIONS: Elective preterm delivery appears to be an effective method for the management of gastroschisis, and a method whose advantages thus far have outweighed the possible complications due to prematurity.

Association of polymorphisms in the mannose-binding lectin gene and pulmonary morbidity in preterm infants.

Deficiency in the collectin mannose-binding lectin (MBL) increases the risk for pulmonary and systemic infections and its complications in children and adults. The aim of this prospective cohort study was to determine the genetic association of sequence variations within the MBL gene with systemic infections and pulmonary short- and long-term complications in preterm infants below 32 weeks gestational age (GA). Three single-nucleotide polymorphisms (SNPs) in the coding region and one SNP in the promotor region of MBL2 were genotyped by direct sequencing and with sequence-specific probes in 284 newborn infants <32 weeks GA. Clinical variables were comprehensively monitored. An association was found between two SNPs and the development of bronchopulmonary dysplasia (BPD), defined as persistent oxygen requirement at 36 weeks postmenstrual age, adjusting for covariates GA, grade of respiratory distress syndrome and days on mechanical ventilation (rs1800450 (exon 1 at codon 54, B variant): odds ratio dominant model (OR)=3.59, 95% confidence interval (CI)=1.62-7.98; rs7096206 (-221, X variant): OR=2.40, 95% CI=1.16-4.96). Haplotype analyses confirmed the association to BPD, and a single haplotype (frequency 56%) including all SNPs in their wild-type form showed a negative association with the development of BPD. We detected no association between the MBL gene variations and the development of early-onset infections or further pulmonary complications. Frequent variants of the MBL gene, leading to low MBL concentrations, are associated with the diagnosis of BPD in preterm infants. This provides a basis for potential therapeutic options and further genetic and proteomic analysis of the function of MBL in the resistance against pulmonary long-term complications in preterm infants.

Common human Toll-like receptor 9 polymorphisms and haplotypes: association with atopy and functional relevance.

BACKGROUND: Toll-like receptor 9 (TLR9) is a pattern-recognition receptor that detects unmethylated CpG motifs prevalent in bacterial and viral DNA. TLR9 stimulation is a key event after bacterial infection, triggering innate immunity and T-helper type 1 skewed adaptive immunity. Synthetic CpG-oligodeoxynucleotides (CpG-ODNs) represent a promising and novel class of immune adjuvants for allergy treatment, vaccination, and cancer therapy. However, common functional TLR9 gene variants could interfere with the clinical utilization of CpG-ODN in immunotherapy. Recently, a possible association of TLR9 polymorphism C-1237T with asthma has been reported. OBJECTIVE: The aim of the present study was to investigate whether TLR9 polymorphisms or haplotypes have functional relevance and are associated with atopy. METHODS: We genotyped five common TLR9 single-nucleotide polymorphisms (SNPs) in promoter, exon, and intron regions of the gene in 527 healthy blood donors, and estimated four common haplotypes. The total IgE and specific IgE levels against the most common aeroallergens were measured (n=303). IFN-alpha production by plasmacytoid dendritic cells (pDCs) was analysed after stimulation with TLR9 ligand CpG-ODN (n=220). RESULTS: No significant influence of common TLR9 polymorphisms and haplotypes on the total and specific IgE levels was found. Functional analysis of CpG-ODN-induced IFN-alpha did not indicate a significant role for common TLR9 gene polymorphisms in TLR9 function. CONCLUSION: We conclude that common genetic differences in the TLR9 gene exert no major influence on allergy susceptibility, and are unlikely to have on impact on clinical application of CpG-ODNs.

Candidate gene studies in focal dystonia.

BACKGROUND: Genetic susceptibility factors for focal idiopathic torsion dystonia (F-ITD) are not established. Mutations in the DYT1 gene can cause focal dystonia, and an association with a polymorphism in the D5 receptor gene (DRD5) has been reported but not confirmed. OBJECTIVE: To investigate a possible role of DYT1 polymorphisms, a CA repeat in the D5 receptor gene (DRD5), the human leukocyte antigen (HLA)-DRB locus, and four polymorphisms in the homocysteine metabolism in the pathogenesis of F-ITD. METHODS: Initially, 100 German patients and 100 matched control subjects were investigated. A second French population with 121 F-ITD patients and matched control subjects was also studied. RESULTS: Two polymorphisms of the beta-cystathionine synthase gene were associated with F-ITD in the German population, but this finding was not replicated in a second independent F-ITD patient and control group of French origin. None of the other investigated polymorphisms was associated with F-ITD. The authors failed to confirm a previously reported association with a polymorphism in DRD5. CONCLUSION: No evidence for an involvement of DYT1, DRD5, HLA-DRB, or polymorphisms in the homocysteine pathway in the pathogenesis of F-ITD was found.

Cytokine gene polymorphisms in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) and psoriasis are genetically determined inflammatory skin disorders characterized by abnormal cytokine production. From association studies there is evidence that functionally relevant cytokine gene polymorphisms contribute to the genetic basis of psoriasis. Association studies in AD have mostly been limited to polymorphisms of T-helper 2-type cytokines, which dominate in acute AD lesions. Unexpectedly, the results of recent genome scans indicate linkage of AD to psoriasis susceptibility loci. Therefore, AD may also be influenced by genes that modulate cutaneous inflammation independently from atopic mechanisms. OBJECTIVES: To investigate further the role of cytokine gene polymorphisms in AD. METHODS: Polymorphisms in the genes encoding tumour necrosis factor-alpha (TNFA-238 G/A, -308 G/A), interleukin (IL)-1beta (IL1B-511 T/C, +3953 T/C), IL-6 (IL6-174 C/G), IL-10 (IL10-1082 A/G) and the IL-1 receptor antagonist (IL1RN intron 2) were investigated in German patients with AD (n = 94) and in healthy nonatopic individuals (n = 214) by polymerase chain reaction-based methods and direct cycle sequencing. RESULTS: No association was found between AD and any of the polymorphisms analysed. This is in contrast to the recently described association between psoriasis and the TNFA-238 and IL1B-511 polymorphisms. CONCLUSIONS: Our data indicate that cytokine gene polymorphisms may act as specific markers of inflammatory skin diseases rather than contribute to a general disposition towards cutaneous inflammation.

Spectrum of binge eating symptomatology in patients treated with clozapine and olanzapine.

The authors explored the binge eating symptomatology in 74 patients receiving clozapine (N = 57) or olanzapine (N = 17), and compared body mass index (BMI, kg/m(2)) and weight gain in patients with and without binge eating symptomatology. Subjects who screened positively for binge eating were interviewed using a modified version of the Questionnaire on Eating and Weight Patterns (QEWP). Current BMIs were assessed cross-sectionally, BMIs at initiation of clozapine/olanzapine treatment retrospectively. Thirty-seven subjects (50%) screened positively. Taking clozapine and olanzapine together, 6/27 (22.2%) females and 3/47 (6.4%) males fulfilled criteria for binge eating disorder, 3/27 (11.1%) females and 2/47 (4.3%) males for bulimia nervosa. Patients who screened positively showed higher current BMIs (26.8 +/- 3.9 vs. 24.7 +/- 3.7 kg/m(2)) and higher BMI increments during clozapine/olanzapine treatment (3.9 +/- 3.1 vs. 2.6 +/- 3.4 kg/m(2)) than patients who screened negatively. We conclude that clozapine/olanzapine may induce binge eating and full blown eating disorders which may have predictive value for weight gain. For future research in this field we suggest a novel DSM-IV research classification "Medication-induced eating disorders".

Extracorporeal shock wave therapy in the treatment of lateral epicondylitis : a randomized multicenter trial.

BACKGROUND: On the basis of observational trials, numerous investigators have recommended extracorporeal shock wave therapy as an alternative treatment for chronic lateral epicondylitis of the elbow. However, there has been no evidence of its efficacy from well-designed randomized clinical trials. The objective of this study was to find out whether extracorporeal shock wave therapy in combination with local anesthesia was superior to placebo therapy in combination with local anesthesia. METHODS: A randomized multicenter trial with a parallel-group design was conducted. Following administration of local anesthesia, either extracorporeal shock wave therapy with three treatments of 2000 pulses each and a positive energy flux density (ED+) of 0.07 to 0.09 mJ/mm (2) or placebo therapy was applied on an outpatient basis. Treatment allocation was blinded for patients and for observers. The primary end point was based on the rate of success, as determined with the Roles and Maudsley score and whether additional treatment was required, twelve weeks after the intervention. Crossover was possible after assessment of the primary end point. Secondary end points were the Roles and Maudsley score, subjective pain rating, and grip strength after six and twelve weeks and after twelve months. The planned number of 272 patients was included in the study. RESULTS: The primary end point could be assessed for 90.8% of the patients. The success rate was 25.8% in the group treated with extracorporeal shock wave therapy and 25.4% in the placebo group, a difference of 0.4% with a 95% confidence interval of -10.5% to 11.3%. Similarly, there was no relevant difference between groups with regard to the secondary end points. Improvement was observed in two-thirds of the patients from both groups twelve months after the intervention. Few side effects were reported. CONCLUSIONS: Extracorporeal shock wave therapy as applied in the present study was ineffective in the treatment of lateral epicondylitis. The previously reported success of this therapy appears to be attributable to inappropriate study designs. Different application protocols might improve clinical outcome. We recommend that extracorporeal shock wave therapy be applied only in high-quality clinical trials until it is proved to be effective.