Charité

About: Charité is a healthcare organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 30624 authors who have published 64507 publications receiving 2437322 citations. The organization is also known as: Charite & Charité – University Medicine Berlin.

Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis

Abstract: BackgroundDupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. MethodsIn two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator’s Global Assessment and a reduction of 2 points or more in that score from baseline at week 16. ResultsWe enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who...

Surgical management of pelvic organ prolapse in women

Abstract: Background Pelvic organ prolapse may occur in up to 50% of parous women. A variety of urinary, bowel and sexual symptoms may be associated with the prolapse. Objectives To determine the effects of the many different surgeries used in the management of pelvic organ prolapse. Search methods We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In Process and handsearching of journals and conference proceedings, healthcare-related bibliographic databases, handsearched conference proceedings (searched 20 August 2012), and reference lists of relevant articles. We also contacted researchers in the field. Selection criteria Randomised or quasi-randomised controlled trials that included surgical operations for pelvic organ prolapse. Data collection and analysis Trials were assessed and data extracted independently by two review authors. Six investigators were contacted for additional information with five responding. Main results Fifty-six randomised controlled trials were identified evaluating 5954 women. For upper vaginal prolapse (uterine or vault) abdominal sacral colpopexy was associated with a lower rate of recurrent vault prolapse on examination and painful intercourse than with vaginal sacrospinous colpopexy. These benefits must be balanced against a longer operating time, longer time to return to activities of daily living and increased cost of the abdominal approach. In single studies the sacral colpopexy had a higher success rate on examination and lower reoperation rate than high vaginal uterosacral suspension and transvaginal polypropylene mesh. Twenty-one trials compared a variety of surgical procedures for anterior compartment prolapse (cystocele). Ten compared native tissue repair with graft (absorbable and permanent mesh, biological grafts) repair for anterior compartment prolapse. Native tissue anterior repair was associated with more recurrent anterior compartment prolapse than when supplemented with a polyglactin (absorbable) mesh inlay (RR 1.39, 95% CI 1.02 to 1.90) or porcine dermis mesh inlay (RR 2.08, 95% CI 1.08 to 4.01), however there was no difference in post-operative awareness of prolapse after absorbable mesh (RR 0.96, 95% CI 0.33 to 2.81) or a biological graft (RR 1.21, 95% CI 0.64 to 2.30). Data on morbidity and other clinical outcomes were lacking. Standard anterior repair was associated with more anterior compartment prolapse on examination than for any polypropylene (permanent) mesh repair (RR 3.15, 95% CI 2.50 to 3.96). Awareness of prolapse was also higher after the anterior repair as compared to polypropylene mesh repair (28% versus 18%, RR 1.57, 95% CI 1.18 to 2.07). However, the reoperation rate for prolapse was similar at 14/459 (3%) after the native tissue repair compared to 6/470 (1.3%) (RR 2.18, 95% CI 0.93 to 5.10) after the anterior polypropylene mesh repair and no differences in quality of life data or de novo dyspareunia were identified. Blood loss (MD 64 ml, 95% CI 48 to 81), operating time (MD 19 min, 95% CI 16 to 21), recurrences in apical or posterior compartment (RR 1.9, 95% CI 1.0 to 3.4) and de novo stress urinary incontinence (RR 1.8, 95% CI 1.0 to 3.1) were significantly higher with transobturator meshes than for native tissue anterior repair. Mesh erosions were reported in 11.4% (64/563), with surgical interventions being performed in 6.8% (32/470). Data from three trials compared native tissue repairs with a variety of total, anterior, or posterior polypropylene kit meshes for vaginal prolapse in multiple compartments. While no difference in awareness of prolapse was able to be identified between the groups (RR 1.3, 95% CI 0.6 to 1.7) the recurrence rate on examination was higher in the native tissue repair group compared to the transvaginal polypropylene mesh group (RR 2.0, 95% CI 1.3 to 3.1). The mesh erosion rate was 35/194 (18%), and 18/194 (9%) underwent surgical correction for mesh erosion. The reoperation rate after transvaginal polypropylene mesh repair of 22/194 (11%) was higher than after the native tissue repair (7/189, 3.7%) (RR 3.1, 95% CI 1.3 to 7.3). Data from three trials compared posterior vaginal repair and transanal repair for the treatment of posterior compartment prolapse (rectocele). The posterior vaginal repair had fewer recurrent prolapse symptoms (RR 0.4, 95% CI 0.2 to 1.0) and lower recurrence on examination (RR 0.2, 95% CI 0.1 to 0.6) and on defecography (MD -1.2 cm, 95% CI -2.0 to -0.3). Sixteen trials included significant data on bladder outcomes following a variety of prolapse surgeries. Women undergoing prolapse surgery may have benefited from having continence surgery performed concomitantly, especially if they had stress urinary incontinence (RR 7.4, 95% CI 4.0 to 14) or if they were continent and had occult stress urinary incontinence demonstrated pre-operatively (RR 3.5, 95% CI 1.9 to 6.6). Following prolapse surgery, 12% of women developed de novo symptoms of bladder overactivity and 9% de novo voiding dysfunction. Authors' conclusions Sacral colpopexy has superior outcomes to a variety of vaginal procedures including sacrospinous colpopexy, uterosacral colpopexy and transvaginal mesh. These benefits must be balanced against a longer operating time, longer time to return to activities of daily living, and increased cost of the abdominal approach. The use of mesh or graft inlays at the time of anterior vaginal wall repair reduces the risk of recurrent anterior wall prolapse on examination. Anterior vaginal polypropylene mesh also reduces awareness of prolapse, however these benefits must be weighted against increased operating time, blood loss, rate of apical or posterior compartment prolapse, de novo stress urinary incontinence, and reoperation rate for mesh exposures associated with the use of polypropylene mesh. Posterior vaginal wall repair may be better than transanal repair in the management of rectocele in terms of recurrence of prolapse. The evidence is not supportive of any grafts at the time of posterior vaginal repair. Adequately powered randomised, controlled clinical trials with blinding of assessors are urgently needed on a wide variety of issues, and they particularly need to include women's perceptions of prolapse symptoms. Following the withdrawal of some commercial transvaginal mesh kits from the market, the generalisability of the findings, especially relating to anterior compartment transvaginal mesh, should be interpreted with caution.

Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions

Abstract: Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 genesets associated with depression, including both genes and gene pathways associated with synaptic structure and neurotransmission. An enrichment analysis provided further evidence of the importance of prefrontal brain regions. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant after multiple testing correction. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding etiology and developing new treatment approaches.

Angiotensin-Neprilysin inhibition in heart failure with preserved ejection fraction

Abstract: Background The angiotensin receptor–neprilysin inhibitor sacubitril–valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients ...

Lanreotide in metastatic enteropancreatic neuroendocrine tumors.

Abstract: Background Somatostatin analogues are commonly used to treat symptoms associated with hormone hypersecretion in neuroendocrine tumors; however, data on their antitumor effects are limited. Methods We conducted a randomized, double-blind, placebo-controlled, multinational study of the somatostatin analogue lanreotide in patients with advanced, well-differentiated or moderately differentiated, nonfunctioning, somatostatin receptor–positive neuroendocrine tumors of grade 1 or 2 (a tumor proliferation index [on staining for the Ki-67 antigen] of <10%) and documented disease-progression status. The tumors originated in the pancreas, midgut, or hindgut or were of unknown origin. Patients were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide (Autogel [known in the United States as Depot], Ipsen) at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks. The primary end point was progression-free survival, defined as the time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.0) or death. Secondary end points included overall survival, quality of life (assessed with the European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-GI.NET21), and safety. Results Most patients (96%) had no tumor progression in the 3 to 6 months before randomization, and 33% had hepatic tumor volumes greater than 25%. Lanreotide, as compared with placebo, was associated with significantly prolonged progression-free survival (median not reached vs. median of 18.0 months, P<0.001 by the stratified log-rank test; hazard ratio for progression or death, 0.47; 95% confidence interval [CI], 0.30 to 0.73). The estimated rates of progression-free survival at 24 months were 65.1% (95% CI, 54.0 to 74.1) in the lanreotide group and 33.0% (95% CI, 23.0 to 43.3) in the placebo group. The therapeutic effect in predefined subgroups was generally consistent with that in the overall population, with the exception of small subgroups in which confidence intervals were wide. There were no significant betweengroup differences in quality of life or overall survival. The most common treatment-related adverse event was diarrhea (in 26% of the patients in the lanreotide group and 9% of those in the placebo group). Conclusions Lanreotide was associated with significantly prolonged progression-free survival among patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 (Ki-67 <10%). (Funded by Ipsen; CLARINET ClinicalTrials.gov number, NCT00353496; EudraCT 2005-004904-35.)