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1دورية أكاديمية
المؤلفون: Nigel Markey, Ben Howitt, Ilyass El-Mansouri, Carel Schwartzenberg, Olga Kotova, Christoph Meier
المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-6 (2024)
الوصف: Abstract The past decade has seen substantial innovation in clinical trials, including new trial formats, endpoints, and others. Also there have been regulatory changes, increasing competitive pressures and other external factors which impact clinical trials. In parallel, trial timelines have increased and success rates remain stubbornly low. This has led many observers to question whether clinical trials have become overly complex and if this complexity is always needed. Here we present a large-scale analysis of protocols and other data from over 16,000 trials. Using a machine learning algorithm, we automatically assessed key features of these trials, such as number of endpoints, number of inclusion–exclusion criteria and others. Using a regression analysis we combined these features into a new metric, the Trial Complexity Score, which correlates with overall clinical trial duration. Looking at this score across different clinical phases and therapeutic areas we see substantial increases over time, suggesting that clinical trials are indeed becoming more complex. We discuss drivers of increasing trial complexity, necessary or helpful (‘good’) complexity versus unnecessary (‘bad’) complexity, and we explore mechanisms of how sponsors of clinical trials can reduce trial complexity where appropriate.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2045-2322Test
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2دورية أكاديمية
المؤلفون: Lara Pozzi, Corina Dommann-Scherrer, Christoph Meier, Peter Wahl
المصدر: Case Reports in Orthopedic Research, Vol 5, Iss 3, Pp 90-96 (2022)
مصطلحات موضوعية: infection, hip, salmonella, Medicine, Orthopedic surgery, RD701-811
الوصف: Periprosthetic joint infection (PJI) with Salmonella is rare. We therefore describe two cases of PJI with Salmonella spp. Case one is a 79-year-old female that presented with fever and acute left hip pain 16 months after revision total hip arthroplasty (THA) performed due to instability. Case two is a 82-year-old male after revision THA due to periprosthetic pseudotumor 22 years after THA. Microbiological work up of intra-operatively obtained specimen showed growth of Salmonella spp. In both patients, implant-retaining treatment was successful. Patients with PJI with Salmonella may be oligosymptomatic, potentially delaying the diagnosis. Successful implant-retraining treatment is possible.
وصف الملف: electronic resource
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3دورية أكاديمية
المؤلفون: Ferda Gronki, Alex Alfieri, Fabian Kalberer, Christoph Meier, Peter Wahl
المصدر: Case Reports in Orthopedic Research, Vol 5, Iss 2, Pp 76-84 (2022)
مصطلحات موضوعية: discoligamentous injury, spinal injury, bilateral total hip arthroplasty, anterior approach, direct anterior approach, complication, Medicine, Orthopedic surgery, RD701-811
الوصف: Although acute spinal injury is rarely reported to complicate total hip arthroplasty (THA), its consequences can be devastating. We present a case of L5-S1 discoligamentous dissociation following single-stage bilateral THA performed sequentially through an anterior approach with a traction hemi-table applied on the operated leg. Internal fixation L5-S1 was required, resulting in prolonged recovery, but without relevant long-term sequelae. Pre-operative assessment of the spine is recommended when considering these procedures to evaluate the risk for this potentially severe complication. Particularly, lateral position may be favoured to avoid extension stresses of the spine. An anterior approach may have to be avoided, as it requires hyperextending the hip. A staged procedure may also be preferred to a single-anaesthesia bilateral procedure, limiting duration of potentially harmful positioning.
وصف الملف: electronic resource
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4دورية أكاديمية
المؤلفون: Faustine Vallon, Christoph Meier, Emanuel Gautier, Peter Wahl
المصدر: Journal of Clinical Medicine, Vol 11, Iss 16, p 4900 (2022)
مصطلحات موضوعية: calcium sulphate, CaSO4, local antibiotics, carrier material, hypercalcaemia, Medicine
الوصف: Local application of antibiotics with calcium-containing carrier materials (CCCM) might deliver large quantities of calcium, with some cases of hypercalcaemia reported. The incidence of symptomatic hypercalcaemia was estimated retrospectively in a consecutive, prospective series of patients treated between 10/2006 and 02/2019 with antibiotic-loaded CCCM for various orthopaedic infections. Risk factors were analysed. In the study period, 215 CCCM applications were performed. Two patients (0.9%) developed symptomatic hypercalcaemia. In one case, hypercalcaemia occurred 14 days after a second CCCM application during a staged septic hip revision. In the other case, hypercalcaemia became symptomatic six days after application of vancomycin-loaded CCCM in a component-retaining septic revision hip arthroplasty. In both cases, hypercalcemia was not imputable solely to the CCCM. Prolonged immobilization, renal impairment and other specific risk factors were present. Implantation of a CCCM for local application of antibiotics exposes the patient to large quantities of calcium during dissolution. This might induce symptomatic hypercalcaemia, a potentially life-threatening complication. The observed incidence of symptomatic hypercalcaemia remained rare (
وصف الملف: electronic resource
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5دورية أكاديمية
المؤلفون: Julia Spoendlin, Eva Blozik, Sereina M. Graber, Marlene Rauch, Carole A. Marxer, Stephan Rüegg, Christoph Meier, Ursula Winterfeld, Alice Panchaud
المصدر: Swiss Medical Weekly, Vol 151, Iss 0708 (2021)
مصطلحات موضوعية: Medicine
وصف الملف: electronic resource
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6دورية أكاديمية
المؤلفون: Julia Spoendlin, Eva Blozik, Sereina M. Graber, Marlene Rauch, Carole A. Marxer, Stephan Rüegg, Christoph Meier, Ursula Winterfeld, Alice Panchaud
المصدر: Swiss Medical Weekly, Vol 151, Iss 0102 (2021)
مصطلحات موضوعية: valproic acid, valproate, antiseizure drugs, Switzerland, claims database, pregnancy, Medicine
الوصف: AIMS OF THE STUDY The prevalence of the use of valproate during pregnancy and by women of childbearing age in Switzerland is not known. We aimed to study the use of antiseizure drugs by these women in Switzerland, with a particular focus on valproate. METHODS We conducted a retrospective descriptive study using the healthcare claims database of the Swiss health insurance Helsana (2014–18). We established two separate study populations: (1) a cohort of pregnancies leading to a delivery, and (2) all women of childbearing age (15–45 years) who were insured with Helsana for at least one year during the study period. We identified the dispensation of valproate, lamotrigine, carbamazepine, levetiracetam, topiramate, pregabalin, gabapentin, phenobarbital, and phenytoin (1) between delivery and three months prior to the estimated date of the last menstrual period, and (2) by calendar year. We quantified exposure prevalence of each antiseizure drug as the number of women with ≥1 prescription fill per 10,000 (1) pregnancies, and (2) women by calendar year. Results were weighted for the demographic distribution of the Helsana population relative to the Swiss population. RESULTS We identified a weighted pregnancy population of 387,418 pregnancies, with a mean maternal age at delivery of 31.9 years (standard deviation 5.1). Lamotrigine was the most frequently dispensed antiseizure drug during pregnancy (20/10,000), followed by levetiracetam (11/10,000), and pregabalin (3.8/10,000). Valproate was dispensed to 1.9/10,000 women during pregnancy and to 1.3/10,000 women within 90 days prior to the last menstrual period but not during pregnancy. The weighted study population of women aged 15–45 years consisted of 2,781,151 women, of whom 74,080 (270/10,000) were exposed to ≥1 of the evaluated antiseizure drugs. Pregabalin was the most frequently dispensed antiseizure drug (64/10,000), followed by lamotrigine (46/10,000), topiramate (32/10,000), and valproate (25/10,000). The use of valproate decreased from 28/10,000 women in 2014 to 21/10,000 women in 2018. CONCLUSIONS The prevalence of exposure to valproate during pregnancy was comparable to Denmark and lower than in other European countries. Despite decreasing exposure prevalence, the use of valproate in women of childbearing age in Switzerland seems higher than the actual clinical need.
وصف الملف: electronic resource
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7دورية أكاديمية
المؤلفون: Tiziano Ronchetti, Christoph Jud, Peter M Maloca, Selim Orgül, Alina T Giger, Christoph Meier, Hendrik P N Scholl, Rachel Ka Man Chun, Quan Liu, Chi-Ho To, Boris Považay, Philippe C Cattin
المصدر: PLoS ONE, Vol 14, Iss 6, p e0218776 (2019)
الوصف: Monitoring subtle choroidal thickness changes in the human eye delivers insight into the pathogenesis of various ocular diseases such as myopia and helps planning their treatment. However, a thorough evaluation of detection-performance is challenging as a ground truth for comparison is not available. Alternatively, an artificial ground truth can be generated by averaging the manual expert segmentations. This makes the ground truth very sensitive to ambiguities due to different interpretations by the experts. In order to circumvent this limitation, we present a novel validation approach that operates independently from a ground truth and is uniquely based on the common agreement between algorithm and experts. Utilizing an appropriate index, we compare the joint agreement of several raters with the algorithm and validate it against manual expert segmentation. To illustrate this, we conduct an observational study and evaluate the results obtained using our previously published registration-based method. In addition, we present an adapted state-of-the-art evaluation method, where a paired t-test is carried out after leaving out the results of one expert at the time. Automated and manual detection were performed on a dataset of 90 OCT 3D-volume stack pairs of healthy subjects between 8 and 18 years of age from Asian urban regions with a high prevalence of myopia.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/1932-6203Test
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8دورية أكاديمية
المؤلفون: Edina Lump, Laura M Castellano, Christoph Meier, Janine Seeliger, Nelli Erwin, Benjamin Sperlich, Christina M Stürzel, Shariq Usmani, Rebecca M Hammond, Jens von Einem, Gisa Gerold, Florian Kreppel, Kenny Bravo-Rodriguez, Thomas Pietschmann, Veronica M Holmes, David Palesch, Onofrio Zirafi, Drew Weissman, Andrea Sowislok, Burkhard Wettig, Christian Heid, Frank Kirchhoff, Tanja Weil, Frank-Gerrit Klärner, Thomas Schrader, Gal Bitan, Elsa Sanchez-Garcia, Roland Winter, James Shorter, Jan Münch
المصدر: eLife, Vol 4 (2015)
مصطلحات موضوعية: HIV, amyloid, molecular tweezer, Medicine, Science, Biology (General), QH301-705.5
الوصف: Semen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a ‘molecular tweezer’ specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion–amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses. We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses.
وصف الملف: electronic resource
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9دورية أكاديمية
المصدر: Swiss Medical Weekly, Vol 142, Iss 0708 (2012)
مصطلحات موضوعية: Adolescents, children, knowledge, Prevention, questionnaire, skin cancer, Medicine
الوصف: BACKGROUND: The skin cancer incidence in Switzerland is one of the highest in Europe and still on the rise. Sun protection is the main preventive measure and of utmost importance during childhood and adolescence, since sunburns within these early phases of life increase the risk of developing skin cancer in adulthood. OBJECTIVES: The aim of this prospective study, the first of its kind in Switzerland, was to investigate the sun protective behaviour of primary and secondary school students in Basel (North-Western Switzerland) and to test their knowledge about adverse health effects of solar radiation and about protective measures. METHODS: Between March and April 2010, supervised classroom surveys during regular school lessons were conducted in 13 public schools using a multiple-choice questionnaire. 960 questionnaires were handed out to 48 school classes. Descriptive statistics and logistic regression analyses were performed on the data of 887 (>90%) students from three different grades (3rd, 6th and 9th grade). RESULTS: Sun-related knowledge was high in one third of all respondents only and significantly depended on student’s age and educational background. Although the oldest students reached the highest knowledge scores, they protected themselves the least from the sun. Sunscreen was the principal form of sun protection mentioned, but was insufficiently applied. Seeking shade and wearing clothing as protective measures were hardly used. High educational background (i.e., of the parents) was a determinant for routine use of sunscreen but was not associated with following other sun protective measures. The desire for a suntan had no impact on the use of sunscreen, but was a significant predictor for not seeking shade and wearing shoulderless shirts when in the sun. More than half of all study participants experienced at least one sunburn during the year preceding the survey. Fair skin type, higher grade, not seeking shade and wearing shoulderless shirts were directly associated with increased odds of sunburn. No association was found for the use of sunscreen and the occurrence of sunburn. CONCLUSIONS: In order to reduce the incidence of skin cancer in Switzerland, it is essential to improve children’s and adolescents’ sun protective behaviour. Future skin cancer prevention campaigns should teach proper use of sunscreen, and emphasise the value of wearing clothing and seeking shade as the most effective sun protection. Furthermore, major efforts are needed to change adolescents’ attitude towards a suntan.
وصف الملف: electronic resource
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10دورية أكاديمية
المؤلفون: Jonas Gosch, Virginia Guiotto, Felix Steinke, Erik Svensson Grape, Cesare Atzori, Kalle Mertin, Tobias Otto, Niklas Ruser, Christoph Meier, Diletta Morelli Venturi, A. Ken Inge, Kirill A. Lomachenko, Valentina Crocellà, Norbert Stock
مصطلحات موضوعية: Biophysics, Biochemistry, Medicine, Physiology, Biotechnology, Inorganic Chemistry, Environmental Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Physical Sciences not elsewhere classified, shaped linker molecules, shaped linker molecule, different pore diameters, sorption measurements revealed, peculiar sorption behavior, framework structures consist, form framework structures, mofs occur exclusively, iv )- mofs, 4 ′-( hexafluoroisopropylidene, 4 ′- sulfonyldibenzoate, 2 , 1 , similar synthetic approach, ray photoelectron spectroscopy, iii oxidation state, 3d electron diffraction, 2 , situ crystallization studies, two porous ce, dependent mof crystallization
الوصف: We report the discovery and characterization of two porous Ce(III)-based metal–organic frameworks (MOFs) with the V-shaped linker molecules 4,4′-sulfonyldibenzoate (SDB 2– ) and 4,4′-(hexafluoroisopropylidene)bis(benzoate) (hfipbb 2– ). The compounds of framework composition [Ce 2 (H 2 O)(SDB) 3 ] ( 1 ) and [Ce 2 (hfipbb) 3 ] ( 2 ) were obtained by using a synthetic approach in acetonitrile that we recently established. Structure determination of 1 was accomplished from 3D electron diffraction (3D ED) data, while 2 could be refined against powder X-ray diffraction (PXRD) data using the crystal structure of an isostructural La-MOF as the starting model. Their framework structures consist of chain-like inorganic building units (IBUs) or hybrid-BUs that are interconnected by the V-shaped linker molecules to form framework structures with channel-type pores. The composition of both compounds was confirmed by PXRD, elemental analysis, as well as NMR and IR spectroscopy. Interestingly, despite the use of (NH 4 ) 2 [Ce IV (NO 3 ) 6 ] in the synthesis, cerium ions in both MOFs occur exclusively in the + III oxidation state as determined by X-ray absorption near edge structure (XANES) and X-ray photoelectron spectroscopy (XPS). Thermal analyses reveal remarkably high thermal stabilities of ≥400 °C for the MOFs. Initial N 2 sorption measurements revealed the peculiar sorption behavior of 2 which prompted a deeper investigation by Ar and CO 2 sorption experiments. The combination with nonlocal density functional theory (NL-DFT) calculations adds to the understanding of the nature of the different pore diameters in 2 . An extensive quasi-simultaneous in situ XANES/XRD investigation was carried out to unveil the formation of Ce-MOFs during the solvothermal syntheses in acetonitrile. The crystallization of the two Ce(III)-MOFs presented herein as well as two previously reported Ce(IV)-MOFs, all obtained by a similar synthetic approach, were studied. While the XRD patterns show time-dependent MOF crystallization, the XANES ...
الإتاحة: https://doi.org/10.1021/acs.inorgchem.3c01862.s001Test
https://figshare.com/articles/journal_contribution/Discovery_and_In_Situ_Crystallization_Studies_of_Cerium-Based_Metal_Organic_Frameworks_with_V_Shaped_Linker_Molecules/24727510Test
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