337 research outputs found
Π‘ΠΎΠ·Π΄Π°Π½ΠΈΠ΅ ΠΌΠΎΠ½ΡΠΌΠ΅Π½ΡΠ° Β«ΠΠΎΠ·ΡΠΎΠΆΠ΄Π΅Π½ΠΈΠ΅ ΠΊΡΡΠΌΡΠΊΠΎΡΠ°ΡΠ°ΡΡΠΊΠΎΠ³ΠΎ Π½Π°ΡΠΎΠ΄Π°Β» ΠΊΠ°ΠΊ ΠΊΡΠ»ΡΡΡΡΠ½ΠΎΠ΅ ΡΠ²Π»Π΅Π½ΠΈΠ΅ Π² ΠΆΠΈΠ·Π½ΠΈ ΠΊΡΡΠΌΡΠΊΠΎΠ³ΠΎ ΠΎΠ±ΡΠ΅ΡΡΠ²Π°
Π ΡΡΠ°ΡΡΠ΅ Π°Π²ΡΠΎΡΠΎΠΌ ΠΎΡ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΎΠ²Π°Π½ Π³ΡΠ°Π΄ΠΎΡΡΡΠΎΠΈΡΠ΅Π»ΡΠ½ΡΠΉ ΠΎΠ±ΡΠ΅ΠΊΡ ΠΠΎΠ½ΡΠΌΠ΅Π½Ρ Β«ΠΠΎΠ·ΡΠΎΠΆΠ΄Π΅Π½ΠΈΠ΅ ΠΊΡΡΠΌΡΠΊΠΎΡΠ°ΡΠ°ΡΡΠΊΠΎΠ³ΠΎ Π½Π°ΡΠΎΠ΄Π°Β» ΠΊΠ°ΠΊ ΠΊΡΠ»ΡΡΡΡΠ½ΠΎΠ΅ ΡΠ²Π»Π΅Π½ΠΈΠ΅ Π² ΠΆΠΈΠ·Π½ΠΈ ΠΊΡΡΠΌΡΠΊΠΎΠ³ΠΎ ΠΎΠ±ΡΠ΅ΡΡΠ²Π°, ΠΏΡΠΈΠ·Π²Π°Π½Π½ΠΎΠ΅ Π²Π½Π΅ΡΡΠΈ Π²ΠΊΠ»Π°Π΄ Π² ΠΏΡΠΎΡΠ΅ΡΡ Π²ΠΎΡΠΏΠΈΡΠ°Π½ΠΈΡ Π΄ΡΡ
ΠΎΠ²Π½ΠΎΡΡΠΈ ΠΈ ΠΊΡΠ»ΡΡΡΡΡ Π² ΠΌΠΎΠ»ΠΎΠ΄ΡΡ
Π»ΡΠ΄ΡΡ
.Π£ ΡΡΠ°ΡΡΡ Π°Π²ΡΠΎΡΠΎΠΌ ΠΎΡ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΎΠ²Π°Π½ΠΎ ΠΌΡΡΡΠΎΠ±ΡΠ΄ΡΠ²Π΅Π»ΡΠ½ΠΈΠΉ ΠΎΠ±βΡΠΊΡ ΠΠΎΠ½ΡΠΌΠ΅Π½Ρ Β«ΠΡΠ΄ΡΠΎΠ΄ΠΆΠ΅Π½Π½Ρ ΠΊΡΠΈΠΌΡΡΠΊΠΎΡΠ°ΡΠ°ΡΡΡΠΊΠΎΠ³ΠΎ Π½Π°ΡΠΎΠ΄ΡΒ» ΡΠΊ ΠΊΡΠ»ΡΡΡΡΠ½Π΅ ΡΠ²ΠΈΡΠ΅ Ρ ΠΆΠΈΡΡΡ ΠΊΡΠΈΠΌΡΡΠΊΠΎΠ³ΠΎ ΡΡΡΠΏΡΠ»ΡΡΡΠ²Π°, ΡΠΎ ΠΏΡΠΈΠ·Π²Π°Π½ΠΈΠ΅ Π΄ΠΎΠ½Π΅ΡΡΠΈ Π²Π½Π΅ΡΠΎΠΊ Ρ ΠΏΡΠΎΡΠ΅Ρ Π²ΠΈΡ
ΠΎΠ²Π°Π½Π½Ρ Π΄ΡΡ
ΠΎΠ²Π½ΠΎΡΡΡ ΡΠ° ΠΊΡΠ»ΡΡΡΡΠΈ ΠΌΠΎΠ»ΠΎΠ΄Ρ.The author describes a monument βRebirth of the Crimean Tatarsβ as a cultural phenomenon in the life of the Crimean society, which can contribute in the process of spiritual and cultural upbringing of young people
ΠΠ°ΡΠ°Π΄ΠΈΠ³ΠΌΠ° ΡΡΠΈΠ΄ΠΈΡΠ½ΠΎΠ³ΠΎ ΡΠΈΠ·ΠΈΠΊΡ Π² ΡΠΈΡΡΠ΅ΠΌΡ Π½Π°ΡΡΠΎΠ½Π°Π»ΡΠ½ΠΎΡ Π±Π΅Π·ΠΏΠ΅ΠΊΠΈ Π£ΠΊΡΠ°ΡΠ½ΠΈ (ΠΏΡΠΈΠΊΠ»Π°Π΄Π½ΠΈΠΉ Π°ΡΠΏΠ΅ΠΊΡ)
Π ΠΎΠ·Π³Π»ΡΠ΄Π°ΡΡΡΡΡ Π·Π°Π³Π°Π»ΡΠ½Π° ΠΌΠΎΠ΄Π΅Π»Ρ ΡΠΈΡΡΠ΅ΠΌΠΈ Π½Π°ΡΡΠΎΠ½Π°Π»ΡΠ½ΠΎΡ Π±Π΅Π·ΠΏΠ΅ΠΊΠΈ. ΠΠΈΠ·Π½Π°ΡΠ°ΡΡΡΡΡ ΠΌΡΡΡΠ΅
ΡΠ° ΡΠΎΠ»Ρ ΡΡΠΈΠ΄ΠΈΡΠ½ΠΎΠ³ΠΎ ΡΠΈΠ·ΠΈΠΊΡ Π² ΡΡΠ½ΠΊΡΡΠΎΠ½ΡΠ²Π°Π½Π½Ρ ΡΠΈΡΡΠ΅ΠΌΠΈ Π½Π°ΡΡΠΎΠ½Π°Π»ΡΠ½ΠΎΡ Π±Π΅Π·ΠΏΠ΅ΠΊΠΈ.
ΠΠ½Π°Π»ΡΠ·ΡΡΡΡΡΡ ΠΊΠ°ΡΠ΅Π³ΠΎΡΡΡ Β«ΡΡΠΈΠ΄ΠΈΡΠ½ΠΈΠΉ ΡΠΈΠ·ΠΈΠΊΒ» ΡΠ° ΠΉΠΎΠ³ΠΎ ΠΎΡΠ½ΠΎΠ²Π½Ρ ΡΠΊΠ»Π°Π΄ΠΎΠ²Ρ, ΡΠΌΠΎΠ²ΠΈ Π²ΠΈΠ½ΠΈΠΊΠ½Π΅Π½Π½Ρ ΡΠ° ΡΡΠ½ΠΊΡΡΠΎΠ½ΡΠ²Π°Π½Π½Ρ. ΠΡΠΎΠΏΠΎΠ½ΡΡΡΡΡΡ ΡΠΌΠΎΠ²ΠΈ ΠΏΡΠΎΡΠΈΠ΄ΡΡ ΡΠΈΠ·ΠΈΠΊΠ°ΠΌ ΡΠ° ΠΏΠΎΠ΄Π°ΡΡΡΡΡ ΠΌΠΎΠ΄Π΅Π»Ρ
Π·Π½ΠΈΠΆΠ΅Π½Π½Ρ ΡΡΠΈΠ΄ΠΈΡΠ½ΠΈΡ
ΡΠΈΠ·ΠΈΠΊΡΠ² Ρ ΡΠΈΡΡΠ΅ΠΌΡ Π½Π°ΡΡΠΎΠ½Π°Π»ΡΠ½ΠΎΡ Π±Π΅Π·ΠΏΠ΅ΠΊΠΈ .
ΠΠ»ΡΡΠΎΠ²Ρ ΡΠ»ΠΎΠ²Π°: Π½Π°ΡΡΠΎΠ½Π°Π»ΡΠ½Π° Π±Π΅Π·ΠΏΠ΅ΠΊΠ°, ΡΡΠΈΠ΄ΠΈΡΠ½ΠΈΠΉ ΡΠΈΠ·ΠΈΠΊ.Π Π°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°Π΅ΡΡΡ ΠΎΠ±ΡΠ°Ρ ΠΌΠΎΠ΄Π΅Π»Ρ ΡΠΈΡΡΠ΅ΠΌΡ Π½Π°ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ. ΠΠΏΡΠ΅Π΄Π΅Π»ΡΠ΅ΡΡΡ ΠΌΠ΅ΡΡΠΎ ΠΈ ΡΠΎΠ»Ρ ΡΡΠΈΠ΄ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΈΡΠΊΠ° ΠΏΡΠΈ ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΡΠΈΡΡΠ΅ΠΌΡ Π½Π°ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ
Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ. ΠΠ½Π°Π»ΠΈΠ·ΠΈΡΡΠ΅ΡΡΡ ΠΊΠ°ΡΠ΅Π³ΠΎΡΠΈΡ Β«ΡΡΠΈΠ΄ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΠΈΡΠΊΒ» ΠΈ Π΅Π³ΠΎ ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ ΡΠΎΡΡΠ°Π²Π»ΡΡΡΠΈΠ΅, ΡΡΠ»ΠΎΠ²ΠΈΡ Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΡ ΠΈ ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ. ΠΡΠ΅Π΄Π»Π°Π³Π°ΡΡΡΡ ΡΡΠ»ΠΎΠ²ΠΈΡ ΠΏΡΠΎΡΠΈΠ²ΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ ΡΠΈΡΠΊΠ°ΠΌ ΠΈ ΠΏΠΎΠ΄Π°Π΅ΡΡΡ ΠΌΠΎΠ΄Π΅Π»Ρ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ ΡΡΠΈΠ΄ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠΈΡΠΊΠΎΠ² Π² ΡΠΈΡΡΠ΅ΠΌΠ΅ Π½Π°ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ
ΠΠ»ΡΡΠ΅Π²ΡΠ΅ ΡΠ»ΠΎΠ²Π°: Π½Π°ΡΠΈΠΎΠ½Π°Π»ΡΠ½Π°Ρ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΡ, ΡΡΠΈΠ΄ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΠΈΡΠΊ.The problems of forming and development of the system of national safety are examined
in the article. The general model of the system of national safety is offered and the role of legal
risk is determined in this system. The location and role of legal risk is determined at functioning of the system of national safety. A category is analysed Β«legal riskΒ» and his basic component elements, terms of origin and functioning. The terms of counteraction risks are offered
and the model of decline of legal risks is given in the system of national safety.
Key words: national safety, legal risk
ΠΡΡΠΎΡΠΈΡ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ ΠΈΠΌΠ΅Π½ ΠΏΡΠΈΠ»Π°Π³Π°ΡΠ΅Π»ΡΠ½ΡΡ Π² ΠΊΡΡΠΌΡΠΊΠΎΡΠ°ΡΠ°ΡΡΠΊΠΎΠΌ ΡΠ·ΡΠΊΠ΅
Π¦Π΅Π»ΡΡ Π΄Π°Π½Π½ΠΎΠΉ ΡΡΠ°ΡΡΠΈ ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½ΠΈΠ΅ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ ΠΈΠ·ΡΡΠ΅Π½Π½ΠΎΡΡΠΈ ΠΈΠΌΠ΅Π½ΠΈ ΠΏΡΠΈΠ»Π°Π³Π°ΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ Π²
ΠΊΡΡΠΌΡΠΊΠΎΡΠ°ΡΠ°ΡΡΠΊΠΎΠΌ ΡΠ·ΡΠΊΠ΅ ΠΊΠ°ΠΊ ΡΠ°ΠΌΠΎΡΡΠΎΡΡΠ΅Π»ΡΠ½ΠΎΠΉ ΡΠ°ΡΡΠΈ ΡΠ΅ΡΠΈ Π² Π»ΠΈΠ½Π³Π²ΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΡΡΠ΄Π°Ρ
XIX β XX Π²Π²., Π° ΡΠ°ΠΊΠΆΠ΅
Π°Π½Π°Π»ΠΈΠ· ΠΎΡΠ½ΠΎΠ²Π½ΡΡ
Π³ΡΠ°ΠΌΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΊΠ°ΡΠ΅Π³ΠΎΡΠΈΠΉ ΠΈΠΌΠ΅Π½ΠΈ ΠΏΡΠΈΠ»Π°Π³Π°ΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ
Multiscale simulation of polymer melt viscoelasticity: Expanded-ensemble Monte Carlo coupled with atomistic nonequilibrium molecular dynamics
We present a powerful framework for computing the viscoelastic properties of polymer melts based on an efficient coupling of two different atomistic models: the first is represented by the nonequilibrium molecular dynamics method and is considered as the microscale model. The second is represented by a Monte Carlo (MC) method in an expanded statistical ensemble and is free from any long time scale constraints. Guided by recent developments in nonequilibrium thermodynamics, the expanded ensemble incorporates appropriately defined "field" variables driving the corresponding structural variables to beyond equilibrium steady states. The expanded MC is considered as the macroscale solver for the family of all viscoelastic models built on the given structural variable(s). The explicit form of the macroscopic model is not needed; only its structure in the context of the general equation for the nonequilibrium reversible irreversible coupling or generalized bracket formalisms of nonequilibrium thermodynamics is required. We illustrate the method here for the case of unentangled linear polymer melts, for which the appropriate structural variable to consider is the conformation tensor c???. The corresponding Lagrange multiplier is a tensorial field ??. We have been able to compute model-independent values of the tensor ??, which for a wide range of strain rates (covering both the linear and the nonlinear viscoelastic regimes) bring results for the overall polymer conformation from the two models (microscale and macroscale) on top of each other. In a second step, by comparing the computed values of ?? with those suggested by the macroscopic model addressed by the chosen structural variable(s), we can identify shortcomings in the building blocks of the model. How to modify the macroscopic model in order to be consistent with the results of the coupled micro-macro simulations is also discussed. From a theoretical point of view, the present multiscale modeling approach provides a solid framework for the design of improved, more accurate macroscopic models for polymer melts.open151
VaxCelerate II: Rapid development of a self-assembling vaccine for Lassa fever
Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d. A self-assembling vaccine is at the core of the approach. It consists of a fusion protein composed of the immunostimulatory Mycobacterium tuberculosis heat shock protein 70 (MtbHSP70) and the biotin binding protein, avidin. Mixing the resulting protein (MAV) with biotinylated pathogen-specific immunogenic peptides yields a self-assembled vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of protein engineering and production, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1 influenza specific peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting Lassa fever virus. We demonstrated that the Lassa fever vaccine induced significantly increased class II peptide specific interferon-Ξ³ CD4+ T cell responses in HLA-DR3 transgenic mice compared to peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each vaccine and by applying safety and efficacy assessment tools that are more relevant to human vaccine responses than current animal models
Resectability and Ablatability Criteria for the Treatment of Liver Only Colorectal Metastases:Multidisciplinary Consensus Document from the COLLISION Trial Group
The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a 'toolbox' of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOGβ€2, ASAβ€3 and Charlson comorbidity index β€8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies.</p
Fundamental limits on quantum dynamics based on entropy change
It is well known in the realm of quantum mechanics and information theory that the entropy is non-decreasing for the class of unital physical processes. However, in general, the entropy does not exhibit monotonic behavior. This has restricted the use of entropy change in characterizing evolution processes. Recently, a lower bound on the entropy change was provided in the work of Buscemi, Das, and Wilde [Phys. Rev. A 93(6), 062314 (2016)]. We explore the limit that this bound places on the physical evolution of a quantum system and discuss how these limits can be used as witnesses to characterize quantum dynamics. In particular, we derive a lower limit on the rate of entropy change for memoryless quantum dynamics, and we argue that it provides a witness of non-unitality. This limit on the rate of entropy change leads to definitions of several witnesses for testing memory effects in quantum dynamics. Furthermore, from the aforementioned lower bound on entropy change, we obtain a measure of non-unitarity for unital evolutions
Impact of Complications After Pancreatoduodenectomy on Mortality, Organ Failure, Hospital Stay, and Readmission Analysis of a Nationwide Audit:Analysis of a Nationwide Audit
OBJECTIVE: To quantify the impact of individual complications on mortality, organ failure, hospital stay, and readmission after pancreatoduodenectomy. SUMMARY OF BACKGROUND DATA: An initial complication may provoke a sequence of adverse events potentially leading to mortality after pancreatoduodenectomy. This study was conducted to aid prioritization of quality improvement initiatives. METHODS: Data from consecutive patients undergoing pancreatoduodenectomy (2014-2017) were extracted from the Dutch Pancreatic Cancer Audit. Population attributable fractions (PAF) were calculated for the association of each complication (ie, postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, delayed gastric emptying, wound infection, and pneumonia) with each unfavorable outcome [ie, in-hospital mortality, organ failure, prolonged hospital stay (>75th percentile), and unplanned readmission), whereas adjusting for confounders and other complications. The PAF represents the proportion of an outcome that could be prevented if a complication would be eliminated completely. RESULTS: Overall, 2620 patients were analyzed. In-hospital mortality occurred in 95 patients (3.6%), organ failure in 198 patients (7.6%), and readmission in 427 patients (16.2%). Postoperative pancreatic fistula and postpancreatectomy hemorrhage had the greatest independent impact on mortality [PAF 25.7% (95% CI 13.4-37.9) and 32.8% (21.9-43.8), respectively] and organ failure [PAF 21.8% (95% CI 12.9-30.6) and 22.1% (15.0-29.1), respectively]. Delayed gastric emptying had the greatest independent impact on prolonged hospital stay [PAF 27.6% (95% CI 23.5-31.8)]. The impact of individual complications on unplanned readmission was smaller than 11%. CONCLUSION: Interventions focusing on postoperative pancreatic fistula and postpancreatectomy hemorrhage may have the greatest impact on in-hospital mortality and organ failure. To prevent prolonged hospital stay, initiatives should in addition focus on delayed gastric emptying
Care after pancreatic resection according to an algorithm for early detection and minimally invasive management of pancreatic fistula versus current practice (PORSCH-trial):design and rationale of a nationwide stepped-wedge cluster-randomized trial
Background: Pancreatic resection is a major abdominal operation with 50% risk of postoperative complications. A common complication is pancreatic fistula, which may have severe clinical consequences such as postoperative bleeding, organ failure and death. The objective of this study is to investigate whether implementation of an algorithm for early detection and minimally invasive management of pancreatic fistula may improve outcomes after pancreatic resection. Methods: This is a nationwide stepped-wedge, cluster-randomized, superiority trial, designed in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. During a period of 22 months, all Dutch centers performing pancreatic surgery will cross over in a randomized order from current practice to best practice according to the algorithm. This evidence-based and consensus-based algorithm will provide daily multilevel advice on the management of patients after pancreatic resection (i.e. indication for abdominal imaging, antibiotic treatment, percutaneous drainage and removal of abdominal drains). The algorithm is designed to aid early detection and minimally invasive step-up management of postoperative pancreatic fistula. Outcomes of current practice will be compared with outcomes after implementation of the algorithm. The primary outcome is a composite of major complications (i.e. post-pancreatectomy bleeding, new-onset organ failure and death) and will be measured in a sample size of at least 1600 patients undergoing pancreatic resection. Secondary endpoints include the individual components of the primary endpoint and other clinical outcomes, healthcare resource utilization and costs analysis. Follow up will be up to 90 days after pancreatic resection. Discussion: It is hypothesized that a structured nationwide implementation of a dedicated algorithm for early detection and minimally invasive step-up management of postoperative pancreatic fistula will reduce the risk of major complications and death after pancreatic resection, as compared to current practice. Trial registration: Netherlands Trial Register: NL 6671. Registered on 16 December 2017
Case-only designs for studying the association of antidepressants and hip or femur fracture.
The purpose of this study is to evaluate the performance and validity of the case-crossover (CCO) and self-controlled case-series (SCCS) designs when studying the association between hip/femur fracture (HF) and antidepressant (AD) use in general practitioner databases. In addition, comparability with cohort and case-control designs is discussed.
Adult patients with HF and who received an AD prescription during 2001-2009 were identified from UK's The Health Improvement Network (THIN) and the Dutch Mondriaan databases. AD exposure was classified into current, recent and past/non-use (reference). In the CCO, for each patient, a case moment (date of HF) and four prior control moments at -91, -182, -273 and -365βdays were defined. In SCCS, incidence of HF was compared between exposure states. Conditional logistic regression was used in the CCO and Poisson regression in the SCCS to compute odds ratios and incidence rate ratios, respectively. In CCO, we adjusted for time-varying co-medication and in SCCS for age.
Adjusted estimates for the effect of current AD exposure on HF were higher in the CCO (co-medication-adjusted odds ratio, THIN: 2.24, 95% confidence interval [CI]: 2.04-2.47; Mondriaan: 2.57, 95%CI [1.50, 4.43]) than in the SCCS (age-adjusted incidence rate ratio, THIN: 1.41, 95%CI [1.32, 1.49]; Mondriaan: 2.14, 95%CI [1.51, 3.03]). The latter were comparable with the traditional designs.
Case-only designs confirmed the association between AD and HF. The CCO design violated assumptions in this study with regard to exchangeability and length of exposure, and transient effects on outcome. The SCCS seems to be an appropriate design for assessing AD-HF association. Copyright Β© 2016 John Wiley & Sons, Ltd
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