Potential determinants of unfavourable healthcare utilisation trajectories during the last year of life of people with incident Alzheimer Disease or Related Syndromes: a nationwide cohort study using administrative data.

BACKGROUND: people approaching the end-of-life frequently face inappropriate care. With Alzheimer Disease or Related Syndromes (ADRS), end-of-life is characterised by progressive decline, but this period remains difficult to identify. This leads to a lack of anticipation and sometimes with unfavourable healthcare utilisation trajectories (HUTs). OBJECTIVE: to quantify unfavourable HUTs during the last year of life and identify their potential determinants in both community and nursing-home settings. DESIGN: nationwide cohort study using administrative database. SETTING: French community and nursing-home residents. SUBJECTS: incident ADRS people identified in 2012, who died up to 31 December 2017. METHODS: we used multidimensional clustering to identify 15 clusters of HUTs, using 11 longitudinal healthcare dimensions during the last year of life. Clusters were qualitatively assessed by pluri-disciplinary experts as favourable or unfavourable HUTs. Individual and contextual potential determinants of unfavourable HUTs were studied by setting using logistic random-effect regression models. RESULTS: 62,243 individuals died before 31 December 2017; 46.8% faced unfavourable end-of-life HUTs: 55.2% in the community and 31.8% in nursing-homes. Individual potential determinants were identified: younger age, male gender, ADRS identification through hospitalisation, shorter survival, life-limiting comorbidities, psychiatric disorders, acute hospitalisations and polypharmacy. In the community, deprivation and autonomy were identified as potential determinants. Contextual potential determinants raised mostly in the community, such as low nurse or physiotherapist accessibilities. CONCLUSIONS: Nearly half of people with ADRS faced unfavourable HUTs during their last year of life. Individual potential determinants should help anticipate advance care planning and palliative care needs assessment. Contextual potential determinants suggest geographical disparities and health inequalities.

Final five-year results of the REMEDEE Registry: Real-world experience with the dual-therapy COMBO stent.

OBJECTIVES: This final report from the REMEDEE Registry assessed the long-term safety and efficacy of the dual-therapy COMBO stent in a large unselected patient population. BACKGROUND: The bio-engineered COMBO stent (OrbusNeich Medical BV, The Netherlands) is a dual-therapy pro-healing stent. Data of long-term safety and efficacy of the this stent is lacking. METHODS: The prospective, multicenter, investigator-initiated REMEDEE Registry evaluated clinical outcomes after COMBO stent implantation in daily clinical practice. One thousand patients were enrolled between June 2013 and March 2014. RESULTS: Five-year follow-up data were obtained in 97.2% of patients. At 5-years, target lesion failure (TLF) (composite of cardiac death, target-vessel myocardial infarction, or target lesion revascularization) was present in 145 patients (14.8%). Definite or probable stent thrombosis (ST) occurred in 0.9%, with no additional case beyond 3-years of follow-up. In males, 5-year TLF-rate was 15.6 versus 12.6% in females (p = .22). Patients without diabetes mellitus (DM) had TLF-rate of 11.4%, noninsulin-treated DM 22.7% (p = .001) and insulin-treated DM 41.2% (p < .001). Patients presenting with non-ST segment elevation acute coronary syndrome (NSTE-ACS) had higher incidence of TLF compared to non-ACS (20.4 vs. 13.3%; p = .008), while incidence with STE-ACS was comparable to non-ACS (10.7 vs. 13.3%; p = .43). CONCLUSION: Percutaneous coronary intervention with the dual-therapy COMBO stent in unselected patient population shows low rates of TLF and ST to 5 years. Remarkably, no case of ST was noted beyond 3 years.

Thermal effects of Ho:YAG laser lithotripsy during retrograde intrarenal surgery and percutaneous nephrolithotomy in an ex vivo porcine kidney model.

PURPOSE: To evaluate the thermal effect of high-power holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripsy in flexible/semirigid ureteroscopy (fURS/sURS) and percutaneous nephrolithotomy (PNL) in a standardized ex vivo porcine kidney model with real-time temperature assessment. METHODS: The experimental setup consisted of three models designed to evaluate the thermal effects of Ho:YAG laser lithotripsy in fURS, sURS and PNL, respectively. In all setups, a postmortem porcine kidney was placed in a 37 °C water bath. Three thermocouples were inserted into the renal parenchyma while a flexible thermocouple was placed 3-4 mm proximal to the laser fiber to measure temperature variations in the collecting system. The thermal impact was evaluated in relation to laser power between 5 and 100 W and various irrigation rates (37 °C, 0-100 ml/min). RESULTS: In all three experimental setups, sufficient irrigation was required to prevent potentially damaging temperatures into the renal pelvis and parenchyma. Even 5 W in fURS can lead to a potentially harming temperature rise if insufficient irrigation is applied. Particularly, high-power settings ≥ 30 W carry an elevated risk for critical temperature rises. The results allow the definition of a specific irrigation threshold for any power setting to prevent critical temperatures in the present study design. CONCLUSIONS: Ho:YAG laser lithotripsy bears the risk of thermal damages to the urinary tract even at low-power settings if inadequate irrigation is applied. Sufficient irrigation is mandatory to perform safe Ho:YAG laser lithotripsy. Based on the results, we developed a formula calculating the approximate ΔT for irrigation rates ≥ 30 ml/min: ΔT = 15 K × (power [W]/irrigation [ml/min]).

[Older people in Ehpad, representations of young adults]. / Personnes âgées en Ehpad, représentations des jeunes adultes.

Studies on social representations of older persons are numerous and come mainly from American literature. However, few studies have examined young people's viewpoint. This article focuses on the representations of older patients among students in Bac Professionnel.

Three-year clinical outcomes after dual-therapy COMBO stent placement: Insights from the REMEDEE registry.

BACKGROUND: The bio-engineered COMBO stent (OrbusNeich Medical BV, The Netherlands) is a dual-therapy pro-healing stent. This novel technology may allow a shorter duration of dual antiplatelet therapy (DAPT) after stenting. We present the first 3 year clinical outcomes of patients treated with COMBO stent. METHODS AND RESULTS: The prospective, multicenter, investigator-initiated, all-comers REMEDEE Registry evaluates clinical outcomes after COMBO stent treatment. A 1,000 patients were enrolled between June 2013 and March 2014. Patients had a mean of 65 years ±11, 26% of the patients were females and 18% diabetics. More than 50% of patients presented with acute coronary syndrome, 60% of treated lesions were AHA/ACC lesion type B2 or C. Target lesion failure (TLF) at 3 year follow-up occurred in 10.7% of patients (N = 105). The separate components cardiac death, target vessel myocardial infarction and target lesion revascularization occurred in 4.1%, 2.0%, and 7.1%, respectively of patients. Definite stent thrombosis (ST) was observed in 0.7% of all patients. At 3-year follow-up there were only 73 patients taking DAPT. CONCLUSIONS: At 3-year follow-up, patients treated with COMBO stent in the present large prospective all-comers cohort, continue to show good clinical outcomes. Clinicaltrials.gov identifier: NCT01874002. CONDENSED ABSTRACT: The COMBO stent is a sirolimus-eluting stent with a luminal anti-CD34-antibody layer, that binds endothelial progenitor cells. These cells can differentiate to endothelial cells and stimulate early endothelialization of the stent. The REMEDEE Registry is the first large, multicenter, prospective, cohort study evaluating the clinical outcomes of 1,000 all-comers patients treated with COMBO stent. Target lesion failure at 3 year follow-up was 10.7% and the rate of definite ST was 0.7%.

Risk Factors for Ureteral Damage in Ureteroscopic stone Treatment: Results of the German Prospective Multicentre Benchmarks of Ureterorenoscopic Stone Treatment-Results in Terms of Complications, Quality of Life, and Stone-Free Rates Project.

BACKGROUND: The Post-Ureteroscopic Lesion Scale (PULS) is a validated, standardised scale that classifies iatrogenic ureteral lesions during ureteroscopy (URS). OBJECTIVE: To determine risk factors for the various PULS-grades caused by URS. METHOD: We prospectively investigated the independent influence of various risk factors in correlation with PULS-Grade 1+ and 2+ on 307 patients with ureterorenoscopic stone treatment from 14 German urologic departments. RESULTS: The following are the outcomes of the study: 117 (38.4%) and 188 (61.6%) of the calculi (median stone size 6 mm) were found in the kidney or ureter; 70% and 82.4% underwent preoperative or postoperative ureteral stenting; 44.3 and 7.2% received laser or ballistic lithotripsy; 60% of the patients presented with PULS grade 1+ and 8% with PULS grade of 2+. Only intracorporal lithotripsy revealed a significant independent risk factor for PULS grade 1+ or 2+. Both laser and ballistic therapies raised the probability of PULS grade 1+ by the factors 3.6 (p < 0.001) and 3.9 (p = 0.021), respectively. The ORs in conjunction with PULS grade 2+ were 3.1 (p = 0.038) and 5.8 (p = 0.014) respectively. Neither endpoint exhibited a significant difference regarding the lithotripsic procedure (laser vs. ballistic). CONCLUSION: Intracorporal lithotripsy is associated with a significant increase in damage to the ureter; further research is needed to determine its long-term effects.

AUXIN BINDING PROTEIN1 links cell wall remodeling, auxin signaling, and cell expansion in arabidopsis.

Cell expansion is an increase in cell size and thus plays an essential role in plant growth and development. Phytohormones and the primary plant cell wall play major roles in the complex process of cell expansion. In shoot tissues, cell expansion requires the auxin receptor AUXIN BINDING PROTEIN1 (ABP1), but the mechanism by which ABP1 affects expansion remains unknown. We analyzed the effect of functional inactivation of ABP1 on transcriptomic changes in dark-grown hypocotyls and investigated the consequences of gene expression on cell wall composition and cell expansion. Molecular and genetic evidence indicates that ABP1 affects the expression of a broad range of cell wall-related genes, especially cell wall remodeling genes, mainly via an SCF(TIR/AFB)-dependent pathway. ABP1 also functions in the modulation of hemicellulose xyloglucan structure. Furthermore, fucosidase-mediated defucosylation of xyloglucan, but not biosynthesis of nonfucosylated xyloglucan, rescued dark-grown hypocotyl lengthening of ABP1 knockdown seedlings. In muro remodeling of xyloglucan side chains via an ABP1-dependent pathway appears to be of critical importance for temporal and spatial control of cell expansion.

Evaluation of clinical outcomes after COMBO stent treatment in patients presenting with acute coronary syndrome.

BACKGROUND: Patients presenting with acute coronary syndrome (ACS) are at increased risk of complications after percutaneous coronary intervention with stent placement compared to patients with stable angina (SA) treated in an elective setting. The novel pro-healing COMBO stent is a bio-engineered drug eluting stent designed to promote vessel healing. Therefore, the stent may reduce this difference in clinical outcomes between elective and ACS-patients and prevent late stent thrombosis. METHODS AND RESULTS: The European, prospective, multicenter, 1000 all-comers patient REMEDEE registry evaluates clinical outcomes after COMBO stent placement in ACS- and elective patients. The primary endpoint at 12 months is target lesion failure (TLF), a composite of cardiac death, target-vessel myocardial infarction and target lesion revascularization. A total of 49.9% (n = 498) of patients presented with acute coronary syndrome. TLF was 7.1% in ACS patients, definite and probable stent thrombosis was observed in 0.5% of ACS patients and in all within 9 days post stenting. We found no significant difference in TLF between ACS and non-ACS patients and a low overall rate of TLF. CONCLUSIONS: The COMBO stent is a safe and efficient device for patients presenting with ACS. Low ST rate and only early stent thrombosis were observed. © 2017 Wiley Periodicals, Inc.

'I want to ski and race, not just ski': a qualitative study on athletes' and stakeholders' perspectives on return-to-sport in high-performance Snowsports.

This study explored stakeholders' perspectives on current practices, challenges and opportunities related to the return-to-sport (RTS) process in high-performance Snowsports. We conducted fourteen semi-structured interviews with athletes, coaches and health professionals from multiple countries using online video platforms. The data were transcribed verbatim and analysed based on constant comparative analysis employing the principles of Grounded Theory. Codes were grouped into categories and main concepts and a conceptual model were derived. According to the participants, RTS should be considered a continuous process to bring the athlete back to competition as fast and safely as possible, whereas speed is often prioritised over safety. Participants described the need for a structured and criteria-based process. Despite the multiple phases and the diversity of involved professionals, the process is individualised and unique, highlighting the value of having the athlete at the centre of the RTS process. It was considered essential to provide a safe environment and build trustworthy relationships. Additionally, access to resources, communication and cooperation among all experts was perceived as critical to successful RTS. Our participants described the value of continuity and an athlete-centred approach to the RTS process. The challenges, such as interprofessional communication, the lack of objective sport-specific criteria, and the diversity of resources and network structures, were perceived as practical issues that influenced the process, which should be tailored for each athlete accordingly to reach a successful RTS.

Discovery of JNJ-1802, a First-in-Class Pan-Serotype Dengue Virus NS4B Inhibitor.

Dengue is a global public health threat, with about half of the world's population at risk of contracting this mosquito-borne viral disease. Climate change, urbanization, and global travel accelerate the spread of dengue virus (DENV) to new areas, including southern parts of Europe and the US. Currently, no dengue-specific small-molecule antiviral for prophylaxis or treatment is available. Here, we report the discovery of JNJ-1802 as a potent, pan-serotype DENV inhibitor (EC50's ranging from 0.057 to 11 nM against the four DENV serotypes). The observed oral bioavailability of JNJ-1802 across preclinical species, its low clearance in human hepatocytes, the absence of major in vitro pharmacology safety alerts, and a dose-proportional increase in efficacy against DENV-2 infection in mice were all supportive of its selection as a development candidate against dengue. JNJ-1802 is being progressed in clinical studies for the prevention or treatment of dengue.

The RNA binding protein Tudor-SN is essential for stress tolerance and stabilizes levels of stress-responsive mRNAs encoding secreted proteins in Arabidopsis.

Tudor-SN (TSN) copurifies with the RNA-induced silencing complex in animal cells where, among other functions, it is thought to act on mRNA stability via the degradation of specific dsRNA templates. In plants, TSN has been identified biochemically as a cytoskeleton-associated RNA binding activity. In eukaryotes, it has recently been identified as a conserved primary target of programmed cell death-associated proteolysis. We have investigated the physiological role of TSN by isolating null mutations for two homologous genes in Arabidopsis thaliana. The double mutant tsn1 tsn2 displays only mild growth phenotypes under nonstress conditions, but germination, growth, and survival are severely affected under high salinity stress. Either TSN1 or TSN2 alone can complement the double mutant, indicating their functional redundancy. TSN accumulates heterogeneously in the cytosol and relocates transiently to a diffuse pattern in response to salt stress. Unexpectedly, stress-regulated mRNAs encoding secreted proteins are significantly enriched among the transcripts that are underrepresented in tsn1 tsn2. Our data also reveal that TSN is important for RNA stability of its targets. These findings show that TSN is essential for stress tolerance in plants and implicate TSN in new, potentially conserved mechanisms acting on mRNAs entering the secretory pathway.

[Nursing practice in nursing homes]. / Spécificités de l'exercice en Ehpad.

This article launches a new section devoted to care homes for dependent elderly people (EHPAD). Created in 2001, these homes accommodate around 685 000 people. They must be more and more medicalised to meet the needs of an increasingly dependent population. This first article provides an overview of this form of accommodation.

[The coordinator nurse in nursing homes, at the crossroads of care]. / Infirmière coordinatrice en ehpad, au carrefour des soins.

Working as a coordinator nurse in a nursing home requires numerous personal and professional qualities. This key position at the heart of the coordination of care deserves greater recognition.

Response to 'Eruptive keratoacanthomas associated with dupilumab therapy'.

Case of a patient developing multiple rashes of squamous cell carcinoma 6 weeks after the introduction of dupilumab due to atopic eczema.

Call for the application of a biopsychosocial and interdisciplinary approach to the return-to-sport framework of snow sports athletes.

Snow sports such as alpine skiing or snowboarding are associated with a high risk of injury and reinjury and are subject to a very special environment with specific rehabilitation challenges that must be addressed. Due to geographic decentralisation, seasonal climatic limitations, alternation of training in off-snow and on-snow settings and unique loading patterns of practising these sports, special rehabilitation structures and processes are required compared with other sports. In addition, returning to preinjury performance requires a high level of confidence and a resumption of risk-taking in demanding situations such as high-speed skiing and high-amplitude jumps. A biopsychosocial and interdisciplinary approach can be viewed as a holistic, athlete-centred approach that promotes interprofessional communication and collaboration. This is particularly central for managing the physical/biological, psychological and social demands of injury management for snow sports. It can help ensure that rehabilitation content is well coordinated and tailored to individual needs. This is because transitions between different rehabilitation phases and caring professionals are well aligned, and rehabilitation is understood not only as purely 'physical recovery' but also as 'psychological recovery' considering the snow sports-specific setting with specific social norms. Ultimately, this may improve the rehabilitation success of snow sports athletes.

Discovery of Acyl-Indole Derivatives as Pan-Serotype Dengue Virus NS4B Inhibitors.

In the absence of any approved dengue-specific treatment, the discovery and development of a novel small-molecule antiviral for the prevention or treatment of dengue are critical. We previously reported the identification of a novel series of 3-acyl-indole derivatives as potent and pan-serotype dengue virus inhibitors. We herein describe our optimization efforts toward preclinical candidates 24a and 28a with improved pan-serotype coverage (EC50's against the four DENV serotypes ranging from 0.0011 to 0.24 µM for 24a and from 0.00060 to 0.084 µM for 28a), chiral stability, and oral bioavailability in preclinical species, as well as showing a dose-proportional increase in efficacy against DENV-2 infection in vivo in mice.

Motion sickness on tilting trains.

Trains that tilt on curves can go faster, but passengers complain of motion sickness. We studied the control signals and tilts to determine why this occurs and how to maintain speed while eliminating motion sickness. Accelerometers and gyros monitored train and passenger yaw and roll, and a survey evaluated motion sickness. The experimental train had 3 control configurations: an untilted mode, a reactive mode that detected curves from sensors on the front wheel set, and a predictive mode that determined curves from the train's position on the tracks. No motion sickness was induced in the untilted mode, but the train ran 21% slower than when it tilted 8° in either the reactive or predictive modes (113 vs. 137 km/h). Roll velocities rose and fell faster in the predictive than the reactive mode when entering and leaving turns (0.4 vs. 0.8 s for a 4°/s roll tilt, P<0.001). Concurrently, motion sickness was greater (P<0.001) in the reactive mode. We conclude that the slower rise in roll velocity during yaw rotations on entering and leaving curves had induced the motion sickness. Adequate synchronization of roll tilt with yaw velocity on curves will reduce motion sickness and improve passenger comfort on tilting trains.

[Home automation for elderly people in the process of losing their autonomy]. / La domotique au service des personnes agées en perte d'autonomie.

The safety of elderly people, particularly dependent at night, is a major factor in preventingthem from remaining in their own home. An experiment in Corrèze using domotics and advanced remote assistance services and involving around one hundred elderly people living at home, took place from summer 2009 to autumn 2010.

Clustering 5-Year Multidimensional Health Care Trajectory Patterns in Alzheimer's Disease and Related Syndromes.

OBJECTIVE: After diagnosis of Alzheimer's disease and related syndromes (ADRS), personalized care adapted to each patient's needs is recommended to provide a care plan and start symptomatic treatments according to guidelines. Over the past decade, dedicated structures and care have been implemented in various settings. Equal access to ADRS care, health care providers and services is crucial to ensure potential health benefits for everyone. However, the extent of use of recommended services and favorable health care utilization trajectories (HUT) may vary according to individual and contextual characteristics. The aim of this article was to (1) describe HUT patterns after multidimensional clustering of similar trajectories, (2) assess the proportion of individuals presenting favorable HUTs, and (3) identify factors associated with favorable HUTs. DESIGN: Cohort study. SETTING AND PARTICIPANTS: A cohort of 103,317 people newly diagnosed with ADRS identified in the French health reimbursement system (SNDS) was followed for 5 years with their monthly utilization on 11 health care dimensions. METHODS: For 3 age groups (65-74, 75-84, ≥85 years), 15 clusters of patients were identified using partitioning around medoids applied to Levenshtein distances. They were qualitatively assessed by pluridisciplinary experts. Individual and contextual determinants of clusters denoting favorable trajectories were identified using mixed random effects multivariable logistic regression models. RESULTS: Clusters with favorable HUTs denoting slow, progressive trajectories centered on at-home care, represented approximatively 25% of the patients. Determinants of favorable HUTs were mostly individual (age, female gender, absence of certain comorbidities, circumstances of ADRS identification, lower deprivation). Contextual determinants were also identified, in particular accessibility to nurses and nursing homes. Inter-territories variance was small but significant in all age groups (from 0.9% to 1.8%). CONCLUSION AND IMPLICATIONS: Favorable HUTs remain the minority and many efforts can still be made to improve HUTs. Qualitative studies could help understanding underlying barriers to favorable HUTs.

A High-Fidelity Phantom for the Simulation and Quantitative Evaluation of Transurethral Resection of the Prostate.

Transurethral resection of the prostate (TURP) is a minimally invasive endoscopic procedure that requires experience and skill of the surgeon. To permit surgical training under realistic conditions we report a novel phantom of the human prostate that can be resected with TURP. The phantom mirrors the anatomy and haptic properties of the gland and permits quantitative evaluation of important surgical performance indicators. Mixtures of soft materials are engineered to mimic the physical properties of the human tissue, including the mechanical strength, the electrical and thermal conductivity, and the appearance under an endoscope. Electrocautery resection of the phantom closely resembles the procedure on human tissue. Ultrasound contrast agent was applied to the central zone, which was not detectable by the surgeon during the surgery but showed high contrast when imaged after the surgery, to serve as a label for the quantitative evaluation of the surgery. Quantitative criteria for performance assessment are established and evaluated by automated image analysis. We present the workflow of a surgical simulation on a prostate phantom followed by quantitative evaluation of the surgical performance. Surgery on the phantom is useful for medical training, and enables the development and testing of endoscopic and minimally invasive surgical instruments.