Nurse-assisted arterio-venous fistula cannulation during home hemodialysis: first results of the DIADIDEAL study / La ponction de fistule assistée par infirmier libéral en hémodialyse à domicile : premiers résultats de l'étude DIADIDEAL.

Introduction: We have launched a pilot study, called DIADIDEAL, to propose nurse-assistance at home for arterio-venous fistula (AVF) cannulation in home hemodialysis (HHD) patients. The aim of the present study was to describe enrollment of the patients and their nurses. Materials: All prevalent HD patients on 30th November 2018 with no medical contraindication to HDD treatment and all incident patients on dialysis from the 30th November 2018 to the 21st April 2023 were eligible. Results: Among 155 prevalent HD patients, 4 patients were included. Among the 276 incident patients on dialysis during the study period, 6 were included. We have phoned 23 nurse centers during the recruitment period. Eight of them agreed to learn in our unit how to cannulate AVF; 27 private nurses were enrolled. Discussion: The results of the DIADIDEAL study will be available in 2024; we hope it will lead to a reimbursement of nurse-AVF cannulation at home in HDD.

Introduction: L'étude DIADIDEAL est une étude pilote sur la ponction de fistule artério-veineuse (FAV) assistée par infirmier libéral en hémodialyse à domicile (HDD). L'objectif de l'étude actuelle est de rapporter le recrutement des patients et de leurs infirmiers diplômés d'État libéraux (IDEL). Matériels et méthodes: Tous les patients prévalents en HD au 30 novembre 2018 n'ayant pas de contre-indication médicale à un traitement par HDD ainsi que tous les patients incidents en dialyse du 30 novembre 2018 au 21 avril 2023 étaient éligibles. Résultats: Parmi les 155 patients prévalents en hémodialyse, 4 ont été inclus. Parmi les 276 patients incidents en dialyse sur la période, 6 ont été inclus dans l'étude. Parmi les 23 cabinets IDEL contactés pour l'étude, 8 ont accepté et 27 IDEL ont été formés à la ponction de FAV. Discussion: Les résultats de l'étude DIADIDEAL seront disponibles en 2024 et viseront à obtenir une nomenclature pour l'acte de ponction de FAV par les IDEL.

Nurse-assisted arterio-venous fistula cannulation during home hemodialysis: first results of the DIADIDEAL study / La ponction de fistule assistée par infirmier libéral en hémodialyse à domicile : premiers résultats de l'étude DIADIDEAL.

Introduction: We have launched a pilot study, called DIADIDEAL, to propose nurse-assistance at home for arterio-venous fistula (AVF) cannulation in home hemodialysis (HHD) patients. The aim of the present study was to describe enrollment of the patients and their nurses. Materials: All prevalent HD patients on 30th November 2018 with no medical contraindication to HDD treatment and all incident patients on dialysis from the 30th November 2018 to the 21st April 2023 were eligible. Results: Among 155 prevalent HD patients, 4 patients were included. Among the 276 incident patients on dialysis during the study period, 6 were included. We have phoned 23 nurse centers during the recruitment period. Eight of them agreed to learn in our unit how to cannulate AVF; 27 private nurses were enrolled. Discussion: The results of the DIADIDEAL study will be available in 2024; we hope it will lead to a reimbursement of nurse-AVF cannulation at home in HDD.

Introduction: L'étude DIADIDEAL est une étude pilote sur la ponction de fistule artério-veineuse (FAV) assistée par infirmier libéral en hémodialyse à domicile (HDD). L'objectif de l'étude actuelle est de rapporter le recrutement des patients et de leurs infirmiers diplômés d'État libéraux (IDEL). Matériels et méthodes: Tous les patients prévalents en HD au 30 novembre 2018 n'ayant pas de contre-indication médicale à un traitement par HDD ainsi que tous les patients incidents en dialyse du 30 novembre 2018 au 21 avril 2023 étaient éligibles. Résultats: Parmi les 155 patients prévalents en hémodialyse, 4 ont été inclus. Parmi les 276 patients incidents en dialyse sur la période, 6 ont été inclus dans l'étude. Parmi les 23 cabinets IDEL contactés pour l'étude, 8 ont accepté et 27 IDEL ont été formés à la ponction de FAV. Discussion: Les résultats de l'étude DIADIDEAL seront disponibles en 2024 et viseront à obtenir une nomenclature pour l'acte de ponction de FAV par les IDEL.

[The benefits of home visits for patients on home hemodialysis]. / Intérêt des visites à domicile pour les patients traités par hémodialyse à domicile.

The success of home hemodialysis depends on several criteria. On the one hand, the patient's willingness to be autonomous, his or her degree of understanding, the technical feasibility at home, and the presence of a third party. Secondly, the quality of initial training (which must respect the patient's rhythm) and follow-up at home. This is a true patient-caregiver partnership, based on trust. Home visits are part of this approach, and help maintain the link, as a team at Caen University Hospital can testify.

[Reception of patients with chronic renal failure, COVID-19]. / Accueil des patients insuffisants rénaux chroniques et Covid-19.

The renal disease center of the university hospital of Caen Normandy (14) is dedicated to the ambulatory care of patients with chronic renal disease, including those treated by dialysis or transplanted. These are fragile patients and, for many of them, coming to the center is inevitable for their care. Faced with the COVID-19 pandemic, the care teams have shown a great capacity to adapt, even to be creative, in order to welcome and care for them in optimal safety conditions.

[Certification, on-the-ground experience of a manager and his team]. / Certification, expérience de terrain d'un cadre et de son équipe.

The certification assessment is an important stage in the life of a healthcare facility. However, instilling a quality culture within a team to lead it towards performance is a long-term endeavour. This cannot work without the existence of a partnership between the paramedical and medical teams, nor without the support of the hospital led by senior quality managers. The challenge is to not limit the quality culture to the certification assessment, which aims to highlight the areas in which the institution conforms and those in which it is failing, but rather to adopt a continuous improvement approach.

Cost-effectiveness of golimumab for the treatment of patients with moderate-to-severe ulcerative colitis in Quebec using a patient level state transition microsimulation.

OBJECTIVE: To conduct cost-effectiveness analyses comparing the addition of golimumab to the standard of care (SoC) for treatment of patients with moderate-to-severe ulcerative colitis (UC) who are refractory to conventional therapies in Quebec (Canada). METHODS: An individual patient state transition microsimulation model was developed to project health outcomes and costs over 10 years, using a payer perspective. The incremental benefit estimates for golimumab were driven by induction response and risk of a flare. Flare risks post-induction were derived for golimumab from the PURSUIT maintenance trial and extension study, while those for SoC were derived from the placebo arms of the Active Ulcerative Colitis Trials (ACT) 1 and 2. Other inputs were derived from multiple sources, including retrospective claims analyses and literature. Costs are reported in 2014 Canadian dollars. A 5% annual discount rate was applied to costs and quality-adjusted life-years (QALYs). RESULTS: Compared with SoC, golimumab was projected to increase the time spent in mild disease or remission states, decrease flare rates, and increase QALYs. These gains were achieved with higher direct medical costs. The incremental cost-effectiveness ratio for golimumab vs SoC was $63,487 per QALY. LIMITATIONS: The long-term flare projections for SoC were based on the data available from the ACT 1 and 2 placebo arms, as data were not available from the PURSUIT maintenance or extension trial. Additionally, the study was limited to only SoC and golimumab, due to the availability of individual patient data to analyze. CONCLUSION: This economic analysis concluded that treatment with golimumab is likely more cost-effective vs SoC when considering cost-effectiveness acceptability thresholds from $50,000-$100,000 per QALY.

Cost-effectiveness of combination daclatasvir-sofosbuvir for treatment of genotype 3 chronic hepatitis C infection in the United States.

BACKGROUND: A phase III trial evaluated the efficacy and safety of Daklinza (daclatasvir or DCV) in combination with sofosbuvir (SOF) for treatment of genotype (GT) 3 hepatitis C virus (HCV) patients. AIM: This study evaluated the cost-effectiveness of DCV + SOF vs SOF in combination with ribavirin (RBV) over a 20-year time horizon from the perspective of a United States (US) payer. METHODS: A published Markov model was adapted to reflect US demographic characteristics, treatment patterns, costs of drug acquisition, monitoring, disease and adverse event management, and mortality risks. Clinical inputs came from the ALLY-3 and VALENCE trials. The primary outcome was the incremental cost-utility ratio. Life-years, incidence of complications, number of patients achieving sustained virological response (SVR), and the total cost per SVR were secondary outcomes. Costs (2014 USD) and quality-adjusted life years (QALYs) were discounted at 3% per year. Deterministic, probabilistic, and scenario sensitivity analyses were conducted. RESULTS: DCV + SOF was associated with lower costs and better effectiveness than SOF + RBV in the base case and in almost all scenarios (i.e. treatment-experienced, non-cirrhotic, time horizons of 5, 10, and 80 years). DCV + SOF was less costly, but also slightly less effective than SOF + RBV in the cirrhotic and treatment-naïve population scenarios. Results were sensitive to variations in the probability of achieving SVR for both treatment arms. DCV + SOF costs less than $50,000 per QALY gained in 79% of all probabilistic iterations compared with SOF + RBV. CONCLUSION: DCV + SOF is a dominant option compared with SOF + RBV in the US for the overall GT 3 HCV patient population.

Cost-utility analysis of memantine extended release added to cholinesterase inhibitors compared to cholinesterase inhibitor monotherapy for the treatment of moderate-to-severe dementia of the Alzheimer's type in the US.

OBJECTIVE: This study evaluates the cost-effectiveness of memantine extended release (ER) as an add-on therapy to acetylcholinesterase inhibitor (AChEI) [combination therapy] for treatment of patients with moderate-to-severe Alzheimer's disease (AD) from both a healthcare payer and a societal perspective over 3 years when compared to AChEI monotherapy in the US. METHODS: A phase III trial evaluated the efficacy and safety of memantine ER for treatment of AD patients taking an AChEI. The analysis assessed the long-term costs and health outcomes using an individual patient simulation in which AD progression is modeled in terms of cognition, behavior, and functioning changes. Input parameters are based on patient-level trial data, published literature, and publicly available data sources. Changes in anti-psychotic medication use are incorporated based on a published retrospective cohort study. Costs include drug acquisition and monitoring, total AD-related medical care, and informal care associated with caregiver time. Incremental cost-utility ratio (ICUR), life years, care time for caregiver, time in community and institution, time on anti-psychotics, time by disease severity, and time without severe symptoms are reported. Costs and health outcomes are discounted at 3% per annum. RESULTS: Considering a societal perspective over 3 years, this analysis shows that memantine ER combined with an AChEI provides better clinical outcomes and lower costs than AChEI monotherapy. Discounted average savings were estimated at $18,355 and $20,947 per patient and quality-adjusted life-years (QALYs) increased by an average of 0.12 and 0.13 from a societal and healthcare payer perspective, respectively. Patients on combination therapy spent an average of 4 months longer living at home and spend less time in moderate-severe and severe stages of the disease. CONCLUSION: Combination therapy for patients with moderate-to-severe AD is a cost-effective treatment compared to AChEI monotherapy in the US.

Cost-effectiveness analyses in multiple sclerosis: a review of modelling approaches.

The growing number of disease-modifying treatments (DMTs) for patients with multiple sclerosis (MS) and the high acquisition costs of these DMTs are likely to increase the demand for information on their cost effectiveness. To improve the comparability and applicability of the findings from future cost-effectiveness analyses, it would be useful to have a clear understanding of the methodological challenges of modelling the cost effectiveness of DMTs in MS and the different approaches taken by such studies to date. In contrast to previous review studies, this review focuses on long-term time horizon (≥10 years) simulation-based cost-effectiveness analyses with homogeneous contexts of analysis (i.e. those with similar study objectives, comparators, and target populations) published over the past decade. By doing so, it provides a clearer picture of how modelling approaches taken in the existing studies truly differ across studies, and reveals major areas for improvement in conducting future cost-effectiveness analyses of DMTs for patients with MS.

Osteopontin: an early innate immune marker of Escherichia coli mastitis harbors genetic polymorphisms with possible links with resistance to mastitis.

BACKGROUND: Mastitis is the most important disease in dairy cows and it causes significant lost of profit to producers. Identification of the genes, and their variants, involved in innate immune responses is essential for the understanding of this inflammatory disease and to identify potential genetic markers for resistance to mastitis. The progeny of dairy cows would benefit from receiving favourable alleles that support greater resistance to infection, thus reducing antibiotic use. This study aims to identify a key gene in the innate immune response to mastitis, led us to evaluate its genetic association with somatic cell score (SCS), which is an indicator of clinical mastitis, and to evaluate its impact on other traits related to milk production. RESULTS: The osteopontin transcript (SPP1) was identified in the somatic cells from cows experimentally infected with Escherichia coli. By selecting bulls with extreme estimated breeding values (EBVs) for SCS, which is an indicator of mammary gland health, four DNA polymorphisms in the SPP1 genomic sequence were found. Statistical analysis revealed that the SNP SPP1c.-1301G>A has an impact on EBV for SCS (P < 0.001) Using an allele substitution model, SPP1c.-1251C>T, SPP1c.-430G>A, and SPP1c.*40A>C have an impact on SCS whereas SPP1c.-1301G>A has an effect on the EBVs for milk yield (second and third lactations), fat and protein percentages (all three lactations). Analysis revealed statistically significant differences between haplotype groups at a comparison-wise level with sire EBVS for SCS for the first (P = 0.012), second (P < 0.001), and third (P < 0.001) lactations. CONCLUSION: This study reports the link between DNA polymorphisms of SPP1, the number of milk immune cells and, potentially, the susceptibility to mastitis. These SNPs were identified by in silico search to be located in transcription factor recognition sites which factors are presumably involved in the Th1 immune response and in the Th2 regulation pathway. Indeed, one SNP abolished the SP1 recognition site, whereas another SNP affected the transcription binding factor IKAROS. All together, these findings support the genetic potential of these variants in terms of selection for the improvement of mastitis resistance in dairy cows.

Spermatozoal transcriptome profiling for bull sperm motility: a potential tool to evaluate semen quality.

Regarding bull fertility, establishing an association between in vitro findings and field fertility requires a multi-parametric approach that measures the integrity of various structures and dynamic functions, such as motion characteristics, among others. The heterogeneous RNA pattern of spermatozoa could be used in genomic analysis for evaluating both spermatogenesis and fertility potential of semen, mainly because of the static status of the transcriptome of this particular differentiated cell. In a previous study, we determined that some spermatozoal transcripts identified by PCR-based cDNA subtraction are associated with non-return rate, a field fertility index. In the present study, the microarray technology was used in conjunction with differential RNA transcript extraction. We have shown that among these genes, some transcripts are also associated with the motility status of a population of sperm cells fractionated from the same ejaculate. We highlighted a systematic data analysis and validation scheme important for the identification of significant transcripts in this context. With such an approach, we found that transcripts encoding a serine/threonine testis-specific protein kinase (TSSK6) and a metalloproteinase non coding RNA (ADAM5P) are associated with high-motility status (P<0.001), also confirmed by quantitative PCR (P=0.0075). This association was found only when transcripts were extracted using the hot-TRIzol protocol, whereas the cold-TRIzol RNA extract comprised mitochondrial transcripts. These results demonstrate that some transcripts previously identified in association with field fertility are also found associated with in vitro motility provided that a stringent RNA extraction protocol is used.

Detection limits of several commercial reverse transcriptase enzymes: impact on the low- and high-abundance transcript levels assessed by quantitative RT-PCR.

BACKGROUND: In functional genomics, transcript measurement is of fundamental importance. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays are the most popular technology and depend on the initial molecular step, the reverse transcription (RT). This study provides a complex overview of the influence of elements such as RT systems, amount of background RNA, and transcript abundance on the efficiency of qRT-PCR. Using qRT-PCR, we compared the efficiency of some commonly used RT systems and measured the production of PCR-amplifiable products and the influence of PCR inhibitor contents. RESULTS: The qRT-PCR assays were conducted using the TaqMan system, although we also tested the SYBR Green I chemistry, which is not compatible with all the RT systems. When dealing with low-abundance transcripts, the SuperScript II system generated more detectable molecules than the four other systems tested: Sensiscript, Omniscript, SuperScript III and PowerScript (P < 0.05). However, the Sensiscript and PowerScript systems were more efficient for detecting high-abundance transcripts in the presence of 1 to 2 mug background RNA (P < 0.05). The most striking aspect was the influence of the dilution of the RT reaction on the subsequent PCR. Indeed, some inhibition was released when diluted RT reactions were used for the quantitative PCR measurements. Furthermore, the amount of background RNA in the RT reaction was also a major component influencing a downstream step in qRT-PCR, the PCR reaction. Whereas Sensiscript was less biased, the other systems contained an important source of PCR inhibitors, interfering as much as 70% with the qRT-PCR. CONCLUSION: This study provides a complex overview of the influence of elements such as RT systems, qRTPCR chemistry, amount of background RNA, and transcript abundance on the efficiency of qRT-PCR. Whereas the most significant influencing factor is the presence of inhibitors in the RT systems, total background RNA is also a major influencing component that affects the PCR reaction. Whenever the aim of a study is to obtain a precise gene expression measurement or to profile the global transcriptome (e.g. microarray), the RT step is critical and should be examined with care.

Binding of the polypyrimidine tract-binding protein-associated splicing factor (PSF) to the hepatitis delta virus RNA.

The hepatitis delta virus (HDV) has a very limited protein coding capacity and must rely on host proteins for its replication. A ribonucleoprotein complex was detected following UV cross-linking between HeLa nuclear proteins and an RNA corresponding to the right terminal stem-loop domain of HDV genomic RNA. Mass spectrometric analysis of the complex revealed the polypyrimidine tract-binding protein-associated splicing factor (PSF) as a novel HDV RNA-interacting protein. Co-immunoprecipitation demonstrated the interaction between HDV RNA and PSF both in vitro in HeLa nuclear extract and in vivo within HeLa cells containing both polarities of the HDV genome. Analysis of the binding of various HDV-derived RNAs to purified, recombinant PSF further confirmed the specificity of the interaction and revealed that PSF directly binds to the terminal stem-loop domains of both polarities of HDV RNA. Our findings provide evidence of the involvement of a host mRNA processing protein in the HDV life cycle.