Integrated home dialysis model: facilitating home-to-home transition.

Peritoneal dialysis (PD) and home hemodialysis (HHD) are the two home dialysis modalities offered to patients. They promote patient autonomy, enhance independence, and are generally associated with better quality of life compared to facility hemodialysis. PD offers some advantages (enhanced flexibility, ability to travel, preservation of residual kidney function, and vascular access sites) but few patients remain on PD indefinitely due to peritonitis and other complications. By contrast, HHD incurs longer and more intensive training combined with increased upfront health costs compared to PD, but is easier to sustain in the long term. As a result, the integrated home dialysis model was proposed to combine the advantages of both home-based dialysis modalities. In this paradigm, patients are encouraged to initiate dialysis on PD and transfer to HHD after PD termination. Available evidence demonstrates the feasibility and safety of this approach and some observational studies have shown that patients who undergo the PD-to-HHD transition have clinical outcomes comparable to patients who initiate dialysis directly on HHD. Nevertheless, the prevalence of PD-to-HHD transfers remains low, reflecting the multiple barriers that prevent the full uptake of home-to-home transitions, notably a lack of awareness about the model, home-care "burnout," clinical inertia after a transfer to facility HD, suboptimal integration of PD and HHD centers, and insufficient funding for home dialysis programs. In this review, we will examine the conceptual advantages and disadvantages of integrated home dialysis, present the evidence that underlies it, identify challenges that prevent its success and finally, propose solutions to increase its adoption.

Protection against Clostridioides difficile disease by a naturally avirulent C. difficile strain.

Clostridioides difficile (C. difficile) strains belonging to the epidemic BI/NAP1/027 (RT027) group have been associated with increased transmissibility and disease severity. In addition to the major toxin A and toxin B virulence factors, RT027 strains also encode the CDT binary toxin. Our lab previously identified a toxigenic RT027 isolate, ST1-75, that is avirulent in mice despite densely colonizing the colon. Here, we show that coinfecting mice with the avirulent ST1-75 and virulent R20291 strains protects mice from colitis due to rapid clearance of the virulent strain and persistence of the avirulent strain. Although avirulence of ST1-75 is due to a mutation in the cdtR gene, which encodes a response regulator that modulates the production of all three C. difficile toxins, the ability of ST1-75 to protect against acute colitis is not directly attributable to the cdtR mutation. Metabolomic analyses indicate that the ST1-75 strain depletes amino acids more rapidly than the R20291 strain and supplementation with amino acids ablates ST1-75's competitive advantage, suggesting that the ST1-75 strain limits the growth of virulent R20291 bacteria by amino acid depletion. Since the germination kinetics and sensitivity to the co-germinant glycine are similar for the ST1-75 and R20291 strains, our results identify the rapidity of in vivo nutrient depletion as a mechanism providing strain-specific, virulence-independent competitive advantages to different BI/NAP1/027 strains. They also suggest that the ST1-75 strain may, as a biotherapeutic agent, enhance resistance to CDI in high-risk patients.

Differences in Antihypertensive Medication Prescription Profiles Between 2009 and 2021: A Retrospective Cohort Study of CARTaGENE.

Background: Although blood pressure (BP) control is critical to prevent cardiovascular diseases, hypertension control rates in Canada are in decline. Objective: To assess this issue, we sought to evaluate the differences in antihypertensive medication prescription profiles in the province of Quebec between 2009 and 2021. Design: This is a retrospective cohort study. Setting: We used data from the CARTaGENE population-based cohort linked to administrative health databases. Patients: Participants with any drug claim in the 6 months prior to the end of follow-up were included. Measurements: Guideline-recommended antihypertensive drug prescription profiles were assessed at the time of enrollment (2009-2010) and end of follow-up (March 2021). Methods: Prescriptions practices from the 2 time periods were compared using Pearson's chi-square tests. A sensitivity analysis was performed by excluding participants in which antihypertensive drugs may not have been prescribed solely to treat hypertension (presence of atrial fibrillation/flutter, ischemic heart disease, heart failure, chronic kidney disease, or migraines documented prior to or during follow-up). Results: Of 8447 participants included in the study, 31.4% and 51.3% filled prescriptions for antihypertensive drugs at the beginning and end of follow-up. In both study periods, guideline-recommended monotherapy was applied in most participants with hypertension (77.9% vs 79.5%, P = .3), whereas optimal 2 and 3-drug combinations were used less frequently (62.0% vs 61.4%, P = .77, 51.9% vs 46.7%, P = .066, respectively). Only the use of long-acting thiazide-like diuretics (9.5% vs 27.7%, P < .001) and spironolactone as a fourth-line agent (8.3% vs 15.9%, P = .054) increased with time but nonetheless remained infrequent. Results were similar in the sensitivity analysis. Limitations: Specific indication of the prescribed antihypertensive medications and follow-up BP data was not available. Conclusions: Application of hypertension guidelines for the choice of antihypertensive drugs remains suboptimal, highlighting the need for education initiatives. This may be an important step to raise BP control rates in Canada.

Contexte: Bien que le contrôle de la pression artérielle (PA) soit essentiel pour prévenir les maladies cardiovasculaires, les taux de maitrise de l'hypertension artérielle sont en déclin au Canada. Objectifs: Pour traiter cette problématique, nous avons cherché à évaluer les différences dans les profils de prescription de médicaments antihypertenseurs dans la province de Québec entre 2009 et 2021. Conception: Étude de cohorte rétrospective. Cadre: Nous avons utilisé les données de la cohorte populationnelle CARTaGENE reliées aux bases de données administratives en santé. Sujets: Ont été inclus les participants qui ont présenté une demande de remboursement de médicament dans les six mois précédant la fin du suivi. Mesures: Les profils de prescription de médicaments antihypertenseurs recommandés dans les lignes directrices ont été évalués au moment de l'inclusion (2009-2010) et à la fin du suivi (mars 2021). Méthodologie: Les profils de prescription des deux périodes ont été comparés à l'aide des tests Chi-Square de Pearson. Une analyse de sensibilité a été réalisée en excluant les participants pour lesquels les antihypertenseurs n'avaient possiblement pas été prescrits uniquement pour traiter l'hypertension (présence de fibrillation auriculaire, cardiopathie ischémique, insuffisance cardiaque, insuffisance rénale chronique ou migraines documentées avant ou pendant le suivi). Résultats: Des 8 447 participants inclus dans l'étude, 31,4 % avait rempli des prescriptions de médicaments antihypertenseurs au début du suivi et 51,3 % à la fin du suivi. Dans les deux périodes à l'étude, la monothérapie recommandée par les directives a été appliquée chez la plupart des participants avec hypertension artérielle (77,9 % c. 79,5 %; P = 0,3), tandis que les combinaisons optimales de deux médicaments (62,0 % c. 61,4 %; P = 0,77) et de trois médicaments (51,9 % c. 46,7 % P = 0,066) ont été utilisées moins fréquemment. Seules les utilisations de diurétiques thiazidiques à action prolongée (9,5 % c. 27,7 %; P < 0,001) et de spironolactone en quatrième intention (8,3 % c. 15,9 %; P = 0,054) ont augmenté avec le temps, mais sont demeurées néanmoins peu fréquentes. Les résultats étaient similaires dans l'analyse de sensibilité. Limites: L'indication précise pour la prescription de médicaments antihypertenseurs et les données de suivi sur la pression artérielle n'étaient pas disponibles. Conclusion: L'application des lignes directrices sur l'hypertension artérielle pour le choix des médicaments antihypertenseurs reste sous-optimale, ce qui souligne un besoin pour des initiatives en matière d'éducation. Cela pourrait constituer une étape importante d'une stratégie visant l'augmentation des taux de contrôle de la PA au Canada.

RNA-based regulation in bacteria-phage interactions.

Interactions of bacteria with their viruses named bacteriophages or phages shape the bacterial genome evolution and contribute to the diversity of phages. RNAs have emerged as key components of several anti-phage defense systems in bacteria including CRISPR-Cas, toxin-antitoxin and abortive infection. Frequent association with mobile genetic elements and interplay between different anti-phage defense systems are largely discussed. Newly discovered defense systems such as retrons and CBASS include RNA components. RNAs also perform their well-recognized regulatory roles in crossroad of phage-bacteria regulatory networks. Both regulatory and defensive function can be sometimes attributed to the same RNA molecules including CRISPR RNAs. This review presents the recent advances on the role of RNAs in the bacteria-phage interactions with a particular focus on clostridial species including an important human pathogen, Clostridioides difficile.

Chronically activated microglia in ALS gradually lose their immune functions and develop unconventional proteome.

Neuroinflammation and chronic activation of microglial cells are the prominent features of amyotrophic lateral sclerosis (ALS) pathology. While alterations in the mRNA profile of diseased microglia have been well documented, the actual microglia proteome remains poorly characterized. Here we performed a functional characterization together with proteome analyses of microglial cells at different stages of disease in the SOD1-G93A model of ALS. Functional analyses of microglia derived from the lumbar spinal cord of symptomatic mice revealed: (i) remarkably high mitotic index (close to 100% cells are Ki67+) (ii) significant decrease in phagocytic capacity when compared to age-matched control microglia, and (iii) diminished response to innate immune challenges in vitro and in vivo. Proteome analysis revealed a development of two distinct molecular signatures at early and advanced stages of disease. While at early stages of disease, we identified several proteins implicated in microglia immune functions such as GPNMB, HMBOX1, at advanced stages of disease microglia signature at protein level was characterized with a robust upregulation of several unconventional proteins including rootletin, major vaults proteins and STK38. Upregulation of GPNMB and rootletin has been also found in the spinal cord samples of sporadic ALS. Remarkably, the top biological functions of microglia, in particular in the advanced disease, were not related to immunity/immune response, but were highly enriched in terms linked to RNA metabolism. Together, our results suggest that, over the course of disease, chronically activated microglia develop unconventional protein signatures and gradually lose their immune identity ultimately turning into functionally inefficient immune cells.

Substitution of dietary monounsaturated fatty acids from olive oil for saturated fatty acids from lard increases low-density lipoprotein apolipoprotein B-100 fractional catabolic rate in subjects with dyslipidemia associated with insulin resistance: a randomized controlled trial.

BACKGROUND: The substitution of monounsaturated acids (MUFAs) for saturated fatty acids (SFAs) is recommended for cardiovascular disease prevention but its impact on lipoprotein metabolism in subjects with dyslipidemia associated with insulin resistance (IR) remains largely unknown. OBJECTIVES: This study aimed to evaluate the impact of substituting MUFAs for SFAs on the in vivo kinetics of apolipoprotein (apo)B-containing lipoproteins and on the plasma lipidomic profile in adults with IR-induced dyslipidemia. METHODS: Males and females with dyslipidemia associated with IR (n = 18) were recruited for this crossover double-blind randomized controlled trial. Subjects consumed, in random order, a diet rich in SFAs (SFAs: 13.4%E; MUFAs: 14.4%E) and a diet rich in MUFAs (SFAs: 7.1%E; MUFAs: 20.7%E) in fully controlled feeding conditions for periods of 4 wk each, separated by a 4-wk washout. At the end of each diet, fasting plasma samples were taken together with measurements of the in vivo kinetics of apoB-containing lipoproteins. RESULTS: Substituting MUFAs for SFAs had no impact on triglyceride-rich lipoprotein apoB-48 fractional catabolic rate (FCR) (Δ = -8.9%, P = 0.4) and production rate (Δ = 0.0%, P = 0.9), although it decreased very low-density lipoprotein apoB-100 pool size (PS) (Δ = -22.5%; P = 0.01). This substitution also reduced low-density lipoprotein cholesterol (LDL-C) (Δ = -7.0%; P = 0.01), non-high-density lipoprotein cholesterol (Δ = -2.5%; P = 0.04), and LDL apoB-100 PS (Δ = -6.0%; P = 0.05). These differences were partially attributed to an increase in LDL apoB-100 FCR (Δ = +1.6%; P = 0.05). The MUFA diet showed reduced sphingolipid concentrations and elevated glycerophospholipid levels compared with the SFA diet. CONCLUSIONS: This study demonstrated that substituting dietary MUFAs for SFAs decreases LDL-C levels and LDL PS by increasing LDL apoB-100 FCR and results in an overall improved plasma lipidomic profile in individuals with IR-induced lipidemia. TRIAL REGISTRATION: This trial was registered as clinicaltrials.gov as NCT03872349.

Optimization of a lipid nanoparticle-based protocol for RNA transfection into primary mononuclear phagocytes.

The effective delivery of synthetic RNA into mononuclear phagocytes is a prerequisite for experimental research and therapeutic development. However, traditional methods are highly ineffective and toxic for these cells. Here, we aimed to optimize a transfection protocol for primary bone marrow-derived phagocytes, specifically dendritic cells and macrophages, using lipid nanoparticles generated by microfluidics. Our results show that a lipid mixture similar to that used in Moderna's COVID-19 messenger RNA vaccine outperforms the others tested. Improved messenger RNA transfection can be achieved by replacing uridine with methylpseudouridine but not methoxyuridine, which interferes with transfection. The addition of diphenyleneiodonium or apocynin can enhance transfection in a cell type-dependent manner without adverse effects, while apolipoprotein E provides no added value. These optimized transfection conditions can also be used for microRNA agonists and antagonists. In sum, this study offers a straightforward, highly efficient, reproducible, and nontoxic protocol to deliver RNA into different primary mononuclear phagocytes in culture.

Individual versus integration of multiple components of central blood pressure and aortic stiffness in predicting cardiovascular mortality in end-stage renal diseases.

Aortic stiffness, measured by carotid-femoral pulse wave velocity (PWV), is a predictor of cardiovascular (CV) mortality in patients with end-stage renal disease (ESRD). Aortic stiffness increases aortic systolic and pulse pressures (cSBP, cPP) and augmentation index adjusted for a heart rate of 75 beats per minute (AIx@75). In this study, we examined if the integration of multiple components of central blood pressure and aortic stiffness (ICPS) into risk score categories could improve CV mortality prediction in ESRD. In a prospective cohort of 311 patients with ESRD on dialysis who underwent vascular assessment at baseline, 118 CV deaths occurred after a median follow-up of 3.1 years. The relationship between hemodynamic parameters and CV mortality was analyzed through Kaplan-Meier and Cox survival analysis. ICPS risk score from 0 to 5 points were calculated from points given to tertiles, and were regrouped into three risk categories (Average, High, Very-High). A strong association was found between the ICPS risk categories and CV mortality (High risk HR = 2.20, 95% CI: 1.05-4.62, P = 0.036); Very-High risk (HR = 4.44, 95% CI: 2.21-8.92, P < 0.001) as compared to the Average risk group. The Very-High risk category remained associated with CV mortality (HR = 3.55, 95% CI: 1.37-9.21, P = 0.009) after adjustment for traditional CV risk factors as compared to the Average risk group. While higher C-statistics value of ICPS categories (C: 0.627, 95% CI: 0.578-0.676, P = 0.001) was not statistically superior to PWV, cPP or AIx@75, the use of ICPS categories resulted in a continuous net reclassification index of 0.56 (95% CI: 0.07-0.99). In conclusion, integration of multiple components of central blood pressure and aortic stiffness may potentially be useful for better prediction of CV mortality in this cohort.

Nickel-Catalyzed Reductive Arylation of Redox Active Esters for the Synthesis of α-Aryl Nitriles: Investigation of a Chlorosilane Additive.

A nickel-catalyzed reductive cross-coupling of redox active N-hydroxyphthalimide (NHP) esters and iodoarenes for the synthesis of α-aryl nitriles is described. The NHP ester substrate is derived from cyanoacetic acid, which allows for a modular synthesis of substituted α-aryl nitriles, an important scaffold in the pharmaceutical sciences. The reaction exhibits a broad scope, and many functional groups are compatible under the reaction conditions, including complex highly functionalized medicinal agents. Mechanistic studies reveal that reduction and decarboxylation of the NHP ester to the reactive radical intermediate are accomplished by a combination of a chlorosilane additive and Zn dust. We demonstrate that stoichiometric chlorosilane is essential for product formation and that chlorosilane plays a role beyond activation of the metal reductant.

Outcomes of Integrated Home Dialysis Care: Results From the Canadian Organ Replacement Register.

RATIONALE & OBJECTIVE: The integrated home dialysis model proposes the initiation of kidney replacement therapy (KRT) with peritoneal dialysis (PD) and a timely transition to home hemodialysis (HHD) after PD ends. We compared the outcomes of patients transitioning from PD to HHD with those initiating KRT with HHD. STUDY DESIGN: Observational analysis of the Canadian Organ Replacement Register (CORR). SETTINGS & PARTICIPANTS: All patients who initiated PD or HHD within the first 90 days of KRT between 2005 and 2018. EXPOSURE: Patients transitioning from PD to HHD (PD+HHD group) versus patients initiating KRT with HHD (HHD group). OUTCOME: (1) A composite of all-cause mortality and modality transfer (to in-center hemodialysis or PD for 90 days) and (2) all hospitalizations (considered as recurrent events). ANALYTICAL APPROACH: A propensity score analysis for which PD+HHD patients were matched 1:1 to (1) incident HHD patients ("incident-match" analysis) or (2) HHD patients with a KRT vintage at least equivalent to the vintage of PD+HHD patients at the transition time ("vintage-matched" analysis). Cause-specific hazards models (composite outcome) and shared frailty models (hospitalization) were used to compare groups. RESULTS: Among 63,327 individuals in the CORR, 163 PD+HHD patients (median of 1.9 years in PD) and 711 HHD patients were identified. In the incident-match analysis, compared to the HHD patients, the PD+HHD group had a similar risk of the composite outcome (HR, 0.88 [95% CI, 0.58-1.32]) and hospitalizations (HR, 1.04 [95% CI, 0.76-1.41]). In the vintage-match analysis, PD+HHD patients had a lower hazard for the composite outcome (HR, 0.61 [95% CI, 0.40-0.94]) but a similar hospitalization risk (HR, 0.85 [95% CI, 0.59-1.24]). LIMITATIONS: Risk of survivor bias in the PD+HHD cohort and residual confounding. CONCLUSIONS: Controlling for KRT vintage, the patients transitioning from PD to HHD had better clinical outcomes than the incident HHD patients. These data support the use of integrated home dialysis for patients initiating home-based KRT. PLAIN-LANGUAGE SUMMARY: The integrated home dialysis model proposes the initiation of dialysis with peritoneal dialysis (PD) and subsequent transition to home hemodialysis (HHD) once PD is no longer feasible. It allows patients to benefit from initial lifestyle advantages of PD and to continue home-based treatments after its termination. However, some patients may prefer to initiate dialysis with HHD from the outset. In this study, we compared the long-term clinical outcomes of both approaches using a large Canadian dialysis register. We found that both options led to a similar risk of hospitalization. In contrast, the PD-to-HHD model led to improved survival when controlling for the duration of kidney failure.

Novel high-oleic oil consumption for cardiometabolic health: a narrative review.

Several cardiometabolic disorders are risk factors for cardiovascular diseases (CVDs), and prevention is imperative in reducing the burden of these diseases on the healthcare system. Although novel high-oleic acid oils (HOOs) are now commonly used for high-temperature frying in both foodservice and the manufacture of processed foods, there are still limited data regarding their effects on CVD risk. This narrative review aims to clarify these effects by comparing HOOs with saturated fatty acid (SFA)-rich and polyunsaturated fatty acid (PUFA)-rich oils, first regarding their physicochemical properties and then concerning their effects on CVD risk factors using recent randomized controlled trials (RCTs). Overall, although HOOs are more stable than PUFA-rich oils, they do not have the same high-temperature stability as SFA-rich oils. RCTs demonstrate that HOO consumption improves the plasma lipid profile compared with SFA-rich oils while showing similar effects to those of PUFA-rich oils on CVD risk factors. Finally, the current literature lacks information on the actual consumption of HOOs, their long-term effects on cardiometabolic health, and the impact of prolonged heating of these oils on CVD risk factors. In sum, the short-term intake of HOOs may be beneficial for cardiometabolic health; however, more research is needed.

Towards real-time active imaging of greenhouse gases using tunable mid-infrared all-fiber lasers.

We report a tunable all-fiber laser emitting a maximum output power of 2.55 W around 3240 nm. The fiber laser cavity based on a fluoride fiber doped with dysprosium ions yields an efficiency of 42% according to the in-band launched pump power at 2825 nm. Due to a custom piezoelectric fiber Bragg grating (FBG) package, mechanical strains applied to the narrowband FBG used as the input cavity coupler allowed for fast tuning of the emission wavelength over a spectral range of 1.5 nm. This laser was deployed in the field in northern Québec (Canada) to assess its performances for remote sensing of methane in the presence of a significant amount of water vapor, i.e., over a hydroelectric reservoir. The preliminary results acquired during this field campaign confirm the great potential of the proposed approach for the development of a real-time active imaging system of greenhouse gases.

The long and sinuous road to phage-based therapy of Clostridioides difficile infections.

With the antibiotic crisis and the rise in antimicrobial resistance worldwide, new therapeutic alternatives are urgently needed. Phage therapy represents one of the most promising alternatives but for some pathogens, such as Clostridioides difficile, important challenges are being faced. The perspective of phage therapy to treat C. difficile infections is complicated by the fact that no strictly lytic phages have been identified so far, and current temperate phages generally have a narrow host range. C. difficile also harbors multiple antiphage mechanisms, and the bacterial genome is often a host of one or multiple prophages that can interfere with lytic phage infection. Nevertheless, due to recent advances in phage host receptor recognition and improvements in genetic tools to manipulate phage genomes, it is now conceivable to genetically engineer C. difficile phages to make them suitable for phage therapy. Other phage-based alternatives such as phage endolysins and phage tail-like bacteriocins (avidocins) are also being investigated but these approaches also have their own limitations and challenges. Last but not least, C. difficile produces spores that are resistant to phage attacks and all current antibiotics, and this complicates therapeutic interventions. This mini-review gives a brief historical overview of phage work that has been carried out in C. difficile, presents recent advances in the field, and addresses the most important challenges that are being faced, with potential solutions.

Risk of repeated drainage in pediatric septic arthritis: patient or method?

How drainage of septic arthritis should be performed remains controversial. The aim of the present study was to compare arthrocentesis (Ac) using double intra-articular needle lavage to arthrotomy (At) as first-line drainage treatment for pediatric hip and knee septic arthritis. The secondary objective was to identify risk factors of second articular drainage. A retrospective review of medical records of children with knee and hip septic arthritis was conducted. Inclusion criteria were: children treated for septic arthritis between 2014 and 2020 with a positive culture of joint fluid. Clinical, biological, radiographical and ultrasound data were recorded at presentation and during follow-up. Patients were divided into 2 groups according to the type of drainage performed: Ac or At. 25 hips and 44 knees were included, 42 treated by Ac (15 hips, 27 knees) and 27 by At (10 hips, 17 knees). There is no significant difference between Ac and At regarding the need for repeated drainage and Ac nor At was reported as risk factor for repeated drainage. The presence of associated musculoskeletal infection (MSI) was a significant risk factor of repeated drainage [odds ratio = 11.8; 95% confidence interval = 1.2-114.2; P < 0.001]. Significantly more associated MSI (P < 0.001), level I virulence germs (P < 0.001) and positive blood culture (<0.001) were found in patients who underwent repeated drainage. There was no significant difference between Ac and At regarding rate of repeated drainage. The risk factors for repeated drainage were: associated with MSI, virulent germs and positive blood culture.

Cross-National Generalizability of WISC-V and CHC Broad Ability Constructs across France, Spain, and the US.

The Cattell-Horn-Carroll (CHC) model is based on psychometric cognitive ability research and is the most empirically supported model of cognitive ability constructs. This study is one in a series of cross-national comparisons investigating the equivalence and generalizability of psychological constructs which align with the CHC model. Previous research exploring the cross-cultural generalizability of cognitive ability measures concluded that the factor analytic models of cognitive abilities generalize across cultures and are compatible with well-established CHC constructs. The equivalence of the psychological constructs, as measured by the Wechsler Intelligence Scale for Children-Fifth Edition (WISC-V), has been established across English-speaking samples. However, few studies have explored the equivalence of psychological constructs across non-English speaking, nationally representative samples. This study explored the equivalence of the WISC-V five-factor model across standardization samples from France, Spain, and the US. The five-factor scoring model demonstrated excellent fit across the three samples independently. Factorial invariance was investigated and the results demonstrated strict factorial invariance across France, Spain, and the US. The results provide further support for the generalizability of CHC constructs across Western cultural populations that speak different languages and support the continued use and development of the CHC model as a common nomenclature and blueprint for cognitive ability researchers and test developers. Suggestions for future research on the CHC model of intelligence are discussed.

Impact of Successive Office Blood Pressure Measurements During a Single Visit on Cardiovascular Risk Prediction: Analysis of CARTaGENE.

BACKGROUND: Multiple office blood pressure (BP) readings correlate more closely with ambulatory BP than single readings. Whether they are associated with long-term outcomes and improve cardiovascular risk prediction is unknown. Our objective was to assess the long-term impact of multiple office BP readings. METHODS: We used data from CARTaGENE, a population-based survey comprising individuals aged 40 to 70 years. Three BP readings (BP1, BP2, and BP3) at 2-minute intervals were obtained using a semiautomated device. They were averaged to generate BP1-2, BP2-3, and BP1-2-3 for systolic BP (SBP) and diastolic BP. Cardiovascular events (major adverse cardiovascular event [MACE]: cardiovascular death, stroke, and myocardial infarction) during a 10-year follow-up were recorded. Associations with MACE were obtained using adjusted Cox models. Predictive performance was assessed with 10-year atherosclerotic cardiovascular disease scores and their associated C statistics. RESULTS: In the 17 966 eligible individuals, 2378 experienced a MACE during follow-up. Crude SBP values ranged from 122.5 to 126.5 mm Hg. SBP3 had the strongest association with MACE incidence (hazard ratio, 1.10 [1.05-1.15] per SD) and SBP1 the weakest (hazard ratio, 1.06 [1.01-1.10]). All models including SBP1 (SBP1, SBP1-2, and SBP1-2-3) were underperformed. At a given SBP value, the excess MACE risk conferred by SBP3 was 2× greater than SBP1. In atherosclerotic cardiovascular disease scores, SBP3 yielded the highest C statistic, significantly higher than most other SBP measures. In contrast to SBP, all diastolic BP readings yielded similar results. CONCLUSIONS: Cardiovascular risk prediction is improved by successive office SBP values, especially when the first reading is discarded. These findings reinforce the necessity of using multiple office BP readings.

Translation and validation of the French version of the adolescent idiopathic scoliosis Truncal Anterior Asymmetry Scoliosis Questionnaire (TAASQ).

PURPOSE: Scoliosis is an abnormality which causes anterior trunk asymmetry. The Truncal Anterior Asymmetry Scoliosis Questionnaire-adolescent idiopathic scoliosis (AIS) (TAASQ) measures the feeling about anterior trunk appearance in girls with AIS. It comprises 14 questions which evaluate frontal asymmetry of breasts, shoulders, and waist as well as behavioral attitude. There is currently no validated questionnaire in French to evaluate truncal asymmetry in AIS girls. The aim of this study was to translate and validate the French version of the TAASQ (TAASQ-VF). METHODS: The study reports the translation and transcultural adaptation of the TAASQ into French. The translation was tested on 20 patients to verify comprehension and modify if necessary. To assess the reliability of the translated version, each domain as well as the total measure were tested for internal consistency. Convergent validity was evaluated on 63 patients and test-retest on a sample of 15. RESULTS: The translation and content validation process resulted in a French version of the TAASQ. Internal consistency was over 0.80 for each item, over 0.70 for each domain, and 0.88 for the total scores. SAQ were used to perform convergent validity with TAASQ-VF. The TAASQ-FV correlated well with many of the SAQ domains (p < 0.05) and every TAASQ-FV domain correlated with at least one SAQ domain (p < 0.05). Test-retest reliability for the total score and for each domain was good. CONCLUSION: The translation and cross-cultural adaptation of the TAASQ questionnaire provides a French version that can measure the feeling about frontal appearance in girls with idiopathic scoliosis.

Virulence and genomic diversity among clinical isolates of ST1 (BI/NAP1/027) Clostridioides difficile.

Clostridioides difficile produces toxins that damage the colonic epithelium, causing colitis. Variation in disease severity is poorly understood and has been attributed to host factors and virulence differences between C. difficile strains. We test 23 epidemic ST1 C. difficile clinical isolates for their virulence in mice. All isolates encode a complete Tcd pathogenicity locus and achieve similar colonization densities. However, disease severity varies from lethal to avirulent infections. Genomic analysis of avirulent isolates reveals a 69-bp deletion in the cdtR gene, which encodes a response regulator for binary toxin expression. Deleting the 69-bp sequence in virulent R20291 strain renders it avirulent in mice with reduced toxin gene transcription. Our study demonstrates that a natural deletion within cdtR attenuates virulence in the epidemic ST1 C. difficile isolates without reducing colonization and persistence. Distinguishing strains on the basis of cdtR may enhance the specificity of diagnostic tests for C. difficile colitis.