BACKGROUND:Patients who receive transplants following kidney failure due to glomerulonephritis (GN-KTx) constitute a significant portion of recipients and may face unique challenges post transplantation, related to the risk of GN recurrence and a higher global burden of immunosuppression. METHODS:We analyzed patient and graft outcomes, including the risk of graft loss in relation to recurrence in GN-KTx, compared to patients transplanted for other causes, using data from the prospective nationwide Swiss Transplant Cohort Study. RESULTS:Among 2631 included patients, 701 were GN-KTx, with IgA nephropathy being the most common GN subtype. GN-KTx recipients were younger and more likely to receive living donor organs. During a mean follow-up period of 5.3 years (IQR: 2.3-8.2), the 5-year cumulative incidence of graft loss was similar across groups, with GN-KTx at 6%. Notably, GN-KTx had a similar incidence of acute rejection as other groups. Recurrence occurred in 16% of GN-KTx within a mean time of 1.7 years (IQR: 0.28-2). Patients with recurrence faced a threefold higher risk of graft loss. Furthermore, disease recurrence was associated with a twofold higher risk of acute rejection compared to non-recurrent GN-KTx. Interestingly, regarding cancer risks, GN-KTx patients had the lowest incidence of skin cancer and no higher risk of non-skin cancers, despite greater exposure to immunosuppression compared to other KTx. CONCLUSIONS:These real-life setting contemporary multicenter data highlight the importance of post-transplant monitoring for GN recurrence, given the strong association with poor graft outcomes and higher rejection rates. This is important in the context of current development of targeted therapies for glomerulonephritis in native kidneys that could be transposed to transplanted kidneys.

Background: Patients who receive transplants following kidney failure due to glomerulonephritis (GN-KTx) constitute a significant portion of recipients and may face unique challenges post transplantation, related to the risk of GN recurrence and a higher global burden of immunosuppression. Methods: We analyzed patient and graft outcomes, including the risk of graft loss in relation to recurrence in GN-KTx, compared to patients transplanted for other causes, using data from the prospective nationwide Swiss Transplant Cohort Study. Results: Among 2631 included patients, 701 were GN-KTx, with IgA nephropathy being the most common GN subtype. GN-KTx recipients were younger and more likely to receive living donor organs. During a mean follow-up period of 5.3 years (IQR: 2.3-8.2), the 5-year cumulative incidence of graft loss was similar across groups, with GN-KTx at 6%. Notably, GN-KTx had a similar incidence of acute rejection as other groups. Recurrence occurred in 16% of GN-KTx within a mean time of 1.7 years (IQR: 0.28-2). Patients with recurrence faced a threefold higher risk of graft loss. Furthermore, disease recurrence was associated with a twofold higher risk of acute rejection compared to non-recurrent GN-KTx. Interestingly, regarding cancer risks, GN-KTx patients had the lowest incidence of skin cancer and no higher risk of non-skin cancers, despite greater exposure to immunosuppression compared to other KTx. Conclusions: These real-life setting contemporary multicenter data highlight the importance of post-transplant monitoring for GN recurrence, given the strong association with poor graft outcomes and higher rejection rates. This is important in the context of current development of targeted therapies for glomerulonephritis in native kidneys that could be transposed to transplanted kidneys.

Background: Nurse-initiated pain protocols (NIPPs) at emergency department (ED) triage remain underused. This study investigated factors associated with patient refusal and nurse use of NIPP, accounting for triage operational context. Methods: This retrospective observational study combined prospectively collected nurse characteristics with retrospective data on NIPP use over 15 months in a tertiary university hospital ED. Outcomes included rates of NIPP refusal and use, documented reasons for refusal, and associations with patient characteristics, nurse characteristics, crowding, and operational pressure. Results: Sixty-three triage nurses managed 16,137 adult patients; 6.2% refused the NIPP. Among consenting patients, NIPP was used in one-third of encounters. Multi-level logistic regression revealed significant variation between nurses in both refusal and use. Refusal was more likely in patients with lower acuity and among nurses trained in Europe or concerned about prescribing responsibility, but less frequent with severe pain or longer triage duration. NIPP use was more frequent with lower acuity, higher pain intensity, longer triage duration, crowding, and among nurses with European training, but decreased in older patients and those arriving by ambulance. Conclusions: NIPP refusal and use at triage were both low, with marked variability between nurses. Patient characteristics and triage operational factors were most strongly associated with outcomes, while nurse-related factors contributed less. These findings support prospective implementation studies to clarify drivers of practice variation and optimize analgesia delivery at triage.

Introduction. Sputum is the most used sample type to monitor the lower respiratory tract microbiota in cystic fibrosis (CF), but young patients often cannot expectorate.Hypothesis. We hypothesized that throat swabs could reflect lower airway colonization and assessed the concordance of bacterial community composition between paired sputum and throat swab samples from children with CF.Aim. We aimed to compare bacterial community diversity and composition between sputum and throat swabs in the full cohort and in patients with paired samples from the same visit.Methodology. The prospective longitudinal multicentre MUCOVIB cohort included 379 samples from 61 CF children. Using V3-V4 16S rRNA amplicon metagenomics, we compared bacterial community diversity and composition between sputum and throat swabs in the full cohort and in 11 patients with paired samples from the same visit.Results. Sputum and throat swabs exhibited similar bacterial diversity, regardless of the exacerbation status, and presented a substantial agreement for detecting pathogens (Cohen's kappa: 0.6). Differences in bacterial abundance were observed (P=0.001), but not presence/absence (P=0.098). Community typing revealed three distinct community types, with 86% of paired samples falling into the same cluster, highlighting the homogeneity between sputum and throat swab microbiota. Network analysis demonstrated slight, non-random similarities in microbial interactions between sample types (adjusted Rand index=0.08 and 0.10). The average beta-diversity distances between samples collected from the same visit were shorter (0.505±0.056 95% confidence interval), compared with sputum (0.695±0.017) or throat swab (0.704±0.045) from the same patient collected during different visits.Conclusion. Throat swabs can provide representative information on lower respiratory microbiota. Clinicians should collect throat swabs rather than relying on sputum samples from previous visits to guide antibiotic prescriptions in CF children unable to expectorate.

Most statistical methods that have been developed to assess the agreement between two quantitative measurement methods have (implicitly) relied on the assumption of a constant "individual" latent trait. This might be inappropriate when the "individual" is not an object but a person. Therefore, the goal of this study was to extend the standard measurement error model to cope with this limit. Four different settings were investigated: first, where the true individual latent trait was constant; second, where it was variable but without exhibiting a time trend; third, where it followed a linear time trend; and fourth, where it exhibited an approximate linear time trend. Two competing methods to estimate the parameters of the general measurement error model were assessed: the GLS estimator of Sprent and the two-stage method of Taffé. It was found that the latter generally performed better than the former to estimate the bias. In addition, it can be used when there is only a single measurement per individual by one of the two measurement methods, which is not the case with the former method.

Background:A total of 24 h ambulatory blood pressure monitoring (ABPM) offers enhanced accuracy for evaluating true blood pressure and associated risks compared to office blood pressure (OBP). However, conflicting results have been reported in studies comparing the two settings, largely due to the statistical bias introduced by the mean difference calculation using the Bland and Altman method, especially if the inherent circadian variation of blood pressure is not considered. This study aimed to assess the difference between OBP and ABPM using a refined statistical approach while accounting for circadian variations at different blood pressure levels. Methods:Multilevel/mixed-effects harmonic regression models were employed to estimate mean 24 h systolic and diastolic blood pressure profiles. The bias plot method, with ABPM as the reference, was used to calculate the OBP- daytime ABPM difference. Results:A total of 647 participants were included with a median of 63 measurements per individual, with most OBP measurements conducted between 8 a.m. and 10 a.m. Analysis showed individual average systolic OBP-ABPM differences ranging from +10 to -30 mmHg and diastolic differences ranging from +20 to -60 mmHg. As ABPM values increase, the patients tend to exhibit a masked effect. Normotensive individuals on ABPM exhibited a white coat effect phenotype, with systolic OBP-ABPM differences ranging from +6 to +9 mmHg. Conversely, hypertensive patients displayed a modest white coat effect for those at the lower hypertension limit and a pronounced masked effect for those at higher hypertension levels. The reduced circadian blood pressure variation observed in hypertensive patients, characterized by a nadir shift to later in the day, contributed to this divergence. Conclusion:Differences between OBP and ABPM depend on mean ABPM blood pressure levels. OBP tends to overestimate in normotensive and underestimate in hypertensive patients. Differences in circadian variation between these groups contribute to the variance.

BACKGROUND AND AIMS:Accurately detecting carotid plaque characteristics is crucial for identifying high-risk patients due to risk of cerebrovascular events and complications during revascularizations. Diagnostic accuracy of individual and overall carotid plaque characteristics using computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US) compared to histology in patients with symptomatic/asymptomatic carotid plaques was aimed. METHODS:After prospective registration on PROSPERO (CRD42022329690), Medline Ovid, Embase, Cochrane Library, and Web of Science were searched without any limitations. QUADAS-2 tool was used to study quality assessment, GRADE framework to assess evidence certainty, and univariate/bivariate random-effect meta-analyses for data analysis. RESULTS:Of 5960 studies screened, 107 were identified, resulting in 253 diagnostic accuracy comparisons of 16 plaque characteristics (28 CT, 120 MRI, and 105 US). CT detected intraplaque hemorrhage (IPH) and lipid-rich necrotic core (LRNC) with good accuracy (86 % [95 %CI 67-95] and 84 % [72-91], respectively) and exhibited very high accuracy for ulceration (92 % [87-95]; 76 % on MRI and 75 % on US) and calcification (90 % [58-98] vs. 89 % [87-91] on MRI). MRI identified LRNC and IPH with good accuracy (86 % [81-89] and 86 % [84-88], respectively), and differentiated between acute/subacute/old IPH (accuracy >87 %). US accurately detected ruptured fibrous cap (85 % [77-91]), comparable to MRI (85 % [79-90]), but demonstrated lower performance for other characteristics. Finally, CT detected overall carotid morphology with 89 % accuracy, followed by MRI (86 %; p = 0.374 to CT), and significantly lower by US (78 %; p < 0.001). CONCLUSION:CT identified key plaque features, especially ulceration and calcification. MRI provided thorough plaque assessment by detecting all features and differentiating IPH age. For overall morphology, CT and MRI surpassed US accuracy.

Introduction Approximately 50% of patients with C3 glomerulopathy (C3G) and primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) reach kidney failure 10 years after diagnosis. Because these patients are generally young, the majority will be listed for kidney transplantation (KTx). However, reported outcomes in patients transplanted for C3G and IC-MPGN are heterogeneous and conflicting, because they are mainly based on retrospective monocentric studies. We thus aimed to provide detailed multicenter data on these patients, taking advantage of the ongoing nationwide Swiss Transplant Cohort Study (STCS). Methods We analyzed patient and graft outcomes, including the risk of graft loss in relation to recurrence of glomerulopathy. Results Forty-one (10 C3G and 31 IC-MPGN) transplanted recipients were included with a mean age at transplantation of 48 ± 16 years. Living donors provided 53% of the organs. During a mean follow-up of 4.7 years, 7 patients (4 C3G and 3 IC-MPGN) presented disease recurrence with a mean time to recurrence of 1.2 years. New-onset or rapidly increasing proteinuria was an early marker of recurrence, preceding significant decline in estimated glomerular filtration rate (eGFR). Following recurrence, 28% lost their graft, compared to 11% of patients without recurrence. Disease recurrence was the primary cause of graft loss in all patients. Finally, 14% of patients died during follow-up. Conclusion This study provides important insights into the epidemiology and outcome of patients with C3G and IC-MPGN and their grafts after KTx. The data also suggest that proteinuria may serve as an early biomarker of disease recurrence and should be considered in patient management as well as an endpoint in current clinical trials using novel complement modulators.

AIMS:There is increasing evidence that plaque instability in the extracranial carotid artery may lead to an increased stroke risk independently of the degree of stenosis. We aimed to determine diagnostic accuracy of vulnerable and stable plaque using noninvasive imaging modalities when compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis. METHODS AND RESULTS:Medline Ovid, Embase, Cochrane Library, and Web of Science were searched for diagnostic accuracy of noninvasive imaging modalities (CT, MRI, US) in the detection of 1) vulnerable/stable plaque, and 2) vulnerable/stable plaque characteristics, compared to histology. The quality of included studies was assessed by QUADAS-2 and univariate and bivariate random-effect meta-analyses were performed. We included 36 vulnerable and 5 stable plaque studies in the meta-analysis, and out of 211 plaque characteristics from remaining studies, we classified 169 as vulnerable and 42 as stable characteristics (28 CT, 120 MRI, 104 US characteristics). We found that MRI had high accuracy [90% (95% CI: 82-95%)] in the detection of vulnerable plaque, similar to CT [86% (95% CI: 76-92%); P > 0.05], whereas US showed less accuracy [80% (95% CI: 75-84%); P = 0.013]. CT showed high diagnostic accuracy in visualizing characteristics of vulnerable or stable plaques (89% and 90%) similar to MRI (86% and 89%; P > 0.05); however, US had lower accuracy (77%, P < 0.001 and 82%, P > 0.05). CONCLUSION:CT and MRI have a similar, high performance in detecting vulnerable carotid plaques, whereas US showed significantly less diagnostic accuracy. Moreover, MRI visualized all vulnerable plaque characteristics allowing for a better stroke risk assessment. REGISTRATION:PROSPERO ID CRD42022329690.

BackgroundSporadic lymphangioleiomyomatosis (S-LAM) is a rare low-grade neoplasm of young women characterized by multiple pulmonary cysts leading to progressive dyspnea and recurrent spontaneous pneumothorax (SP). The diagnosis of S-LAM may be delayed by several years. To reduce this delay, chest computed tomography (CT) screening has been proposed to uncover cystic lung disease in women presenting with SP. However, the probability to discover S-LAM in this population has not been determined precisely. The aim of this study was to calculate the probability of finding S-LAM in women presenting with (a) SP, and (b) apparent primary SP (PSP) as first manifestation of S-LAM.MethodsCalculations were made by applying the Bayes theorem to published epidemiological data on S-LAM, SP and PSP. Each term of the Bayes equation was determined by meta-analysis, and included: (1) the prevalence of S-LAM in the general female population, (2) the incidence rate of SP and PSP in the general female population, and (3) the incidence rate of SP and apparent PSP in women with S-LAM.ResultsThe prevalence of S-LAM in the general female population was 3.03 per million (95% confidence interval 2.48, 3.62). The incidence rate of SP in the general female population was 9.54 (8.15, 11.17) per 100,000 person-years (p-y). The incidence rate of SP in women with S-LAM was 0.13 (0.08, 0.20). By combining these data in the Bayes theorem, the probability of finding S-LAM in women presenting with SP was 0.0036 (0.0025, 0.0051). For PSP, the incidence rate in the general female population was 2.70 (1.95, 3.74) per 100,000 p-y. The incidence rate of apparent PSP in women with S-LAM was 0.041 (0.030, 0.055). With the Bayes theorem, the probability of finding S-LAM in women presenting with apparent PSP as first disease manifestation was 0.0030 (0.0020, 0.0046). The number of CT scans to perform in women to find one case of S-LAM was 279 for SP and 331 for PSP.ConclusionThe probability of discovering S-LAM at chest CT in women presenting with apparent PSP as first disease manifestation was low (0.3%). Recommending chest CT screening in this population should be reconsidered.

Abstract Excessive antibiotic use and antimicrobial resistance are major global public health threats. We developed ePOCT+, a digital Clinical Decision Support Algorithm in combination with C-reactive protein test, haemoglobin test, pulse oximeter and mentorship, to guide healthcare providers in managing acutely sick children under 15 years old. To evaluate the impact of ePOCT + compared to usual care, we conducted a cluster-randomized controlled trial in Tanzanian primary care facilities (NCT05144763). Over 11 months, 23 593 consultations were included in 20 ePOCT + health facilities, and 20 713 in 20 usual care facilities. Antibiotics were prescribed in 23.2% of consultations in ePOCT + facilities, and 70.1% in usual care facilities (adjusted difference, -46.4%, 95% confidence interval (CI) -57.6 to -35.2). Day 7 clinical failure in ePOCT + facilities was non-inferior to usual care facilities (adjusted relative risk 0.97, 95% CI 0.85 to 1.10). Using ePOCT + could help address the urgent problem of antimicrobial resistance by safely reducing antibiotic prescribing. *Shared second authorship; contributed equally. **Shared last authorship; contributed equally.

Excessive antibiotic use and antimicrobial resistance are major global public health threats. We developed ePOCT+, a digital clinical decision support algorithm in combination with C-reactive protein test, hemoglobin test, pulse oximeter and mentorship, to guide health-care providers in managing acutely sick children under 15 years old. To evaluate the impact of ePOCT+ compared to usual care, we conducted a cluster randomized controlled trial in Tanzanian primary care facilities. Over 11 months, 23,593 consultations were included from 20 ePOCT+ health facilities and 20,713 from 20 usual care facilities. The use of ePOCT+ in intervention facilities resulted in a reduction in the coprimary outcome of antibiotic prescription compared to usual care (23.2% versus 70.1%, adjusted difference −46.4%, 95% confidence interval (CI) −57.6 to −35.2). The coprimary outcome of day 7 clinical failure was noninferior in ePOCT+ facilities compared to usual care facilities (adjusted relative risk 0.97, 95% CI 0.85 to 1.10). There was no difference in the secondary safety outcomes of death and nonreferred secondary hospitalizations by day 7. Using ePOCT+ could help address the urgent problem of antimicrobial resistance by safely reducing antibiotic prescribing. Clinicaltrials.gov Identifier: NCT05144763

Study objective: We aimed to assess the analgesic and anxiolytic efficacy of distraction, a nonpharmacologic intervention provided by 3-dimensional (3D) virtual reality (VR) compared with that provided by 2-dimensional (2D) VR during minor emergency department (ED) procedures. Methods: This randomized controlled study conducted in the ED of a teaching hospital included patients aged more than or equal to 18 years undergoing minor procedures. The patients watched the same computer-generated VR world either in 3D in a head-mounted display (intervention) or in 2D on a laptop screen (control). Our main outcomes were pain and anxiety during the procedure, assessed on a 100-mm visual analog scale. Secondary outcomes included the impression of telepresence in the computer-generated world assessed using the Igroup Presence Questionnaire, and the prevalence and intensity of cybersickness measured on a 100-mm visual analog scale. Results: The final analysis included 117 patients. The differences in median procedural pain and anxiety levels between the 2D and 3D VR groups were not significant: -3 mm (95% confidence interval [CI] -14 to 8) and -4 mm (95% CI -15 to 3), respectively; the difference in telepresence was 2.0 point (95% CI 0 to 2.0), and the proportion difference of cybersickness was -4% (95% CI -22 to 14), with an intensity difference of -5 mm (95% CI -9 to 3). Conclusion: During minor procedures in adult patients in the ED, distraction by viewing a 3D virtual world in a head-mounted VR display did not result in lower average levels of procedural pain and anxiety than that by 2D viewing on a screen despite a higher sense of telepresence. There were no significant differences in the prevalence and intensity of cybersickness between the 2 groups.

Recently, a new statistical methodology to assess the bias and precision of a new measurement method, which circumvents the deficiencies of the Bland and Altman (1986, Lancet 327: 307–310) limits of agreement method, was developed by Taffé (2018, Statistical Methods in Medical Research 27: 1650–1660). Later, the methodology was extended to assess the agreement. In addition, to allow for inferences, simultaneous confidence bands around the bias, precision, and agreement lines were developed (Taffé, 2020, Statistical Methods in Medical Research 29: 778–796). The goal of this article is to introduce the extended biasplot command, which implements these latest developments, and to illustrate its use by applying it to simulated data included with the command. Note that the Taffé method assumes that there are several measurements by one of the two measurement methods and possibly as few as one measurement by the other for each individual. The repeated measurements need not come from the reference standard but from any of the two measurement methods. This is a great advantage because it may sometimes be more feasible to gather repeated measurements either with the reference standard or the new measurement method.

ABSTRACT Objective Research suggests that therapeutic communication could enhance patient comfort during medical procedures. Few studies have been conducted in clinical settings, with adequate blinding. Our hypothesis was that a positive message could lead to analgesia and anxiolysis, and that this effect would be enhanced by an empathetic interaction with the nurse performing the procedure, compared with an audio-taped message. This study aimed to modulate the contents and delivery vector of a message regarding peripheral intravenous catheter (PIC) placement in the emergency department (ED). Methods This study was a 2 + 2 randomized controlled trial registered on ClinicalTrials.gov (NCT03502655). A positive versus standard message was delivered through audio tape (double-blind) in the first phase (N = 131) and through the nurse placing the catheter (single-blind) in the second phase (N = 120). Results By design, low practitioner empathic behavior was observed in the first phase (median, 1 of 5 points). In the second phase, higher empathic behavior was observed in the positive than in the standard message (median, 2 versus 3, p < .001). Contrary to our hypothesis, the intervention did not affect pain or anxiety reports due to PIC placement in either phase (all p values > .2). Conclusions The positive communication intervention did not impact pain or anxiety reports after PIC. There might have been a floor effect, with low PIC pain ratings in a context of moderate pain due to the presenting condition. Hence, such a therapeutic communication intervention might not be sufficient to modulate a mild procedural pain in the ED.

In this study, we have further extended the methodology proposed, first, by Lin et al. (2002) and, later, extended by Stevens et al. (2017, 2018), on the coverage probability/probability of agreement, by relaxing the strong parametric assumptions regarding the distribution of the latent trait and developing inference methods allowing to compute both pointwise and simultaneous confidence bands. The methodology requires repeated measurements by at least one of the two measurement methods and accommodates heteroscedastic measurement errors. It performs often very well even when one has only one measurement by one of the two measurement methods and at least five repeated measurements from the other. It circumvents some of the deficiencies of the Bland & Altman limits of agreement method and provides a more direct assessment of the agreement level.

Background:Despite the growing burden of diabetes worldwide, evidence regarding the optimal models of care to improve the quality of diabetes care remains equivocal. This study aimed to identify profiles of patients with distinct ambulatory care use patterns and to examine the association of these profiles with the quality of diabetes care.Methods:We performed a cross-sectional study of the baseline data of 550 non-institutionalized adults included in a prospective, community-based, cohort study on diabetes care conducted in Switzerland. Clusters of participants with distinct patterns of ambulatory healthcare use were identified using discrete mixture models. To measure the quality of diabetes care, we used both processes of care indicators (eye and foot examination, microalbuminuria screening, blood cholesterol and glycated hemoglobin measurement [HbA1c], influenza immunization, blood pressure measurement, physical activity and diet advice) and outcome indicators (12-Item Short-Form Health Survey [SF-12], Audit of Diabetes-Dependent Quality of Life [ADDQoL], Patient Assessment of Chronic Illness Care [PACIC], Diabetes Self-Efficacy Scale, HbA1c value, and blood pressure <140/90 mmHg). For each profile of ambulatory healthcare use, we calculated adjusted probabilities of receiving processes of care and estimated adjusted outcomes of care using logistic and linear regression models, respectively.Results:Four profiles of ambulatory healthcare use were identified: participants with more visits to the general practitioner [GP] than to the diabetologist and receiving concomitant podiatry care ("GP & podiatrist", n=86); participants visiting almost exclusively their GP ("GP only", n=195); participants with a substantially higher use of all ambulatory services ("High users", n=96); and participants reporting more visits to the diabetologist and less visits to the GP than other profiles ("Diabetologist first", n=173). Whereas participants belonging to the "GP only" profile were less likely to report most processes related to the quality of diabetes care, outcomes of care were relatively comparable across all ambulatory healthcare use profiles.Conclusions:Slight differences in quality of diabetes care appear across the four ambulatory healthcare use profiles identified in this study. Overall, however, results suggest that room for improvement exists in all profiles, and further investigation is necessary to determine whether individual characteristics (like diabetes-related factors) and/or healthcare factors contribute to the differences observed between profiles.