RATIONALE:Patients with severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-related diffuse alveolar hemorrhage (DAH) face high mortality. In the PEXIVAS trial, plasma exchange (PLEX) did not reduce death or end-stage kidney disease, but only 9% had severe DAH. OBJECTIVES:This study aimed to assess whether PLEX lowers mortality in patients with severe DAH. METHODS:We emulated a target trial using retrospective data from a national multicenter cohort of patients with severe AAV-related DAH. The primary endpoint was 30-day mortality after intensive care unit (ICU) admission, analyzed using a Cox model adjusted for prespecified confounders. MEASUREMENTS AND MAIN RESULTS:We included 184 patients (median age 66 [53-75] years; 51% female; 51% with granulomatosis with polyangiitis; 53% MPO (Myeloperoxydase)-ANCA positive). Of these, 144 (78.3%) received PLEX, and 40 (21.7%) did not. Baseline characteristics were similar, except for more severe renal impairment (creatinine 357 vs 171 µmol/L, P = .01) and more frequent cyclophosphamide use (77% vs 55%, P = .01) in the PLEX group. Severity at ICU admission (median Simplified Acute Physiology Score II score: 42) and mechanical ventilation needs (54%) were comparable between groups. At 30 days, overall survival was 85%. No significant difference in mortality was observed between the PLEX and no-PLEX groups: 30-day survival was 85% (95% CI, 81-90) with PLEX vs 88% (95% CI, 77-96) without (hazard ratio, 1.23; 95% CI, 0.57-3.89). Secondary outcomes were also similar. CONCLUSIONS:In this emulated target trial, PLEX did not reduce 30-day mortality in patients with severe AAV-related DAH.
Patients with schizophrenia often experience substantial impairments in social functioning and activities of daily living (ADLs). Previous studies have highlighted links between sociodemographic and clinical factors and daily life functioning. However, routinely collected, non-scale-based clinical and sociodemographic characteristics have rarely been systematically evaluated as a standalone predictive framework. Understanding whether such variables alone can inform functional outcomes in schizophrenia may have important implications for public health. Using the French multicentric psychosocial rehabilitation database REHABase, we predicted five dimensions of the Social Autonomy Scale (a validated, clinician-administered questionnaire widely used in France): personal care, basic ADLs, financial autonomy, complex ADLs, and social and affective relationships. We used a SuperLearner ensemble machine learning method with a large set of routinely collected socio-demographic and basic clinical predictors descriptive of schizophrenia patients. Our sample comprised 948 participants. Averaged R2 on hold-out testing sets were higher for basic ADLs (mean R2: 0.35) than for social and affective relationships (0.16), financial autonomy (0.14), complex ADLs (0.13), and personal care (0.01). Factors associated with improved functioning included: being in a relationship, higher education, lower Clinical Global Impression scores, higher Global Assessment of Functioning scores, living in personal housing, being employed, mid-range illness duration, a history of suicide attempts and psychiatric comorbidities. Our findings indicate an association between socio-demographic and standard clinical variables routinely assessed in practice and outcomes in social functioning and ADLs. However, these variables account for only a limited proportion of the observed variance. This underscores the need for more specialized and precise assessments, e.g., based on cognitive abilities, to better understand and address patient functioning. We recommend targeted interventions focused on improving clinical symptoms, housing conditions, and supporting employment. Finally, clinicians should not assume that patients with seemingly protective factors, such as shorter illness duration, or absence of comorbidities, do not require further support.
Gut colonization by the Gram-negative bacillus Klebsiella pneumoniae is a significant risk factor for extra-intestinal infections. However, the mechanisms by which this opportunistic pathogen causes disseminated infections remain poorly understood. To investigate this phenomenon, 22 strain pairs of Klebsiella spp. were sequentially isolated from rectal swabs and blood samples of ICU patients. All strains adhered to intestinal epithelial cells in vitro, but failed to invade or disrupt epithelial barrier integrity. Few phenotypic differences between strains of the same pair were observed regarding their biofilm-forming capacities and ampicillin resistance. Whole genome sequencing of five pairs showed diverse sequence types, the presence of numerous antibiotics resistance genes but few virulence genes. Pairwise comparison of genomic sequences of blood and fecal isolates evidenced a few single nucleotide polymorphisms and small insertions-deletions, mostly affecting genes involved in biosynthesis of surface structures (such as capsules, pili). Most genetic changes were driven by horizontal gene transfer events, with the notable acquisition of a plasmid that enhanced bacterial fitness by eliminating competitors. In addition, some blood isolates had reduced the number of antibiotic resistance genes, underscoring the high plasticity of the Klebsiella resistome. Finally, one bloodstream isolate carried a mutS mutation, conferring a hypermutator phenotype that could increase evolvability despite the fitness burden. Together, these findings indicate that within-host genetic adaptations, rather than the acquisition of virulence traits, can enhance the colonization, competitiveness and ultimately the ability of K. pneumoniae to cause invasive infections.
BACKGROUND:The management of calcified coronary lesions remains challenging. Although several devices for advanced plaque modification are available, their relative efficacy is debated. AIMS:We aimed to compare intravascular lithotripsy (IVL)- and rotational atherectomy (RA)-based strategies for calcified plaque preparation during percutaneous coronary interventions (PCI). METHODS:This multicentre, prospective, randomised non-inferiority trial compared IVL with RA for plaque preparation in moderate-to-severe stable calcified coronary lesions. All interventions were guided by optical frequency domain imaging. A non-inferiority margin of 0.75 mm2 was prospectively defined based on prior intracoronary imaging studies, and the sample size calculation was based on a standard deviation of 1.9 mm2, a one-sided alpha risk of 5%, and a power of 80%, under the assumption of no true difference between groups. The primary endpoint was the minimal stent area (MSA) following stent implantation. The target lesion failure (TLF) rate was analysed after 12 months. RESULTS:A total of 169 patients (RA: n=86, IVL: n=83; 81.1% male; mean age 71.8±8.2 years) were included in the final analysis. The baseline characteristics of each group were balanced. Calcified nodules were identified in 48% of the patients. IVL was not inferior to RA for the primary endpoint (6.0±2.3 mm2 vs 5.9±2.2 mm2, respectively; p for non-inferiority<0.05). Adequate geometrical stent expansion was similar in both groups (RA: 65.1%, IVL: 65.1%; p=0.994), whereas major strut malapposition was more frequently observed in the RA group (RA: 80.2% vs IVL: 57.8%; p=0.002). There was no difference between groups in terms of periprocedural complications. The TLF rates between groups after 12 months were equivalent (RA: 1.2%, IVL: 2.4%; p=0.61). CONCLUSIONS:In this trial, the IVL strategy was non-inferior to the RA strategy regarding MSA for PCI in moderate-to-severe calcified coronary lesions, with a comparable safety profile and equivalent clinical outcomes.
Background: The benefits of multidisciplinary rehabilitation programs on pain and function in people with chronic low back pain (CLBP) are fairly well documented in the literature. However, these positive effects tend to fade over time due to low long-term patient adherence. Objective: The study aimed to evaluate the impact of a smartphone app on adherence to an exercise program for people with CLBP at 6 months. The secondary aims were to assess the effectiveness of the app on pain, disability, fears, and beliefs related to physical activity, physical capacity, and qualitative adherence (correctness of exercise execution) at 6 months. Methods: A total of 110 people with CLBP were included and randomized into 2 groups: 54 in the intervention group (IG) who received education on the use of the app in addition to usual care (a 3-week multidisciplinary rehabilitation program with self-management education) and 56 in the control group (CG) who received only usual care. Part B of the Exercise Adherence Rating Scale was used as the primary outcome to assess adherence to the 6-month exercise program. Secondary outcomes were pain (Numeric Rating Scale), disability (Oswestry Disability Index), barriers and facilitators to performing physical activity (Evaluation of Physical Activity Perception), physical capacity (battery of tests), and qualitative adherence (correctness of exercise execution). Statistical analyses were performed according to the intention-to-treat principle. A linear mixed model compared the primary end point between the groups at 6 months. Results: A total of 71 of 110 participants (n=35 in the CG vs n=36 in the IG) were evaluated at 6 months. We did not observe any significant difference in the Exercise Adherence Rating Scale score between the CG and the IG (group difference 0.01, 95% CI-2.4 to 2.4; P=.97). The same findings were found for pain, disability, and barriers and facilitators to physical activity, except for the motivation criterion. The 6-Minute Walk Test (group difference [log] 0.06, 95% CI 0.01-0.12; P=.06), cycle ergometer (group difference 9.30, 95% CI 0.48-18.13; P=.04), Ito (group difference [log] 0.31, 95% CI 0.01-0.62; P=.04), plank (group difference [log] 0.29, 95% CI 0.03-0.54; P=.03), and qualitative adherence (IG mean 12.6, SD 1.3 vs CG mean 11.4, SD 1.4; P=.02) differed between the groups in favor of the IG. All outcomes improved from baseline to 6 months in the IG but not in the CG. Conclusions: The smartphone app did not impact adherence to an exercise program at 6 months in individuals with CLBP. Similar results were found for pain and function. Nevertheless, the app could be a useful self-management tool in view of the positive effects on physical capacity and qualitative adherence.
