Inadequate access to clinical bacteriology testing in low-resource settings compromises individual patient care and contributes to antimicrobial resistance. Funders, policy makers, and health administrators working to expand bacteriology testing in sub-Saharan Africa require evidence-based guidance. The aim of this study was to assemble a costed consensus list of minimum equipment and consumables required to implement and operate a functional clinical bacteriology laboratory in secondary and tertiary care hospitals in sub-Saharan Africa, to guide funders and health administrators. A consensus list of minimum materials for diagnosing bloodstream infections was assembled by experts from Africa, North America, and Europe, representing academia, funders, and implementers. A modelling study was performed to estimate costs across several testing scenarios developed using a formal framework for forecasting testing volumes and reagent usage. Outcomes assessed were consumable costs per hospital admission and per investigation of septic episode and costs of non-recurring items at the time of establishment of a laboratory. Data from two accredited bacteriology laboratories providing individual patient care in Benin and Ethiopia were used to inform expected positivity rates, reagent usage, and testing volumes. Supplier quotes from North America and Europe were used to provide average unit costs and 95% uncertainty ranges. The estimated mean consumable cost per hospital admission was, in 2023 USD, $6·23 (95% uncertainty range 5·42-7·54) in the strict minimum scenario and $10·86 (9·82-12·31) in the standard scenario. The mean cost for the minimal equipment list at the time of establishment of a laboratory was estimated at $30 763 (28 403-33 043; plus an annual equipment maintenance cost of $3076 [2840-3304]), which includes purchase of commercial quality control strains and other non-recurring consumables. Available data suggest that costs from national distributors in sub-Saharan Africa could be three-fold higher than those described. Finally, we provide a transparent and adaptable basis for estimating minimal testing volumes and reagent usage, enabling tailored procurement planning in regions currently without clinical bacteriology laboratories. These results inform national antimicrobial resistance action plans on supply procurement, costing, and the ability to benchmark and forecast minimal acceptable testing volumes for the diagnosis of bloodstream infections for individual patient care. Fonds de recherche du Québec - Santé.
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Aggressive cancers such as triple-negative breast cancer (TNBC) and pancreatic cancer remain difficult to treat because their malignant behavior is driven by complex gene networks rather than single oncogenic targets. Here, we identify an extracellular vesicle (EV)-associated miRNA signature functionally linked to NFAT3 activity and demonstrate its ability to suppress tumor aggressiveness. Functional analyses revealed that a combination of fifteen miRNAs (miR-Comb 15) was required to fully reproduce the anti-tumoral effects of NFAT3-regulated EVs across TNBC and pancreatic cancer models, whereas individual miRNAs showed only partial activity. These effects were associated with coordinated regulation of validated target genes controlling proliferation and invasion, supporting a network-modulating mechanism of action. To facilitate therapeutic translation, we used EVs derived from HEK 293T cells, a non-tumoral, scalable, and readily engineerable EV source. Using an optimized exogenous pH-gradient loading strategy, miR-Comb 15 was efficiently incorporated into EVs without affecting vesicle integrity or intrinsic bioactivity. HEK 293T EVs loaded with miR-Comb 15 consistently showed the strongest anti-tumoral activity in vitro and in vivo among the delivery platforms evaluated. Together, these findings identify a functional NFAT3-dependent EV-miRNA program and support EV-mediated delivery of combinatorial miRNA therapeutics as a promising strategy for aggressive cancers.
To identify disparities in the access to and use of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in inflammatory rheumatic and musculoskeletal diseases (iRMDs). A systematic search of literature was conducted in Embase, Medline (to 30 May 2023), and relevant congress databases (to June 2023). Interventional and observational studies reporting measures of disparity in access to, receipt of, or utilisation of b/tsDMARDs in iRMDs were eligible. Outcomes included access to b/tsDMARDs, likelihood to receive treatment, time to first initiation, treatment adherence, and treatment persistence. Disparities across these outcomes are reported. Reporting follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews guidance. Of 4218 publications identified, 104 were included in this scoping review. All studies were observational; 70% reported data from patients with rheumatoid arthritis, and 65% were from North America or Europe. Gender (58%) and age (54%) were commonly investigated factors. Lower gross domestic product/capita (n = 7 publications) was associated with reduced access to b/tsDMARDs, whereas older age (n = 20 publications) and receiving government-funded health insurance (eg, Medicare/Medicaid) (n = 6 publications) were negatively associated with the likelihood of receiving b/tsDMARDs. No clear association was identified for any disparity factors and time to the initiation of b/tsDMARDs. Disparities in access to and use of b/tsDMARDs are reported in the literature along with the role of commonly studied social determinants of health (SDoH). More research is needed to identify the full spectrum of existing disparities and to reveal the role of SDoH, including the lesser-studied ones.
We report on the case of a pediatric patient with homozygous familial hypercholesterolemia (HoFH) who developed significant coronary artery disease (CAD). Percutaneous coronary intervention (PCI) guided by intravascular ultrasound (IVUS) was performed. A 6-year-old female patient was diagnosed with HoFH following the identification of cutaneous xanthomas. Genetic test identified a homozygous mutation in the LDLR gene. Cardiovascular assessment including a coronary CT angiography revealed a severe (70-90%) stenosis of the ostium of the left main coronary artery (LMCA) without significant lesions in other coronary branches. Given the severity of the lesion, PCI was indicated. The patient underwent PCI via the right femoral artery. The LMCA lesion was confirmed (70-90% stenosis, TIMI 3 flow) and a drug-eluting stent was deployed. Intravascular ultrasound (IVUS) played a crucial role in guiding the intervention, ensuring optimal stent expansion and apposition. Post-procedure, dual antiplatelet therapy (aspirin + clopidogrel) was initiated, clopidogrel was stopped after six months. A six-month follow-up CT angiogram demonstrated satisfactory stent positioning, despite metallic artifacts limiting full assessment. Two years after angioplasty, there have been no clinical, electrocardiographic, or echocardiographic signs of myocardial ischemia. This case highlights the feasibility and safety of LMCA stenting in pediatric patients with HoFH. Given the challenges of coronary interventions in pediatric patients, IVUS should be considered a critical adjunct to angiography in complex cases of early-onset coronary artery disease.
Families of children with neurodisabilities often face significant child behavioral challenges that can affect overall family functioning and well-being. This randomized controlled trial (RCT) used family resilience theory as the investigative framework to examine the impact of an online parenting program designed to address child behavioral challenges. Parents of children with a range of neurodisabilities were randomized into three groups: a self-directed online parenting program, the same program with coaching support, and a control group. Family well-being was measured using the SCORE-15 at baseline, 5, and 10 months. The primary analysis included a per-protocol sample comprising self-directed participants who completed ≥ 8 of 12 modules, coached participants who completed ≥ 8 modules and ≥ 8 coaching sessions, and all control-group participants. Linear mixed models (LMMs) were used to analyze the repeated measures data, followed by standard linear regression models to assess the average intervention effect at each time point. Clinically significant changes were calculated via the reliable change index (RCI). Of the 454 families randomized, 422 participants had at least one available SCORE-15 assessment (self-directed: n = 140; coached: n = 139; control: n = 143). Descriptively, mean SCORE-15 scores remained relatively stable in both intervention groups but increased over time in the control group (lower scores indicate better family functioning). Broader results from the full-sample analysis are reported separately (publication forthcoming). The present analyses focus on the 248 participants who met the per-protocol adherence criteria (self-directed: n = 36; coached: n = 60; control: n = 152). Families that reported higher baseline family well-being were associated with greater adherence to the intervention. Participants in both intervention groups demonstrated significant improvements in family well-being relative to the control group. The coached version of the intervention demonstrated a more robust and persistent impact relative to the self-directed version, particularly with respect to communication-related subscales. Across both versions of the intervention 10%-28% of participants experienced reliable clinical change. The findings from our analysis suggest that both versions of the parenting program led to notable enhancements in aspects of family well-being, with the coached group exhibiting particularly remarkable improvements. Our study highlights that parenting interventions can contribute to the well-being of the entire family system, extending beyond individual child and parent outcomes typically addressed by these programs. This study looked at how effective online parenting programs are for families of children with neurodisabilities like autism and cerebral palsy. Some parents had extra help through coaching, while others did not. These programs taught parents how to handle challenging child behaviors and improve family life. The study found that while both versions of the program had some positive impact, families who received extra coaching seemed to benefit more, especially in how they communicate and solve problems together. Our results suggest that with the right support, families can get better at dealing with the challenges that come with parenting children with these conditions. Our hope is that these findings will help create better programs for families who need extra support.
Screening for multidrug-resistant pulmonary tuberculosis (MDR-PTB) by using the Xpert MTB/ RIF test to detect rifampicin resistance as a surrogate marker for this form of tuberculosis may lead to suboptimal treatment if resistance to other drugs in the treatment regimen is not also determined. The objective of this study was to analyze the patterns of drug resistance to anti-tuberculosis drugs in patients with rifampicin-resistant pulmonary tuberculosis (RR-PTB) who were treated with the standardized 9-11-month regimen in Yaoundé, Cameroon. This retrospective, cross-sectional study examined the results of anti-tuberculosis drug susceptibility tests in RR-PTB patients who received the standardized 9-11-month treatment regimen at the specialized MDR-PTB treatment center of the Jamot Hospital in Yaoundé from 2013 to 2022. A total of 322 RR-PTB patients were included in the study. Of these, 281 (87.3%) were resistant to at least one of the tested drugs. The pattern of resistance was 43.2% for one drug, 41.6% for two drugs, and 2.5% for three or more drugs. Resistance to isoniazid was the most common (87.3%), followed by ethambutol (42.2%), fluoroquinolones (3.4%), and amikacin (1.9%). The majority of RR-PTB patients in Yaoundé had MDR-PTB, and pre-extensively drug-resistant TB was rare. However, the GeneXpert-based strategy for identifying drug-resistant cases (which detects only rifampicin resistance) could lead to the initiation of suboptimal treatment for a non-negligible proportion of patients in our setting. This could result in the amplification of resistance and the transmission of increasingly resistant strains within the community. We recommend that the National Tuberculosis Control Program (NTCP) of Cameroon should adopt and rapidly roll out the new short-course treatment regimen recommended by the World Health Organization given the lack of rapid tests in our country capable of detecting resistance to the various drugs used in the standard 9-11-month regimen. Le dépistage de la tuberculose pulmonaire multirésistante (TBP-MR) en utilisant la résistance à la rifampicine obtenue par le test Xpert MTB/RIF comme marqueur de substitution de cette forme de tuberculose risque de conduire à un traitement sous-optimal si sa résistance aux autres médicaments du régime thérapeutique n’est pas déterminée. L’objectif de cette étude était d’analyser les profils de résistance aux médicaments antituberculeux chez les patients atteints de la tuberculose pulmonaire résistante à la rifampicine (TBP-RR) traités par le régime thérapeutique standardisé de 9 à 11 mois à Yaoundé, Cameroun. Il s’agissait d’une étude transversale rétrospective des résultats des tests de sensibilité aux médicaments antituberculeux de patients atteints de TBP-RR traités par le régime thérapeutique standardisé de 9 à 11 mois au centre spécialisé de traitement de la TBP-MR de l’Hôpital Jamot de Yaoundé entre 2013 et 2022. Au total, 322 patients atteints de TBP-RR ont été inclus dans l‘étude. Parmi eux, 281 (87,3 %) étaient résistants à au moins un des médicaments testés. Le profil de résistance était de 43,2 % pour un seul médicament, 41,6 % pour deux médicaments et 2,5 % pour trois médicaments ou plus. La résistance à l'isoniazide était la plus fréquente (87,3 %), suivie de l‘éthambutol (42,2 %), des fluoroquinolones (3,4 %) et de l'amikacine (1,9 %). La majorité des patients TBP-RR à Yaoundé avait une TBP-MR, et la TB pré-ultrarésistante était rare. Malgré cela, la stratégie de recherche de cas de résistance aux médicaments basée sur GeneXpert (qui identifie uniquement celle à la rifampicine) peut conduire à l’initiation d’un traitement sous-optimal pour une proportion non négligeable de patients dans notre milieu. Cela pourrait conduire à une amplification de la résistance et à la transmission de souches avec une résistance de plus en plus avancée au sein de la communauté. Nous recommandons que le Programme national de lutte contre la tuberculose (PNLT) du Cameroun adopte et généralise rapidement le nouveau régime thérapeutique court recommandé par l’Organisation mondiale de la Santé, compte tenu de la non-disponibilité des tests rapides dans notre pays permettant de détecter la résistance aux différents médicaments utilisés dans le régime standardisé de 9 à 11 mois.
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The Motor Function Measure (MFM) is an important evaluation tool used to monitor the progression of most neuromuscular diseases. However, the MFM is subject to inter-rater variability, and patients must produce their best effort, which can be difficult for children. In response to these issues, we developed a digital app named MFM-Play, designed to optimise completion of the MFM in a fun manner. The objective of this study was to explore barriers and levers to the MFM-Play's use by therapists. We conducted a qualitative study with rehabilitation professionals who had tested the app in a previous reliability study. Individual interviews based on the Technology Acceptance Model were followed by a focus group based on the interview results. Thematic analysis was performed on transcripts. Seven therapists participated in the interviews and seven others in the focus group. The results revealed the multi-dimensional features related to adopting the MFM-Play app. Barriers related to ease of use, training and organisational constraints were identified, and were partly due to the additional mental burden of learning to use the technology. However, therapists who were at ease with the digital tool found it useful for their practice. The app also modified patient-therapist dynamics, fostering greater patient autonomy, but sometimes disrupted therapists' habits, by calling into question assessment methods. The MFM-Play app offers considerable practical and efficiency benefits; however, its successful adoption depends on overcoming technical, organisational, and user-specific barriers. This involves providing support for the change in the therapist's stance within the triadic patient-therapist-tablet relationship.
Accurate detection and characterizstion of wrist fractures are essential for optimal management of wrist trauma. This study aimed to evaluate the diagnostic performance of a computed tomography (CT)-like 3D-multiecho fast field echo (mFFE) magnetic resonance imaging (MRI) sequence for the detection and morphological characterisation of traumatic wrist fractures compared with cone-beam computed tomography (CBCT). This retrospective study included 66 patients with recent wrist trauma and suspected fracture between October 2022 and September 2023. Two musculoskeletal radiologists (R1 and R2) independently reviewed CBCT and 3D-mFFE CT-like MRI images. The diagnostic performance of the 3D-mFFE sequence for detecting and characterising traumatic bone injuries was assessed using a consensus interpretation by a third radiologist (R3) as the reference standard. Sixty-three traumatic bone injuries were identified in 38 of the 66 patients (58%). For injury detection with the 3D-mFFE sequence, sensitivity, specificity, and accuracy were 0.62, 0.99, and 0.96 for R1 and 0.60, 1.00, and 0.96 for R2. For CBCT, sensitivity, specificity, and accuracy were 0.68, 1.00, and 0.97 for R1 and 0.70, 1.00, and 0.97 for R2. Agreement between the 3D-mFFE sequence and the reference standard for fracture characterisation was strong to near perfect for both comminution (κ = 0.69-0.87) and displacement (κ = 0.63-0.92). The CT-like 3D-mFFE MRI sequence demonstrated diagnostic performance comparable to CBCT for the morphological assessment of wrist fractures. When incorporated into a standard MRI protocol, this sequence may allow both detection and characterisation of traumatic bone injuries within a single, radiation-free examination.
The aim of the study was to assess overall and cause-specific mortality among employees and former employees of the main public transport company in the Paris region. The cohort included all personnel employed between 1980 and 2012 with at least 1 year of service. Vital status and causes of death were obtained from national registries and classified according to the European shortlist for causes of death. Occupations were categorized into 22 distinct groups, and complete occupational histories were reconstructed. Cox proportional hazards models were used to estimate survival by socio-professional group and hazard ratios of death by occupation. Standardized mortality ratios (SMRs) were calculated to compare mortality with that of the general population of the Paris region. A total of 96,634 individuals (78,702 men and 17,932 women) were included. By the end of follow-up, 14.6% of men and 6.5% of women had died. A social gradient in survival was observed with marked differences in the hazard ratios of mortality across occupational categories. Among men, significant excess mortality was found for kidney cancer (SMR = 1.24), acute myocardial infarction (SMR = 1.17), chronic liver disease (SMR = 1.11), and suicide (SMR = 1.20). Among women, mortality due to transport accidents was significantly in excess (SMR = 1.85). Specific excesses were found by occupation: for example, in men, tumors in skilled maintenance workers (SMR = 1.67), ischemic heart disease in bus drivers (SMR = 1.21), security staff (SMR = 2.02), and unskilled workers (SMR = 1.18), and in women, cerebrovascular diseases in bus drivers (SMR = 1.85). These findings highlight occupational inequalities in mortality and support strengthening targeted prevention strategies for high-risk workgroups.
Changes in certain global parameters, such as climate and ecosystems, which were anticipated for several decades and confirmed during the second half of the 20th century, have accelerated significantly. This raises the question of the possible or proven impacts of this acceleration. In the field of human health, as well as animal health and environmental quality, the consequences are already significant. The case of zoonoses, infectious and parasitic diseases that can be transmitted between humans and other vertebrates, illustrates where these changes may lead.This brief overview first outlines the challenges and difficulties of ensuring access to reliable, accessible data sources and then presents a few examples. Awareness at the highest levels is necessary to reverse this trend. L’évolution de certains paramètres planétaires (climat, écosystèmes), pressentie depuis quelques décennies et confirmée durant la seconde moitié du XXe siècle, s’est nettement accélérée. La question des impacts possibles ou avérés de cette accélération est donc posée. Dans le domaine de la santé humaine, traitée ici, comme pour la santé animale et la qualité de l’environnement, des conséquences sont déjà notables. Le cas particulier des zoonoses, ces maladies infectieuses et parasitaires, transmissibles, dont les agents peuvent circuler entre humains et autres vertébrés, illustre assez bien ce à quoi ces changements peuvent conduire. Cette courte synthèse rappelle d’abord les enjeux et difficultés à surmonter pour pouvoir disposer de sources de données fiables et accessibles, puis présente quelques exemples. Une prise de conscience aux plus hauts niveaux est nécessaire pour espérer renverser la tendance.
The scale of IVF centres currently ranges from small, stand-alone units to large networked organizations operating across multiple regions or countries. This diversity in organizational models may influence clinical outcomes, patient experience, professional practice, innovation and long-term sustainability. In parallel with broader healthcare trends, the fertility sector has undergone rapid consolidation over the last decade, prompting renewed debate regarding the relationship between centre size, governance structures, quality of care and efficiency. This opinion paper critically examines the strengths and limitations of both small and large IVF centres, with particular attention to the concepts of critical mass, technology adoption, human resources, quality management and professional autonomy. Beyond size alone, the discussion also covers how evolving governance models, particularly the growing influence of managerial and financial decision making, may reshape scientific leadership and clinical practice within fertility centres. Importantly, the authors acknowledge the scarcity of high-quality comparative evidence linking organizational scale to live birth outcomes or patient-reported measures. Rather than advocating for a single optimal size, they propose the concept of a 'sustainable or balanced scale', defined as an organizational equilibrium where operational robustness, leadership, science and innovation coexist with uncompromising personalized, patient-centred care.
The gut-brain axis is a key target in neuroinflammatory disorders. We investigated the protective effects of Mela Rosa Marchigiana pulp callus extract (MRME), a phytocomplex with a unique triterpenic profile. Using a validated transwell co-culture model of the intestinal-neural interface, differentiated Caco-2 cells formed a polarized epithelial barrier (apical), while BV2 microglia or SH-SY5Y neurons were seeded in the basolateral compartment. Apical MRME pretreatment preserved Caco-2 barrier integrity against lipopolysaccharide or dextran sodium sulfate-induced damage. MRME maintained occludin integrity and transepithelial electrical resistance (TEER), effectively neutralizing "leaky gut"-like conditions. By stabilizing the barrier, MRME exerted indirect neuroprotection since high-throughput live-cell imaging revealed dose-dependent reductions in reactive oxygen species generation and apoptosis (caspase-3/7 activation) in both BV2 and SH-SY5Y cells. MRME demonstrated a microbiologically neutral profile, exerting no inhibitory effects on either pathogenic or probiotic strains up to 10,000 μg/mL. MRME provides dual protection by strengthening the intestinal barrier and shielding the neural environment from systemic inflammation through host cellular modulation rather than microbial interference. These findings suggest MRME as a promising nutraceutical candidate for gut-brain axis dysregulation.
Synthetic data offer significant potential for cardiology research by enabling data sharing, preserving privacy, and supporting machine learning model development. By generating artificial patient records that reflect real-world distributions, synthetic data can accelerate clinical research, improve model performance for rare cardiovascular conditions, and facilitate transnational collaborations that would otherwise be restricted by data-sharing barriers. Despite these advantages, the increasing use of synthetic data raises important ethical, regulatory, and methodological concerns that remain insufficiently addressed. Key challenges include assessing the validity and generalizability of synthetic datasets, understanding their limitations in representing complex and heterogeneous patient populations, and preventing the amplification of existing biases in cardiovascular care. Current regulatory frameworks, including the General Data Protection Regulation (GDPR) and Health Insurance Portability and Accountability Act (HIPAA), do not fully address emerging risks such as reidentification and data leakage, and there is no harmonized guidance to govern the use of synthetic data as stand-alone evidence for medical device evaluation or therapeutic research. In this viewpoint, we argue that responsible integration of synthetic data in cardiology requires, first, clear differentiation between synthetic data as a privacy-preserving distributional substitute and synthetic data as a counterfactual simulation tool, and, second, fit-for-purpose governance frameworks that pair rigorous utility and fidelity testing with explicit, adversary-aware privacy evaluation before synthetic cohorts are accepted as evidence in research or product evaluation. A prerequisite for that governance is conceptual clarity about what synthetic data are being used for. Synthetic data in health care serve 2 fundamentally distinct roles that carry entirely different validity requirements, failure modes, and regulatory implications, yet they are routinely conflated. The first role is as a privacy-preserving distributional substitute: the goal is statistical fidelity to the real data distribution, so that analyses of the synthetic dataset yield results equivalent to those of the original. The second role is as a tool for counterfactual simulation: the goal is to generate data that could not have been observed, such as rare conditions, hypothetical interventions, or extrapolations to new populations. These 2 roles are methodologically distinct. A dataset that accurately reflects real-world distributions may be inadequate for extrapolating findings to underrepresented subgroups. Conversely, a simulator optimized for novel scenario generation may systematically diverge from real-world distributions. This distinction informs every subsequent discussion of validity, bias, and regulation in this viewpoint and our proposed 4 concrete actions for the cardiology research community, including mandatory 3-layer (fidelity, utility, and privacy) validation, systematic subgroup reporting, explicit intended-use scoping, and domain-specific acceptability thresholds for synthetic data-based evidence.
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Genu recurvatum is a serious complication of intra-quadriceps injections. This study reports on 25 cases of genu recurvatum collected during 104 pediatric orthopedic surgery missions in the Central African Republic. Of these cases, 12 could be reviewed with sufficient follow-up and/or radiographic evaluation. Genu recurvatum impairs walking and makes running impossible. It becomes extremely severe when it is bilateral or exceeds 90°. Treatment options are limited due to osteoarticular changes that occur during growth. These changes include trochlear hypoplasia, flattening of the anterior aspect of the femoral condyles, and anterior subluxation of the tibia. Despite the fact that the genu recurvatum was corrected immediately postoperatively, the knee was stiff in extension in all but one of the reviewed cases. Fortunately, intra-quadriceps injections are currently prohibited, so this complication should become rare. Le genu recurvatum est une grave complication de l’injection intraquadricipitale. Matériel et méthode. Ce travail rapporte une série de 25 cas colligés lors de 104 missions de chirurgie orthopédique infantile réalisées en République centrafricaine, parmi lesquels 12 cas ont pu être revus avec un recul suffisant et/ou un bilan radiographique. Le genu recurvatum handicape la marche et rend la course impossible; il devient gravissime quand il est bilatéral et quand il dépasse 90°. Les possibilités thérapeutiques sont limitées en raison des remaniements ostéo-articulaires se produisant au cours de la croissance avec hypoplasie de la trochlée, aplatissement de la partie antérieure des condyles fémoraux, subluxation antérieure du tibia. Malgré une bonne correction du recurvatum obtenue en postopératoire immédiat, le genou était raide en extension dans tous les cas revus sauf un. Les injections intraquadricipitales sont heureusement proscrites actuellement et cette complication devrait devenir exceptionnelle.
Distributed analytics enables analyses to be conducted when data is partitioned across multiple sites and cannot be pooled in one location. The primary motivation for using these methods is to protect confidentiality of line-level data. Distributed analytics methods rely on exchanging intermediate numerical outputs generated locally at each participating site. However, the absence of line-level data exchange should not be mistaken for privacy protection. To address this, the GRIIS developed a framework for evaluating privacy, helping users distinguish different levels of privacy preservation when applying distributed methods. This work was especially important, as earlier research demonstrated that an existing distributed method could be reverse-engineered to recover line-level data, which underscores that the distributed nature of an approach does not guarantee data privacy. In the framework, we define data privacy as guaranteed if line-level data cannot be uniquely recovered from the numerical outputs exchanged or disclosed during the execution of the approach. By eliciting line-level data as a set of unknown variables subject to constraints derived from the procedure, we can, in some settings, mathematically prove that privacy is protected under this definition. Achieving this depends on the nature of the variables included (binary, continuous), the results shared at the end of the procedure and the availability of external information. Ultimately, this work plays a critical role in supporting the responsible use of distributed analytics. By establishing governance mechanisms to evaluate and mitigate privacy risks, it helps ensure that these methods can be adopted appropriately and at scale across the country.
To evaluate the impact of continuous renal replacement therapy (CRRT) on plasma amino acid (AA) concentrations in patients with acute metabolic decompensation of organic acidemias (OAs), and to explore whether AA supplementation during CRRT may mitigate AA depletion. Multicenter retrospective observational study. PICUs managing acute metabolic decompensations of OAs. Patients with confirmed OAs who underwent CRRT for severe acute metabolic decompensation. CRRT was initiated according to current guidelines in cases of severe decompensation. Standard metabolic management included high caloric intake through carbohydrates and lipids with temporary protein withdrawal (24-48 hr). In one patient, AA supplementation (2 g/kg) during CRRT combined with thiamin and citrate (anaplerotic therapy) was administered. Plasma AA concentrations were measured before and after CRRT in nine patients with a median age of 21 days (interquartile range [IQR], 3-570 d). Quantitative variables are expressed as medians (IQR, 25th-75th). Before CRRT, 31% (95% CI, 24-39) of plasma AAs were below the normal range compared with 69% (95% CI, 59-77) after CRRT (p < 0.0001). A significant increase in lactatemia was observed following CRRT, without evidence of organ failure: median 2.2 mmol/L (IQR, 1.3-2.3) before CRRT vs. 5.3 mmol/L (IQR, 3.2-7.1) after CRRT; Hodges-Lehmann median difference +3.2 (95% CI, 0.8-5.6; p = 0.0065). In the patient receiving AA supplementation with anaplerotic therapy, plasma AA status improved markedly, with 65% of AAs below normal before CRRT vs. 15% after CRRT. In acute decompensated OAs, CRRT performed without protein supplementation, as currently recommended, significantly reduces total plasma AA concentrations and may impair restoration of anabolism. AA infusion during CRRT could help preserve or restore protein anabolism. Prospective studies are needed to assess the safety and efficacy of AA supplementation during CRRT, with or without anaplerotic therapy, in this setting.