External quality assurance of chest X-ray interpretation to strengthen diagnosis of childhood TB.

BACKGROUND: Chest X-ray (CXR) misinterpretation negatively affects the accuracy of childhood TB diagnosis. External quality assurance (EQA) could strengthen CXR reading skills. We assessed the uptake, performance and challenges of an EQA of CXR interpretation within the childhood TB-Speed decentralisation study in six resource-limited countries. METHODS: Every quarter, TB suggestive or unreadable CXRs and 10% of remaining CXRs from children with presumptive TB were selected for blind re-reading by national re-readers. The proportion of CXRs selected for EQA and re-read assessed the uptake. The performance was assessed by the proportion of discordant interpretations and the sensitivity and specificity of clinicians' vs re-readers' interpretations. Challenges were retrieved from country reports. RESULTS: Of 513 eligible CXRs, 309 (60.8%) were selected for EQA and 278/309 (90.0%) re-read. The proportion of discordant interpretation was between 13/48 (27%) in Sierra Leone and 7/13 (53.8%) in Cote d'Ivoire during the first EQA and decreased after the EQAs periods in 3/5 countries. Clinician sensitivity reached 100% in all countries over EQA. Specificity ranged between 13% in Sierra Leone and 65% in Cambodia (first EQA) and increased in 4/5 countries after the EQA periods. CXR transfer and re-readers' workload were the main challenges. CONCLUSION: EQA can enhance CXR interpretation for childhood TB diagnosis, provided operational challenges are overcome.

CONTEXTE: Les erreurs d'interprétation du radio thoracique (CXR, pour l'anglais « chest X-ray ¼) compromettent la précision du diagnostic de la TB chez les enfants. La mise en place d'une assurance qualité externe (EQA, pour l'anglais « external quality assurance ¼) pourrait améliorer les compétences en lecture des CXR. Nous avons examiné l'adoption, l'efficacité et les obstacles liés à une EQA pour l'interprétation des CXR dans le cadre de l'étude de décentralisation Child TB-Speed, menée dans six pays à ressources limitées. MÉTHODES: Chaque trimestre, les CXRs évocatrices de TB ou illisibles, ainsi que 10% des autres CXRs d'enfants atteints de TB présumés, ont été choisies pour une relecture en aveugle par des experts nationaux. La proportion de CXRs sélectionnées pour EQA et relues a permis d'analyser le taux de participation. La performance a été mesurée en fonction du nombre d'interprétations discordantes, ainsi que de la sensibilité et de la spécificité des interprétations des cliniciens comparées à celles des relecteurs. Les contestations ont été extraites des rapports nationaux. RÉSULTATS: Parmi les 513 CXR éligibles, 309 (60,8%) ont été retenus pour l'EQA, et 278 sur 309 (90,0%) ont été réévalués. La proportion d'interprétations discordantes variait de 13 sur 48 (27%) en Sierra Leone à 7 sur 13 (53,8%) en Côte d'Ivoire lors de la première EQA, et a diminué après les périodes d'EQA dans trois des cinq pays. La sensibilité des cliniciens a atteint 100% dans tous les pays durant l'EQA. La spécificité a fluctué entre 13% en Sierra Leone et 65% au Cambodge (première EQA), et a augmenté dans quatre des cinq pays après les périodes d'EQA. Le transfert des CXRs ainsi que la charge de travail des relecteurs ont représenté les principaux défis rencontrés. CONCLUSION: L'EQA a le potentiel d'optimiser l'analyse des CXRs pour le diagnostic de la TB chez l'enfant, sous réserve de surmonter les obstacles opérationnels.

Citrus pectin modulates chicken peripheral blood mononuclear cell proteome in vitro.

Citrus pectin (CP) is a dietary fiber used in animal nutrition with anti-inflammatory properties. CP downregulates chicken immunoregulatory monocytes' functions, like chemotaxis and phagocytosis, in vitro. The molecular underlying background is still unknown. This study investigated the activity of CP on chicken peripheral blood mononuclear cells (PBMC) proteome. An overall number of 1503 proteins were identified and quantified. The supervised sparse variant partial least squares-discriminant analysis (sPLS-DA) for paired data highlighted 373 discriminant proteins between CP-treated and the control group, of which 50 proteins with the highest abundance in CP and 137 in the control group were selected for Gene Ontology (GO) analyses using ProteINSIDE. Discriminant Protein highly abundant in CP-treated cells were involved in actin cytoskeleton organization and negative regulation of cell migration. Interestingly, MARCKSL1, a chemotaxis inhibitor, was upregulated in CP-treated cells. On the contrary, CP incubation downregulated MARCKS, LGALS3, and LGALS8, which are involved in cytoskeleton rearrangements, cell migration, and phagocytosis. In conclusion, these results provide a proteomics background to the anti-inflammatory activity of CP, demonstrating that the in vitro downregulation of phagocytosis and chemotaxis is related to changes in proteins related to the cytoskeleton.

Evaluation of a short training course of chest X-ray interpretation for the diagnosis of paediatric TB.

BACKGROUND: Chest X-ray (CXR) interpretation is challenging for the diagnosis of paediatric TB. We assessed the performance of a three half-day CXR training module for healthcare workers (HCWs) at low healthcare levels in six high TB incidence countries. METHODS: Within the TB-Speed Decentralization Study, we developed a three half-day training course to identify normal CXR, CXR of good quality and identify six TB-suggestive features. We performed a pre-post training assessment on a pre-defined set of 20 CXR readings. We compared the proportion of correctly interpreted CXRs and the median reading score before and after the training using the McNemar test and a linear mixed model. RESULTS: Of 191 HCWs, 43 (23%) were physicians, 103 (54%) nurses, 18 (9.4%) radiology technicians and 12 (6.3%) other professionals. Of 2,840 CXRs with both assessment, respectively 1,843 (64.9%) and 2,277 (80.2%) were correctly interpreted during pre-training and post-training (P < 0.001). The median reading score improved significantly from 13/20 to 16/20 after the training, after adjusting by country, facility and profession (adjusted ß = 3.31, 95% CI 2.44-4.47). CONCLUSION: Despite some limitations of the course assessment that did not include abnormal non-TB suggestive CXR, study findings suggest that a short CXR training course could improve HCWs' interpretation skills in diagnosing paediatric TB.

CONTEXTE: L'interprétation de la radiographie thoracique (CXR) est un défi pour le diagnostic de la TB pédiatrique. Nous avons évalué la performance d'un module de formation de trois demi-journées sur la CXR destiné aux agents de santé (HCWs) dans six pays où l'incidence de la TB est élevée et où les ressources en services de santé sont limitées. MÉTHODES: Dans le cadre de l'étude de décentralisation TB-Speed, nous avons mis au point un cours de formation de trois demi-journées pour identifier une CXR normale, une CXR de bonne qualité et six caractéristiques suggestives de la TB. Nous avons effectué une évaluation avant et après la formation sur un ensemble prédéfini de 20 clichés radiologiques. Nous avons comparé la proportion de CXR correctement interprétées et le score médian de lecture avant et après la formation à l'aide du test de McNemar et d'un modèle linéaire mixte. RÉSULTATS: Sur les 191 HCWs, 43 (23%) étaient des médecins, 103 (54%) des infirmières, 18 (9,4%) des techniciens en radiologie et 12 (6,3%) d'autres professionnels. Sur 2 840 CXR avec les deux évaluations, respectivement 1 843 (64,9%) et 2 277 (80,2%) ont été correctement interprétées avant et après la formation (P < 0,001). Le score médian de lecture s'est amélioré de manière significative, passant de 13/20 à 16/20 après la formation, après ajustement par pays, établissement et profession (ß ajusté = 3,31; IC 95% 2,44­4,47). CONCLUSION: Malgré certaines limites de l'évaluation du cours qui n'incluait pas de CXR anormale non évocatrice de TB, les résultats de l'étude suggèrent qu'une formation courte sur la CXR pourrait améliorer les compétences d'interprétation des HCWs dans le diagnostic de la TB pédiatrique.

Conjugated linoleic acid (CLA) modulates bovine peripheral blood mononuclear cells (PBMC) proteome in vitro.

Conjugated linoleic acid (CLA) is a group of natural isomers of the n-6 polyunsaturated fatty acid (PUFA) linoleic acid, exerting biological effects on cow physiology. This study assessed the impact of the mixture 50:50 (vol:vol) of CLA isomers (cis-9, trans-11 and trans-10, cis-12) on bovine peripheral blood mononuclear cells (PBMC) proteome, identifying 1608 quantifiable proteins. A supervised multivariate statistical analysis, sparse variant partial least squares - discriminant analysis (sPLS-DA) for paired data identified 407 discriminant proteins (DP), allowing the clustering between the CLA and controls. The ProteINSIDE workflow found that DP with higher abundance in the CLA group included proteins related to innate immune defenses (PLIN2, CD36, C3, C4, and AGP), with antiapoptotic (SERPINF2 and ITIH4) and antioxidant effects (HMOX1). These results demonstrated that CLA modulates the bovine PBMC proteome, supports the antiapoptotic and immunomodulatory effects observed in previous in vitro studies on bovine PBMC, and suggests a cytoprotective role against oxidative stress. SIGNIFICANCE: In this study, we report for the first time that the mixture 50:50 (vol:vol) of cis-9, trans-11, and trans-10, cis-12-CLA isomers modulates the bovine PBMC proteome. Our results support the immunomodulatory and antiapoptotic effects observed in bovine PBMC in vitro. In addition, the present study proposes a cytoprotective role of CLA mixture against oxidative stress. We suggest a molecular signature of CLA treatment based on combining a multivariate sparse discriminant analysis and a clustering method. This demonstrates the great value of sPLS-DA as an alternative option to identify discriminant proteins with relevant biological significance.

Mindfulness in Parkinson's disease: A French national survey and a pilot intervention feasibility trial using the MBSR program (M-Park).

BACKGROUND: Non-pharmacological complementary interventions, particularly mind-body practices, are of growing importance in the management of Parkinson's disease (PD). Among these, mindfulness meditation seems particularly effective, especially on anxiety and depression symptoms. However, current knowledge on mindfulness standardized programs in PD is still limited, particularly in France. Aiming at improving this knowledge we designed the M-PARK study in two phases. Phase 1 consisted in a French national survey to explore expectations, needs and initiatives for mindfulness meditation for PD patients. Phase 2 was a clinical trial with objectives to assess feasibility, acceptability and effects of a mindfulness (MBSR) program proposed to PD patients. METHODS: In phase 1, online questionnaires were addressed to members of a French PD patient's association (France Parkinson) and French MBSR qualified instructors. In Phase 2, a clinical trial involving 30 PD patients consisted of a standard MBSR program with two additional evaluation visits one month before and after the program. Data collection included a global clinical evaluation, assessment of depression and anxiety symptoms, sleep, pain and quality of life and a face-to-face interview for qualitative assessment of the acceptability and lived experience during the program. Three MBSR programs were proposed to three groups of ten patients: two were online due to the pandemic situation, one proposed to patients with no or minor fluctuations (group 1) and one for patients with slight to moderate fluctuations (group 2), and the last one face-to-face for patients with no or minor fluctuations (group 3). RESULTS: French survey: 209 responses were collected for the questionnaire sent to the members of the association France Parkinson; and 68 for the questionnaire sent to the instructors. Two-thirds of patients surveyed had heard of mindfulness meditation (66%), but were unaware of what this approach really consisted and how it could really help them. Few instructors (29%) had had to deal with patients with PD in their current practice. Yet 90% of patients surveyed indicated they were in favor of introducing this type of approach into their care. CLINICAL TRIAL: The results indicated that the program is feasible and acceptable both online and face-to-face for patients with PD. Among the 30 patients enrolled, 25 completed the program. No unwanted effects related to mindfulness meditation practice were observed. The results showed a statistically significant reduction in anxiety symptoms, depressive symptoms, and improvement in quality of life. Furthermore, no statistically significant change was measured for pain or sleep quality. There was no striking difference in results observed between the patient groups. For the qualitative analysis, major themes highlighted were in relation with: (i) the lived experience during program; (ii) changes in the daily life; and (iii) disease-related changes. A large majority of patients who completed the program (24/25) described their participation as positive or very positive. They reported better management of stress and emotions, as well as greater autonomy in implementing new behavioral strategies, particularly in terms of self-care, acceptance, and de-identification from the disease. CONCLUSION: Despite high expectations, PD patients are poorly informed about available mindfulness programs. This study however shows that these programs, whether offered online or face-to-face, are particularly beneficial, especially for anxiety and depressive symptoms, at least in mild-to-moderate stages of the disease.

Comparative electroencephalography analysis: Marathon runners during tapering versus sedentary controls reveals no significant differences.

INTRODUCTION: Previous studies described various adaptive neuroplastic brain changes associated with physical activity (PA). EEG studies focused mostly on effects during or shortly after short bouts of exercise. This is the first study to investigate the capability of EEG to display PA-induced long-lasting plasticity in runners compared to a sedentary control group. METHODS: Thirty trained runners and 30 age- and sex-matched sedentary controls (SC) were included as a subpopulation of the ReCaP (Running effects on Cognition and Plasticity) study. PA was measured with the International Physical Activity Questionnaire (IPAQ). Resting-state EEG of the runners was recorded in the tapering phase of the training for the Munich marathon 2017. Power spectrum analyses were conducted using standardized low-resolution electromagnetic tomography (sLORETA) and included the following frequency bands: delta: 1.5-6 Hz, theta: 6.5-8.0 Hz, alpha1: 8.5-10 Hz, alpha2: 10.5-12.0 Hz, beta1: 12.5-18.0 Hz, beta2: 18.5-21.0 Hz, beta3: 21.5-30.0 Hz, and total power (1.5-30 Hz). RESULTS: PA (IPAQ) and BMI differed significantly between the groups. The other included demographic parameters were comparable. Statistical nonparametric mapping showed no significant power differences in EEG between the groups. DISCUSSION: Heterogeneity in study protocols, especially in time intervals between exercise cessation and EEG recordings and juxtaposition of acute exercise-induced effects on EEG in previous studies, could be possible reasons for the differences in results. Future studies should record EEG at different time points after exercise cessation and in a broader spectrum of exercise intensities and forms to further explore the capability of EEG in displaying long-term exercise-induced plasticity.

Idiopathic intracranial hypertension secondary to fluoroquinolone therapy: French pharmacovigilance data review.

We investigate spontaneous reports of IIH related to fluoroquinolones recorded in the French national pharmacovigilance database in order to detect a possible pharmacovigilance signal. The association between IIH risk and fluoroquinolone exposure was assessed using a case/non-case study. Between 1985 and July 2023, 17 reports of IIH after fluoroquinolone exposure were recorded. No specific fluoroquinolone was predominant. IIH led to death in one case and blindness in one case. The Reporting Odds Ratio was 2.58 (95% confidence interval 1.59-4.19). We highlight statistically significant disproportionality, which constitutes a pharmacovigilance signal. IIH risk after fluoroquinolone exposure is a class effect.

Towards the Improvement of Soil Salinity Mapping in a Data-Scarce Context Using Sentinel-2 Images in Machine-Learning Models.

Several recent studies have evidenced the relevance of machine-learning for soil salinity mapping using Sentinel-2 reflectance as input data and field soil salinity measurement (i.e., Electrical Conductivity-EC) as the target. As soil EC monitoring is costly and time consuming, most learning databases used for training/validation rely on a limited number of soil samples, which can affect the model consistency. Based on the low soil salinity variation at the Sentinel-2 pixel resolution, this study proposes to increase the learning database's number of observations by assigning the EC value obtained on the sampled pixel to the eight neighboring pixels. The method allowed extending the original learning database made up of 97 field EC measurements (OD) to an enhanced learning database made up of 691 observations (ED). Two classification machine-learning models (i.e., Random Forest-RF and Support Vector Machine-SVM) were trained with both OD and ED to assess the efficiency of the proposed method by comparing the models' outcomes with EC observations not used in the models´ training. The use of ED led to a significant increase in both models' consistency with the overall accuracy of the RF (SVM) model increasing from 0.25 (0.26) when using the OD to 0.77 (0.55) when using ED. This corresponds to an improvement of approximately 208% and 111%, respectively. Besides the improved accuracy reached with the ED database, the results showed that the RF model provided better soil salinity estimations than the SVM model and that feature selection (i.e., Variance Inflation Factor-VIF and/or Genetic Algorithm-GA) increase both models´ reliability, with GA being the most efficient. This study highlights the potential of machine-learning and Sentinel-2 image combination for soil salinity monitoring in a data-scarce context, and shows the importance of both model and features selection for an optimum machine-learning set-up.

Evaluating newly approved drugs in combination regimens for multidrug-resistant tuberculosis with fluoroquinolone resistance (endTB-Q): study protocol for a multi-country randomized controlled trial.

BACKGROUND: Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients. METHODS: endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations. DISCUSSION: This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen. TRIAL REGISTRATION: ClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.

Protein signatures of spontaneous lipolysis and lipoprotein lipase activity in cow's milk.

Spontaneous milk lipolysis refers to the breakdown of triacylglycerols in milk. Lipolysis impacts the organoleptic value of milk by causing off-flavours and reduces the technological properties of milk. Lipolysis is caused by lipoprotein lipase (LPL), a tightly regulated enzyme in milk. Our objective was to identify robust biomarkers of lipolysis and putative regulators of LPL enzyme in bovine milk. To achieve this goal, we used feed restriction as a lever to generate highly contrasted samples with regard to milk lipolysis. We combined statistical methods on proteomics data, milk lipolysis and LPL activity values. Following this strategy, we identified CD5L and GP2 as robust biomarkers of high lipolysis in cow milk. We also identified HID1, SURF4 and CUL9 as putative inhibitors of the lipolytic process in the milk. We thus proposed 5 putative biomarkers to be considered in future tools to manage milk lipolysis. SIGNIFICANCE: This manuscript is notable in three aspects. First, this is the first evaluation of the milk proteome relative to milk lipolysis or LPL activity. Second, the relationship between the abundance of proteins and milk traits was evaluated by a combination of univariate and multivariate analyses. Third, we provide a short list of five proteins to be tested in a larger population to feed the pipeline of biomarker discovery.

Risk factors for conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia: A retrospective case-control study.

OBJECTIVES: General anesthesia for cesarean is associated with an increased risk of maternal morbidity compared with neuraxial anesthesia. Reducing the rate of general anesthesia for urgent cesarean in women with epidural analgesia may improve maternal outcomes. Our objective was to identify the rate and factors associated with the conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia. STUDY DESIGN: We performed a retrospective case-control study including singleton-laboring women with epidural analgesia who delivered after 37 gestational weeks by urgent cesarean (Port Royal Maternity unit, 2012-2017). Cases were all women who required conversion from neuraxial analgesia to general anesthesia. Controls were women just before and after each case included. Factors associated with the conversion to general anesthesia were identified using logistic regression analysis. RESULTS: Among 3,300 laboring women with an epidural analgesia who delivered by urgent cesarean during the study period, 113 (3.4%,) had a conversion to general anesthesia. Factors associated with conversion to general anesthesia were a cervical dilation ≥ 5 cm at the time of epidural placement (aOR 2.55, 95%CI 1.05-6.21), asymmetric sensory blockade (aOR 3.39, 95%CI 1.11-10.36), need for ≥2 rescue top-ups (aOR 2.88, 95%CI 1.29-6.44), and category 1 cesarean (aOR 3.61, 95%CI 1.77-7.33). CONCLUSION: Among women with labor epidural analgesia, suboptimal analgesia significantly increased the risk for conversion to general anesthesia for urgent cesarean. Epidural placement without delay during labor, regular checks of epidural analgesia efficiency, and epidural replacement in case of inadequate epidural analgesia may decrease the rate of avoidable general anesthesia for urgent cesarean.

Capacity Building in Sub-Saharan Africa as Part of the INTENSE-TBM Project During the COVID-19 Pandemic.

Tuberculous meningitis (TBM) is the most severe and disabling form of tuberculosis (TB), with at least 100,000 cases per year and a mortality rate of up to 50% in individuals co-infected with human immunodeficiency virus type 1 (HIV-1). To evaluate the efficacy and safety of an intensified anti-tubercular regimen and an anti-inflammatory treatment, the INTENSE-TBM project includes a phase III randomised clinical trial (TBM-RCT) in four countries in sub-Saharan Africa (SSA). Within this framework, we designed a comprehensive capacity-building work package ensuring all centres had, or would acquire, the ability to conduct the TBM-RCT and developing a network of skilled researchers, clinical centres and microbiology laboratories. Here, we describe these activities, identify strengths/challenges and share tools adaptable to other projects, particularly in low- and lower-middle income countries with heterogeneous settings and during the coronavirus disease 2019 (COVID-19) pandemic. Despite major challenges, TBM-RCT initiation was achieved in all sites, promoting enhanced local healthcare systems and encouraging further clinical research in SSA. In terms of certified trainings, the achievement levels were 95% (124/131) for good clinical practice, 91% (39/43) for good clinical laboratory practice and 91% (48/53) for infection prevention and control. Platform-based research, developed as part of capacity-building activities for specific projects, may be a valuable tool in fighting future infectious diseases and in developing high-level research in Africa.

The INTENSE-TBM project aimed to design a comprehensive work-package on capacity building, ensuring all centres would acquire the ability to conduct a phase III randomised clinical trial on TBM in sub-Saharan Africa, to reduce tuberculous meningitis mortality and morbidity in patients with/without HIV-1 co-infection. Therefore, the INTENSE-TBM project is an example of how an international clinical research consortium can provide opportunities to enhance local capacity building and promote centres without previous experience in clinical research. This article provides practical approaches for implementing effective capacity-building programmes. We highlight how to overcome limitations imposed by the COVID-19 pandemic to successfully complete clinics, laboratory set-ups and personnel training, so as to optimise resources and empower African institutions on a local level. At the same time, our experience shows how capacity-building programmes can deliver long-lasting impact that extends beyond the original aims of the project (e.g. HIV and TB), and support local health systems in fighting other infectious disease (e.g. COVID-19). Research projects in low- and lower-middle income countries with heterogeneous settings could stand to benefit the most.

Knowledge, attitudes and practices on childhood TB among healthcare workers.

BACKGROUND: Increasing childhood TB case detection requires the deployment of diagnostic services at peripheral healthcare level. Capacity and readiness of healthcare workers (HCWs) are key to the delivery of innovative approaches.METHODS: In 2019, HCWs from five district hospitals (DHs) and 20 primary healthcare centres (PHCs) in Cambodia, Cameroon, Cote d´Ivoire, Sierra Leone and Uganda completed a self-administered knowledge-attitudes-practices (KAP) questionnaire on childhood TB. We computed knowledge and attitudes as scores and identified HCW characteristics associated with knowledge scores using linear regression.RESULT: Of 636 eligible HCWs, 497 (78%) participated. Median knowledge scores per country ranged between 7.4 and 12.1 (/18). Median attitude scores ranged between 2.8 and 3.3 (/4). Between 13.3% and 34.4% of HCWs reported diagnosing childhood with (presumptive) TB few times a week. Practising at PHC level, being female, being involved in indirect TB care, having a non-permanent position, having no previous research experience and working in Cambodia, Cameroon, Cote d´Ivoire and Sierra Leone as compared to Uganda were associated with a lower knowledge score.CONCLUSION: HCWs had overall limited knowledge, favourable attitudes and little practice of childhood TB diagnosis. Increasing HCW awareness, capacity and skills, and improving access to effective diagnosis are urgently needed.

[Reprint of: Severe pre-eclampsia: guidelines for clinical practice from the French Society of anesthesiology and intensive care (SFAR) and the French College of gynaecologists and obstetricians (CNGOF)]. / Republication de : recommandations formalisées d'experts. Prise en charge de la patiente avec une pré-éclampsie sévère­RFE communes Société française d'anesthésie-réanimation (SFAR)­Collège national des gynécologues et obstétriciens français (CGNOF).

OBJECTIVE: To provide national guidelines for the management of women with severe preeclampsia. DESIGN: A consensus committee of 26 experts was formed. A formal conflict of interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. METHODS: The last SFAR and CNGOF guidelines on the management of women with severe preeclampsia was published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analyzed according to the GRADE® methodology. RESULTS: The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1±), 9 have a moderate level of evidence (GRADE 2±), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations. CONCLUSIONS: There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe preeclampsia.

Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial.

BACKGROUND: Treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings. METHODS: endTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations. DISCUSSION: The lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.

The ID NOW COVID-19, a high-speed high-performance assay.

The ID NOW COVID-19 assay is a promising tool for the rapid identification of COVID-19 patients. However, its performances were questioned. We evaluate the ID NOW COVID-19 in comparison to a reference RT-PCR using a collection of 48 fresh nasopharyngeal swabs sampled on universal transport media (UTM). Only 2 false negatives of the ID NOW COVID-19 were identified. They display PCR cycle threshold values of 37.5 and 39.2. The positive percent agreement and the negative percent agreement were 94.9% and 100%, respectively. The Kappa value was 0.88. The ID NOW COVID-19 combines high-speed and accurate processing. Using UTM, the ID NOW COVID-19 could be repeated in the case of invalid result. Further analyses, such as screening of genetic variants or genome sequencing, could also be performed with the same sample. As for all tests, the results should be interpreted according to clinical and epidemiological context.

When and how should I transfuse during obstetric hemorrhage?

The incidence of maternal hemorrhage and blood transfusion has increased over time. Causes of massive hemorrhage, defined as a transfusion > 10 units of erythrocytes, include abnormal placental insertion, preeclampsia, and placental abruption. Although ratio-based transfusion has been described for managing massive hemorrhage, a goal-directed approach using laboratory or point-of-care data may lead to better outcomes. Autotransfusion, which involves the collection, washing, and filtration of maternal shed blood, avoids many of the complications associated with allogeneic blood transfusion. In this review, we provide an overview of transfusion practices related to the management of obstetric hemorrhage.

Clinical profiles of placenta accreta spectrum: the PACCRETA population-based study.

OBJECTIVE: To describe and compare the characteristics of women with placenta accreta spectrum (PAS) and their pregnancy outcomes according to the presence of placenta praevia and a prior caesarean section. DESIGN: Prospective population-based study. SETTING: All 176 maternity hospitals of eight French regions. POPULATION: Two hundred and forty-nine women with PAS, from a source population of 520 114 deliveries. METHODS: Women with PAS were classified into two risk-profile groups, with or without the high-risk combination of placenta praevia (or an anterior low-lying placenta) and at least one prior caesarean. These two groups were described and compared. MAIN OUTCOME MEASURES: Population-based incidence of PAS, characteristics of women, pregnancies, deliveries and pregnancy outcomes. RESULTS: The PAS population-based incidence was 4.8/10 000 (95% CI 4.2-5.4/10 000). After exclusion of women lost to follow up from the analysis, the group with placenta praevia and a prior caesarean included 115 (48%) women and the group without this combination included 127 (52%). In the group with both factors, PAS was more often suspected antenatally (77% versus 17%; P < 0.001) and more often percreta (38% versus 5%; P < 0.001). This group also had more hysterectomies (53% versus 21%, P < 0.001) and higher rates of blood product transfusions, maternal complications, preterm births and neonatal intensive care unit admissions. Sensitivity analysis showed similar results after exclusion of women who delivered vaginally. CONCLUSION: More than half the cases of PAS occurred in women without the combination of placenta praevia and a prior caesarean delivery, and these women had better maternal and neonatal outcomes. We cannot completely rule out that some of the women who delivered vaginally had placental retention rather than PAS; however, we found similar results among women who delivered by caesarean. TWEETABLE ABSTRACT: Half the women with PAS do not have both placenta praevia and a prior caesarean delivery, and they have better maternal outcomes.