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1.
Cell ; 169(5): 878-890.e15, 2017 May 18.
Article in English | MEDLINE | ID: mdl-28525755

ABSTRACT

Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes. Only a few somatic hypermutations are required for broad antiviral activity, and germline-approximating variants display enhanced GPCL recognition, suggesting that such antibodies could be elicited more efficiently with suitably optimized GP immunogens. Our findings inform the development of both broadly effective immunotherapeutics and vaccines against filoviruses.


Subject(s)
Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/isolation & purification , Ebola Vaccines/immunology , Hemorrhagic Fever, Ebola/immunology , Survivors , Amino Acid Sequence , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/immunology , Antibodies, Viral/chemistry , Antibodies, Viral/immunology , Chlorocebus aethiops , Cross Reactions , Ebolavirus/classification , Ebolavirus/immunology , Female , Ferrets , Hemorrhagic Fever, Ebola/virology , Humans , Kinetics , Mice , Mice, Inbred BALB C , Models, Molecular , Sequence Alignment , Vero Cells
2.
Brief Bioinform ; 25(3)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38557673

ABSTRACT

IMPRINTS-CETSA (Integrated Modulation of Protein Interaction States-Cellular Thermal Shift Assay) provides a highly resolved means to systematically study the interactions of proteins with other cellular components, including metabolites, nucleic acids and other proteins, at the proteome level, but no freely available and user-friendly data analysis software has been reported. Here, we report IMPRINTS.CETSA, an R package that provides the basic data processing framework for robust analysis of the IMPRINTS-CETSA data format, from preprocessing and normalization to visualization. We also report an accompanying R package, IMPRINTS.CETSA.app, which offers a user-friendly Shiny interface for analysis and interpretation of IMPRINTS-CETSA results, with seamless features such as functional enrichment and mapping to other databases at a single site. For the hit generation part, the diverse behaviors of protein modulations have been typically segregated with a two-measure scoring method, i.e. the abundance and thermal stability changes. We present a new algorithm to classify modulated proteins in IMPRINTS-CETSA experiments by a robust single-measure scoring. In this way, both the numerical changes and the statistical significances of the IMPRINTS information can be visualized on a single plot. The IMPRINTS.CETSA and IMPRINTS.CETSA.app R packages are freely available on GitHub at https://github.com/nkdailingyun/IMPRINTS.CETSA and https://github.com/mgerault/IMPRINTS.CETSA.app, respectively. IMPRINTS.CETSA.app is also available as an executable program at https://zenodo.org/records/10636134.


Subject(s)
Mobile Applications , Software , Proteome , Algorithms , Research Design
3.
Nature ; 587(7834): 460-465, 2020 11.
Article in English | MEDLINE | ID: mdl-33149301

ABSTRACT

Atrial fibrillation, the most common cardiac arrhythmia, is an important contributor to mortality and morbidity, and particularly to the risk of stroke in humans1. Atrial-tissue fibrosis is a central pathophysiological feature of atrial fibrillation that also hampers its treatment; the underlying molecular mechanisms are poorly understood and warrant investigation given the inadequacy of present therapies2. Here we show that calcitonin, a hormone product of the thyroid gland involved in bone metabolism3, is also produced by atrial cardiomyocytes in substantial quantities and acts as a paracrine signal that affects neighbouring collagen-producing fibroblasts to control their proliferation and secretion of extracellular matrix proteins. Global disruption of calcitonin receptor signalling in mice causes atrial fibrosis and increases susceptibility to atrial fibrillation. In mice in which liver kinase B1 is knocked down specifically in the atria, atrial-specific knockdown of calcitonin promotes atrial fibrosis and increases and prolongs spontaneous episodes of atrial fibrillation, whereas atrial-specific overexpression of calcitonin prevents both atrial fibrosis and fibrillation. Human patients with persistent atrial fibrillation show sixfold lower levels of myocardial calcitonin compared to control individuals with normal heart rhythm, with loss of calcitonin receptors in the fibroblast membrane. Although transcriptome analysis of human atrial fibroblasts reveals little change after exposure to calcitonin, proteomic analysis shows extensive alterations in extracellular matrix proteins and pathways related to fibrogenesis, infection and immune responses, and transcriptional regulation. Strategies to restore disrupted myocardial calcitonin signalling thus may offer therapeutic avenues for patients with atrial fibrillation.


Subject(s)
Arrhythmias, Cardiac/metabolism , Calcitonin/metabolism , Fibrinogen/biosynthesis , Heart Atria/metabolism , Myocardium/metabolism , Paracrine Communication , Animals , Arrhythmias, Cardiac/pathology , Arrhythmias, Cardiac/physiopathology , Atrial Fibrillation , Collagen Type I/metabolism , Female , Fibroblasts/metabolism , Fibrosis/metabolism , Fibrosis/pathology , Heart Atria/cytology , Heart Atria/pathology , Heart Atria/physiopathology , Humans , Male , Mice , Myocardium/cytology , Myocardium/pathology , Myocytes, Cardiac/metabolism , Receptors, Calcitonin/metabolism
4.
Methods ; 224: 10-20, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38295893

ABSTRACT

AMPs are short, mainly cationic membrane-active peptides found in all living organism. They perform diverse roles including signaling and acting as a line of defense against bacterial infections. AMPs have been extensively investigated as templates to facilitate the development of novel antimicrobial therapeutics. Understanding the interplay between these membrane-active peptides and the lipid membranes is considered to be a significant step in elucidating the specific mechanism of action of AMPs against prokaryotic and eukaryotic cells to aid the development of new therapeutics. In this review, we have provided a brief overview of various NMR techniques commonly used for studying AMP structure and AMP-membrane interactions in model membranes and whole cells.


Subject(s)
Antimicrobial Cationic Peptides , Antimicrobial Peptides , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/analysis , Antimicrobial Cationic Peptides/chemistry , Cell Membrane/chemistry , Magnetic Resonance Spectroscopy/methods
5.
J Am Chem Soc ; 146(23): 15860-15868, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38814791

ABSTRACT

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a benchmark hole-transporting (p-type) polymer that finds applications in diverse electronic devices. Most of its success is due to its facile synthesis in water, exceptional processability from aqueous solutions, and outstanding electrical performance in ambient. Applications in fields like (opto-)electronics, bioelectronics, and energy harvesting/storage devices often necessitate the complementary use of both p-type and n-type (electron-transporting) materials. However, the availability of n-type materials amenable to water-based polymerization and processing remains limited. Herein, we present a novel synthesis method enabling direct polymerization in water, yielding a highly conductive, water-processable n-type conjugated polymer, namely, poly[(2,2'-(2,5-dihydroxy-1,4-phenylene)diacetic acid)-stat-3,7-dihydrobenzo[1,2-b:4,5-b']difuran-2,6-dione] (PDADF), with remarkable electrical conductivity as high as 66 S cm-1, ranking among the highest for n-type polymers processed using green solvents. The new n-type polymer PDADF also exhibits outstanding stability, maintaining 90% of its initial conductivity after 146 days of storage in air. Our synthetic approach, along with the novel polymer it yields, promises significant advancements for the sustainable development of organic electronic materials and devices.

6.
Antimicrob Agents Chemother ; 68(7): e0160123, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38829050

ABSTRACT

We examined the correlation between three different methods of Mycobacterium tuberculosis quantification: time to positivity (TTP), log10 CFU, and an assay to detect differentially detectable M. tuberculosis (DD Mtb) from three different prospective studies. Participants with DD Mtb have significantly more variation in the CFU/TTP correlation than participants with no DD Mtb (P < 0.001). This may impact the design of early bactericidal activity studies that use TTP as the primary outcome.


Subject(s)
Bacterial Load , Mycobacterium tuberculosis , Mycobacterium tuberculosis/drug effects , Humans , Bacterial Load/methods , Prospective Studies , Male , Adult , Female
7.
Ann Surg ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38887938

ABSTRACT

OBJECTIVE: To analyse outcomes after adult right ex-situ split graft liver transplantations (RSLT) and compare with available outcome benchmarks from whole liver transplantation (WLT). SUMMARY BACKGROUND DATA: Ex-situ SLT may be a valuable strategy to tackle the increasing graft shortage. Recently established outcome benchmarks in WLT offer a novel reference to perform a comprehensive analysis of results after ex-situ RSLT. METHODS: This retrospective multicenter cohort study analyzes all consecutive adult SLT performed using right ex-situ split grafts from 01.01.2014 to 01.06.2022. Study endpoints included 1 year graft and recipient survival, overall morbidity expressed by the comprehensive complication index (CCI©) and specific post-LT complications. Results were compared to the published benchmark outcomes in low-risk adult WLT scenarii. RESULTS: In 224 adult right ex-situ SLT, 1y recipient and graft survival rates were 96% and 91.5%, within the WLT benchmarks. The 1y overall morbidity was also within the WLT benchmark (41.8 CCI points vs. <42.1). Detailed analysis, revealed cut surface bile leaks (17%, 65.8% Grade IIIa) as a specific complication without a negative impact on graft survival. There was a higher rate of early hepatic artery thrombosis (HAT) after SLT, above the WLT benchmark (4.9% vs. ≤4.1%), with a significant impact on early graft but not patient survival. CONCLUSION: In this multicentric study of right ex-situ split graft LT, we report 1-year overall morbidity and mortality rates within the published benchmarks for low-risk WLT. Cut surface bile leaks and early HAT are specific complications of SLT and should be acknowledged when expanding the use of ex-situ SLT.

8.
Oncologist ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38970398

ABSTRACT

BACKGROUND: Currently available predictive models for chemotherapy-related toxicity are not sufficiently discriminative in older patients with cancer and do not consider moderate toxicities. The purpose of this study was to identify factors associated with moderate and severe chemotherapy toxicities in older patients with cancer. MATERIALS AND METHODS: Patients aged 70+ recruited in the prospective ELCAPA cohort were analyzed. A total of 837 patients with data on toxicities had received chemotherapy without other systemic treatment and were included between 2015 and 2022. To adjust for any imbalances in the distribution of covariates between patients receiving single-agent chemotherapy vs combination chemotherapy, we applied overlap weighting (a propensity-score-based technique). We used multinomial logistic regression. RESULTS: Median (interquartile range) age was 81 (77-84). Forty-one percent experienced moderate toxicity, and 33% experienced severe toxicity. Hematologic toxicities accounted for 53% of severe toxicities and 66% of moderate toxicities. Age <80 years, cancer type, metastatic status, Eastern Cooperative Oncology Group performance status (ECOG-PS) >1, no cognitive impairment were associated with combination chemotherapy decision. In a univariate analysis with overlap weighting, no factors were associated with moderate toxicity. Hemoglobin < 0 g/dL and a CIRS-G score >12 were associated with severe toxicity. In a multivariate analysis, only hemoglobin < 10 g/dL was independently associated with severe toxicity, adjusted OR 2.96 (95% CI, 1.20-7.29). CONCLUSION: By addressing indication bias for combination chemotherapy decision, only anemia and not cancer type, combination chemotherapy was predicting for severe chemotherapy-related toxicity in older patients with cancer. We did not find any predictors of moderate chemotherapy-related toxicity.

9.
Liver Transpl ; 30(8): 805-815, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38466885

ABSTRACT

The purpose of this study was to propose an innovative intraoperative criterion in a liver transplantation setting that would judge arterial flow abnormality that may lead to early hepatic arterial occlusion, that is, thrombosis or stenosis, when left untreated and to carry out reanastomosis. After liver graft implantation, and after ensuring that there is no abnormality on the Doppler ultrasound (qualitative and quantitative assessment), we intraoperatively injected indocyanine green dye (0.01 mg/Kg), and we quantified the fluorescence signal at the graft pedicle using ImageJ software. From the obtained images of 89 adult patients transplanted in our center between September 2017 and April 2019, we constructed fluorescence intensity curves of the hepatic arterial signal and examined their relationship with the occurrence of early hepatic arterial occlusion (thrombosis or stenosis). Early hepatic arterial occlusion occurred in 7 patients (7.8%), including 3 thrombosis and 4 stenosis. Among various parameters of the flow intensity curve analyzed, the ratio of peak to plateau fluorescence intensity and the jagged wave pattern at the plateau phase were closely associated with this dreaded event. By combining the ratio of peak to plateau at 0.275 and a jagged wave, we best predicted the occurrence of early hepatic arterial occlusion and thrombosis, with sensitivity/specificity of 0.86/0.98 and 1.00/0.94, respectively. Through a simple composite parameter, the indocyanine green fluorescence imaging system is an additional and promising intraoperative modality for identifying recipients of transplant at high risk of developing early hepatic arterial occlusion. This tool could assist the surgeon in the decision to redo the anastomosis despite normal Doppler ultrasonography.


Subject(s)
Hepatic Artery , Indocyanine Green , Liver Transplantation , Optical Imaging , Thrombosis , Humans , Liver Transplantation/adverse effects , Liver Transplantation/methods , Indocyanine Green/administration & dosage , Hepatic Artery/diagnostic imaging , Male , Female , Middle Aged , Optical Imaging/methods , Thrombosis/etiology , Thrombosis/diagnostic imaging , Aged , Adult , Postoperative Complications/etiology , Postoperative Complications/diagnostic imaging , Postoperative Complications/epidemiology , Postoperative Complications/diagnosis , Ultrasonography, Doppler/methods , Predictive Value of Tests , Arterial Occlusive Diseases/etiology , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/diagnosis , Arterial Occlusive Diseases/surgery , Liver/diagnostic imaging , Liver/blood supply , Liver/surgery , Coloring Agents/administration & dosage , Constriction, Pathologic/etiology , Monitoring, Intraoperative/methods , Retrospective Studies , Intraoperative Care/methods
10.
Mol Syst Biol ; 19(5): e11443, 2023 05 09.
Article in English | MEDLINE | ID: mdl-36942755

ABSTRACT

Metabolism is controlled to ensure organismal development and homeostasis. Several mechanisms regulate metabolism, including allosteric control and transcriptional regulation of metabolic enzymes and transporters. So far, metabolism regulation has mostly been described for individual genes and pathways, and the extent of transcriptional regulation of the entire metabolic network remains largely unknown. Here, we find that three-quarters of all metabolic genes are transcriptionally regulated in the nematode Caenorhabditis elegans. We find that many annotated metabolic pathways are coexpressed, and we use gene expression data and the iCEL1314 metabolic network model to define coregulated subpathways in an unbiased manner. Using a large gene expression compendium, we determine the conditions where subpathways exhibit strong coexpression. Finally, we develop "WormClust," a web application that enables a gene-by-gene query of genes to view their association with metabolic (sub)-pathways. Overall, this study sheds light on the ubiquity of transcriptional regulation of metabolism and provides a blueprint for similar studies in other organisms, including humans.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Humans , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Gene Expression Regulation , Software
11.
J Med Virol ; 96(8): e29836, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39078052

ABSTRACT

Primary effusion lymphoma (PEL) is a rare B-cell non-Hodgkin lymphoma associated with Kaposi Sarcoma-associated herpesvirus (KSHV/HHV8) infection. Lymphoma cells are coinfected with Epstein-Barr virus (EBV) in 60-80% of cases. Tools allowing a reliable PEL diagnosis are lacking. This study reports PEL diagnosis in 4 patients using a Flow-Fluorescence in situ hybridization (FlowFISH) technique that allowed detection of differentially expressed EBV and HHV8 transcripts within the same sample, revealing viral heterogeneity of the disease. Moreover, infected cells exhibited variable expressions of CD19, CD38, CD40, and CD138. Therefore, FlowFISH is a promising tool to diagnose and characterize complex viral lymphoproliferations.


Subject(s)
Herpesvirus 4, Human , Herpesvirus 8, Human , In Situ Hybridization, Fluorescence , Lymphoma, Primary Effusion , Humans , Herpesvirus 8, Human/genetics , Herpesvirus 8, Human/isolation & purification , In Situ Hybridization, Fluorescence/methods , Lymphoma, Primary Effusion/virology , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/isolation & purification , Male , Aged , Middle Aged , Female , Herpesviridae Infections/virology , Herpesviridae Infections/diagnosis , Epstein-Barr Virus Infections/virology , Epstein-Barr Virus Infections/complications , Aged, 80 and over
12.
Ann Surg Oncol ; 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38592622

ABSTRACT

BACKGROUND: Hypothermic liver perfusion decreases ischemia/reperfusion injury during hepatectomy under standard total vascular exclusion (TVE) of the liver. This surgery needs venovenous bypass and is hampered by high morbi-mortality. TVE preserving the inferior vena cava (IVC) flow is hemodynamically well tolerated but remains limited in duration when performed under liver normothermia. The objective of this study was to report the results of TVE preserving the caval flow, modified to allow hypothermic liver perfusion and obviate splanchnic congestion. PATIENTS AND METHODS: The technique, indicated for tumors abutting large tributaries of the hepatic veins but sparing their roots in IVC and the latter, was applied when TVE was anticipated to last for ≥ 60 min. It combines continuous TVE preserving the IVC flow with hypothermic liver perfusion and temporary portacaval shunt (PCS). Results are given as median (range). RESULTS: Vascular control was achieved in 13 patients with excellent hemodynamical tolerance. PCS was direct or via an interposed synthetic graft (five and eight cases, respectively). Liver temperature dropped to 16.5 (6-24) °C under perfusion of 2 (2-4) L of cold perfusate. TVE lasted 67 (54-125) min and 4.5 (0-8) blood units were transfused. Resection was major in nine cases and was complete in all cases. Five complications occurred in four patients, and the 90-day mortality rate was zero. CONCLUSIONS: This technique maintains stable hemodynamics and combines the advantages of in situ or ex situ standard TVE with hypothermic liver perfusion, without their inherent prolongation of ischemia time and need for venovenous bypass.

13.
Phys Rev Lett ; 132(15): 150607, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38682990

ABSTRACT

The Gottesman-Kitaev-Preskill (GKP) code encodes a logical qubit into a bosonic system with resilience against single-photon loss, the predominant error in most bosonic systems. Here we present experimental results demonstrating quantum error correction of GKP states based on reservoir engineering of a superconducting device. Error correction is made fully autonomous through an unconditional reset of an auxiliary transmon qubit. We show that the lifetime of the logical qubit is increased from quantum error correction, therefore reaching the point at which more errors are corrected than generated.

14.
Malar J ; 23(1): 22, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38229097

ABSTRACT

BACKGROUND: Chronic carriage of asymptomatic low-density Plasmodium falciparum parasitaemia in the dry season may support maintenance of acquired immunity that protects against clinical malaria. However, the relationship between chronic low-density infections and subsequent risk of clinical malaria episodes remains unclear. METHODS: In a 2-years study (December 2014 to December 2016) in eastern Gambia, nine cross-sectional surveys using molecular parasite detection were performed in the dry and wet season. During the 2016 malaria transmission season, passive case detection identified episodes of clinical malaria. RESULTS: Among the 5256 samples collected, 444 (8.4%) were positive for P. falciparum. A multivariate model identified village of residence, male sex, age ≥ 5 years old, anaemia, and fever as independent factors associated with P. falciparum parasite carriage. Infections did not cluster over time within the same households or recurred among neighbouring households. Asymptomatic parasite carriage at the end of dry season was associated with a higher risk of infection (Hazard Ratio, HR = 3.0, p < 0.0001) and clinical malaria (HR = 1.561, p = 0.057) during the following transmission season. Age and village of residence were additional predictors of infection and clinical malaria during the transmission season. CONCLUSION: Chronic parasite carriage during the dry season is associated with an increased risk of malaria infection and clinical malaria. It is unclear whether this is due to environmental exposure or to other factors.


Subject(s)
Malaria, Falciparum , Malaria , Male , Humans , Child, Preschool , Plasmodium falciparum , Seasons , Gambia/epidemiology , Cross-Sectional Studies , Malaria, Falciparum/diagnosis , Prevalence
15.
J Pediatr Hematol Oncol ; 46(5): e331-e333, 2024 07 01.
Article in English | MEDLINE | ID: mdl-38652075

ABSTRACT

Multiple myeloma is a rare disease in pediatrics, where about 30 cases are described under 15 years old. It is even rarer when atypical multiple myeloma occurs in the context of autoimmunity. This case describes a 9-year-old female with autoimmune lymphoproliferative-like disease and combined immune deficiency that developed acute kidney failure with monoclonal peak associated with RAC2 and TNFRSF9 variants. An adapted protocol from the backbone adult multiple myeloma standard of care with the addition of an allogeneic hematopoietic stem cell transplant was used. The patient, now nearly a year posttransplant, shows 100% chimerism with no sign of relapse.


Subject(s)
Hematopoietic Stem Cell Transplantation , Humans , Female , Child , Acute Kidney Injury/etiology , Acute Kidney Injury/pathology , Multiple Myeloma/complications , Multiple Myeloma/pathology , Autoimmune Lymphoproliferative Syndrome/complications , Autoimmune Lymphoproliferative Syndrome/pathology , Autoimmune Lymphoproliferative Syndrome/diagnosis , Autoimmune Lymphoproliferative Syndrome/genetics
16.
Curr Cardiol Rep ; 26(6): 601-622, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38625456

ABSTRACT

PURPOSE OF REVIEW: Invasive cardiologists are exposed to large amounts of ionizing radiation. This review aims to summarize the main occupational risks in a radiation-exposed cardiology practice. RECENT FINDINGS: We carried out a literature review on the subject. The studies reviewed allowed us to list six main health risk categories possibly associated with radiation exposure among cardiologists: deoxyribonucleic acid (DNA) and biochemical damages; cancers; ocular manifestations; olfaction, vascular, and neuropsychological alterations; musculoskeletal problems; and reproductive risks. Our descriptive analysis demonstrates higher risks of DNA damage and lens opacities among radiation-exposed cardiology staff. Surveys and questionnaires have demonstrated a higher risk of musculoskeletal disease in exposed workers. Studies reported no difference in cancer frequency between radiation-exposed workers and controls. Changes in olfactory performance, neuropsychological aspects, and vascular changes have also been reported. Limited literature supports the security of continuing radiation-exposed work during pregnancy. Therefore, there is an urgent need to increase knowledge of the occupational risks of radiation exposure and to adopt technologies to reduce them.


Subject(s)
Cardiologists , Occupational Exposure , Radiation Exposure , Humans , Occupational Exposure/adverse effects , Radiation Exposure/adverse effects , Radiation Injuries/etiology , Occupational Diseases/etiology , Radiation, Ionizing , Risk Factors , DNA Damage/radiation effects
17.
Int J Environ Health Res ; : 1-14, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38332610

ABSTRACT

Decentralized water systems (DWS) distribute water in remote African areas. Throughout an intervention in Maniema, Congo, the influence of a DWS performing chlorination in the community's water quality was measured. Additionally, a socio-economic and WASH practices survey was conducted in the communities. Free residual chlorine (FRC) and microbiological contamination were measured; at the borehole, treatment site, distribution points, and households's water containers. In Big Five, water was collected from unimproved sources before DWS construction. Despite that, only 16,6% of households used efficient water treatment methods, resulting in 73% of water stored unsafe for consumption. After construction, household water quality drastically improved, regardless of FRC fluctuations; 93% of samples were classified as low health risk (safe). The renovation guaranteed continuous supply through electro-chlorinators in RVA, where chlorination was intermittent. Water from DWS with adequate chlorine levels prevented microbiological contamination in households for 12 hours. Although economically attractive, the system's sustainability will require future evaluation.

18.
HPB (Oxford) ; 26(1): 102-108, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38038484

ABSTRACT

BACKGROUND: In response to the pandemic, the International Hepato-Pancreato-Biliary Association (IHPBA) developed the IHPBA-COVID Registry to capture data on HPB surgery outcomes in COVID-positive patients prior to mass vaccination programs. The aim was to provide a tool to help members gain a better understanding of the impact of COVID-19 on patient outcomes following HPB surgery worldwide. METHODS: An online registry updated in real time was disseminated to all IHPBA, E-AHPBA, A-HPBA and A-PHPBA members to assess the effects of the pandemic on the outcomes of HPB procedures, perioperative COVID-19 management and other aspects of surgical care. RESULTS: One hundred twenty-five patients from 35 centres in 18 countries were included. Seventy-three (58%) patients were diagnosed with COVID-19 preoperatively. Operative mortality after pancreaticoduodenectomy and major hepatectomy was 28% and 15%, respectively, and 2.5% after cholecystectomy. Postoperative complication rates of pancreatic procedures, hepatic interventions and biliary interventions were respectively 80%, 50% and 37%. Respiratory complication rates were 37%, 31% and 10%, respectively. CONCLUSION: This study reveals a high risk of mortality and complication after HPB surgeries in patient infected with COVID-19. The more extensive the procedure, the higher the risk. Nonetheless, an increased risk was observed across all types of interventions, suggesting that elective HPB surgery should be avoided in COVID positive patients, delaying it at distance from the viral infection.


Subject(s)
Biliary Tract Surgical Procedures , COVID-19 , Humans , COVID-19/epidemiology , Pancreaticoduodenectomy/adverse effects , Hepatectomy , Registries
19.
Ann Pharm Fr ; 82(4): 727-738, 2024 Jun.
Article in French | MEDLINE | ID: mdl-38408723

ABSTRACT

The reform of derogatory access authorisations (DAs) on 1st July 2021 has distorted the routine of the hospital pharmacists dealing with innovative medicines that are waiting for marketing authorization or approval. There are two distinct categories of DAs: Compassionate Access Authorisations (CAAs) are granted by the French National Agency for the Safety of Medicines (ANSM) while Early Access Authorisations (EAPs) are granted at the request of pharmaceutical companies by the French National Authority for Health (HAS). All AAPs and a majority of the AACs are supported by a Protocol for Therapeutic Use and Data Collection (PTU-DC). The aim of this study is to assess the impact of the reform on pharmacy process one year following its implementation, and to identify the risks related to the new circuits. The working group, composed of three pharmacists carried out an initial assessment of the effects first measured the impact of the reform on medicine processes in DAs. They performed a comparison of the changes in their management methods: 3 months prior to the reform (M0), and 3 (M3) and 12 months (M12) post-reform. Risks analysis was conducted using the Failure Modes, Effects and Criticality Analysis (FMEA) method. The analysis was limited to the process steps specific related to DAs drugs were analyzed. The critical severity of the risk situations identified was rated. A critical hierarchy matrix was used to establish priority actions. The priority actions to be taken were determined using the critical hierarchy matrix. Over the span of one year, the number of DAs in our establishment showed a 31.7% increase, from 41 at M0 to 54 at M12. At M0, the proportion of drugs needed inclusion via a drug-specific digital platform, specific to each drug, stood at 27% (11/41) of drugs at M0 while at M12, it rose to 52% (28/54). The percentage of PTU-DCs therefore increased by a factor of 1.7, rising from 29% (12/41) at M0 to 47% (21/45) at M3 and 60% (32/54) at M12. For orders, which are always nominative, approval depends on both the presence of the PTU-DC tracking sheet being present in 12% of PAAs, and the inclusion number in 26% of PAAs. The risk analysis shows 49 failure modes leading to risk situations. Among the failure modes, 36 have a consequence of acceptable or tolerable criticality under control, whilst 13 are deemed of unacceptable criticality. A suitable control method exists has been identifies for 5 of them. Finally, the ranking evaluation of criticalities has highlighted 4 situations which require immediate action as a priority: delivery times, obtaining completed tracking sheets and ordering procedures. The aim of the DAs reform is to simplify access to innovative medicines. However, the reform has significant and damaging repercussions on pharmaceutical activities. Corrective measures need to be taken in conjunction with all parties involved in the circuits including laboratories and service providers (CROs), authorities and healthcare professionals.


Subject(s)
Pharmacists , Pharmacy Service, Hospital , Workload , France , Humans , Pharmacy Service, Hospital/organization & administration , Risk Assessment , Compassionate Use Trials , Drug Approval
20.
Sante Publique ; 35(5): 19-33, 2024 01 03.
Article in French | MEDLINE | ID: mdl-38172045

ABSTRACT

This article reports changes in tobacco and vaping consumption in France over the last thirty years and the issues they raise for public authorities in terms of prevention and management of the social and health consequences. This report is the result of a joint analysis by Santé publique France (SpF) and the French Monitoring Center for Drugs and Drug Addiction (OFDT). It shows that there has been a "generational shift" in tobacco consumption and social representations of cigarettes since the mid-2010s, with a sharp decline in tobacco initiation among adolescents, which has become less common and reported at an older age, which was one of the objectives of the national tobacco reduction plans. However, smoking remains fairly stable among adults, predominantly among men, with gaps between men and women persisting since the early 2000s. Beyond the gender gap, social disparities in consumption remain significant, both among youth and adults. However, while the prevalence of smoking is no longer increasing, the prevalence of vaping is rising, which is a public health concern since some of these practices involve nicotine consumption. This also entails the risk of a "renormalization" of the act of smoking, a matter of concern for health authorities in France as in other European countries. The analysis concludes that the statistical information system and qualitative surveys need to be adapted to ensure a reliable monitoring of the situation, taking into account the rapid transformations of the market.


Cet article fait le point sur les évolutions en matière de consommation de tabac et de produits de vapotage, en France, depuis une trentaine d'années, et les enjeux qu'elles soulèvent pour les pouvoirs publics, en termes de prévention et de prise en charge des conséquences sociosanitaires. Produit d'une analyse conjointe de Santé publique France (SpF) et de l'Observatoire français des drogues et des tendances addictives (OFDT), il montre d'abord un « tournant générationnel ¼ dans la consommation de tabac et les représentations sociales de la cigarette depuis le milieu des années 2010, avec un recul marqué de l'expérimentation parmi les adolescents, qui est devenue à la fois moins courante et plus tardive, ce qui était un des objectifs des plans nationaux de réduction du tabagisme successivement mis en place depuis 2014. Le tabagisme reste néanmoins assez stable parmi les adultes, prédominant chez les hommes, avec des écarts entre hommes et femmes qui se maintiennent depuis le début des années 2000. Au-delà du différentiel de genre, les disparités sociales de consommation restent importantes, parmi les jeunes comme à l'âge adulte. Cependant, si la prévalence du tabagisme ne progresse plus, celle du vapotage augmente, ce qui constitue un point d'attention dès lors qu'une partie de ces pratiques induit une consommation de nicotine. Cela induit également le risque d'une « renormalisation ¼ de l'acte de fumer, qui constitue un point de vigilance des autorités sanitaires, en France comme dans d'autres pays européens. L'analyse se conclut sur la nécessité de continuer à adapter le système d'information statistique et les enquêtes qualitatives pour permettre un suivi épidémiologique de la situation qui reste performant.


Subject(s)
Electronic Nicotine Delivery Systems , Tobacco Products , Male , Adult , Adolescent , Humans , Female , Smoking/epidemiology , Tobacco Smoking/epidemiology , France/epidemiology
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