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Background No study has been conducted to demonstrate the feasibility of an opioid-free anesthesia (OFA) protocol in cardiac surgery to improve patient care. The aim of the present study was to evaluate the effect of OFA on post-operative morphine consumption and the post-operative course. Methods After retrospectively registering to clinicaltrial.gov (NCT03816592), we performed a retrospective matched cohort study (1:1) on cardiac surgery patients with cardiopulmonary bypass between 2018 and 2019. Patients were divided into two groups: OFA (lidocaine, dexamethasone and ketamine) or opioid anaesthesia (OA) (sufentanil). The main outcome was the total postoperative morphine consumption in the 48 h after surgery. Secondary outcomes were rescue analgesic use, a major adverse event composite endpoint, and ICU and hospital length of stay (LOS). Results One hundred ten patients were matched (OFA: n  = 55; OA: n = 55). On inclusion, demographic and surgical data for the OFA and OA groups were comparable. The total morphine consumption was higher in the OA group than in the OFA group (15 (6–34) vs 5 mg (2–18), p  = 0.001). The pain score during the first 48 post-operative hours did not differ between the two groups. Creatinine values did not differ on the first post-operative day (80 (IQR: 66–115) vs 77 mmol/l (IQR: 69–95), p  = 0.284). Incidence of the composite endpoint was lower in the OFA group (25 patients (43%) vs 38 patients (68%), p  = 0.021). The time to extubation and the ICU stays were shorter in the OFA group (3 (1–5) vs 5 (3–6) hours, p = 0.001 and 2 (1–3) vs 3 (2–5) days, p  = 0.037). Conclusion The use of OFA was associated with lower morphine consumption. OFA might be associated with shorter intubation time and ICU stays. Further randomized studies are needed to confirm these results. Trial registration This study was retrospectively registered to ct2 (identifier: NCT03816592 ) on January 25, 2019.

Background: No study has been conducted to demonstrate the feasibility of an opioid-free anesthesia (OFA) protocol in cardiac surgery to improve patient care. The aim of the present study was to evaluate the effect of OFA on post-operative morphine consumption and the post-operative course. Methods: After retrospectively registering to clinicaltrial.gov (NCT03816592), we performed a retrospective matched cohort study (1:1) on cardiac surgery patients with cardiopulmonary bypass between 2018 and 2019. Patients were divided into two groups: OFA (lidocaine, dexamethasone and ketamine) or opioid anaesthesia (OA) (sufentanil). The main outcome was the total postoperative morphine consumption in the 48 hours after surgery. Secondary outcomes were rescue analgesic use, a major adverse event composite endpoint, and ICU and hospital length of stay (LOS). Results: 110 patients were matched (OFA: n=55; OA: n=55). On inclusion, demographic and surgical data for the OFA and OA groups were comparable. The total morphine consumption was higher in the OA group than in the OFA group (15 (6-34) vs 5 mg (2-18), p=0.001). The pain score during the first 48 post-operative hours did not differ between the two groups. Creatinine values did not differ on the first post-operative day (80 (IQR: 66-115) vs 77 mmol/l (IQR: 69-95), p=0.284). Incidence of the composite endpoint was lower in the OFA group (25 patients (43%) vs 38 patients (68%), p=0.021). The time to extubation and the ICU stays were shorter in the OFA group (3 (1-5) vs 5 (3-6) hours, p=0.001 and 2 (1-3) vs 3 (2-5) days, p=0.037). Conclusion: The use of OFA was associated with lower morphine consumption. OFA might be associated with shorter intubation time and ICU stays. Further randomized studies are needed to confirm these results.

There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment. In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults with HCC who tolerated sorafenib (≥400 mg/day for ≥20 of last 28 days of treatment), progressed on sorafenib, and had Child-Pugh A liver function were enrolled. Participants were randomly assigned (2:1) by a computer-generated randomisation list and interactive voice response system and stratified by geographical region, Eastern Cooperative Oncology Group performance status, macrovascular invasion, extrahepatic disease, and α-fetoprotein level to best supportive care plus oral regorafenib 160 mg or placebo once daily during weeks 1–3 of each 4-week cycle. Investigators, patients, and the funder were masked to treatment assignment. The primary endpoint was overall survival (defined as time from randomisation to death due to any cause) and analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01774344. Between May 14, 2013, and Dec 31, 2015, 843 patients were screened, of whom 573 were enrolled and randomised (379 to regorafenib and 194 to placebo; population for efficacy analyses), and 567 initiated treatment (374 received regorafenib and 193 received placebo; population for safety analyses). Regorafenib improved overall survival with a hazard ratio of 0·63 (95% CI 0·50–0·79; one-sided p<0·0001); median survival was 10·6 months (95% CI 9·1–12·1) for regorafenib versus 7·8 months (6·3–8·8) for placebo. Adverse events were reported in all regorafenib recipients (374 [100%] of 374) and 179 (93%) of 193 placebo recipients. The most common clinically relevant grade 3 or 4 treatment-emergent events were hypertension (57 patients [15%] in the regorafenib group vs nine patients [5%] in the placebo group), hand–foot skin reaction (47 patients [13%] vs one [1%]), fatigue (34 patients [9%] vs nine patients [5%]), and diarrhoea (12 patients [3%] vs no patients). Of the 88 deaths (grade 5 adverse events) reported during the study (50 patients [13%] assigned to regorafenib and 38 [20%] assigned to placebo), seven (2%) were considered by the investigator to be related to study drug in the regorafenib group and two (1%) in the placebo group, including two patients (1%) with hepatic failure in the placebo group. Regorafenib is the only systemic treatment shown to provide survival benefit in HCC patients progressing on sorafenib treatment. Future trials should explore combinations of regorafenib with other systemic agents and third-line treatments for patients who fail or who do not tolerate the sequence of sorafenib and regorafenib. Bayer.

To evaluate drug-related problems in the elderly, various lists of potentially inappropriate medications have been published in North America. Unfortunately, these lists are hardly applicable in France. The purpose of this study was to establish a list of inappropriate medications for French elderly using the Delphi method. A two-round Delphi method was used to converge to an agreement between a pool of 15 experts from various parts of France and from different backgrounds (five geriatricians, five pharmacologists, two pharmacists, two general practitioners, one pharmacoepidemiologist). In round one, they were sent a questionnaire based on a literature review listing medications and clinical situations. They were asked to comment on the potential inappropriateness of the criteria proposed using a 5-point Likert scale (from strong agreement to strong disagreement) and to suggest therapeutic alternatives and new criteria. In round two, the experts confirmed or cancelled their previous answers from the synthesis of the responses of round one. After round two, a final list of potentially inappropriate drugs was established. The final list proposed 36 criteria applicable to people >/=75 years of age. Twenty-nine medications or medication classes applied to all patients, and five criteria involved medications that should be avoided in specific medical conditions. Twenty-five medications or medication classes were considered with an unfavourable benefit/risk ratio, one with a questionable efficacy and eight with both unfavourable benefit/risk ratio and questionable efficacy. This expert consensus should provide prescribers with an epidemiological tool, a guideline and a list of alternative therapies.

In December 2024, L’Initiative-Expertise France organized a workshop in Musanze, Rwanda, for National Malaria Control and Elimination Programmes (NMC/EPs) representatives from 19 sub-Saharan African countries. The workshop focused on surveillance, modeling, climate forecasting, and innovative control methods to mitigate climate change impacts on malaria. Participants shared challenges, experiences and best practices. Key challenges highlighted include shifts in malaria transmission seasons, disease spread to mid-altitude regions, and infrastructure damage from extreme weather. Additional factors, such as drug and insecticide resistance, the spread of Anopheles stephensi , and changes in vector behaviour, are exacerbating malaria transmission in African cities. Participants stressed the need for collaborative efforts to tackle these evolving threats. This comment reflects the expertise and insights of 19 NMCPs actively managing malaria control and aims at raising awareness, inform policy discussions, and strengthen global partnerships to address the intersection of malaria and climate change.

The Democratic Republic of the Congo faces a high tuberculosis (TB) burden. In 2022, 61% of an estimated 402,000 TB cases were reported (World Health Organization Global tuberculosis report). To enhance case detection, the national TB program (NTP) introduced a program quality and efficiency approach (PQE), integrating systematic TB screening into outpatient departments (OPDs). Observational data of the PQE on the TB care cascade (from screening to treatment) across 70 sites in Kinshasa that initiated PQE during the first quarter of 2023 are presented. Data were collected monthly and validated during supervision visits, and disaggregated by sex, healthcare facility type (public, private, or faith-based), facility level (primary or secondary), and OPD within each facility. In 2024, 639,464 individuals were consulted in various OPDs in the participating facilities, 57% of which were female. The median number needed to screen (NNS) was 22.1, with an interquartile range of [9.5–104.3]. There was a significantly lower NNS observed in general practice and human immunodeficiency virus departments. Throughout the TB care cascade, women were less likely than men to be screened, tested, or treated. These findings, to be interpreted within the context of Kinshasa pilot facilities, provide insights to the NTP for developing PQE implementation research aimed at understanding the reasons for these discrepancies and informing NTP scale-up at the national level.

In France, the conservation of geological heritage has a complex history that dates back to the middle of the 19th century. Two regulatory tools, \"Site Classe\", established in 1906, and Natural Reserves, created in 1976, have served to protect geological sites in the past. Nonetheless, these tools are long to implement vis-a-vis to the rapid destruction of geological objects in the French territory. Due to this juridical void, the state created in 2015 two prefectural decrees for the protection of geological sites of interest. These tools allow the Prefect to: (i) determine a departmental list of geological sites of importance; (ii) define appropriate regulations for their conservation through the Prefectural Decree of the Protection of the Geotope (APPG). Their decentralised legal proceedings appear to be easy to administer, as they only require the advice of regional and departmental commissions as well as some local stakeholders. Our article reports the first enactment of the APPG in France, in a peri-urban to urban area, the Yvelines department. By relying on the programmes of Strategy of Creation of Protected metropolitan Areas (SCAP) and the National Inventory of the Geological Heritage (INPG), two geological sites of international value threatened by anthropic activities were selected for the APPG: the Lutetian fossil sites of Grignon and the Ferme de l'Orme. If successfully enacted, the APPG could prove advantageous because it is a tool adapted to the protection of geological objects and to its socio-economic and environmental context. However, after almost two years, the proceedings of the APPG have not been finalised. Optional yet beneficial steps, as well as unforeseen requests, delayed the process considerably. Given that the APPG do not confer protection to the geological sites during this period, their efficacy must be questioned in a fast-evolving region where land pressure is high and geological sites disappear quickly. However, the French juridical system has improved in the recent years in that it encourages Earth Sciences specialists to form part of local consultative instances (CSRPN, CDNPS) and thereby influence the decisions concerning the protection of these highly threatened sites.

Background: The IFCT-1603 trial evaluated atezolizumab in small cell lung cancer (SCLC). The purpose of the present study was to determine whether circulating tumor DNA (ctDNA), prospectively collected at treatment initiation, was associated with the prognosis of SCLC, and whether it identified patients who benefited from atezolizumab. Methods: 68 patients were included in this study: 46 patients were treated with atezolizumab and 22 with conventional chemotherapy. Circulating DNA was extracted from plasma and NGS (Next Generation Sequencing) looked for mutations in the TP53, RB1, NOTCH1, NOTCH2, and NOTCH3 genes. ctDNA was detectable when at least one somatic mutation was identified, and its relative abundance was quantified by the variant allele fraction (VAF) of the most represented mutation. Results: We found that 49/68 patients (70.6%) had detectable baseline ctDNA. The most frequently identified mutations were TP53 (32/49; 65.3%) and RB1 (25/49; 51.0%). Patients with detectable ctDNA had a significantly lower disease control rate at week 6 compared with patients with no detectable ctDNA, regardless of the nature of the treatment. Detection of ctDNA was associated with a poor OS prognosis. The detection of ctDNA at a relative abundance greater than the median value was significantly associated with poor overall survival (OS) and progression free survival (PFS). Interestingly, the benefit in overall survival (OS) associated with low ctDNA was more pronounced in patients treated with atezolizumab than in patients receiving chemotherapy. Among patients whose relative ctDNA abundance was below the median, those treated with atezolizumab tended to have higher OS than those in the chemotherapy arm. Conclusion: ctDNA is strongly associated with the prognosis of SCLC patients treated with second-line immunotherapy. Its analysis seems justified for future SCLC clinical trials.

PurposeMandibular repositioning devices (MRDs) are an effective treatment option for obstructive sleep apnea syndrome (OSAS), particularly in patients who refuse or cannot tolerate continuous positive airway pressure (CPAP). However, sex differences in the response to therapy and predictors of response are not clearly defined. This analysis of data from the long-term prospective ORCADES trial compared MRD efficacy in men and women with OSAS.MethodsThe ORCADES study included patients with newly diagnosed mild-to-moderate or severe OSAS who refused or were non-compliant with CPAP. MRD therapy was titrated over 3–6 months. The primary endpoint was treatment success (≥ 50% decrease in apnea-hypopnea index (AHI)). Complete response was defined using a range of AHI cut-off values (< 5/h, < 10/h, < 15/h).ResultsOverall treatment success rates were 89% in women and 76% in men (p = 0.019); corresponding rates in those with severe OSAS (AHI > 30/h) were 100% and 68% (p = 0.0015). In women vs. men, overall complete response rates at AHI cut-off values of < 5/h, <10/h, and < 15/h were 49 vs. 34% (p = 0.0052), 78 vs. 62% (p = 0.016), and 92 vs. 76% (p = 0.0032). On multivariate analysis, significant predictors of MRD treatment success were overbite and baseline apnea index in men, and neck circumference and no previous CPAP therapy in women. There were sex differences in the occurrence of side effects. Temporomandibular joint pain was the most common reason for stopping MRD therapy.ConclusionsMRD therapy was effective in women with OSA of any severity, with significantly higher response rates compared with men especially in severe OSAS.Trial registrationwww.clinicaltrials.gov (NCT01326143).

Cell‐free plasma DNA (cfDNA) and mimicking circulating tumor cells (mCTCs) have demonstrated tremendous potential for molecular diagnosis of cancer and have been rapidly implemented in specific settings. However, widespread clinical adoption still faces some obstacles. The purpose was to compare the performance of a BEAMing (beads, emulsion, amplification, and magnetics) assay (OncoBEAM™‐epidermal growth factor receptor [EGFR] [Sysmex Inostics]) and a next‐generation sequencing assay (NGS; 56G Oncology panel kit, Swift Bioscience) to detect the p.T790M EGFR mutation in cfDNA of non‐small cell lung cancer (NSCLC) patients. CfDNA samples (n = 183) were collected within our hospital from patients having a known EGFR sensitizing mutation, and presenting disease progression while under first‐line therapy. EGFR mutations were detected using NGS in 42.1% of samples during progression in cfDNA. Testing using the OncoBEAM™‐EGFR assay enabled detection of the p.T790M EGFR mutation in 40/183 NSCLC patients (21.8%) versus 20/183 (10.9%), using the NGS assay. Samples that were only positive with the OncoBEAM™‐EGFR assay had lower mutant allelic fractions (Mean = 0.1304%; SD ± 0.1463%). In addition, we investigated the detection of p.T790M in mCTCs using H1975 cells. These cells spiked into whole blood were enriched using the ClearCellFX1 microfluidic device. Using the OncoBEAM™‐EGFR assay, p.T790M was detected in as few as 1.33 tumoral cells/mL. Overall, these findings highlight the value of using the OncoBEAM™‐EGFR to optimize detection of the p.T790M mutation, as well as the complementary clinical value that each of the mutation detection assay offers: NGS enabled the detection of mutations in other oncogenes that may be relevant to secondary resistance mechanisms, whereas the OncoBEAM™‐EGFR assay achieved higher sensitivity for detection of clinically actionable mutations. In cell‐free DNA and mimicking circulating tumor cells (sensitivity at 1.33 tumoral cells/mL whole blood), for the first time, we highlighted the value of using the OncoBEAMTM‐epidermal growth factor receptor (EGFR) to optimize detection of the p.T790M mutation, as well as the complementary clinical value that each of the mutation detection assay offers: next‐generation sequencing provided enhanced coverage of EGFR mutations, and enabled the detection of mutations in other oncogenes, whereas the OncoBEAMTM‐EGFR assay achieved higher sensitivity for detection of clinically actionable mutations such as p.T790M.