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Introduction: Faced to the growing development of collecting systematic molecular analyses in relapsed pediatric cancers to transform their targeted matched therapies, this study aimed to assess the clinical and therapeutic indications of systematic diagnostic genomic explorations performed in pediatric solid cancers to determine which type of screening and if it afford at relapse time an accurate targeted strategy., Methods: A total of 280 patients less than 22 years, referred at the University Hospitals of Strasbourg for a newly diagnosed solid tumor from January 2015 to December 2021, were prospectively genomically investigated since diagnosis. Using 7 different molecular tests going from single-gene methods (IHC, FISH, RT-PCR, Sanger sequencing, droplet digital PCR) to largescale analyses (Next-Generation sequencing, RNAsequencing and FoundationOne®CDx), we explored retrospectively the molecular findings in those pediatric solid tumors (except hematolymphoid cancers) to improve diagnosis, prognosis assessment and relapse therapeutics., Results: One hundred and ninety-eight patients (71%) underwent molecular biology (MB) at diagnosis. Thirty-eight different histologies were grouped into cerebral tumors (30%), sarcomas (26%, bone and soft tissues), various blastomas (27%), and other entities (17%). Over a median 40-month follow-up, the overall survival rate of patients was 85% and the relapse rate 28%. Of the 326 analyses carried out, 245 abnormalities (single nucleotide variations: 50%, fusions: 25%, copy number alteration: 20%) concerning 70 oncogenes were highlighted. The overall clinical impact rate was 84%. Broad-spectrum analyses had a higher therapeutic impact (57%) than the targeted analyses (28%). 75% of broad-spectrum tests found an actionable variant conducting 23% of patients to receive rapidly a matched targeted therapy since first relapse., Conclusion: Our experience highlighted the clinical utility of molecular profiling of solid tumors as soon as at diagnosis in children to expect improving access to innovative agents at relapse., (© 2024. The Author(s).)

Background: The prevalence of post-surgical lumbar neuropathic radiculopathy is approximately 30%. Poor response to the recommended treatments for neuropathic pain, namely antidepressants and/or gabapentinoids, requires the development of new techniques to prevent chronic pain. One such well-tolerated technique is the administration of autologous plasma enriched in platelets and fibrin (PRF). This approach is largely used in regenerative medicine owing to the anti-inflammatory and analgesic properties of PRF. It could also be an interesting adjuvant to surgery, as it reduces neurogenic inflammation and promotes nerve recovery, thereby reducing the incidence of residual postoperative chronic pain. The aim of the present study is to evaluate the benefit of periradicular intraoperative application of PRF on the residual postsurgical neuropathic pain after disc herniation surgery., Methods: A randomized, prospective, interventional, controlled, single-blind study with evaluation by a blind outcome assessor will be performed in Strasbourg University Hospital. We will compare a control group undergoing conventional surgery to an experimental group undergoing surgery and periradicular administration of PRF (30 patients in each arm). The primary outcome is the intensity of postoperative neuropathic radicular pain, measured by a visual analog scale (VAS) at 6 months post-surgery. The secondary outcomes are the characteristics of neuropathic pain (NPSI), the quality of life (SF-12 and PGIC), the presence of anxiety/depression symptoms (HAD), and the consumption of analgesics. We will also carry out transcriptomic analysis of a panel of pro- and anti-inflammatory cytokines in blood samples, before surgery and at 6 months follow-up. These gene expression results will be correlated with clinical data, in particular, with the apparition of postoperative neuropathic pain., Discussion: This study is the first randomized controlled trial to assess the efficacy of PRF in the prevention of neuropathic pain following surgery for herniated disc. This study addresses not only a clinical question but will also provide information on the physiopathological mechanisms of neuropathic pain., Trial Registration: This study is registered at ClinicalTrials.gov: NCT05196503 , February 24, 2022., (© 2023. The Author(s).)

Background: In survival analysis, data can be modeled using either a multiplicative hazards regression model (such as the Cox model) or an additive hazards regression model (such as Lin's or Aalen's model). While several diagnostic tools are available to check the assumptions underpinning each type of model, there is no defined procedure to fit these models optimally. Moreover, the two types of models are rarely combined in survival analysis. Here, we propose a strategy for optimal fitting of multiplicative and additive hazards regression models in survival analysis., Methods: This section details our proposed strategy for optimal fitting of multiplicative and additive hazards regression models, with a focus on the assumptions underpinning each type of model, the diagnostic tools used to check these assumptions, and the steps followed to fit the data. The proposed strategy draws on classical diagnostic tools (Schoenfeld and martingale residuals) and less common tools (pseudo-observations, martingale residual processes, and Arjas plots)., Results: The proposed strategy is applied to a dataset of patients with myocardial infarction (TRACE data frame). The effects of 5 covariates (age, sex, diabetes, ventricular fibrillation, and clinical heart failure) on the hazard of death are analyzed using multiplicative and additive hazards regression models. The proposed strategy is shown to fit the data optimally., Conclusions: Survival analysis is improved by using multiplicative and additive hazards regression models together, but specific steps must be followed to fit the data optimally. By providing different measures of the same effect, our proposed strategy allows for better interpretation of the data.

Background: Macrocyclic lactone (ML) anthelmintics are used for chemoprophylaxis for heartworm infection in dogs and cats. Cases of dogs becoming infected with heartworms, despite apparent compliance to recommended chemoprophylaxis with approved preventives, has led to such cases being considered as suspected lack of efficacy (LOE). Recently, microfilariae collected from a small number of LOE isolates were used as a source of infection of new host dogs and confirmed to have reduced susceptibility to ML in controlled efficacy studies using L3 challenge in dogs. A specific Dirofilaria immitis laboratory isolate named JYD-34 has also been confirmed to have less than 100% susceptibility to ML-based preventives. For preventive claims against heartworm disease, evidence of 100% efficacy is required by FDA-CVM. It was therefore of interest to determine whether JYD-34 has a genetic profile similar to other documented LOE and confirmed reduced susceptibility isolates or has a genetic profile similar to known ML-susceptible isolates., Methods: In this study, the 90Mbp whole genome of the JYD-34 strain was sequenced. This genome was compared using bioinformatics tools to pooled whole genomes of four well-characterized susceptible D. immitis populations, one susceptible Missouri laboratory isolate, as well as the pooled whole genomes of four LOE D. immitis populations. Fixation indexes (F ST ), which allow the genetic structure of each population (isolate) to be compared at the level of single nucleotide polymorphisms (SNP) across the genome, have been calculated. Forty-one previously reported SNP, that appeared to differentiate between susceptible and LOE and confirmed reduced susceptibility isolates, were also investigated in the JYD-34 isolate., Results: The F ST analysis, and the analysis of the 41 SNP that appeared to differentiate reduced susceptibility from fully susceptible isolates, confirmed that the JYD-34 isolate has a genome similar to previously investigated LOE isolates, and isolates confirmed to have reduced susceptibility, and to be dissimilar to the susceptible isolates., Conclusions: These results provide additional evidence for the link between genotype and the reduced susceptibility phenotype observed in such isolates as JYD-34. Further work on other isolates showing reduced susceptibility to ML is required to demonstrate the value of genetic analysis in predicting the response to ML chemoprophylaxis. The authors suggest that genetic analysis may be useful in helping to interpret the results of in vivo efficacy testing of ML heartworm preventives against D. immitis isolates.

Background: The aim of the present national prospective population-based study was to assess the early morbidity of esophageal atresia (EA)., Methods: All 38 multidisciplinary French centers that care for patients with EA returned a specific questionnaire about the 1-year outcome for each patient. This information was centralized, checked, and entered into a database., Results: From the total population of 307 EA patients born in 2008 and 2009, data about the 1-year outcome were obtained from 301 (98%) patients, of whom 4% were lost to follow-up and 5% died. Medical complications occurred in 34% of the patients: anastomotic leaks (8%), recurrent tracheoesophageal fistula (4%), and anastomotic stenosis (22%); all of the latter group needed dilation (median, 2 dilations/patient). A new hospitalization was required for 59% of patients (2.5 hospitalizations/patient) for digestive (52%) or respiratory (48%) reasons. Twelve percent of patients required antireflux surgery at a median age of 164 days (range, 33-398 days), and 1% underwent an aortopexy for severe tracheomalacia. The weight/age Z-score was -0.8 (range, -5.5 to 3.7 months) at 12 months. Fifteen percent of patients were undernourished at 12 months of age, whereas 37% presented with respiratory symptoms and 15% had dysphagia at the last follow-up. Significant independent factors associated with medical complications were anastomotic esophageal tension (p = .0009) and presence of a gastrostomy (p = .0002); exclusive oral feeding at discharge was associated with a decreased risk of complications (p = .007)., Conclusions: Digestive and respiratory morbidities remain frequent during the first year of life and are associated with difficult anastomosis and lack of full oral feeding.

Background: Breast cancer is a major public health challenge. Organized mammography screening (OS) is considered one way to reduce breast cancer mortality. EU recommendations prone mass deployment of OS, and back in 2004, France introduced a national OS programme for women aged 50-74 years. However, in 2012, participation rate was still just 52.7%, well short of the targeted 70% objective. In an effort to re-address the (in) efficiency of the programme, the French National Cancer Institute has drafted an expert-group review of the ethical issues surrounding breast cancer mammography screening., Discussion: Prompted by emerging debate over the efficiency of the screening scheme and its allied public information provision, we keynote the experts' report based on analysis of epidemiological data and participation rate from the public health authorities. The low coverage of the OS scheme may be partly explained by the fact that a significant number of women undergo mammography outside OS and thus outside OS criteria. These findings call for further thinking on (i) the ethical principles of beneficence and non-malfeasance underpinning this public health initiative, (ii) the reasons behind women's and professionals' behavior, and (iii) the need to analyze how information provision to women and the doctor-patient relationship need to evolve in response to scientific controversy over the risks and benefits of conducting mammographic screening., Summary: This work calls for a reappraisal of the provision of screening programme information. We advocate a move to integrate the points sparking debate over the efficiency of the screening scheme to guarantee full transparency. The perspective is to strengthen the respect for autonomy allowing women to make an informed choice in their decision on whether or not to participate.

Background: Truck driving is the second most common occupation among Canadian men. Transportation of goods via roads is of crucial importance for the Canadian economy. The industry is responsible annually for $17 billion in GDP and is projected to increase by 28% over the next 10 years. Recruitment is an issue with 20% of drivers projected to retire or leave the profession in the next 10 years. Despite the reliance on transport truck drivers for the delivery of goods which affects Canada's economy and daily living of residents, little is known about the health care needs of this large cohort of primarily male lone workers from a drivers' perspective. Transport truck drivers are independent workers whose non traditional workplace is their tractor, the truck stops and the journey on the road.The objective of this study was to obtain a contextually informed description of lifestyle issues, health and disease risk factors experienced by drivers and perceived by their managers in the truck driving occupation., Methods: Using a grounded theory approach, 4 focus groups were conducted with drivers (n = 16) and managers (n = 10) from two trucking companies in Southwestern Ontario to identify the lived experience of the drivers as it relates to preventable risks to health and wellness. A semi structured guided interview was used to explore the lifestyle context of transport truck driving and organizational aspects of the occupation (workplace culture, working conditions and health and wellness promotion)., Results: The predominant themes described stress, workplace, communication, lifestyle, driving culture, family, and fatigue concerns. In terms of the transportation work environment, drivers and managers were aware of the profession's potential to foster lifestyle related chronic diseases but described challenges in making the profession more amenable to a healthy lifestyle., Conclusions: Workplace environmental determinants are significant in shaping health behaviours. Chronic disease health risks were the main health concerns identified. Health risks were exacerbated by working conditions (job demands, work hours, financial pressure and the sedentary nature of the job). Workplace health strategies will need to take into account the unique challenges of the occupation.

Background: Hypertension is an important and modifiable cardiovascular risk factor that remains under-detected and under-treated, especially in the older individuals. Community-led interventions that integrate primary health care and local resources are promising approaches to improve awareness and management of hypertension and other cardiovascular risk factors. We aimed to evaluate the effect of a community-based Cardiovascular Health Awareness Program (CHAP) on participants' blood pressure., Methods: This study followed a cohort of community residents that participated in CHAP across 22 mid-sized Ontario communities over an 18-month period. The participants' baseline risk factors, including blood pressure, and subsequent measures of blood pressure were recorded. We employed a bivariate linear mixed-effect model to estimate the change of systolic and diastolic blood pressure over time among the participants who attended more than two CHAP sessions., Results: Of 13,596 participants, 2498 attended more than two CHAP sessions. For those repeated participants (attending more than two sessions) initially identified with high blood pressure, the average reduction of systolic blood pressure was from 142 to 123 mmHg over an 18-month period, a monthly rate ratio of 0.992 (95% CI: 0.991,0.994; p < 0.01). Similarly, the average reduction of diastolic blood pressure was from 78 to 69 mmHg, a monthly rate ratio of 0.993 (95% CI: 0.991,0.994; p < 0.01). The average blood pressure of the participants with normal baseline blood pressure remained controlled and unchanged. We also found that older adult participants who lived alone, were diagnosed with hypertension, reported healthier eating habits, and presented with a higher baseline systolic blood pressure had significantly greater odds of attending more than one session., Conclusions: CHAP was associated with a reduction in systolic and diastolic blood pressure for those participants who attended more than one session. The magnitude of blood pressure reductions was significant clinically and statistically.

Background: Very low birthweight infants are at risk for deficits in cognitive and language development, as well as attention and behaviour problems. Maternal sensitive behaviour (i.e. awareness of infant cues and appropriate responsiveness to those cues) in interaction with her very low birthweight infant is associated with better outcomes in these domains; however, maternal anxiety interferes with the mother's ability to interact sensitively with her very low birthweight infant. There is a need for brief, cost-effective and timely interventions that address both maternal psychological distress and interactive behaviour. The Cues and Care trial is a randomized controlled trial of an intervention designed to reduce maternal anxiety and promote sensitive interaction in mothers of very low birthweight infants., Methods and Design: Mothers of singleton infants born at weights below 1500 g are recruited in the neonatal intensive care units of 2 tertiary care hospitals, and are randomly assigned to the experimental (Cues) intervention or to an attention control (Care) condition. The Cues intervention teaches mothers to attend to their own physiological, cognitive, and emotional cues that signal anxiety and worry, and to use cognitive-behavioural strategies to reduce distress. Mothers are also taught to understand infant cues and to respond sensitively to those cues. Mothers in the Care group receive general information about infant care. Both groups have 6 contacts with a trained intervener; 5 of the 6 sessions take place during the infant's hospitalization, and the sixth contact occurs after discharge, in the participant mother's home. The primary outcome is maternal symptoms of anxiety, assessed via self-report questionnaire immediately post-intervention. Secondary outcomes include maternal sensitive behaviour, maternal symptoms of posttraumatic stress, and infant development at 6 months corrected age., Discussion: The Cues and Care trial will provide important information on the efficacy of a brief, skills-based intervention to reduce anxiety and increase sensitivity in mothers of very low birthweight infants. A brief intervention of this nature may be more readily implemented as part of standard neonatal intensive care than broad-based, multi-component interventions. By intervening early, we aim to optimize developmental outcomes in these high risk infants., Trial Registration: Current Controlled Trials ISRCTN00918472. The Cues and Care Trial: A randomized controlled trial of an intervention to reduce maternal anxiety and improve developmental outcomes in very low birthweight infants.